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Verdelho Machado M. Refractory Celiac Disease: What the Gastroenterologist Should Know. Int J Mol Sci 2024; 25:10383. [PMID: 39408713 PMCID: PMC11477276 DOI: 10.3390/ijms251910383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 09/20/2024] [Accepted: 09/25/2024] [Indexed: 10/20/2024] Open
Abstract
Fewer than 1% of patients with celiac disease (CD) will develop refractory CD (RCD). As such, most gastroenterologists might never need to manage patients with RCD. However, all gastroenterologists must be familiarized with the basic concepts of RCD and non-responsive CD (NRCD), since it can present as a severe disease with high mortality, not only due to intestinal failure, but also due to progression to enteropathy-associated T cell lymphoma (EATL) and a higher susceptibility to life-threatening infections. The diagnostic workup and differential diagnosis with other causes of gastrointestinal symptoms and villous atrophy, as well as the differentiation between type I and II RCD, are complex, and may require specialized laboratories and reference hospitals. Immunosuppression is efficient in the milder RCDI; however, the treatment of RCDII falls short, with current options probably only providing transient clinical improvement and delaying EATL development. This review summarizes the current diagnostic and therapeutic approach for patients with RCD that all doctors that manage patients with CD should know.
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Affiliation(s)
- Mariana Verdelho Machado
- Gastroenterology Department, Hospital de Vila Franca de Xira, 2600-009 Lisbon, Portugal; ; Tel.: +351-912620306
- Gastroenterology Department, Faculdade de Medicina, Lisbon University, 1649-028 Lisboa, Portugal
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2
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Viteri C, Arteaga C, Robayo V, Hidalgo K, Guevara D. Trends in Nutrition and Andean Food for People with Celiac Disease: A review study. SALUD, CIENCIA Y TECNOLOGÍA - SERIE DE CONFERENCIAS 2024; 3. [DOI: 10.56294/sctconf2024.1177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Celiac disease is characterized by nutritional imbalances due to intestinal inflammation caused by gluten, which hinders the absorption of essential nutrients. Iron deficiency anemia is common, as well as the lack of vitamins and minerals, some of which are reversed with a gluten-free diet. Andean foods constitute an option in the diet of celiac patients due to their high nutritional quality in proteins, carbohydrates, vitamins, minerals, and fiber, which are generally deficient nutrients. Studies suggest that products such as quinoa, corn, and rice can be viable substitutes in baking, extruded products, and beverages, offering nutritious and acceptable options. However, despite the positive trend towards including these foods in the diet of people with CD, challenges are identified, such as nutritional education to promote their consumption. In conclusion, it is suggested that Andean nutrition and food offer valuable options for people with CD, but effective strategies are needed to integrate them into patients' diets
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Simón E, Molero-Luis M, Fueyo-Díaz R, Costas-Batlle C, Crespo-Escobar P, Montoro-Huguet MA. The Gluten-Free Diet for Celiac Disease: Critical Insights to Better Understand Clinical Outcomes. Nutrients 2023; 15:4013. [PMID: 37764795 PMCID: PMC10537989 DOI: 10.3390/nu15184013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 09/10/2023] [Accepted: 09/15/2023] [Indexed: 09/29/2023] Open
Abstract
The gluten-free diet (GFD) remains a complex paradigm in managing celiac disease (CeD) in children and adults, and there are many reasons why GFD adherence should be strict to improve outcomes. However, this is a challenging task for patients, since they need to have access to quality healthcare resources that facilitate optimal GFD adherence. Understanding the strengths and weaknesses of the GFD, tackling coexisting nutritional deficiencies, and dealing with complex situations, such as seronegative CeD or non-responsive CeD, all require the involvement of a multidisciplinary team. The short- and long-term follow-up of CeD patients should preferably be performed by a combined Gastroenterology and Nutrition service with well-defined quality standards and the multidisciplinary involvement of physicians, nurses, dietitians, and psychologists. Nutritional advice and counseling by an experienced dietitian can reduce the costs associated with long-term follow-up of CeD patients. Likewise, psychological interventions may be essential in specific scenarios where implementing and sustaining a lifelong GFD can cause a significant psychological burden for patients. This manuscript aims to provide guidelines to improve clinical practice in the follow-up and monitoring of CeD patients and provide information on the nutritional risks of an ill-advised GFD. Clinicians, biochemists, food technologists, dietitians, and psychologists with a global view of the disease have been involved in its writing.
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Affiliation(s)
- Edurne Simón
- GLUTEN3S Research Group, Department of Nutrition and Food Science, University of the Basque Country, 01006 Vitoria-Gasteiz, Spain
| | - Marta Molero-Luis
- Laboratory of Gastroenterology and Trace Elements, Department of Laboratory Medicine, Hospital Universitario La Paz, 28046 Madrid, Spain
| | - Ricardo Fueyo-Díaz
- PROSAM Research Group (S69-23R), Department of Psychology and Sociology, Universidad de Zaragoza, 50009 Zaragoza, Spain
| | - Cristian Costas-Batlle
- Department of Nutrition and Dietetics, Bradford Teaching Hospitals NHS Foundation Trust, Bradford BD9 6DA, UK
| | - Paula Crespo-Escobar
- ADViSE Research Group, Department of Health Science, European University Miguel de Cervantes, 47012 Valladolid, Spain
- Department of Nutrition and Obesity, Hospital Recoletas Campo Grande, 47007 Valladolid, Spain
| | - Miguel A Montoro-Huguet
- Gastroenterology, Hepatology and Nutrition Unit, University Hospital San Jorge, 22004 Huesca, Spain
- Department of Medicine, Faculty of Health and Sport Sciences, University of Zaragoza, 22002 Huesca, Spain
- Aragon Health Research Institute (IIS Aragon), 50009 Zaragoza, Spain
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4
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Hu B, Lin ZY, Cai Y, Sun YX, Yang SQ, Guo JL, Zhang S, Sun DL. A cross-sectional study on the effect of dietary zinc intake on the relationship between serum vitamin D3 and HOMA-IR. Front Nutr 2022; 9:945811. [PMID: 36352900 PMCID: PMC9638013 DOI: 10.3389/fnut.2022.945811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 10/06/2022] [Indexed: 11/18/2022] Open
Abstract
Introduction Serum vitamin D3 concentration is associated with the risk of insulin resistance. Zinc has also been reported to be associated with a lower risk of insulin resistance. In addition, zinc is an essential cofactor in the activation of vitamin D3. However, the effect of dietary zinc intake on the relationship between vitamin D3 and insulin resistance risk has not been fully studied. Therefore, we designed this cross-sectional study to assess the impact of changes in zinc intake on the relationship between vitamin D3 and insulin resistance risk. Study design and methods This study analyzed data from the national Health and Nutrition Examination Survey (NHANES) from 2005 to 2018, involving 9,545 participants. Participants were stratified by zinc intake category (low zinc intake <9.58 mg/ day; High zinc intake: ≥9.58 mg/ day). Results In this cross-sectional study, serum vitamin D3 levels were independently associated with the risk of insulin resistance in both the low and high Zinc intakes (β: −0.26, 95%Cl: −0.56~0.04 vs. β: −0.56, 95%Cl: −1.01~-0.11). In addition, this association was influenced by different dietary zinc intakes (interaction P < 0.05). Conclusions Our results suggest that zinc intake may influence the association between serum vitamin D3 and the risk of insulin resistance. Further randomized controlled trials are needed to provide more evidence of this finding.
