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Alsofi SA, Alaghbari NA, Al-Sonboli NN, Jowah HM. Prevalence and Clinical Profile of Celiac Disease in Yemeni Children: A Five-Year Retrospective Study at Al-Sabeen Hospital. Cureus 2025; 17:e82824. [PMID: 40416247 PMCID: PMC12100572 DOI: 10.7759/cureus.82824] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/22/2025] [Indexed: 05/27/2025] Open
Abstract
INTRODUCTION Celiac disease (CD) is an autoimmune condition triggered by gluten ingestion. Limited data are available on its prevalence and characteristics in Yemen, a region facing socioeconomic challenges intensified by conflict. This study aimed to estimate the prevalence of CD and evaluate the demographic, clinical, and nutritional profiles of affected children. METHODS This five-year retrospective study analyzed data from 120 children diagnosed with CD at Al-Sabeen Hospital, Sana'a, Yemen, from January 2018 to December 2023. Children of any age and sex clinically suspected of having CD based on gastrointestinal (e.g., chronic diarrhea) and/or extraintestinal manifestations (e.g., failure to thrive) were included, with non-CD causes excluded via European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN)-guided testing. Diagnosis followed the guidelines of the ESPGHAN guidelines, using transglutaminase 2 antibody (tTA-IgA) and endomysial antibody IgA (EMA IgA) levels, with biopsy recommended for tTA-IgA <10× the upper limit of normal. Data on demographics, nutritional status, clinical manifestations, and associations were collected via a structured questionnaire and analyzed using IBM SPSS Statistics for Windows, Version 26.0 (Released 2019; IBM Corp., Armonk, New York, United States), with chi-square tests assessing significance (p<0.05). RESULTS Among 3,570 admissions, CD prevalence was 3.4% (n=120), with a female predominance (58.3%, n=70) and 70% (n=84) diagnosed before the age of one year (mean 12 ± 3.5 months). Malnutrition affected 60.0% of cases, significantly associated with rural residency (p=0.015), low family income (p=0.001), unprotected water sources (p=0.030), and incomplete vaccination (p<0.001). Chronic diarrhea (85.0%) and pallor (81.7%) were the most common manifestations. No significant associations were found for sex (p=0.705) or animal contact (p=0.053). CONCLUSIONS CD prevalence in Yemeni children exceeds the global average, with malnutrition being a major comorbidity linked to socioeconomic and environmental factors. Targeted screening, biopsy-confirmed diagnosis for ambiguous cases, and nutritional interventions are critical in conflict-affected settings such as Yemen. Future multicenter studies with genetic testing are recommended to enhance our understanding and management.
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Affiliation(s)
- Shafa A Alsofi
- Department of Pediatrics, Faculty of Medicine and Health Sciences, Sana'a University, Sana'a, YEM
- Department of Pediatrics, Al-Sabeen Maternity and Child Hospital, Sana'a, YEM
| | - Nasher A Alaghbari
- Department of Pediatrics, Faculty of Medicine and Health Sciences, Sana'a University, Sana'a, YEM
| | - Najla N Al-Sonboli
- Department of Pediatrics, Faculty of Medicine and Health Sciences, Sana'a University, Sana'a, YEM
- Department of Pediatrics, Al-Sabeen Maternity and Child Hospital, Sana'a, YEM
| | - Haitham M Jowah
- Department of Pediatric Surgery, Faculty of Medicine and Health Sciences, Sana'a University, Sana'a, YEM
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Scarampi M, Mengoli C, Miceli E, Di Stefano M. Vitamins and Celiac Disease: Beyond Vitamin D. Metabolites 2025; 15:78. [PMID: 39997703 PMCID: PMC11857425 DOI: 10.3390/metabo15020078] [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: 12/16/2024] [Revised: 01/14/2025] [Accepted: 01/22/2025] [Indexed: 02/26/2025] Open
Abstract
Celiac disease is a chronic inflammatory condition of the small bowel caused, in genetically predisposed subjects, by the ingestion of gluten and characterised by a broad clinical polymorphism, ranging from patients with an asymptomatic or paucisymptomatic disease. The clinical presentation ranges from the presence of minor, apparently unrelated symptoms or first-degree kinship with known patients to severe intestinal malabsorption and all its clinical consequences and complications. Even if a large body of research improved our understanding of the molecular basis of celiac disease pathophysiology, enhancing the identification of new targets for future new treatments, an accurate gluten-free diet remains the mainstay of the therapy for this condition, restoring a normal absorptive mucosa. It is very rare, nowadays, to deal with patients with severe malabsorption syndrome secondary to celiac disease. Consequently, physicians are currently less prone to search for nutritional deficiencies in celiac disease. To pinpoint the possibility of both a disease-related and a diet-induced vitamin deficiency, we reviewed the literature on vitamin deficiency in this condition and reported the impact both in untreated and treated patients with celiac disease. A gluten-free diet must be tailored for each patient to meet nutritional targets: the pre-existence or diet-induced intake inadequacies should be carefully considered for an effective management of celiac disease.
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Affiliation(s)
| | | | | | - Michele Di Stefano
- 1st Department of Medicine, IRCCS “S.Matteo” Hospital Foundation, 27100 Pavia, Italy; (M.S.); (C.M.); (E.M.)
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Wichka I, Lai PK. Rapid discovery of Transglutaminase 2 inhibitors for celiac disease with boosting ensemble machine learning. Comput Struct Biotechnol J 2024; 23:3669-3679. [PMID: 39498152 PMCID: PMC11532751 DOI: 10.1016/j.csbj.2024.10.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Revised: 10/07/2024] [Accepted: 10/13/2024] [Indexed: 11/07/2024] Open
Abstract
Celiac disease poses a significant health challenge for individuals consuming gluten-containing foods. While the availability of gluten-free products has increased, there is still a need for therapeutic treatments. The advancement of computational drug design, particularly using bio-cheminformatics-oriented machine learning, offers promising avenues for developing such therapies. One promising target is Transglutaminase 2 (TG2), a protein involved in the autoimmune response triggered by gluten consumption. In this study, we utilized data from approximately 1100 TG2 inhibition assays to develop ligand-based molecular screening techniques using ensemble machine-learning models and extensive molecular feature libraries. Various classifiers, including tree-based methods, artificial neural networks, and graph neural networks, were evaluated to identify primary systems for predictive analysis and feature significance assessment. Boosting ensembles of perceptron deep learning and low-depth random forest weak learners emerged as the most effective, achieving over 90 % accuracy, significantly outperforming a baseline of 64 %. Key features, such as the presence of a terminal Michael acceptor group and a sulfonamide group, were identified as important for activity. Additionally, a regression model was created to rank active compounds. We developed a web application, Celiac Informatics (https://celiac-informatics-v1-2b0a85e75868.herokuapp.com), to facilitate the screening of potential therapeutic molecules for celiac disease. The web app also provides drug-likeness reports, supporting the development of novel drugs.
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Affiliation(s)
| | - Pin-Kuang Lai
- Corresponding author at: Department of Chemical Engineering and Materials Science, Stevens Institute of Technology, Hoboken, NJ 07030, USA.
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Bose D. Introduction to Nutrition and Autoimmune Diseases. ADVANCES IN MEDICAL DIAGNOSIS, TREATMENT, AND CARE 2024:415-431. [DOI: 10.4018/979-8-3693-5528-2.ch015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Celiac disease is an autoimmune hereditary disorder that occurs in genetically predisposed people where the ingestion of gluten leads to damage in their small intestine. When people with celiac disease consume gluten, their body mounts an immune response that attacks the villi of small intestine, which are small finger like projections that promote nutrient absorption. A damaged villi is incapable of absorbing food properly. If left untreated, celiac disease can lead to additional serious health problems. Gluten free diet is the only option to keep the symptoms low. Recently, probiotics have acquired significant attention because of their potential benefits in a wide range of biomedical applications. Thus, administering probiotics as a plausible therapeutic measure for improving the gut health and overall quality of life of patients suffering with this disease is of notable concern. The chapter aims to examine such probiotic applications for patients suffering from celiac disease through comprehensive literature analysis with emphasis on dietary supplements and requirements.
