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Mouslih A, El Rhazi K, Bahra N, Lakhdar Idrissi M, Hida M. Celiac Disease in Moroccan Children: Diagnostic Characteristics and Determinants of Diagnosis Delay. Cureus 2023; 15:e50800. [PMID: 38125690 PMCID: PMC10731523 DOI: 10.7759/cureus.50800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/19/2023] [Indexed: 12/23/2023] Open
Abstract
Advances in the field of celiac disease have led to a better understanding of the disease, but it remains underdiagnosed and poses a daily challenge to clinicians to make a timely diagnosis. This study aims to analyze and describe diagnosis characteristics, diagnosis delay, and the factors influencing this delay in Moroccan children. Our study included 324 children diagnosed during the study period from January 01, 2010, to December 30, 2019, at the Department of Pediatrics, Hassan II University Hospital in Fez, Morocco. Data were collected using a collection grid and then analyzed using SPSS 26 software (IBM Corp., Armonk, NY). The results showed a female predominance (n=197, 60.8%), with a diagnosis age of 73.8±46.8 months. The mean age onset of symptoms was 51.3±41.2 months, and the diagnosis delay was 22.2±22.6 months, with only 32.7% (n=106) diagnosed less than 12 months after symptom onset. The most common consultation reason was diarrhea (n=149, 46%) and growth delay (n=105, 32.4%) and 50.5% (n=98) of parents consulted a pediatrician first. The three clinical, serologic, and histologic criteria made it possible to agree on the diagnosis, with the clinical profile dominated by the digestive form at 84.9% (n=279), serologic with the presence of IgA transglutaminase antibodies (95.7%; n=310), and histologic with villous atrophy at 91.7% (n=297). Unfortunately, 14.8% (n=48) of the children were diagnosed with a celiac crisis. The multivariate logistic regression analysis showed that as symptoms onset age increased, so did the risk of late diagnosis (OR=0.96, 95% CI: 0.94 to 0.97, p<0.001). Age of diagnosis was also associated with delayed diagnosis (OR=19.68, 95% CI: 8.77 to 44.15, p<0.001). The combination of these variables and the diagnosis delay argues in favor of adopting a diagnosis strategy that includes raising awareness among healthcare professionals of the need to identify typical and atypical cases early in order to reduce the adverse effects of late diagnosis and the complications that can result. This methodology for improving diagnoses may also unearth previously unknown aspects of celiac disease in Moroccan children.
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Affiliation(s)
- Assia Mouslih
- Laboratory of Epidemiology and Health Research, Faculty of Medicine and Pharmacy, Sidi Mohammed Ben Abdellah University, Fez, MAR
| | - Karima El Rhazi
- Laboratory of Epidemiology and Health Research, Faculty of Medicine and Pharmacy, Sidi Mohammed Ben Abdellah University, Fez, MAR
| | - Nassiba Bahra
- Laboratory of Epidemiology and Health Research, Faculty of Medicine and Pharmacy, Sidi Mohammed Ben Abdellah University, Fez, MAR
| | - Mounia Lakhdar Idrissi
- Department of Pediatrics, Faculty of Medicine and Pharmacy/ Epidemiology and Health Science Research Laboratory, Hassan II University Hospital, Fez, MAR
- Laboratory of Epidemiology and Health Research, Faculty of Medicine and Pharmacy, Sidi Mohammed Ben Abdellah University, Fez, MAR
| | - Moustapha Hida
- Department of Pediatrics, Faculty of Medicine and Pharmacy/ Epidemiology and Health Science Research Laboratory, Hassan II University Hospital, Fez, MAR
- Laboratory of Epidemiology and Health Research, Faculty of Medicine and Pharmacy, Sidi Mohammed Ben Abdellah University, Fez, MAR
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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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Influence of Compliance to Diet and Self-Efficacy Expectation on Quality of Life in Patients with Celiac Disease in Spain. Nutrients 2020; 12:nu12092672. [PMID: 32887250 PMCID: PMC7551960 DOI: 10.3390/nu12092672] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Revised: 08/28/2020] [Accepted: 08/29/2020] [Indexed: 01/09/2023] Open
Abstract