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Affiliation(s)
- Biao Hu
- Department of Clinical Medicine, The Second Clinical School of Guangzhou Medical University, Guangzhou, China
| | - Zheng-yang Lin
- Department of Clinical Medicine, The Second Clinical School of Guangzhou Medical University, Guangzhou, China
| | - Yuan Cai
- Department of Preventive Medicine, School of Public Health, Guangzhou Medical University, Guangzhou, China
| | - Yue-xin Sun
- Department of Clinical Medicine, The Second Clinical School of Guangzhou Medical University, Guangzhou, China
| | - Shu-qi Yang
- Department of Clinical Medicine, The Second Clinical School of Guangzhou Medical University, Guangzhou, China
| | - Jiang-long Guo
- Department of Medical Imaging, The Second Clinical School of Guangzhou Medical University, Guangzhou, China
| | - Shi Zhang
- Department of Clinical Medicine, The Second Clinical School of Guangzhou Medical University, Guangzhou, China
- *Correspondence: Shi Zhang
| | - Dong-lin Sun
- Guangzhou Medical University, Guangzhou, China
- Dong-lin Sun
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5
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Kvamme JM, Sørbye S, Florholmen J, Halstensen TS. Population-based screening for celiac disease reveals that the majority of patients are undiagnosed and improve on a gluten-free diet. Sci Rep 2022; 12:12647. [PMID: 35879335 PMCID: PMC9314380 DOI: 10.1038/s41598-022-16705-2] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 07/14/2022] [Indexed: 12/30/2022] Open
Abstract
The impact of a gluten-free diet (GFD) on screen-detected celiac disease (CD) is currently ambiguous. We aimed to identify the population-based prevalence of undiagnosed adult CD and examine the impact of a GFD on screen-detected CD. In total, 12,981 adults participated in a population-based health study in Tromsø, Norway. Participants with increased levels of anti-tissue transglutaminase-2 IgA or anti-deamidated gliadin peptide IgG were invited to undergo gastroduodenoscopy with both histological and immunohistochemical examination of small-bowel biopsies. The prevalence of previously diagnosed CD was 0.37%. Additionally, the prevalence of previously undiagnosed CD was 1.10%. Thus, 1.47% of the population had CD, of whom 75% were previously undiagnosed. A GFD resulted in significant improvements in overall gastrointestinal symptoms, diarrhea, and health-related quality of life, with reduced abdominal discomfort (76%) and improved levels of energy (58%). The large majority of patients with adult CD were undiagnosed and benefited from a GFD with reduced gastrointestinal symptoms and improved health-related quality of life. In clinical practice, there should be a low threshold for CD testing even in the absence of abdominal complaints because most adult patients appear to consider their symptoms a part of their normal state and therefore remain untested and undiagnosed.Trial registration: Clinical Trials. Gov Identifier: NCT01695681.
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Affiliation(s)
- Jan-Magnus Kvamme
- Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, 9037, Tromsø, Norway. .,Department of Gastroenterology, University Hospital of North Norway, 9037, Tromsø, Norway.
| | - Sveinung Sørbye
- Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, 9037, Tromsø, Norway.,Department of Pathology, University Hospital of North Norway, 9037, Tromsø, Norway
| | - Jon Florholmen
- Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, 9037, Tromsø, Norway
| | - Trond S Halstensen
- Institute of Oral Biology, University of Oslo, P.O. Box 1052, 0316, OsloBlindern, Norway.,Medical Department, Lovisenberg Diaconal Hospital, Oslo, Norway
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Systematic approach to celiac disease: a comprehensive review for primary providers. ROMANIAN JOURNAL OF INTERNAL MEDICINE 2022; 60:93-102. [DOI: 10.2478/rjim-2022-0002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Indexed: 11/20/2022] Open
Abstract
Abstract
Celiac disease is an immune-mediated illness to gluten exposure in genetically susceptible patients. It is characterized by chronic lymphocytic inflammation of the small bowel leading to villous atrophy and its associated complications. The global prevalence of celiac disease is increasing, due in part to improved screening tests and simplified diagnostic criteria. Novel therapies are being developed and include proteolytic enzymes, sequestering agents, and immunotherapies. A strict gluten-free diet, however, remains the mainstay of treatment. In this comprehensive review, we discuss the epidemiology, definitions, diagnosis, and treatment of celiac disease.
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7
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The Role of Pseudocereals in Celiac Disease: Reducing Nutritional Deficiencies to Improve Well-Being and Health. J Nutr Metab 2022; 2022:8502169. [PMID: 35186332 PMCID: PMC8850039 DOI: 10.1155/2022/8502169] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 12/16/2021] [Accepted: 01/11/2022] [Indexed: 12/19/2022] Open
Abstract
Celiac disease or gluten-dependent enteropathy is a chronic autoimmune pathology triggered by dietary gluten in genetic predisposed individuals, mediated by transglutaminase 2 IgA autoantibodies and associated with a deteriorating immune and inflammatory response. This leads to intestinal villous atrophy, impairing the intestinal mucosa structure and function of secretion, digestion, and absorption. The result is macro- and micronutrient deficiency, including fat soluble vitamins and minerals, and a consequent nutritional status depletion. A lifelong gluten-free diet is the only available treatment for celiac patients in order to assure normal intestinal mucosa and remission of gastrointestinal symptoms. However, a gluten-free diet can itself cause other nutritional deficiencies due to its restrictive nature regarding gluten-containing cereals. A group of gluten-free cereals, known as pseudocereals, is increasingly recognized as valuable options for gluten-free diets due to their high nutritional value. Amaranth, quinoa, millet, and buckwheat are examples of gluten-free nutrient-dense grains that can be used as alternatives to the conventional gluten-containing grains and improve the variety and nutritional quality of the celiac diet. Current work reviews the nutritional pitfalls of a gluten-free diet and analyses how pseudocereals can contribute to revert those deficiencies and optimize the nutritional value of this mandatory diet for the celiac population.
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8
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Tarar ZI, Zafar MU, Farooq U, Basar O, Tahan V, Daglilar E. The Progression of Celiac Disease, Diagnostic Modalities, and Treatment Options. J Investig Med High Impact Case Rep 2021; 9:23247096211053702. [PMID: 34693776 PMCID: PMC8767653 DOI: 10.1177/23247096211053702] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Celiac disease (CD) is an autoimmune disorder that affects genetically predisposed individuals who are sensitive to gluten and related proteins. It affects children and adults with increasing prevalence in the older age groups. Both adaptive and innate immune responses play role in CD pathogenesis which results in damage of lamina propria and deposition of intraepithelial lymphocytes. There are other proposed mechanisms of CD pathogenesis like gastrointestinal infections, intestinal microbiota, and early introduction of gluten. The diagnosis of CD is based on clinical symptoms and serological testing, though a majority of cases are asymptomatic, and small intestinal biopsies are required to confirm the diagnosis. Celiac disease is generally associated with other autoimmune diseases, and it is advisable to test these patients for diseases like type 1 diabetes mellitus, Addison’s disease, thyroid diseases, inflammatory bowel disease, and autoimmune hepatitis. The patient with a new diagnosis of CD requires close follow-up after starting treatment to see symptom improvement and check dietary compliance. A newly diagnosed patient is advised to follow with a dietitian to better understand the dietary restrictions as about 20% of patients stay symptomatic even after starting treatment due to noncompliance or poor understanding of diet restrictions. The most effective treatment for CD is a gluten-free diet, but work on non-dietary therapy is in process and few medications are in the clinical trial phase.