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Adams DW, Moleski S, Jossen J, Tye-Din JA. Clinical Presentation and Spectrum of Gluten Symptomatology in Celiac Disease. Gastroenterology 2024; 167:51-63. [PMID: 38636679 DOI: 10.1053/j.gastro.2024.01.052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 12/31/2023] [Accepted: 01/02/2024] [Indexed: 04/20/2024]
Abstract
Views on the clinical presentation and symptomatology of celiac disease have evolved alongside advances in disease detection and understanding of disease pathogenesis. Although historically regarded as a pediatric illness characterized by malabsorption, it is now better viewed as an immune illness of gluten-specific T cells with systemic manifestations affecting all ages. Its broad presentation, including frequent extraintestinal manifestations and asymptomatic disease, contributes to suboptimal disease detection. Adverse symptoms greatly impact patient quality of life and can result from chronic gluten exposure in untreated disease or those poorly responsive to the gluten-free diet. They can also present as acute symptoms after episodic gluten exposure. Functional gastrointestinal disease is a common comorbidity. Biomarkers like interleukin-2 that are highly sensitive and specific for celiac disease highlight a role for gluten-specific T cells in acute gluten symptomatology. A mechanistic understanding of symptoms will inform approaches to better measure and treat them effectively.
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Affiliation(s)
- Dawn W Adams
- Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Stephanie Moleski
- Department of Medicine, Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
| | - Jacqueline Jossen
- Departments of Medicine and Pediatrics, The Celiac Disease Center at Columbia University, New York, New York
| | - Jason A Tye-Din
- Immunology Division, Walter and Eliza Hall Institute, Melbourne, Victoria, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia; Department of Gastroenterology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
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Grizzi F, Hegazi MA. Functional foods and celiac disease prevalent in North America and globally. FUNCTIONAL FOODS AND CHRONIC DISEASE 2024:105-114. [DOI: 10.1016/b978-0-323-91747-6.00006-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Mousavi Maleki MS, Ebrahimi Kiasari R, Seyed Mousavi SJ, Hashemi-Moghaddam H, Shabani AA, Madanchi H, Sardari S. Bromelain-loaded nanocomposites decrease inflammatory and cytotoxicity effects of gliadin on Caco-2 cells and peripheral blood mononuclear cells of celiac patients. Sci Rep 2023; 13:21180. [PMID: 38040898 PMCID: PMC10692183 DOI: 10.1038/s41598-023-48460-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Accepted: 11/27/2023] [Indexed: 12/03/2023] Open
Abstract
Enzyme therapy can be an appropriate treatment option for celiac disease (CeD). Here, we developed Bromelain-Loaded Nanocomposites (BLNCs) to improve the stability and retention of bromelain enzyme activity. After the characterization of BLNCs, the cytotoxicity of BLNCs was determined on the Caco-2 cell line. The effect of BLNCs on gliadin degradation and the production of pro-inflammatory cytokines and anti-inflammatory molecules in peripheral blood mononuclear cells (PBMCs) obtained from celiac patients were assessed. Furthermore, the expression of CXCR3 and CCR5 genes was measured in CaCo-2 cells treated with gliadin, gliadin-digested with BLNCs, and bromelain. Our study demonstrated that the Bromelain entrapment efficiency in these nanoparticles was acceptable, and BLNCs have no toxic effect on cells. SDS-PAGE confirmed the digestion effect of bromelain released from nanocomposites. When Caco-2 cells were treated with gliadin digested by free bromelain and BLNCs, the expression of CXCR3 and CCR5 genes was significantly decreased. PBMCs of celiac patients treated with Bromelain and BLNCs decreased inflammatory cytokines (IL-1β, IL-6, TNF-α, and IFN-γ) production compared to untreated PBMCs. This treatment also increased IL-10 and CTLA-4 in PBMCs of CeD patients. According to the promising results of this study, we can hope for the therapeutic potential of BLNCs for CeD.
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Affiliation(s)
- Masoumeh Sadat Mousavi Maleki
- Department of Biotechnology, School of Medicine, Semnan University of Medical Sciences, Semnan, 35131-38111, Iran
- Gene Therapy and Regenerative Medicine Research Center, Hope Generation Foundation, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
| | - Ramin Ebrahimi Kiasari
- Drug Design and Bioinformatics Unit, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, 13198, Iran
| | - Seyed Javad Seyed Mousavi
- Drug Design and Bioinformatics Unit, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, 13198, Iran
| | | | - Ali Akbar Shabani
- Department of Biotechnology, School of Medicine, Semnan University of Medical Sciences, Semnan, 35131-38111, Iran
| | - Hamid Madanchi
- Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran.
- Department of Biotechnology, School of Medicine, Semnan University of Medical Sciences, Semnan, 35131-38111, Iran.
- Drug Design and Bioinformatics Unit, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, 13198, Iran.
| | - Soroush Sardari
- Drug Design and Bioinformatics Unit, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, 13198, Iran.
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Mouslih A, El Rhazi K, Bahra N, Lakhdar Idrissi M, Hida M. Gluten-Free Diet Compliance in Children With Celiac Disease and Its Effect on Clinical Symptoms: A Retrospective Cohort Study. Cureus 2023; 15:e50217. [PMID: 38077661 PMCID: PMC10710191 DOI: 10.7759/cureus.50217] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/09/2023] [Indexed: 09/29/2024] Open
Abstract
UNLABELLED A gluten-free diet (GFD) is the only scientifically proven treatment for celiac disease (CD). Strict adherence to this diet in children yields excellent results in terms of the clinical symptoms present at the time of diagnosis. Despite the constraints associated with following this diet, it remains the only hope for children with CD to have a better quality of life and life expectancy. METHODS A retrospective descriptive cohort study was carried out on children diagnosed with CD in the pediatrics department of the Hassan II University Hospital in Fez, Morocco. The children were followed up for 18 months, during which time they were seen as outpatients at different frequencies depending on their clinical condition and degree of compliance with the diet. RESULTS Only half of the diagnosed children continued to follow our structure. Compliance with the gluten-free diet varied from 58.7% (n = 84) of children who strictly followed the GFD to 3.5% (n = 5) of children who never followed the diet. Compliance was significantly correlated with the child's age, with adolescents being the least compliant (p = 0.03). Similarly, a correlation was observed between compliance with the diet and the disappearance of symptoms (p <0.01), the persistence of certain symptoms (p = 0.02), and the occurrence of complications (p = 0.01). The majority of children (87.3%) had their clinical symptoms resolved within a mean delay of 6.4±3.6 months, with a mode of three months. The speed of symptom resolution differed from one symptom to another but remained statistically correlated with the degree of GFD compliance (p = 0.03). CONCLUSION Despite the excellent results of a GFD on clinical symptoms in children, the discrepancies observed between compliance and non-compliance call for close follow-up of children with CD to avoid complications and repercussions on the vital prognosis in adulthood.
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Affiliation(s)
- Assia Mouslih
- Laboratory of Epidemiology, Clinical Research, and Community Health, Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah University, Fez, MAR
| | - Karima El Rhazi
- Laboratory of Epidemiology, Clinical Research, and Community Health, Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah University, Fez, MAR
| | - Nassiba Bahra
- Laboratory of Epidemiology, Clinical Research, and Community Health, Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah University, Fez, MAR
| | - Mounia Lakhdar Idrissi
- Department of Pediatric Diseases, Faculty of Medicine and Pharmacy, Hassan II Hospital, Fez, MAR
- Laboratory of Epidemiology and Health Science Research, Faculty of Medicine and Pharmacy, Sidi Mohammed Ben Abdellah University, Fez, MAR
| | - Moustapha Hida
- Department of Pediatric Diseases, Faculty of Medicine and Pharmacy, Hassan II Hospital, Fez, MAR
- Laboratory of Epidemiology and Health Science Research, Faculty of Medicine and Pharmacy, Sidi Mohammed Ben Abdellah University, Fez, MAR
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Denholm J, Schreiber B, Evans S, Crook O, Sharma A, Watson J, Bancroft H, Langman G, Gilbey J, Schönlieb CB, Arends M, Soilleux E. Multiple-instance-learning-based detection of coeliac disease in histological whole-slide images. J Pathol Inform 2022; 13:100151. [PMID: 36605111 PMCID: PMC9808019 DOI: 10.1016/j.jpi.2022.100151] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 10/21/2022] [Accepted: 10/21/2022] [Indexed: 11/06/2022] Open
Abstract
We present a multiple-instance-learning-based scheme for detecting coeliac disease, an autoimmune disorder affecting the intestine, in histological whole-slide images (WSIs) of duodenal biopsies. We train our model to detect 2 distinct classes, normal tissue and coeliac disease, on the patch-level, and in turn leverage slide-level classifications. Using 5-fold cross-validation in a training set of 1841 (1163 normal; 680 coeliac disease) WSIs, our model classifies slides as normal with accuracy (96.7±0.6)%, precision (98.0±1.7)%, and recall (96.8±2.5)%, and as coeliac disease with accuracy (96.7±0.5)%, precision (94.9±3.7)%, and recall (96.5±2.9)% where the error bars are the cross-validation standard deviation. We apply our model to 2 test sets: one containing 191 WSIs (126 normal; 65 coeliac) from the same sources as the training data, and another from a completely independent source, containing 34 WSIs (17 normal; 17 coeliac), obtained with a scanner model not represented in the training data. Using the same-source test data, our model classifies slides as normal with accuracy 96.5%, precision 98.4% and recall 96.1%, and positive for coeliac disease with accuracy 96.5%, precision 93.5%, and recall 97.3%. Using the different-source test data the model classifies slides as normal with accuracy 94.1% (32/34), precision 89.5%, and recall 100%, and as positive for coeliac disease with accuracy 94.1%, precision 100%, and recall 88.2%. We discuss generalising our approach to screen for a range of pathologies.