The purpose of this study is to understand the health-related quality of life (HRQoL) in patients with celiac disease (CD) and analyze its main determinants. A transversal descriptive study of 738 patients with celiac disease was carried out. A series of questionnaires were answered related to their HRQoL, adherence to a gluten-free diet (GFD), and self-efficacy beliefs among other relevant variables. Regression analyses were carried out in order to explore the predictive variables in adherence to the GFD and HRQoL. A total of 61.2% showed a good HRQoL, and the main predictors of HRQoL were specific self-efficacy, adherence to the diet, risk perception, time since diagnosis, and age. While 68.7% of participants showed good or excellent adherence to the GFD, and the main predictors of adherence were specific self-efficacy, perceived adoption of recommended behaviors, HRQoL and gender. The HRQoL of patients with CD, and adherence to the GFD in Spain, are good. It is the self-efficacy expectation, measured specifically and not generally, which is the best predictor of both adherence and HRQoL. It is necessary to develop programs to improve the HRQoL of patients with CD that focus on improving specific self-efficacy.
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Abstract
Recent statistics report that 3 million people, or 1% of the population in the United States (U.S.), are affected by celiac disease (CD). In addition, in the U.S., as many as 1 in 80 children is affected with CD. However, CD can be challenging to diagnose and many children are not correctly diagnosed or live without a diagnosis for several years. Symptoms, if present, are often nonspecific and may be common manifestations of many pediatric illnesses. The purpose of this review is to examine the current evidence regarding incidence, pathophysiology, diagnosis, and treatment of a child with CD. Clinical implications for nurses caring for children and families are discussed.
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Salehi F. Improvement of gluten-free bread and cake properties using natural hydrocolloids: A review. Food Sci Nutr 2019; 7:3391-3402. [PMID: 31762992 PMCID: PMC6848842 DOI: 10.1002/fsn3.1245] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2019] [Revised: 09/05/2019] [Accepted: 09/14/2019] [Indexed: 01/14/2023] Open
Abstract
The main wheat component responsible for bread and cake quality is gluten. Celiac disease is an autoimmune digestive disease that is caused by the digestion of gluten, and the only treatment of this disease is a gluten-free diet. Various gluten-free formulations (composite and wheatless flours) have applied gums (as gluten substitutes) to mimic the viscoelastic properties of gluten. In the bakery products, gums have been used to improve dough performance, bread and cake characteristics, textural and sensorial quality, and extension the products shelf life. This paper reviews the effect of the most common and new hydrocolloids (balangu seed, wild sage seed, basil seed, cress seed, xanthan, guar, starch carrageenan, methylcellulose, carboxy methyl cellulose, hydroxyl propyl methyl cellulose, and locust bean gums) on the rheological, physicochemical, textural, and quality characteristics of gluten-free breads and cakes. Gums affect gelatinization and retrogradation of starch through a strong association of amylose with gum, resulting in a decrease in the retrogradation of starch. Gums addition increased volume and porosity of the breads and cakes and resulted in softer products.
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Affiliation(s)
- Fakhreddin Salehi
- Department of Biosystems EngineeringFaculty of AgricultureBu‐Ali Sina UniversityHamedanIran
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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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Bettini AC, Beretta GD, Sironi P, Mosconi S, Labianca R. Chemotherapy in Small Bowel Adenocarcinoma Associated with Celiac Disease: A Report of Three Cases. TUMORI JOURNAL 2018; 89:193-5. [PMID: 12841670 DOI: 10.1177/030089160308900217] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Tumors of the small intestine are rare and usually occur in association with genetic disease and chronic intestinal inflammation. We report three cases of small bowel adenocarcinoma in patients affected by celiac disease who received a safe chemotherapy regimen (FOLFOX IV or LV5FU2) after tumor resection.