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Affiliation(s)
| | | | - Umer Farooq
- Loyola Medicine/MacNeal Hospital, Berwyn, IL, USA
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Martín-Masot R, Ortiz Pérez P, Torcuato Rubio E, Blasco Alonso J, Herrador López M, Gallego Fernández C, Navas-López VM. The New Molecules Are Changing the Course of Pediatric Chronically Active Ulcerative Colitis: A Series of Pediatric Cases. JPGN REPORTS 2021; 2:e100. [PMID: 37205967 PMCID: PMC10191510 DOI: 10.1097/pg9.0000000000000100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Accepted: 06/08/2021] [Indexed: 05/21/2023]
Abstract
Chronically active ulcerative colitis (UC) constitutes a challenge in an era where medical therapeutic options have increased while experience with colectomies has decreased. The change in the therapeutic paradigm of the disease means that patients with chronically active UC are being managed waiting to find their therapeutic target. We present 2 cases of children with chronically active UC who did not respond to intravenous steroids nor sequential therapy. A response was obtained with ustekinumab and tofacitinib, 2 drugs widely used in adults but still with little evidence in children. Highlighting the important role of patients and their families helped decision-making, facilitating the work of the medical team. With multidisciplinary management and close follow-up, they have been able to avoid surgery entering complete clinical remission.
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Affiliation(s)
- Rafael Martín-Masot
- From the Pediatric Gastroenterology and Nutrition Unit, Hospital Regional Universitario de Málaga, Málaga, Spain
| | - Pilar Ortiz Pérez
- From the Pediatric Gastroenterology and Nutrition Unit, Hospital Regional Universitario de Málaga, Málaga, Spain
| | - Encarnación Torcuato Rubio
- From the Pediatric Gastroenterology and Nutrition Unit, Hospital Regional Universitario de Málaga, Málaga, Spain
| | - Javier Blasco Alonso
- From the Pediatric Gastroenterology and Nutrition Unit, Hospital Regional Universitario de Málaga, Málaga, Spain
| | - Marta Herrador López
- From the Pediatric Gastroenterology and Nutrition Unit, Hospital Regional Universitario de Málaga, Málaga, Spain
| | - Carmen Gallego Fernández
- From the Pediatric Gastroenterology and Nutrition Unit, Hospital Regional Universitario de Málaga, Málaga, Spain
| | - Víctor Manuel Navas-López
- From the Pediatric Gastroenterology and Nutrition Unit, Hospital Regional Universitario de Málaga, Málaga, Spain
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10
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Persistent Alterations in Plasma Lipid Profiles Before Introduction of Gluten in the Diet Associated With Progression to Celiac Disease. Clin Transl Gastroenterol 2020; 10:1-10. [PMID: 31082858 PMCID: PMC6602763 DOI: 10.14309/ctg.0000000000000044] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Celiac disease (CD) is a chronic enteropathy characterized by an autoimmune reaction in the small intestine of genetically susceptible individuals. The underlying causes of autoimmune reaction and its effect on host metabolism remain largely unknown. Herein, we apply lipidomics to elucidate the early events preceding clinical CD in a cohort of Finnish children, followed up in the Type 1 Diabetes Prediction and Prevention study.
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11
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Ho SSC, Keenan JI, Day AS. The Role of Gastrointestinal-Related Fatty Acid-Binding Proteins as Biomarkers in Gastrointestinal Diseases. Dig Dis Sci 2020; 65:376-390. [PMID: 31529416 DOI: 10.1007/s10620-019-05841-x] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Accepted: 09/10/2019] [Indexed: 12/14/2022]
Abstract
The fatty acid-binding proteins play a major role in intracellular transportation of long-chain fatty acids. Nine fatty acid-binding proteins have been identified, with each having individual tissue-specific functions in addition to regulation of fatty acids. This review focuses on the three fatty acid-binding proteins found in the gastrointestinal tract and discusses their role as diagnostic or disease monitoring markers in neonatal necrotizing enterocolitis, acute mesenteric ischemia, celiac disease, and inflammatory bowel disease. Of these three fatty acid-binding proteins, intestinal fatty acid-binding protein is of the most interest due to its exclusive expression in the gastrointestinal tract. The elevation of intestinal fatty acid-binding protein in blood and urine reflects enterocyte damage, regardless of the underlying cause. The short half-life of intestinal fatty acid-binding protein also means it is a relatively sensitive marker. In contrast, there is currently less evidence to support liver fatty acid-binding protein and ileal bile acid-binding protein as sensitive biomarkers in these conditions. More extensive studies with specific endpoints are required to validate the roles of these fatty acid-binding proteins in gastrointestinal diseases.
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Affiliation(s)
- Shaun S C Ho
- Department of Paediatrics, University of Otago Christchurch, 2 Riccarton Avenue, Christchurch, 8011, New Zealand
| | - Jacqueline I Keenan
- Department of Surgery, University of Otago Christchurch, 2 Riccarton Avenue, Christchurch, 8011, New Zealand
| | - Andrew S Day
- Department of Paediatrics, University of Otago Christchurch, 2 Riccarton Avenue, Christchurch, 8011, New Zealand.
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12
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Multifactorial Etiology of Anemia in Celiac Disease and Effect of Gluten-Free Diet: A Comprehensive Review. Nutrients 2019; 11:nu11112557. [PMID: 31652803 PMCID: PMC6893537 DOI: 10.3390/nu11112557] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Revised: 10/14/2019] [Accepted: 10/15/2019] [Indexed: 12/13/2022] Open
Abstract
Celiac disease (CD) is a multisystemic disorder with different clinical expressions, from malabsorption with diarrhea, anemia, and nutritional compromise to extraintestinal manifestations. Anemia might be the only clinical expression of the disease, and iron deficiency anemia is considered one of the most frequent extraintestinal clinical manifestations of CD. Therefore, CD should be suspected in the presence of anemia without a known etiology. Assessment of tissue anti-transglutaminase and anti-endomysial antibodies are indicated in these cases and, if positive, digestive endoscopy and intestinal biopsy should be performed. Anemia in CD has a multifactorial pathogenesis and, although it is frequently a consequence of iron deficiency, it can be caused by deficiencies of folate or vitamin B12, or by blood loss or by its association with inflammatory bowel disease (IBD) or other associated diseases. The association between CD and IBD should be considered during anemia treatment in patients with IBD, because the similarity of symptoms could delay the diagnosis. Vitamin B12 deficiency is common in CD and may be responsible for anemia and peripheral myeloneuropathy. Folate deficiency is a well-known cause of anemia in adults, but there is little information in children with CD; it is still unknown if anemia is a symptom of the most typical CD in adult patients either by predisposition due to the fact of age or because biochemical and clinical manifestations take longer to appear.