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Affiliation(s)
- J. Denholm
- Lyzeum Ltd, Salisbury House, Station Road, Cambridge CB1 2LA, Cambridgeshire, UK
- Department of Applied Maths and Theoretical Physics, University of Cambridge, Centre for Mathematical Sciences, Wilberforce Road, Cambridge CB3 0WA, Cambridgeshire, UK
- Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, Cambridgeshire, UK
| | - B.A. Schreiber
- Department of Applied Maths and Theoretical Physics, University of Cambridge, Centre for Mathematical Sciences, Wilberforce Road, Cambridge CB3 0WA, Cambridgeshire, UK
- Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, Cambridgeshire, UK
| | - S.C. Evans
- Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, Cambridgeshire, UK
| | - O.M. Crook
- The Alan Turing Institute, 96 Euston Rd, London NW1 2DB, UK
| | - A. Sharma
- Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, Cambridgeshire, UK
| | - J.L. Watson
- Oxford Medical School, University of Oxford, S Parks Road, Oxford OX1 3PL, Oxfordshire, UK
| | - H. Bancroft
- Department of Cellular Pathology, Birmingham Heartlands Hospital, University Hospitals Birmingham, 45 Bordesley Green East, Birmingham B9 5SS, West Midlands, UK
| | - G. Langman
- Department of Cellular Pathology, Birmingham Heartlands Hospital, University Hospitals Birmingham, 45 Bordesley Green East, Birmingham B9 5SS, West Midlands, UK
| | - J.D. Gilbey
- Department of Applied Maths and Theoretical Physics, University of Cambridge, Centre for Mathematical Sciences, Wilberforce Road, Cambridge CB3 0WA, Cambridgeshire, UK
| | - C.-B. Schönlieb
- Department of Applied Maths and Theoretical Physics, University of Cambridge, Centre for Mathematical Sciences, Wilberforce Road, Cambridge CB3 0WA, Cambridgeshire, UK
| | - M.J. Arends
- Division of Pathology, University of Edinburgh, Cancer Research UK Edinburgh Centre, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XR, Lothian, Scotland
| | - E.J. Soilleux
- Lyzeum Ltd, Salisbury House, Station Road, Cambridge CB1 2LA, Cambridgeshire, UK
- Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, Cambridgeshire, UK
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Makharia GK, Chauhan A, Singh P, Ahuja V. Review article: Epidemiology of coeliac disease. Aliment Pharmacol Ther 2022; 56 Suppl 1:S3-S17. [PMID: 35815830 DOI: 10.1111/apt.16787] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 01/05/2022] [Accepted: 01/11/2022] [Indexed: 12/12/2022]
Abstract
Coeliac disease is an immune-mediated disease caused by ingestion of gluten in genetically susceptible individuals. Coeliac disease has been thought to affect mainly people of European origin but subsequently many studies revealed that it affects people living in North America, Oceania, South America, Asia as well as Africa. The global pooled seroprevalence and prevalence of biopsy-confirmed coeliac disease are 1.4% and 0.7% respectively. The pooled incidence rates in women and men are 17.4 (95% CI: 13.7-21.1) and 7.8 (95% CI: 6.3-9.2) per 100 000 person-years respectively. The systematic reviews, based on many population-based data, suggest that both the prevalence and the incidence of coeliac disease has increased over past three decades, which may be attributable not only to an increase in the detection rate (improvement in diagnostic tests, simplification of diagnostic criteria and increase in awareness about the disease) but also because of modernisation and globalisation related changes in the dietary practices including increase in the use of convenience food and dietary gluten. In addition to genetic factors, while there are many environmental risk factors, including age at the first introduction of gluten, breastfeeding, caesarean section, exposure to antibiotics and gut microbiome; the amount of gluten ingestion during early part of life, however, has been shown to increase the risk of coeliac disease, and this is relevant from the point of view of primary prevention. In this review, we have reviewed and summarised the literature, up till year 2021, related to the global and continent-wise epidemiology and risk factors associated with coeliac disease.
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Affiliation(s)
- Govind K Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Ashish Chauhan
- Department of Gastroenterology, Indira Gandhi Medical College and Hospital, Shimla, India
| | - Prashant Singh
- Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
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Saha BK, Saha S, Bonnier A, Saha BN. Association between idiopathic pulmonary hemosiderosis and celiac disease in pediatric patients: A scoping review of the literature over the past 50 years. Pediatr Pulmonol 2022; 57:1127-1144. [PMID: 35088581 DOI: 10.1002/ppul.25847] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 01/17/2022] [Accepted: 01/24/2022] [Indexed: 11/05/2022]
Abstract
INTRODUCTION Idiopathic pulmonary hemosiderosis (IPH) is a rare cause of diffuse alveolar hemorrhage, the mechanism of which is currently unknown. Nearly one-third of pediatric patients with IPH test positive for Celiac disease (CD) serology. Several hypothetical mechanisms have been proposed to unify the coexistence of these two entities, also referred to as Lane-Hamilton syndrome (LHS). METHOD This manuscript is a scoping review of the medical literature. Medline, Embase, and PubMed Central databases were searched between 1971 and 2021 with appropriate search words to identify all cases of pediatric LHS. RESULTS A total of 20 manuscripts with 23 pediatric patients with LHS were identified. The mean age was 11 years, and 13/23 (56.5%) of the children were boys. Hemoptysis was present in 57% of patients during diagnosis. Bronchoscopy with bronchoalveolar lavage demonstrating hemosiderin laden macrophages was the primary mode of diagnostic confirmation. Only three patients underwent lung biopsy. Any significant GI symptom was reported in a minority of patients (22%). Iron deficiency anemia on presentation was described in 83% of children. The majority of patients were malnourished. Serology for CD was positive in all patients, as was the histopathologic analysis of the small bowel biopsy. No patients had any other autoantibody positivity. The introduction of gluten free diet (GFD) was associated with a positive response in 20/23 patients. CONCLUSION All pediatric patients with IPH should undergo screening for CD. Low serum ferritin in patients with IPH could be suggestive of coexisting CD. Strict GFD should be tried as the initial therapy.
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Affiliation(s)
- Biplab K Saha
- Department of Pulmonary and Critical Care Medicine, Ozarks Medical Center, West Plains, Missouri, USA
| | - Santu Saha
- Department of Internal Medicine, Bangladesh Medical College, Dhaka, Bangladesh
| | - Alyssa Bonnier
- Department of Critical Care Nursing, Goldfarb School of Nursing, Barnes Jewish College, St. Louis, Missouri, USA
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de Sousa Franckilin LR, Dos Santos ACPM, Freitas FEDA, Vieira IG, de Freitas Jorge CE, Neri DG, de Abreu MVC, Fonseca JK, Loffi RG, Foureaux G. Gluten: do only celiac patients benefit from its removal from the diet? FOOD REVIEWS INTERNATIONAL 2022. [DOI: 10.1080/87559129.2021.2024566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Affiliation(s)
| | | | | | | | | | | | | | | | - Renato Guimarães Loffi
- Departamento de Ciência, Tecnologia e Inovação, Treini Biotecnologia Ltda, Belo Horizonte, Brazil
| | - Giselle Foureaux
- Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
- Departamento de Nutrição, Angiogold: Medicina Integrativa, Belo Horizonte, Brazil
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Asrani P, Ali A, Tiwari K. Millets as an alternative diet for gluten-sensitive individuals: A critical review on nutritional components, sensitivities and popularity of wheat and millets among consumers. FOOD REVIEWS INTERNATIONAL 2022. [DOI: 10.1080/87559129.2021.2012790] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Affiliation(s)
- Purva Asrani
- Indian Council of Agricultural Research, National Institute for Plant Biotechnology, New Delhi, India
| | - Ansheef Ali
- Division of Biochemistry, Indian Agricultural Research Institute, New Delhi, India
| | - Keshav Tiwari
- Indian Council of Agricultural Research, National Institute for Plant Biotechnology, New Delhi, India
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Rajput MS, Chauhan A, Makharia GK. Epidemiology of Celiac Disease. ADVANCES IN CELIAC DISEASE 2022:7-22. [DOI: 10.1007/978-3-030-82401-3_2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Woodford KB. Casomorphins and Gliadorphins Have Diverse Systemic Effects Spanning Gut, Brain and Internal Organs. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18157911. [PMID: 34360205 PMCID: PMC8345738 DOI: 10.3390/ijerph18157911] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 07/14/2021] [Accepted: 07/17/2021] [Indexed: 12/11/2022]
Abstract
Food-derived opioid peptides include digestive products derived from cereal and dairy diets. If these opioid peptides breach the intestinal barrier, typically linked to permeability and constrained biosynthesis of dipeptidyl peptidase-4 (DPP4), they can attach to opioid receptors. The widespread presence of opioid receptors spanning gut, brain, and internal organs is fundamental to the diverse and systemic effects of food-derived opioids, with effects being evidential across many health conditions. However, manifestation delays following low-intensity long-term exposure create major challenges for clinical trials. Accordingly, it has been easiest to demonstrate causal relationships in digestion-based research where some impacts occur rapidly. Within this environment, the role of the microbiome is evidential but challenging to further elucidate, with microbiome effects ranging across gut-condition indicators and modulators, and potentially as systemic causal factors. Elucidation requires a systemic framework that acknowledges that public-health effects of food-derived opioids are complex with varying genetic susceptibility and confounding factors, together with system-wide interactions and feedbacks. The specific role of the microbiome within this puzzle remains a medical frontier. The easiest albeit challenging nutritional strategy to modify risk is reduced intake of foods containing embedded opioids. In future, constituent modification within specific foods to reduce embedded opioids may become feasible.