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13
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Caio G, Volta U, Sapone A, Leffler DA, De Giorgio R, Catassi C, Fasano A. Celiac disease: a comprehensive current review. BMC Med 2019; 17:142. [PMID: 31331324 PMCID: PMC6647104 DOI: 10.1186/s12916-019-1380-z] [Citation(s) in RCA: 531] [Impact Index Per Article: 88.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 06/27/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Celiac disease remains a challenging condition because of a steady increase in knowledge tackling its pathophysiology, diagnosis, management, and possible therapeutic options. MAIN BODY A major milestone in the history of celiac disease was the identification of tissue transglutaminase as the autoantigen, thereby confirming the autoimmune nature of this disorder. A genetic background (HLA-DQ2/DQ8 positivity and non-HLA genes) is a mandatory determinant of the development of the disease, which occurs with the contribution of environmental factors (e.g., viral infections and dysbiosis of gut microbiota). Its prevalence in the general population is of approximately 1%, with female predominance. The disease can occur at any age, with a variety of symptoms/manifestations. This multifaceted clinical presentation leads to several phenotypes, i.e., gastrointestinal, extraintestinal, subclinical, potential, seronegative, non-responsive, and refractory. Although small intestinal biopsy remains the diagnostic 'gold standard', highly sensitive and specific serological tests, such as tissue transglutaminase, endomysial and deamidated gliadin peptide antibodies, have become gradually more important in the diagnostic work-up of celiac disease. Currently, the only treatment for celiac disease is a life-long, strict gluten-free diet leading to improvement in quality of life, ameliorating symptoms, and preventing the occurrence of refractory celiac disease, ulcerative jejunoileitis, and small intestinal adenocarcinoma and lymphoma. CONCLUSIONS The present review is timely and provides a thorough appraisal of various aspects characterizing celiac disease. Remaining challenges include obtaining a better understanding of still-unclear phenotypes such as slow-responsive, potential (minimal lesions) and seronegative celiac disease. The identification of alternative or complementary treatments to the gluten-free diet brings hope for patients unavoidably burdened by diet restrictions.
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Affiliation(s)
- Giacomo Caio
- Department of Medical Sciences, University of Ferrara, Via Aldo Moro 8, Cona, 44124 Ferrara, Italy
- Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA 02114 USA
| | - Umberto Volta
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy
| | - Anna Sapone
- Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA 02114 USA
- Takeda Pharmaceuticals International Co, Cambridge, MA 02139 USA
| | - Daniel A. Leffler
- Takeda Pharmaceuticals International Co, Cambridge, MA 02139 USA
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA 02115 USA
| | - Roberto De Giorgio
- Department of Medical Sciences, University of Ferrara, Via Aldo Moro 8, Cona, 44124 Ferrara, Italy
| | - Carlo Catassi
- Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA 02114 USA
- Department of Pediatrics, Center for Celiac Research, Università Politecnica delle Marche, 60121 Ancona, Italy
| | - Alessio Fasano
- Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA 02114 USA
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14
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Alimetov AY, Poliakov PP, Onopriev AV, Avakimyan AV, Zanin SA, Kade AK. Сapsule endoscopy for diagnosis of celiac disease. TERAPEVT ARKH 2019; 91:91-96. [PMID: 31094178 DOI: 10.26442/00403660.2019.02.000068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
In this review we analyzed the guidelines for diagnosis and management of celiac disease, as well as the recent studies published on this issue. Capsule endoscopy could be used in patients unwilling or unable to undergo conventional endoscopy, in patients who have discordant results between serological and histopathological investigation, in patients with nonresponsive or refractory celiac disease.
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Affiliation(s)
- A Ya Alimetov
- Kuban State Medical University of the Ministry of Health of the Russian Federation, Krasnodar, Russia.,Krasnodar Municipal Clinical Emergency Hospital, Krasnodar, Russia
| | - P P Poliakov
- Kuban State Medical University of the Ministry of Health of the Russian Federation, Krasnodar, Russia
| | - A V Onopriev
- Kuban State Medical University of the Ministry of Health of the Russian Federation, Krasnodar, Russia
| | - A V Avakimyan
- Regional Clinical Hospital №2, Krasnodar, Russia.,Klinika-A OOO (Limited Liability Company), Krasnodar, Russia
| | - S A Zanin
- Kuban State Medical University of the Ministry of Health of the Russian Federation, Krasnodar, Russia
| | - A Kh Kade
- Kuban State Medical University of the Ministry of Health of the Russian Federation, Krasnodar, Russia
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15
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Dennis M, Lee AR, McCarthy T. Nutritional Considerations of the Gluten-Free Diet. Gastroenterol Clin North Am 2019; 48:53-72. [PMID: 30711211 DOI: 10.1016/j.gtc.2018.09.002] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/16/2023]
Abstract
Celiac disease (CD) is an autoimmune-related disease causing inflammation in the small intestine triggered by the ingestion of gluten in the diet. The gluten-free diet (GFD) is the only treatment. Nutritional deficiencies of macronutrients and micronutrients are frequently found in untreated or newly diagnosed CD. A registered dietitian nutritionist is uniquely qualified to educate on the GFD and assess and support nutritional status at diagnosis and long term as well as helping patients with nonresponsive CD. Quality of life is important to address in individuals with CD because the GFD affects all aspects of life.
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Affiliation(s)
- Melinda Dennis
- Celiac Center, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Dana 603, Boston, MA 02215, USA
| | - Anne R Lee
- Celiac Disease Center at Columbia University Medical Center, Harkness Pavilion, 180 Fort Washington Avenue, 9th Floor, Suite 936, New York, NY 10032, USA.
| | - Tara McCarthy
- Division of Gastroenterology, Hepatology and Nutrition, Celiac Center, Boston Children's Hospital, 330 Longwood Avenue, Boston, MA 02215, USA
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Gliszczyńska-Świgło A, Klimczak I, Rybicka I. Chemometric analysis of minerals in gluten-free products. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2018; 98:3041-3048. [PMID: 29194641 DOI: 10.1002/jsfa.8803] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Revised: 11/09/2017] [Accepted: 11/26/2017] [Indexed: 06/07/2023]
Abstract
BACKGROUND Numerous studies indicate mineral deficiencies in people on a gluten-free (GF) diet. These deficiencies may indicate that GF products are a less valuable source of minerals than gluten-containing products. In the study, the nutritional quality of 50 GF products is discussed taking into account the nutritional requirements for minerals expressed as percentage of recommended daily allowance (%RDA) or percentage of adequate intake (%AI) for a model celiac patient. Elements analyzed were calcium, potassium, magnesium, sodium, copper, iron, manganese, and zinc. Analysis of %RDA or %AI was performed using principal component analysis (PCA) and hierarchical cluster analysis (HCA). RESULTS Using PCA, the differentiation between products based on rice, corn, potato, GF wheat starch and based on buckwheat, chickpea, millet, oats, amaranth, teff, quinoa, chestnut, and acorn was possible. In the HCA, four clusters were created. The main criterion determining the adherence of the sample to the cluster was the content of all minerals included to HCA (K, Mg, Cu, Fe, Mn); however, only the Mn content differentiated four formed groups. CONCLUSION GF products made of buckwheat, chickpea, millet, oats, amaranth, teff, quinoa, chestnut, and acorn are better source of minerals than based on other GF raw materials, what was confirmed by PCA and HCA. © 2017 Society of Chemical Industry.