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Tittel SR, Dunstheimer D, Hilgard D, Knauth B, Fröhlich-Reiterer E, Galler A, Wurm M, Holl RW, For the DPV Initiative. Coeliac disease is associated with depression in children and young adults with type 1 diabetes: results from a multicentre diabetes registry. Acta Diabetol 2021; 58:623-631. [PMID: 33483854 PMCID: PMC8076130 DOI: 10.1007/s00592-020-01649-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Accepted: 11/28/2020] [Indexed: 02/06/2023]
Abstract
AIMS To analyse the association between coeliac disease (CD) and depression in children, adolescents, and young adults with type 1 diabetes (T1D). METHODS We included 79,067 T1D patients aged 6-20 years, with at least six months of diabetes duration, and treatment data between 1995 and 2019 were documented in the diabetes patient follow-up registry. We categorized patients into four groups: T1D only (n = 73,699), T1 + CD (n = 3379), T1D + depression (n = 1877), or T1D + CD + depression (n = 112). RESULTS CD and depression were significantly associated (adjusted OR: 1.25 [1.03-1.53]). Females were more frequent in both the depression and the CD group compared with the T1D only group. Insulin pumps were used more frequently in T1D + CD and T1D + depression compared with T1D only (both p < .001). HbA1c was higher in T1D + depression (9.0% [8.9-9.0]), T1D + CD + depression (8.9% [8.6-9.2]), both compared with T1D only (8.2% [8.2-8.2], all p < .001). We found comorbid autism, attention deficit hyperactivity disorder, anxiety, schizophrenia, and eating disorders more frequently in the T1D + CD + depression group compared with T1D only (all p < .001). CONCLUSIONS CD and depression are associated in young T1D patients. The double load of T1D and CD may lead to an increased risk for depression. Depression was associated with additional psychological and neurological comorbidities. Aside from imperative CD screening after T1D diagnosis and regular intervals, depression screening might be helpful in routine care, especially in patients with diagnosed CD.
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Affiliation(s)
- Sascha René Tittel
- Institute for Epidemiology and Medical Biometry, ZIBMT, Ulm University, Albert-Einstein-Allee 41, 89081 Ulm, Germany
- German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany
| | - Désirée Dunstheimer
- Paediatrics and Adolescent Medicine, Medical Faculty University of Augsburg, Augsburg, Germany
| | | | - Burkhild Knauth
- Department of Pediatrics and Adolescent Medicine, CJD Berchtesgaden, Berchtesgaden, Germany
| | - Elke Fröhlich-Reiterer
- Division of General Pediatrics, Department of Paediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria
| | - Angela Galler
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Michael Wurm
- Clinic St. Hedwig, University Children’s Hospital Regensburg (KUNO Clinics), University of Regensburg, Regensburg, Germany
| | - Reinhard Walter Holl
- Institute for Epidemiology and Medical Biometry, ZIBMT, Ulm University, Albert-Einstein-Allee 41, 89081 Ulm, Germany
- German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany
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Abstract
Dermatitis herpetiformis (DH), presenting with an intense itch and blistering symmetrical rash, typically on the elbows, knees, and buttocks, is a cutaneous manifestation of celiac disease. Though overt gastrointestinal symptoms are rare, three-fourths of patients with DH have villous atrophy in the small bowel, and the rest have celiac-type inflammatory changes. DH affects mostly adults and slightly more males than females. The mean age at onset is about 50 years. DH diagnosis is confirmed by showing granular immunoglobulin A deposits in the papillary dermis. The DH autoantigen, transglutaminase 3, is deposited at the same site in tightly bound immune complexes. At present, the DH-to-celiac disease prevalence is 1:8. The incidence of DH is decreasing, whereas that of celiac disease is increasing, probably because of improved diagnostics. In DH, the treatment of choice for all patients is a gluten-free diet (GFD) in which uncontaminated oats are allowed. At onset, most patients need additional dapsone to rapidly control the rash and itching. Dapsone can be stopped after a mean of 2 years, and a strict lifelong GFD alone is required. Dietary adherence offers an excellent long-term prognosis for patients with DH, with a normal quality of life and all-cause mortality.
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Affiliation(s)
- Timo Reunala
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
| | - Kaisa Hervonen
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Dermatology, Tampere University Hospital, Tampere, Finland
| | - Teea Salmi
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Dermatology, Tampere University Hospital, Tampere, Finland
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Beuthin J, Veronesi M, Grosberg B, Evans RW. Gluten‐Free Diet and Migraine. Headache 2020; 60:2526-2529. [PMID: 33022759 DOI: 10.1111/head.13993] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 09/15/2020] [Indexed: 01/22/2023]
Affiliation(s)
- Justin Beuthin
- Hartford Healthcare Headache Center University of Connecticut School of Medicine West Hartford CT USA
| | - Maria Veronesi
- Hartford Healthcare Headache Center University of Connecticut School of Medicine West Hartford CT USA
| | - Brian Grosberg
- Hartford Healthcare Headache Center University of Connecticut School of Medicine West Hartford CT USA
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Gayathri D, Ramesha A. Gluten‑hydrolyzing probiotics: An emerging therapy for patients with celiac disease (Review). WORLD ACADEMY OF SCIENCES JOURNAL 2020. [DOI: 10.3892/wasj.2020.55] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Affiliation(s)
- Devaraja Gayathri
- Department of Microbiology, Davangere University, Davangere, Karnataka 577007, India
| | - Alurappa Ramesha
- Department of Microbiology, Davangere University, Davangere, Karnataka 577007, India
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21
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Cartee A, Murray JA. The gluten-free diet: an historical perspective and its use by people without coeliac disease. Med J Aust 2020; 212:111-112. [PMID: 31981420 DOI: 10.5694/mja2.50488] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- Amanda Cartee
- Mayo Clinic, Rochester, MN, United States of America
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22
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Demir E, Comba A. The evolution of celiac disease publications: a holistic approach with bibliometric analysis. Ir J Med Sci 2019; 189:267-276. [DOI: 10.1007/s11845-019-02080-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Accepted: 08/03/2019] [Indexed: 01/15/2023]
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Abstract
Historically, a gluten-free diet was recommended only for those with celiac disease or IgE-mediated wheat allergy. With changes in food allergy labeling in the United States and the publication of several best-selling books, gluten-related disorders have come to the forefront of popular culture. As a result, there has been a dramatic increase in the number of gluten-free diet followers, many for nontraditional reasons. As "going gluten-free" has become mainstream, it is imperative that health care providers acquire the knowledge to identify true gluten-related disorders to effectively counsel their patients and minimize potential complications from following such a restrictive diet.
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Affiliation(s)
- Michelle Pearlman
- Department of Internal Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern, 5323 Harry Hines Boulevard, Dallas, TX 75390-9151, USA
| | - Lisa Casey
- Department of Internal Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern, 5323 Harry Hines Boulevard, Dallas, TX 75390-9151, USA.