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Affiliation(s)
| | - Inga Klimczak
- Faculty of Commodity Science, Poznan University of Economics and Business, Poznan, Poland
| | - Iga Rybicka
- Faculty of Commodity Science, Poznan University of Economics and Business, Poznan, Poland
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17
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Fukunaga M, Ishimura N, Fukuyama C, Izumi D, Ishikawa N, Araki A, Oka A, Mishiro T, Ishihara S, Maruyama R, Adachi K, Kinoshita Y. Celiac disease in non-clinical populations of Japan. J Gastroenterol 2018; 53:208-214. [PMID: 28389733 DOI: 10.1007/s00535-017-1339-9] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2016] [Accepted: 03/28/2017] [Indexed: 02/04/2023]
Abstract
BACKGROUND Celiac disease is a chronic autoimmune enteropathy caused by gluten ingestion. While its prevalence in Western countries is reported to be as high as 1%, the prevalence has not been evaluated in a large-scale study of a Japanese population. The aim of our study was to clarify the possible presence of celiac disease in a Japanese non-clinical population as well as in patients showing symptoms suggestive of the disease. METHODS Serum samples were collected from 2008 non-clinical adults and 47 patients with chronic unexplained abdominal symptoms between April 2014 and June 2016. The anti-tissue transglutaminase (TTG) immunoglobulin A antibody titer was determined as a screening test for celiac disease in all subjects, and individuals with a value of >2 U/mL subsequently underwent testing for the presence of serum endomysial IgA antibody (EMA) as confirmation. Those testing positive for EMA or with a high concentration (>10 U/mL) of TTG were further investigated by histopathological examinations of duodenal mucosal biopsy specimens and HLA typing tests. RESULTS Of the 2008 non-clinical adults from whom serum samples were collected, 161 tested positive for TTG, and all tested negative for EMA. Four subjects who had a high TTG titer were invited to undergo confirmatory testing, and the histopathological results confirmed the presence of celiac disease in only a single case (0.05%). Of the 47 symptomatic patients, one (2.1%) was found to have a high TTG titer and was diagnosed with celiac disease based on duodenal histopathological findings. CONCLUSION The presence of celiac disease in a non-clinical Japanese population was low at 0.05% and was rarely found in patients with unexplained chronic abdominal symptoms.
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Affiliation(s)
- Mai Fukunaga
- Department of Gastroenterology and Hepatology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan
| | - Norihisa Ishimura
- Department of Gastroenterology and Hepatology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan.
| | - Chika Fukuyama
- Department of Gastroenterology and Hepatology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan
| | - Daisuke Izumi
- Department of Gastroenterology and Hepatology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan
| | - Nahoko Ishikawa
- Department of Pathology, Shimane University School of Medicine, Izumo, Japan
| | - Asuka Araki
- Department of Pathology, Shimane University School of Medicine, Izumo, Japan
| | - Akihiko Oka
- Department of Gastroenterology and Hepatology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan
| | - Tomoko Mishiro
- Health Center, Shimane Environment and Health Public Corporation, Matsue, Japan
| | - Shunji Ishihara
- Department of Gastroenterology and Hepatology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan
| | - Riruke Maruyama
- Department of Pathology, Shimane University School of Medicine, Izumo, Japan
| | - Kyoichi Adachi
- Health Center, Shimane Environment and Health Public Corporation, Matsue, Japan
| | - Yoshikazu Kinoshita
- Department of Gastroenterology and Hepatology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan
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Abstract
BACKGROUND Although the diagnostic process in celiac disease (CeD) has been addressed in several international guidelines, little is known about the actual proceeding in current clinical practice. This study investigated the initial presentation, the diagnostic process, follow-up evaluations, and adherence to a gluten-free diet in CeD patients in a real-life setting in Switzerland from a patient's perspective. METHODS We performed a large patient survey among unselected CeD patients in Switzerland. RESULTS A total of 1689 patients were analyzed. The vast majority complained of both gastrointestinal and nonspecific symptoms (71.5%), whereas 1.8% reported an asymptomatic disease course. A total of 35.8% CeD patients were diagnosed by a nongastroenterologist. The diagnostic process differed between nongastroenterologists and gastroenterologists, with the latter more often using duodenal biopsy alone or in combination with serology (94.7% vs. 63.0%) and nongastroenterologists more frequently establishing the diagnosis without endoscopy (37.0% vs. 5.3%, P<0.001). Follow-up serology after 6 months was performed only in half of all patients (49.4%), whereas 69.9% had at least 1 follow-up serology within the first year after diet initiation. About 39.7% had a follow-up endoscopy with duodenal biopsies (after a median of 12 mo; range, 1 to 600 mo). The likelihood of receiving any follow-up examination was higher in patients initially diagnosed by a gastroenterologist. CONCLUSIONS A significant proportion of CeD patients are diagnosed by nongastroenterologists. Under the diagnostic lead of the latter, more than a third of the patients receive their diagnosis on the basis of a positive serology and/or genetics only, in evident violation of current diagnostic guidelines, which may lead to an overdiagnosis of this entity.
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19
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Walker MM, Ludvigsson JF, Sanders DS. Coeliac disease: review of diagnosis and management. Med J Aust 2017; 207:173-178. [PMID: 28814219 DOI: 10.5694/mja16.00788] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2016] [Accepted: 05/26/2017] [Indexed: 12/12/2022]
Abstract
Coeliac disease is an immune-mediated systemic disease triggered by exposure to gluten, and manifested by small intestinal enteropathy and gastrointestinal and extra-intestinal symptoms. Recent guidelines recommend a concerted use of clear definitions of the disease. In Australia, the most recent estimated prevalence is 1.2% in adult men (1:86) and 1.9% in adult women (1:52). Active case finding is appropriate to diagnose coeliac disease in high risk groups. Diagnosis of coeliac disease is important to prevent nutritional deficiency and long term risk of gastrointestinal malignancy. The diagnosis of coeliac disease depends on clinico-pathological correlation: history, presence of antitransglutaminase antibodies, and characteristic histological features on duodenal biopsy (when the patient is on a gluten-containing diet). Human leucocyte antigen class II haplotypes DQ2 or DQ8 are found in nearly all patients with coeliac disease, but are highly prevalent in the general population at large (56% in Australia) and testing can only exclude coeliac disease for individuals with non-permissive haplotypes. Adhering to a gluten free diet allows duodenal mucosal healing and alleviates symptoms. Patients should be followed up with a yearly review of dietary adherence and a health check. Non-coeliac gluten or wheat protein sensitivity is a syndrome characterised by both gastrointestinal and extra-intestinal symptoms related to the ingestion of gluten and possibly other wheat proteins in people who do not have coeliac disease or wheat allergy recognised by diagnostic tests.
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20
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Rybicka I, Gliszczyńska-Świgło A. Minerals in grain gluten-free products. The content of calcium, potassium, magnesium, sodium, copper, iron, manganese, and zinc. J Food Compost Anal 2017. [DOI: 10.1016/j.jfca.2017.02.006] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Luján-Sanchis M, Pérez-Cuadrado-Robles E, García-Lledó J, Juanmartiñena Fernández JF, Elli L, Jiménez-García VA, Egea-Valenzuela J, Valle-Muñoz J, Carretero-Ribón C, Fernández-Urién-Sainz I, López-Higueras A, Alonso-Lázaro N, Sanjuan-Acosta M, Sánchez-Ceballos F, Rosa B, González-Vázquez S, Branchi F, Ruano-Díaz L, Prieto-de-Frías C, Pons-Beltrán V, Borque-Barrera P, González-Suárez B, Xavier S, Argüelles-Arias F, Herrerías-Gutiérrez JM, Pérez-Cuadrado-Martínez E, Sempere-García-Argüelles J. Role of capsule endoscopy in suspected celiac disease: A European multi-centre study. World J Gastroenterol 2017; 23:703-711. [PMID: 28216978 PMCID: PMC5292345 DOI: 10.3748/wjg.v23.i4.703] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2016] [Revised: 12/08/2016] [Accepted: 01/04/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To analyze the diagnostic yield (DY), therapeutic impact (TI) and safety of capsule endoscopy (CE).
METHODS This is a multi-centre, observational, analytical, retrospective study. A total of 163 patients with suspicion of celiac disease (CD) (mean age = 46.4 ± 17.3 years, 68.1% women) who underwent CE from 2003 to 2015 were included. Patients were divided into four groups: seronegative CD with atrophy (Group-I, n = 19), seropositive CD without atrophy (Group-II, n = 39), contraindication to gastroscopy (Group-III, n = 6), seronegative CD without atrophy, but with a compatible context (Group-IV, n = 99). DY, TI and the safety of CE were analysed.
RESULTS The overall DY was 54% and the final diagnosis was villous atrophy (n = 65, 39.9%), complicated CD (n = 12, 7.4%) and other enteropathies (n = 11, 6.8%; 8 Crohn’s). DY for groups I to IV was 73.7%, 69.2%, 50% and 44.4%, respectively. Atrophy was located in duodenum in 24 cases (36.9%), diffuse in 19 (29.2%), jejunal in 11 (16.9%), and patchy in 10 cases (15.4%). Factors associated with a greater DY were positive serology (68.3% vs 49.2%, P = 0.034) and older age (P = 0.008). On the other hand, neither sex nor clinical presentation, family background, positive histology or HLA status were associated with DY. CE results changed the therapeutic approach in 71.8% of the cases. Atrophy was associated with a greater TI (92.3% vs 45.3%, P < 0.001) and 81.9% of the patients responded to diet. There was one case of capsule retention (0.6%). Agreement between CE findings and subsequent histology was 100% for diagnosing normal/other conditions, 70% for suspected CD and 50% for complicated CD.
CONCLUSION CE has a high DY in cases of suspicion of CD and it leads to changes in the clinical course of the disease. CE is safe procedure with a high degree of concordance with histology and it helps in the differential diagnosis of CD.
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RYBICKA I, GLISZCZYNSKA-SWIGLO A. Gluten-Free Flours from Different Raw Materials as the Source of Vitamin B 1, B 2, B 3 and B 6. J Nutr Sci Vitaminol (Tokyo) 2017; 63:125-132. [DOI: 10.3177/jnsv.63.125] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Affiliation(s)
- Iga RYBICKA
- Department of Technology and Instrumental Analysis, Faculty of Commodity Science, Poznan University of Economics and Business
| | - Anna GLISZCZYNSKA-SWIGLO
- Department of Technology and Instrumental Analysis, Faculty of Commodity Science, Poznan University of Economics and Business
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23
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Pace LA, Crowe SE. Duodenal Bulb Biopsies Remain Relevant in the Diagnosis of Adult Celiac Disease. Clin Gastroenterol Hepatol 2016; 14:1589-1592. [PMID: 27565522 PMCID: PMC5941945 DOI: 10.1016/j.cgh.2016.08.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2016] [Revised: 08/17/2016] [Accepted: 08/17/2016] [Indexed: 02/07/2023]
Affiliation(s)
- Laura A Pace
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Utah, Salt Lake City, Utah
| | - Sheila E Crowe
- Department of Medicine, Division of Gastroenterology, University of California San Diego, La Jolla, California
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24
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Les pathologies digestives liées au blé ou au gluten : certitudes et doutes. CAHIERS DE NUTRITION ET DE DIÉTÉTIQUE 2016. [DOI: 10.1016/j.cnd.2016.06.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Claro da Silva T, Hiller C, Gai Z, Kullak-Ublick GA. Vitamin D3 transactivates the zinc and manganese transporter SLC30A10 via the Vitamin D receptor. J Steroid Biochem Mol Biol 2016; 163:77-87. [PMID: 27107558 DOI: 10.1016/j.jsbmb.2016.04.006] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2015] [Revised: 03/15/2016] [Accepted: 04/13/2016] [Indexed: 01/11/2023]
Abstract
Vitamin D3 regulates genes critical for human health and its deficiency is associated with an increased risk for osteoporosis, cancer, diabetes, multiple sclerosis, hypertension, inflammatory and immunological diseases. To study the impact of vitamin D3 on genes relevant for the transport and metabolism of nutrients and drugs, we employed next-generation sequencing (NGS) and analyzed global gene expression of the human-derived Caco-2 cell line treated with 500nM vitamin D3. Genes involved in neuropeptide signaling, inflammation, cell adhesion and morphogenesis were differentially expressed. Notably, genes implicated in zinc, manganese and iron homeostasis were largely increased by vitamin D3 treatment. An ∼10-fold increase in ceruloplasmin and ∼4-fold increase in haptoglobin gene expression suggested a possible association between vitamin D and iron homeostasis. SLC30A10, the gene encoding the zinc and manganese transporter ZnT10, was the chiefly affected transporter, with ∼15-fold increase in expression. SLC30A10 is critical for zinc and manganese homeostasis and mutations in this gene, resulting in impaired ZnT10 function or expression, cause manganese intoxication, with Parkinson-like symptoms. Our NGS results were validated by real-time PCR in Caco-2 cells, as well as in duodenal biopsies taken from healthy human subjects treated with 0.5μg vitamin D3 daily for 10 days. In addition to increasing gene expression of SLC30A10 and the positive control TRPV6, vitamin D3 also increased ZnT10 protein expression, as indicated by Western blot and cytofluorescence. In silico identification of potential vitamin D responsive elements (VDREs) in the 5'-flanking region of the SLC30A10 promoter and dual-luciferase reporter assay showed enhanced promoter activity in the presence of vitamin D receptor (VDR) and retinoid X receptor (RXR) constructs, as well as vitamin D3, but not when one of these factors was absent. Electrophoretic mobility shift assay (EMSA) and competition EMSA revealed binding of select sequences, namely, nt -1623/-1588 and nt -1758/-1723 relative to the transcription start site, to VDR-containing nuclear extracts. In conclusion, we have shown that vitamin D3 transactivates the SLC30A10 gene in a VDR-dependent manner, resulting in increased ZnT10 protein expression. Because SLC30A10 is highly expressed in the small intestine, it is possible that the control of zinc and manganese systemic levels is regulated by vitamin D3 in the intestine. Zinc, manganese and vitamin D are important for bone metabolism and brain health. Future examination of a possible role for supplementation or chelation of zinc and manganese, alongside vitamin D3 administration, will further our understanding of its potential benefit in the treatment of specific illnesses, such as osteoporosis and Parkinson's disease.