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24
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Addressing Barriers for Patients with Celiac Disease When Assessing for Gluten in Medications. J Acad Nutr Diet 2018; 118:1365-1369. [DOI: 10.1016/j.jand.2018.03.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Accepted: 03/28/2018] [Indexed: 11/23/2022]
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Dermatitis Herpetiformis: A Common Extraintestinal Manifestation of Coeliac Disease. Nutrients 2018; 10:nu10050602. [PMID: 29757210 PMCID: PMC5986482 DOI: 10.3390/nu10050602] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2018] [Revised: 05/04/2018] [Accepted: 05/09/2018] [Indexed: 12/20/2022] Open
Abstract
Dermatitis herpetiformis (DH) is a common extraintestinal manifestation of coeliac disease presenting with itchy papules and vesicles on the elbows, knees, and buttocks. Overt gastrointestinal symptoms are rare. Diagnosis of DH is easily confirmed by immunofluorescence biopsy showing pathognomonic granular immunoglobulin A (IgA) deposits in the papillary dermis. A valid hypothesis for the immunopathogenesis of DH is that it starts from latent or manifest coeliac disease in the gut and evolves into an immune complex deposition of high avidity IgA epidermal transglutaminase (TG3) antibodies, together with the TG3 enzyme, in the papillary dermis. The mean age at DH diagnosis has increased significantly in recent decades and presently is 40⁻50 years. The DH to coeliac disease prevalence ratio is 1:8 in Finland and the United Kingdom (U.K.). The annual DH incidence rate, currently 2.7 per 100,000 in Finland and 0.8 per 100,000 in the U.K., is decreasing, whereas the reverse is true for coeliac disease. The long-term prognosis of DH patients on a gluten-free diet is excellent, with the mortality rate being even lower than for the general population.
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Sood A, Midha V, Makharia G, Thelma BK, Halli SS, Mehta V, Mahajan R, Narang V, Sood K, Kaur K. A simple phenotypic classification for celiac disease. Intest Res 2018; 16:288-292. [PMID: 29743842 PMCID: PMC5934602 DOI: 10.5217/ir.2018.16.2.288] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Revised: 01/01/2018] [Accepted: 01/03/2018] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND/AIMS Celiac disease is a global health problem. The presentation of celiac disease has unfolded over years and it is now known that it can manifest at different ages, has varied presentations, and is prone to develop complications, if not managed properly. Although the Oslo definitions provide consensus on the various terminologies used in literature, there is no phenotypic classification providing a composite diagnosis for the disease. METHODS Various variables identified for phenotypic classification included age at diagnosis, age at onset of symptoms, clinical presentation, family history and complications. These were applied to the existing registry of 1,664 patients at Dayanand Medical College and Hospital, Ludhiana, India. In addition, age was evaluated as below 15 and below 18 years. Cross tabulations were used for the verification of the classification using the existing data. Expert opinion was sought from both international and national experts of varying fields. RESULTS After empirical verification, age at diagnosis was considered appropriate in between A1 (<18) and A2 (≥18). The disease presentation has been classified into 3 types-P1 (classical), P2 (non-classical) and P3 (asymptomatic). Complications were considered as absent (C0) or present (C1). A single phenotypic classification based on these 3 characteristics, namely age at the diagnosis, clinical presentation, and intestinal complications (APC classification) was derived. CONCLUSIONS APC classification (age at diagnosis, presentation, complications) is a simple disease explanatory classification for patients with celiac disease aimed at providing a composite diagnosis.
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Affiliation(s)
- Ajit Sood
- Department of Gastroenterology, Dayanand Medical College, Ludhiana, India
| | - Vandana Midha
- Department of Internal Medicine, Dayanand Medical College, Ludhiana, India
| | - Govind Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - B. K. Thelma
- Department of Genetics, University of Delhi South Campus, New Delhi, India
| | - Shivalingappa S Halli
- Department of Community Health Sciences, Faculty of Medicine, University of Manitoba, Winnipeg, Canada
| | - Varun Mehta
- Department of Gastroenterology, Dayanand Medical College, Ludhiana, India
| | - Ramit Mahajan
- Department of Gastroenterology, Dayanand Medical College, Ludhiana, India
| | - Vikram Narang
- Department of Pathology, Dayanand Medical College, Ludhiana, India
| | - Kriti Sood
- Department of Pathology, Dayanand Medical College, Ludhiana, India
| | - Kirandeep Kaur
- Department of Pharmacology, Dayanand Medical College, Ludhiana, India
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Van Kalleveen MW, de Meij T, Plötz FB. Clinical spectrum of paediatric coeliac disease: a 10-year single-centre experience. Eur J Pediatr 2018; 177:593-602. [PMID: 29392394 DOI: 10.1007/s00431-018-3103-4] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Revised: 01/15/2018] [Accepted: 01/17/2018] [Indexed: 02/07/2023]
Abstract
UNLABELLED This study was undertaken to gain insight in the clinical spectrum of paediatric coeliac disease (CD) in a Dutch teaching hospital. We retrospectively compared the frequency of CD in children with a wide spectrum of complaints with and without CD antibodies in serum and were interested if certain complaints are more pathognomonic for CD. Furthermore, we expected that over a period of 10-year incidence rates of CD would have increased and shifted towards an atypical presentation with more non-gastrointestinal symptoms with increasing age. A retrospective, single-centre, case-control study was performed. All patients who presented at the Department of Paediatrics, Tergooi Hospital, with symptoms suspected for CD were eligible for inclusion during the study period from 1 January 2007 till 31 December 2016. Children were diagnosed with CD according to the 2005 and 2012 ESPGHAN guideline between 2007 and 2016, respectively. Demographic data, presenting symptoms, prevalence of associated conditions and serology results were examined. A total of 105 new cases of paediatric CD were observed, with an average of 10 new cases each year. The calculated incidence was 21.09 (CI 17.49-25.22)/100,000 under 18 years of age. About 40% were infants and toddlers, predominantly presenting with gastrointestinal symptoms. Primary and high school children had more display of atypical symptoms (p = 0.001, p = 0.017) and non-gastrointestinal symptoms (p = 0.009, p = 0.009) than infants and toddlers. In 8.6% of the CD patients, mostly primary school aged female patients, the serology was repeated at least once in time to become positive. The median time for serology to become positive was 609 days (range 140-1054). CONCLUSION As it is well known, our study supports the increasing notion of a shift in the clinical spectrum of presenting symptoms in paediatric CD towards an atypical presentation, with more non-gastrointestinal symptoms and a diagnosis at a later age in a Dutch population, whereas the number of new cases did not increase over the years. What is Known: • The clinical spectrum of paediatric coeliac disease is shifting towards a presentation with more atypical and non-GI symptoms. • The incidence of paediatric coeliac disease is still increasing as is the age at which it is diagnosed. What is New: • An average of 10 paediatric CD cases are diagnosed per year in our general teaching hospital. • The calculated (gender-specific) incidence rates are higher than previously reported.
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Affiliation(s)
- Michael W Van Kalleveen
- Department of Paediatrics, Tergooi Hospital, Rijksstraatweg 1, 1261 AN, Blaricum, The Netherlands.
| | - Tim de Meij
- Department of Paediatric Gastroenterology, VU Medical Centre (VUmc), Amsterdam, The Netherlands
| | - Frans B Plötz
- Department of Paediatrics, Tergooi Hospital, Rijksstraatweg 1, 1261 AN, Blaricum, The Netherlands
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28
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Pappas TN, Swanson S. The life, times, and health care of Harry L Hopkins: Presidential advisor and perpetual patient. JOURNAL OF MEDICAL BIOGRAPHY 2018; 26:49-59. [PMID: 27342698 DOI: 10.1177/0967772015588646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
Harry Hopkins was the most important nontitled allied leader in World War II. He was the advisor to President Roosevelt who managed the diplomacy between Roosevelt, Churchill, and Stalin from 1941 to 1946. Throughout these times, Hopkins was ill and required transfusions, admissions to the hospital, and nutritional supplementation to keep him well enough to travel the world and manage the allied war diplomacy. There has been no unifying theory to account for all his symptoms and his reported pathologic and autopsy findings. In this paper, we will review his political and medical history and a differential diagnosis of his illness.