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Affiliation(s)
- Tatiana Claro da Silva
- Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, University of Zurich, Switzerland.
| | - Christian Hiller
- Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, University of Zurich, Switzerland.
| | - Zhibo Gai
- Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, University of Zurich, Switzerland.
| | - Gerd A Kullak-Ublick
- Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, University of Zurich, Switzerland.
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Datta Mitra A, Gupta A, Jialal I. Folate Insufficiency Due to Celiac Disease in a 49-Year-Old Woman of Southeast Asian-Indian Ethnicity. Lab Med 2016; 47:259-62. [PMID: 27406144 DOI: 10.1093/labmed/lmw036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2016] [Indexed: 11/13/2022] Open
Abstract
The clinical presentation of celiac disease has evolved from chronic diarrhea and malnutrition to mild nutrient insufficiencies. Recently diagnosed adults with celiac disease should be assessed for micronutrient deficiencies because early institution of a gluten-free diet (GFD) prevents morbidity and reduces the incidence of gastrointestinal malignant neoplasms and osteoporosis. In this report, we present the case of a 49-year-old woman of Southeast Asian-Indian descent living in the United States who had folate insufficiency, as manifested by low serum and red blood cell (RBC) folate levels. Further investigation, including serologic testing and intestinal biopsy, confirmed a diagnosis of celiac disease and other nutrient deficiencies. Managing the condition of this patient with folate supplements and implementation of a recommended GFD reversed the folate insufficiency. In conclusion, when serum and/or RBC levels are low in a person of Southeast Asian-Indian descent living in a country with folate fortification of the grain supply, such as the United States, the medical team needs to look for an organic cause, as in our patient, to diagnose and manage celiac disease early and, hopefully, forestall complications.
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Affiliation(s)
| | - Asha Gupta
- Department of Internal Medicine, Division of Gastroenterology and Hepatology
| | - Ishwarlal Jialal
- Department of Pathology and Laboratory Medicine Division of Endocrinology and Metabolism, University of California Davis Medical Center, Sacramento, CA
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Harris LA, Umar SB, Baffy N, Heitkemper MM. Irritable Bowel Syndrome and Female Patients. Gastroenterol Clin North Am 2016; 45:179-204. [PMID: 27261893 DOI: 10.1016/j.gtc.2016.02.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Irritable bowel syndrome is probably the most common functional gastrointestinal disorder and is characterized by abdominal pain along with altered bowel function. It is a disorder of female predominance. This article focuses on how being female influences the pathophysiology, diagnosis, management, and treatment of this common disorder and discusses the evidence and important controversies related to these areas.
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Affiliation(s)
- Lucinda A Harris
- Division of Gastroenterology & Hepatology, Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA.
| | - Sarah B Umar
- Division of Gastroenterology & Hepatology, Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA
| | - Noemi Baffy
- Division of Gastroenterology & Hepatology, Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA
| | - Margaret M Heitkemper
- School of Nursing, Biobehavioral Nursing and Health Systems, University of Washington, Seattle, WA, USA
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Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract and includes both Crohn's disease and ulcerative colitis. Patients with IBD often present with abdominal pain, diarrhea, and rectal bleeding but may also have a wide variety of other symptoms such as weight loss, fever, nausea, vomiting, and possibly obstruction. Given that the presentation of IBD is not specific, the differential diagnosis is broad and encompasses a wide spectrum of diseases, many of which can mimic and/or even coexist with IBD. It is important for physicians to differentiate symptoms due to refractory IBD from symptoms due to IBD mimics when a patient is not responding to standard IBD treatment. Many of the various IBD mimics include infectious etiologies (viral, bacterial, mycobacterial, fungal, protozoal, and helminthic infections), vascular causes, other immune causes including autoimmune etiologies, drug-induced processes, radiation-induced, and other etiologies such as small intestinal bacterial overgrowth, diverticulitis, and bile acid malabsorption. Thoughtful consideration and evaluation of these potential etiologies through patient history and physical examination, as well as appropriate tests, endoscopic evaluation, and cross-sectional imaging is required to evaluate any patient presenting with symptoms consistent with IBD.
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Iacucci M, Poon T, Gui XS, Ghosh S. High definition i-SCAN endoscopy with water immersion technique accurately reflects histological severity of celiac disease. Endosc Int Open 2016; 4:E540-6. [PMID: 27227112 PMCID: PMC4874797 DOI: 10.1055/s-0042-105955] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2015] [Accepted: 03/07/2016] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND AND AIMS Severe villous atrophy can be revealed with conventional white light endoscopy (WLE), however, milder grades or patchy villous atrophy are more difficult to detect. Novel endoscopic techniques such as high definition i-SCAN endoscopy with the water immersion technique (i-SCAN-HDWI) may provide the ability to visualize duodenal villi more accurately. We aimed to determine the performance of i-SCAN-HDWI in evaluating the severity of histological damage in the duodenum of patients with celiac disease. PATIENTS AND METHODS A retrospective cohort study was performed in a single tertiary academic endoscopic center. We studied 58 patients (46 women; median age 36.5 years, range 18 - 72 years) with positive anti-TTG IgA antibody. The villous pattern of the second part of the duodenum was assessed by WLE and i-SCAN-HDWI. The endoscopic grades in both techniques were correlated using Marsh histologic grades by Spearman correlation coefficient. The diagnostic accuracy of i-SCAN-HDWI for detection of patchy or complete atrophy of the villi was evaluated. RESULTS A significant correlation was demonstrated between endoscopic grade using i-SCAN-HDWI and Marsh histologic grade (r = 0.732; P < 0.00001). The correlation between WLE grade and Marsh histologic grade was inferior to i-SCAN-HDWI (r = 0.31; P = 0.01). The sensitivity of i-SCAN-HDWI was 96 % (95 %CI: 85 - 99 %) and the specificity was 63 % (95 %CI: 26 - 90 %) in diagnosing abnormal biopsy consistent with celiac disease. CONCLUSION i-SCAN-HDWI endoscopy can reflect the histological severity of celiac disease more accurately than conventional WLE alone. This novel endoscopic imaging can improve the diagnostic yield of duodenal biopsies in celiac patients, especially for those with a patchy distribution of villous damage.