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Affiliation(s)
| | - Sven Swanson
- 2 Department of Pathology, Athens Regional Medical Center, USA
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Cui C, Basen T, Philipp AT, Yusin J, Krishnaswamy G. Celiac disease and nonceliac gluten sensitivity. Ann Allergy Asthma Immunol 2017; 118:389-393. [PMID: 28390579 DOI: 10.1016/j.anai.2017.01.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Revised: 01/08/2017] [Accepted: 01/09/2017] [Indexed: 12/16/2022]
Affiliation(s)
- Chongwei Cui
- Department of Allergy and Immunology, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California
| | - Tyler Basen
- Department of Allergy and Immunology, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California
| | - Ami Thakor Philipp
- Department of Allergy and Immunology, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California
| | - Joseph Yusin
- Department of Allergy and Immunology, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California
| | - Guha Krishnaswamy
- Wake Forest School of Medicine and Wake Baptist Hospital, Winston Salem, North Carolina; W.G. (Bill) Hefner Veterans Affairs Medical Center and Affiliated Clinics, Salisbury, North Carolina.
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Parzanese I, Qehajaj D, Patrinicola F, Aralica M, Chiriva-Internati M, Stifter S, Elli L, Grizzi F. Celiac disease: From pathophysiology to treatment. World J Gastrointest Pathophysiol 2017; 8:27-38. [PMID: 28573065 PMCID: PMC5437500 DOI: 10.4291/wjgp.v8.i2.27] [Citation(s) in RCA: 154] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2016] [Revised: 03/08/2017] [Accepted: 03/23/2017] [Indexed: 02/06/2023] Open
Abstract
Celiac disease, also known as "celiac sprue", is a chronic inflammatory disorder of the small intestine, produced by the ingestion of dietary gluten products in susceptible people. It is a multifactorial disease, including genetic and environmental factors. Environmental trigger is represented by gluten while the genetic predisposition has been identified in the major histocompatibility complex region. Celiac disease is not a rare disorder like previously thought, with a global prevalence around 1%. The reason of its under-recognition is mainly referable to the fact that about half of affected people do not have the classic gastrointestinal symptoms, but they present nonspecific manifestations of nutritional deficiency or have no symptoms at all. Here we review the most recent data concerning epidemiology, pathogenesis, clinical presentation, available diagnostic tests and therapeutic management of celiac disease.
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Collin P, Salmi TT, Hervonen K, Kaukinen K, Reunala T. Dermatitis herpetiformis: a cutaneous manifestation of coeliac disease. Ann Med 2017; 49:23-31. [PMID: 27499257 DOI: 10.1080/07853890.2016.1222450] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Dermatitis herpetiformis (DH) is an itchy blistering skin disease with predilection sites on elbows, knees, and buttocks. Diagnosis is confirmed by showing granular immunoglobulin A deposits in perilesional skin. DH is one manifestation of coeliac disease; the skin symptoms heal with gluten free diet (GFD) and relapse on gluten challenge. Of the first-degree relatives, 5% may be affected by either condition. Tissue transglutaminase (TG2) is the autoantigen in coeliac disease and epidermal transglutaminase (TG3) in DH. Both diseases conditions exhibit TG2-specific autoantibodies in serum and small bowel mucosa; patients with DH have IgA-TG3 in the skin. There are some divergencies between these two phenotypes. One-fourth of DH patients do not have small bowel mucosal villous atrophy, but virtually all have coeliac-type inflammatory changes. The skin symptoms respond slowly to GFD. The incidence of coeliac disease is increasing, whereas the opposite is true for DH. A female predominance is evident in coeliac disease, while DH may be more common in males. Coeliac disease carries the risk of small intestinal T-cell lymphoma; in DH B-cell lymphomas at any site may prevail. Adult coeliac disease carries a slightly increased elevated mortality risk, whereas in DH, the relative mortality rate is significantly decreased. Key messages Dermatitis herpetiformis is a cutaneous manifestation of coeliac disease; both conditions are genetically determined and gluten-dependent. Gastrointestinal symptoms and the degree of villous atrophy are less obvious in dermatitis herpetiformis than in coeliac disease. Both show tissue transglutaminase (TG2) specific autoantibodies in serum and small bowel mucosa. In addition, TG3-targeted IgA antibodies are found in the skin of DH patients Both conditions carry an increased elevated risk of lymphoma, in coeliac disease small intestinal T-cell lymphoma, in dermatitis herpetiformis mainly B-cell lymphoma at various sites. Coeliac disease is currently eight times more common that DH; the incidence of DH is decreasing in contrast to that of coeliac disease, where it is increasing.
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Affiliation(s)
- Pekka Collin
- a Department of Gastroenterology and Alimentary Tract Surgery , Tampere University Hospital , Tampere , Finland
| | - Teea T Salmi
- b Department of Dermatology , Tampere University Hospital , Tampere , Finland.,c School of Medicine , University of Tampere , Tampere , Finland
| | - Kaisa Hervonen
- b Department of Dermatology , Tampere University Hospital , Tampere , Finland.,c School of Medicine , University of Tampere , Tampere , Finland
| | - Katri Kaukinen
- c School of Medicine , University of Tampere , Tampere , Finland.,d Department of Internal Medicine , Tampere University Hospital , Tampere , Finland
| | - Timo Reunala
- b Department of Dermatology , Tampere University Hospital , Tampere , Finland.,c School of Medicine , University of Tampere , Tampere , Finland
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32
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Stein R, Katz D. Celiac Disease. FOODBORNE DISEASES 2017:475-526. [DOI: 10.1016/b978-0-12-385007-2.00024-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Elder JE, Hardikar W. Ocular Manifestations of Gastrointestinal Disease. THE EYE IN PEDIATRIC SYSTEMIC DISEASE 2017:263-293. [DOI: 10.1007/978-3-319-18389-3_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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MOCAN OANA, DUMITRAŞCU DANL. The broad spectrum of celiac disease and gluten sensitive enteropathy. CLUJUL MEDICAL (1957) 2016; 89:335-342. [PMID: 27547052 PMCID: PMC4990427 DOI: 10.15386/cjmed-698] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2016] [Accepted: 06/29/2016] [Indexed: 12/27/2022]
Abstract
The celiac disease is an immune chronic condition with genetic transmission, caused by the intolerance to gluten. Gluten is a protein from cereals containing the following soluble proteins: gliadine, which is the most toxic, and the prolamins. The average prevalence is about 1% in USA and Europe, but high in Africa: 5.6% in West Sahara. In the pathogenesis several factors are involved: gluten as external trigger, genetic predisposition (HLA, MYO9B), viral infections, abnormal immune reaction to gluten. Severity is correlated with the number of intraepithelial lymphocytes, cryptic hyperplasia and villous atrophy, as well as with the length of intestinal involvement. The severity is assessed according to the Marsh-Oberhuber staging. Diagnostic criteria are: positive serological tests, intestinal biopsy, the reversal after gluten free diet (GFD). Beside refractory forms, new conditions have been described, like the non celiac gluten intolerance. In a time when more and more people adhere to GFD for nonscientific reasons, practitioners should be updated with the progress in celiac disease knowledge.
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Affiliation(s)
- OANA MOCAN
- Biochemistry Department, Iuliu Hatieganu University of Medicine and Pharmacy, Polaris Medical Rehabilitation Hospital, Suceagu, Cluj County, Romania
| | - DAN L. DUMITRAŞCU
- 2nd Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
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Sams A, Hawks J. Celiac disease as a model for the evolution of multifactorial disease in humans. Hum Biol 2015; 86:19-36. [PMID: 25401984 DOI: 10.3378/027.086.0102] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/04/2013] [Indexed: 11/05/2022]
Abstract
Celiac disease (CD) is a multifactorial chronic inflammatory condition that results in injury of the mucosal lining of the small intestine upon ingestion of wheat gluten and related proteins from barley and rye. Although the exact mechanisms leading to CD are not fully understood, the genetic basis of CD has been relatively well characterized. In this review we briefly review the history of discovery, clinical presentation, pathophysiology, and current understanding of the genetics underlying CD risk. Then, we discuss what is known about the current distribution and evolutionary history of genes underlying CD risk in light of other evolutionary models of disease. Specifically, we conclude that the set of loci underlying CD risk did not cohesively evolve as a response to a single past selection event such as the development of agriculture. Rather, deterministic and stochastic evolutionary processes have both contributed to the present distribution of variation in CD risk loci. Selection has shaped some components of this network, but this selection appears to have occurred at different points in the past. Other parts of the CD risk network have likely arisen due to stochastic processes such as genetic drift.
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Affiliation(s)
- Aaron Sams
- Cornell University, Ithaca, New York, USA
| | - John Hawks
- University of Wisconsin-Madison, Madison, Wisconsin, USA
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Abstract
Coeliac disease is a common disorder that can arise at any age and typically presents with a broad spectrum of symptoms. The disease is thought to be underdiagnosed, in part owing to the fact that coeliac disease is often characterized by associated conditions and extraintestinal manifestations that can misdirect and impede diagnosis. Some of these manifestations are direct consequences of autoimmunity, such as dermatitis herpetiformis or gluten ataxia, whereas others are indirectly related to inflammation and/or malabsorption including anaemia, osteoporosis, short stature and delayed puberty. Any organ from the central nervous system to joints, liver or teeth can be affected. In some cases, extraintestinal symptoms are the only clinical manifestations of coeliac disease or occur in conjunction with diarrhoea and malabsorptive symptoms. An increased awareness among medical practitioners of the variety of extraintestinal manifestations of coeliac disease is essential to improve diagnosis and treatment.
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Affiliation(s)
- Daniel A Leffler
- The Celiac Centre at Beth Israel Deaconess Medical Centre, 330 Brookline Avenue, Boston, MA 02215, USA
| | - Peter H R Green
- Celiac Disease Centre at Columbia University, 180 Fort Washington Avenue, HP 934, New York, NY 10032, USA
| | - Alessio Fasano
- Centre for Celiac Research, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA
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El-Salhy M, Hatlebakk JG, Gilja OH, Hausken T. The relation between celiac disease, nonceliac gluten sensitivity and irritable bowel syndrome. Nutr J 2015; 14:92. [PMID: 26345589 PMCID: PMC4561431 DOI: 10.1186/s12937-015-0080-6] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2015] [Accepted: 08/28/2015] [Indexed: 12/22/2022] Open
Abstract
Wheat products make a substantial contribution to the dietary intake of many people worldwide. Despite the many beneficial aspects of consuming wheat products, it is also responsible for several diseases such as celiac disease (CD), wheat allergy, and nonceliac gluten sensitivity (NCGS). CD and irritable bowel syndrome (IBS) patients have similar gastrointestinal symptoms, which can result in CD patients being misdiagnosed as having IBS. Therefore, CD should be excluded in IBS patients. A considerable proportion of CD patients suffer from IBS symptoms despite adherence to a gluten-free diet (GFD). The inflammation caused by gluten intake may not completely subside in some CD patients. It is not clear that gluten triggers the symptoms in NCGS, but there is compelling evidence that carbohydrates (fructans and galactans) in wheat does. It is likely that NCGS patients are a group of self-diagnosed IBS patients who self-treat by adhering to a GFD.
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Affiliation(s)
- Magdy El-Salhy
- Section for Gastroenterology, Department of Medicine, Stord Hospital, Stord, Norway.
- Section for Neuroendocrine Gastroenterology, Division of Gastroenterology, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
- National Centre for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen, Norway.
| | - Jan Gunnar Hatlebakk
- Section for Neuroendocrine Gastroenterology, Division of Gastroenterology, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
- National Centre for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen, Norway.
| | - Odd Helge Gilja
- Section for Neuroendocrine Gastroenterology, Division of Gastroenterology, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
- National Centre for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen, Norway.
- National Centre for Ultrasound in Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway.
| | - Trygve Hausken
- Section for Neuroendocrine Gastroenterology, Division of Gastroenterology, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
- National Centre for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen, Norway.
- National Centre for Ultrasound in Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway.
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Elli L, Roncoroni L, Bardella MT. Non-celiac gluten sensitivity: Time for sifting the grain. World J Gastroenterol 2015; 21:8221-8226. [PMID: 26217073 PMCID: PMC4507091 DOI: 10.3748/wjg.v21.i27.8221] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2015] [Revised: 04/01/2015] [Accepted: 05/27/2015] [Indexed: 02/06/2023] Open
Abstract
In the last few years, a new nomenclature has been proposed for the disease induced by the ingestion of gluten, a protein present in wheat, rice, barley and oats. Besides celiac disease and wheat allergy, the most studied forms of gluten-related disorders characterized by an evident immune mechanism (autoimmune in celiac disease and IgE-mediated in wheat allergy), a new entity has been included, apparently not driven by an aberrant immune response: the non-celiac gluten sensitivity (NCGS). NCGS is characterized by a heterogeneous clinical picture with intestinal and extraintestinal symptoms arising after gluten ingestion and rapidly improving after its withdrawal from the diet. The pathogenesis of NCGS is largely unknown, but a mixture of factors such as the stimulation of the innate immune system, the direct cytotoxic effects of gluten, and probably the synergy with other wheat molecules, are clues for the complicated puzzle. In addition, the diagnostic procedures still remain problematic due to the absence of efficient diagnostic markers; thus, diagnosis is based upon the symptomatic response to a gluten-free diet and the recurrence of symptoms after gluten reintroduction with the possibility of an important involvement of a placebo effect. The temporary withdrawal of gluten seems a reasonable therapy, but the timing of gluten reintroduction and the correct patient management approach are have not yet been determined.
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Robinson BL, Davis SC, Vess J, Lebel J. Primary care management of celiac disease. Nurse Pract 2015; 40:28-35. [PMID: 25574900 DOI: 10.1097/01.npr.0000459728.54533.ac] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
: Celiac disease is an autoimmune disorder with genetic predisposition that affects as many as 1 in 100 individuals. Treatment is a lifelong, strict adherence to a gluten-free diet. Management by a primary care provider may lead to increased adherence and can minimize effects of nonadherence to the diet.
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Affiliation(s)
- Brittani Ledford Robinson
- Brittani Ledford Robinson is a family nurse practitioner at Gastroenterology Associates, Greenville, S.C. Stephanie C. Davis is a graduate coordinator and associate professor at Clemson University School of Nursing, Clemson, S.C. Joy Vess is an instructor at Medical University of South Carolina College of Nursing, Charleston, S.C. Joseph Lebel is a physician at Physician, Gastroenterology Associates, Greenville, S.C
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Mansueto P, Seidita A, D'Alcamo A, Carroccio A. Non-celiac gluten sensitivity: literature review. J Am Coll Nutr 2014; 33:39-54. [PMID: 24533607 DOI: 10.1080/07315724.2014.869996] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND A significant percentage of the general population report problems caused by wheat and/or gluten ingestion, even though they do not have celiac disease (CD) or wheat allergy (WA), because they test negative both for CD-specific serology and histopathology and for immunoglobulin E (IgE)-mediated assays. Most patients report both gastrointestinal and nongastrointestinal symptoms, and all report improvement of symptoms on a gluten-free diet. This clinical condition has been named non-celiac gluten sensitivity (NCGS). AIM We attempt to define the current pathogenic, clinical, and diagnostic criteria of this "new" disease, to provide a practical view that might be useful to evaluate, diagnose, and manage NCGS patients. METHODS We reviewed the international literature through PubMed and Medline, using the search terms "wheat (hyper)sensitivity," "wheat allergy," "wheat intolerance," "gluten (hyper)sensitivity," and "gluten intolerance," and we discuss current knowledge about NCGS. RESULTS It has been demonstrated that patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course. NCGS diagnosis can be reached only by excluding CD and WA. Recent evidence shows that a personal history of food allergy in infancy, coexistent atopy, positive for immunoglobulin G (IgG) antigliadin antibodies and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients. CONCLUSIONS Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroups. Key teaching points: • Most patients report both gastrointestinal and nongastrointestinal symptoms, and all agree that there is an improvement of symptoms on a gluten-free diet. • NCGS diagnosis can be reached only by excluding celiac disease and wheat allergy. • Patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course. • A personal history of food allergy in infancy, coexistent atopy, positive IgG antigliadin antibodies (AGA) and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients. • Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroup.
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Affiliation(s)
- Pasquale Mansueto
- a Internal Medicine, University Hospital of Palermo , Palermo , ITALY
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Abstract
The diagnostic criteria for celiac disease (CD) have undergone significant change during the past several decades following a better understanding of the pathogenesis of the disease and the identification of sensitive and specific serum markers. In 2012, the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition published new diagnostic algorithms, which for the first time questioned the need for histological evaluation in all patients, and identified specific requirements for omitting intestinal biopsies from diagnosis requirements. Here, we briefly review the evolution of the diagnostic algorithms, emerging data which may be integrated into the diagnosis algorithm in the future and suggest key points which should be considered while we continue to develop and refine the diagnostic criteria for CD in an age of personalized medicine.