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Affiliation(s)
- Marietta Iacucci
- Gastroenterology, University of Calgary, Calgary, AB, Canada,Corresponding author Marietta Iacucci, MD PhD Division of GastroenterologyTRW 6D253280 Hospital Drive NWCalgaryAlbertaCanada T2N 4Z6+1-403-592-5090
| | - Tiffany Poon
- Gastroenterology, University of Calgary, Calgary, AB, Canada
| | - X. Sean Gui
- Pathology, University of Calgary, Calgary, AB, Canada
| | - Subrata Ghosh
- Gastroenterology, University of Calgary, Calgary, AB, Canada
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Celiac Disease and Gluten-Free Oats: A Canadian Position Based on a Literature Review. Can J Gastroenterol Hepatol 2016; 2016:1870305. [PMID: 27446825 PMCID: PMC4904695 DOI: 10.1155/2016/1870305] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2015] [Accepted: 08/22/2015] [Indexed: 12/14/2022] Open
Abstract
This paper provides an overview of the latest scientific data related to the safety of uncontaminated oats (<20 ppm of gluten) in the diet of individuals with celiac disease (CD). It updates the previous Health Canada position posted on the Health Canada website in 2007 and a related paper published in 2009. It considers a number of recent studies published between January 2008 and January 2015. While recognizing that a few people with celiac disease seem to be clinically intolerant to oats, this review concludes that oats uncontaminated by gluten-containing cereals (wheat, rye, and barley) can be safely ingested by most patients with celiac disease and that there is no conclusive evidence that the consumption of uncontaminated or specially produced oats containing no greater than 20 ppm gluten by patients with celiac disease should be limited to a specific daily amount. However, individuals with CD should observe a stabilization phase before introducing uncontaminated oats to the gluten-free diet (GFD). Oats uncontaminated with gluten should only be introduced after all symptoms of celiac disease have resolved and the individual has been on a GFD for a minimum of 6 months. Long-term regular medical follow-up of these patients is recommended but this is no different recommendation to celiac individuals on a GFD without oats.
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Abstract
Iron is an important micronutrient that may be depleted in celiac disease. Iron deficiency and anemia may complicate well-established celiac disease, but may also be the presenting clinical feature in the absence of diarrhea or weight loss. If iron deficiency anemia occurs, it should be thoroughly evaluated, even if celiac disease has been defined since other superimposed causes of iron deficiency anemia may be present. Most often, impaired duodenal mucosal uptake of iron is evident since surface absorptive area in the duodenum is reduced, in large part, because celiac disease is an immune-mediated disorder largely focused in the proximal small intestinal mucosa. Some studies have also suggested that blood loss may occur in celiac disease, sometimes from superimposed small intestinal disorders, including ulceration or neoplastic diseases, particularly lymphoma. In addition, other associated gastric or colonic disorders may be responsible for blood loss. Rarely, an immune-mediated hemolytic disorder with increased urine iron loss may occur that may respond to a gluten-free diet. Reduced expression of different regulatory proteins critical in iron uptake has also been defined in the presence and absence of anemia. Finally, other rare causes of microcytic anemia may occur in celiac disease, including a sideroblastic form of anemia reported to have responded to a gluten-free diet.
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Welstead L. The Gluten-Free Diet in the 3rd Millennium: Rules, Risks and Opportunities. Diseases 2015; 3:136-149. [PMID: 28943615 PMCID: PMC5548243 DOI: 10.3390/diseases3030136] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2015] [Revised: 06/18/2015] [Accepted: 06/19/2015] [Indexed: 12/17/2022] Open
Abstract
The gluten-free diet has long been considered the standard treatment for celiac disease. However, a significant number of patients continue to experience persistent symptoms despite following a gluten-free diet. Inadvertent gluten ingestion, fermentable carbohydrates, cross-contamination, and social or financial burdens present obstacles to maintaining a gluten-free diet. Proper diet education and follow-up by an expert Registered Dietitian (RD) is essential to ensure adequate nutrition on the gluten-free diet. Patients may experience unintended weight gain or elevated cholesterol levels after initiating the gluten-free diet due to adequate absorption and healing of the intestines. This review deals with the evolving gluten-free diet, optimal recommendations while considering the overall health of patients, and multi-factorial aspects of the permanent lifestyle change.
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Affiliation(s)
- Lori Welstead
- Section of Gastroenterology, Hepatology and Nutrition, University of Chicago Medicine, Chicago, IL 60637, USA.
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Gottlieb K, Dawson J, Hussain F, Murray JA. Development of drugs for celiac disease: review of endpoints for Phase 2 and 3 trials. Gastroenterol Rep (Oxf) 2015; 3:91-102. [PMID: 25725041 PMCID: PMC4423465 DOI: 10.1093/gastro/gov006] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2014] [Accepted: 01/09/2015] [Indexed: 12/27/2022] Open
Abstract
Celiac disease is a lifelong disorder for which there is currently only one known, effective treatment: a gluten-free diet. New treatment approaches have recently emerged; several drugs are in Phase 2 trials and results appear promising; however, discussion around regulatory endpoints is in its infancy. We will briefly discuss the drugs that are under development and then shift our attention to potential trial endpoints, such as patient-reported outcomes, histology, serology, gene expression analysis and other tests. We will outline the differing requirements for proof-of-concept Phase 2 trials and Phase 3 registration trials, with a particular emphasis on current thinking in regulatory agencies. We conclude our paper with recommendations and a glossary of regulatory terms, to enable readers who are less familiar with regulatory language to take maximum advantage of this review.
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Affiliation(s)
- Klaus Gottlieb
- Immunology and Internal Medicine - Medical Strategy & Science, Quintiles, Durham, NC, USA, Corporate Communications, Quintiles, Durham, NC, USA and Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Jill Dawson
- Immunology and Internal Medicine - Medical Strategy & Science, Quintiles, Durham, NC, USA, Corporate Communications, Quintiles, Durham, NC, USA and Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Fez Hussain
- Immunology and Internal Medicine - Medical Strategy & Science, Quintiles, Durham, NC, USA, Corporate Communications, Quintiles, Durham, NC, USA and Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Joseph A Murray
- Immunology and Internal Medicine - Medical Strategy & Science, Quintiles, Durham, NC, USA, Corporate Communications, Quintiles, Durham, NC, USA and Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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Sulic AM, Kurppa K, Rauhavirta T, Kaukinen K, Lindfors K. Transglutaminase as a therapeutic target for celiac disease. Expert Opin Ther Targets 2014; 19:335-48. [PMID: 25410283 DOI: 10.1517/14728222.2014.985207] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
INTRODUCTION The only current treatment for celiac disease is a strict gluten-free diet. The ubiquitous presence of gluten in groceries, however, makes the diet burdensome and difficult to maintain, and alternative treatment options are thus needed. Here, the important role of transglutaminase 2 (TG2) in the pathogenesis of celiac disease makes it an attractive target for drug development. AREAS COVERED The present paper gives an overview of TG2 and addresses its significance in the pathogenesis of celiac disease. Moreover, the article summarizes preclinical studies performed with TG2 inhibitors and scrutinizes issues related to this therapeutic approach. EXPERT OPINION Activation of TG2 in the intestinal mucosa is central in celiac disease pathogenesis and researchers have therefore suggested TG2 inhibitors as a potential therapeutic approach. However, a prerequisite for such a drug is that it should be specific for TG2 and not affect the activity of other members of the transglutaminase family. Such compounds have already been introduced and tested in vitro, but a major obstacle to further development is the lack of a well-defined animal model for celiac disease. Nonetheless, with encouraging results in preclinical studies clinical trials with TG2 inhibitors are eagerly awaited.
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Affiliation(s)
- Ana-Marija Sulic
- Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital , Tampere , Finland +358 50 3186306; +358 3 3641369 ;
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