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Piscaglia AC. Intestinal stem cells and celiac disease. World J Stem Cells 2014; 6:213-229. [PMID: 24772248 PMCID: PMC3999779 DOI: 10.4252/wjsc.v6.i2.213] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2013] [Revised: 02/07/2014] [Accepted: 03/12/2014] [Indexed: 02/06/2023] Open
Abstract
Stem cells (SCs) are the key to tissue genesis and regeneration. Given their central role in homeostasis, dysfunctions of the SC compartment play a pivotal role in the development of cancers, degenerative disorders, chronic inflammatory pathologies and organ failure. The gastrointestinal tract is constantly exposed to harsh mechanical and chemical conditions and most of the epithelial cells are replaced every 3 to 5 d. According to the so-called Unitarian hypothesis, this renewal is driven by a common intestinal stem cell (ISC) residing within the crypt base at the origin of the crypt-to-villus hierarchical migratory pattern. Celiac disease (CD) can be defined as a chronic immune-mediated disease that is triggered and maintained by dietary proteins (gluten) in genetically predisposed individuals. Many advances have been achieved over the last years in understanding of the pathogenic interactions among genetic, immunological and environmental factors in CD, with a particular emphasis on intestinal barrier and gut microbiota. Conversely, little is known about ISC modulation and deregulation in active celiac disease and upon a gluten-free diet. Nonetheless, bone marrow-derived SC transplantation has become an option for celiac patients with complicated or refractory disease. This manuscript summarizes the “state of the art” regarding CD and ISCs, their niche and potential role in the development and treatment of the disease.
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Gasbarrini GB, Mangiola F, Gerardi V, Ianiro G, Corazza GR, Gasbarrini A. Coeliac disease: an old or a new disease? History of a pathology. Intern Emerg Med 2014; 9:249-56. [PMID: 24435555 DOI: 10.1007/s11739-013-1044-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Accepted: 12/26/2013] [Indexed: 01/02/2023]
Abstract
The celiac disease is an ancient pathology, present since the introduction of the wheat in the diet, of which the first description of the compatible clinical symptoms and signs goes back to 250 A.D. Today it is known that the expression of this pathology is multifaceted, ranging from clinical features indicative of bowel disease and malabsorption, until symptoms once unexpected, because of their extra-digestive clinical features. With our work, we wanted to retrace the history of this disease, correlating it with the intake of gluten present in wheat after cooking , ever since mankind has increased the cultivation of cereals. Re-evaluating the clinical and instrumental methods for the diagnosis of Celiac Disease, and benefitting from the most modern techniques for the morphological, biochemical and genetic study of the patients, we sought to understand whether the incidence of the disease is actually increased or if has been considered less frequent for the lower valuation of the signs once deemed more atypical, but currently considered preliminary indicative of the pathology, for its association with other autoimmune diseases, and for the study of some genetic and familiar characteristics. Each of these factors has led the modern medicine to increase epidemiological studies and expand the research potential carriers of celiac disease with safer diagnostic tests.
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Affiliation(s)
- Susan S Baker
- Digestive Diseases and Nutrition Center, Department of Pediatrics University at Buffalo, Buffalo, New York
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Gasbarrini G, Rickards O, Martínez-Labarga C, Pacciani E, Chilleri F, Laterza L, Marangi G, Scaldaferri F, Gasbarrini A. Origin of celiac disease: How old are predisposing haplotypes? World J Gastroenterol 2012; 18:5300-4. [PMID: 23066327 PMCID: PMC3468865 DOI: 10.3748/wjg.v18.i37.5300] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2012] [Revised: 06/29/2012] [Accepted: 07/09/2012] [Indexed: 02/06/2023] Open
Abstract
We recently presented the case of a first century AD young woman, found in the archaeological site of Cosa, showing clinical signs of malnutrition, such as short height, osteoporosis, dental enamel hypoplasia and cribra orbitalia, indirect sign of anemia, all strongly suggestive for celiac disease (CD). However, whether these findings were actually associated to CD was not shown based on genetic parameters. To investigate her human leukocyte antigen (HLA) class II polymorphism, we extracted DNA from a bone sample and a tooth and genotyped HLA using three HLA-tagging single nucleotide polymorphisms for DQ8, DQ2.2 and DQ2.5, specifically associated to CD. She displayed HLA DQ 2.5, the haplotype associated to the highest risk of CD. This is the first report showing the presence of a HLA haplotype compatible for CD in archaeological specimens.
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46
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Abstract
Celiac disease results from the interplay of genetic, environmental, and immunologic factors. An understanding of the pathophysiology of celiac disease, in which the trigger (wheat, rye, and barley) is known, will undoubtedly reveal basic mechanisms that underlie other autoimmune diseases (eg, type 1 diabetes) that share many common pathogenic perturbations. This review describes seminal findings in each of the 3 domains of the pathogenesis of celiac disease, namely genetics, environmental triggers, and immune dysregulation, with a focus on newer areas of investigation such as non-HLA genetic variants, the intestinal microbiome, and the role of the innate immune system.
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Affiliation(s)
- Sonia S Kupfer
- University of Chicago Celiac Disease Center, Chicago, IL, USA.
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47
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Abstract
Coeliac disease is a permanent inflammatory disorder of the small bowel affecting approximately 1% of the population. The only effective treatment that exists is exclusion of gluten from the diet. The present paper aims to review the literature as to whether oats are safe to eat for people with coeliac disease. Much data exist on the restrictive nature that adhering to a gluten-free diet imposes on an individual. If oats could be eaten, this would help reduce the restrictive nature of the diet. This in turn could lead to an increase in the quality of life. Oats are of high-nutritional value, providing a rich source of fibre, vitamins and minerals. The fibre source contains soluble fibre which is believed to help reduce LDL-cholesterol. A systematic review of the literature was conducted. Earlier studies conducted are difficult to compare as they used different methodologies and it is not known whether samples of oats in the studies were contaminated with gluten from other cereals. Many studies reviewed do not state the strain of oat used. Recent research has suggested that it may only be in certain strains of oats which could produce a toxic response to people with coeliac disease. In conclusion, research suggests that the risk from consuming oats may be less harmful than first thought; however, may vary according to the strain of oat. Handling that risk in clinical practice remains controversial.
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48
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Newton KP, Singer SA. Celiac disease in children and adolescents: special considerations. Semin Immunopathol 2012; 34:479-496. [PMID: 22549889 DOI: 10.1007/s00281-012-0313-0] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2012] [Accepted: 04/10/2012] [Indexed: 02/06/2023]
Abstract
Although there are many commonalities between adult and pediatric celiac disease (CD), special considerations must be taken into account when working with children and adolescents. In this patient population, there are unique aspects of the epidemiology, pathogenesis, presentation, diagnosis, and management of CD. In terms of management, early and timely recognition of CD can maximize childhood and adolescent development and prevent complications. This requires insight into the unique presentations of CD in the pediatric population. Furthermore, health care providers must use proper screening methods and continue surveillance of at-risk individuals throughout childhood. Potential interventions for primary prevention of CD in children, although not completely understood, may offer some benefit. The goals of this article are to discuss in detail these special considerations when dealing with pediatric CD.
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Affiliation(s)
- Kimberly P Newton
- Rady Childrens Hospital, 3020 Children's Way MC5030, San Diego, CA 92123, USA.
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49
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Pitchumoni CS, Pitchumoni CS, Pitchumoni CS, Chen N. Celiac Disease. GERIATRIC GASTROENTEROLOGY 2012:501-510. [DOI: 10.1007/978-1-4419-1623-5_52] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Erriu M, Sanna S, Nucaro A, Orrù G, Garau V, Montaldo C. HLA-DQB1 Haplotypes and their Relation to Oral Signs Linked to Celiac Disease Diagnosis. Open Dent J 2011; 5:174-8. [PMID: 22135701 PMCID: PMC3227877 DOI: 10.2174/1874210601105010174] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2011] [Revised: 08/22/2011] [Accepted: 08/30/2011] [Indexed: 01/06/2023] Open
Abstract
Objectives: Celiac disease (CD) is an autoimmune disorder that can be divided into typical and atypical forms. Atypical forms can show extraintestinal manifestations among which oral signs are very frequent. Considering that the pathogenesis of CD is related to a positivity to specific HLA-DQB1 haplotypes, we tested whether the presence of the HLA-DQB1*02 allele could be a hypothetical cause of the development of oral manifestations. Subjects and Methods: For this study was been examined the oral condition of 98 Sardinian patients, all affected by CD and all on a gluten-free diet for at least 1 year. Then was been determined each patient’s HLA-DQB1 haplotype and compared these results with clinical information. Results: The statistical analysis evidenced that the absence of the HLA-DQB1*02 allele predisposes to oral manifestations such as dental enamel defects (DED) and recurrent aphthous stomatitis (RAS) (Pvalue=5.98x10-05, OR = 0.23, CI: (0.10 - 0.45) per each copy of the HLA allele). Conclusions: These results showed that the presence of the HLA-DQB1*02 allele influences the development of oral signs in a dose-dependent manner and also how the HLA haplotype connected to oral signs could have a fundamental role for the diagnosis of atypical forms of CD.
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Affiliation(s)
- Matteo Erriu
- Department of Surgery and Odontostomatological Sciences, University of Cagliari. Cagliari
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