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Malakouti M, Kataria A, Ali SK, Schenker S. Elevated Liver Enzymes in Asymptomatic Patients - What Should I Do? J Clin Transl Hepatol 2017; 5:394-403. [PMID: 29226106 PMCID: PMC5719197 DOI: 10.14218/jcth.2017.00027] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2017] [Revised: 06/22/2017] [Accepted: 07/12/2017] [Indexed: 12/14/2022] Open
Abstract
Elevated liver enzymes are a common scenario encountered by physicians in clinical practice. For many physicians, however, evaluation of such a problem in patients presenting with no symptoms can be challenging. Evidence supporting a standardized approach to evaluation is lacking. Although alterations of liver enzymes could be a normal physiological phenomenon in certain cases, it may also reflect potential liver injury in others, necessitating its further assessment and management. In this article, we provide a guide to primary care clinicians to interpret abnormal elevation of liver enzymes in asymptomatic patients using a step-wise algorithm. Adopting a schematic approach that classifies enzyme alterations on the basis of pattern (hepatocellular, cholestatic and isolated hyperbilirubinemia), we review an approach to abnormal alteration of liver enzymes within each section, the most common causes of enzyme alteration, and suggest initial investigations.
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Affiliation(s)
- Mazyar Malakouti
- Division of Gastroenterology and Nutrition, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
- *Correspondence to: Archish Kataria, Department of Internal Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MC 7878, San Antonio, TX 78229, USA. Tel: +1-210-665-7038, Fax: +1-210-567-4856, E-mail: ; Mazyar Malakouti, Division of Gastroenterology and Nutrition, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MC 7878, San Antonio, TX 78229, USA. Tel: +1-204-803-2523, Fax: +1-210-567-4856, E-mail:
| | - Archish Kataria
- Department of Internal Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
- *Correspondence to: Archish Kataria, Department of Internal Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MC 7878, San Antonio, TX 78229, USA. Tel: +1-210-665-7038, Fax: +1-210-567-4856, E-mail: ; Mazyar Malakouti, Division of Gastroenterology and Nutrition, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MC 7878, San Antonio, TX 78229, USA. Tel: +1-204-803-2523, Fax: +1-210-567-4856, E-mail:
| | - Sayed K. Ali
- Department of Internal Medicine, University of Central Florida, College of Medicine, Orlando, FL, USA
| | - Steven Schenker
- Division of Gastroenterology and Nutrition, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
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García-Molina MD, Barro F. Characterization of Changes in Gluten Proteins in Low-Gliadin Transgenic Wheat Lines in Response to Application of Different Nitrogen Regimes. FRONTIERS IN PLANT SCIENCE 2017; 8:257. [PMID: 28289425 PMCID: PMC5326781 DOI: 10.3389/fpls.2017.00257] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Accepted: 02/10/2017] [Indexed: 05/27/2023]
Abstract
Gluten proteins are major determinants of the bread making quality of wheat but also of important gluten-related disorders. The gluten protein accumulation during grain filling is strongly influenced by nitrogen fertilization. We have characterized the gluten proteins in low-gliadin wheat lines as influenced by nitrogen treatments in two experiments. These transgenic lines, D783, D793, C655, D577, and E82 were obtained by using two different RNAi silencing fragments and two endosperm-specific promoters to drive the silencing fragments (d-hordein and γ-gliadin). In Experiment 1, we used three nitrogen fertilizer rates (120, 360, and 1080 mg N) added at sowing stage and combined with two sulfur rates (8 and 30 mg S); Experiment 2 included two nitrogen levels (120 and 1080 mg N), which were added according to the greatest demand per plant using split applications. The protein quantification was accomplished by Reverse-Phase High-Performance Liquid Chromatography and gluten content (ppm) determined using monoclonal antibody R5 (Competitive R5 ELISA). The results showed differences in protein accumulation between the two transgenic lines with the same silencing fragment but different promoter. Lines D793 and E82 showed low gliadin and an increment in glutenin content with increasing nitrogen. Competitive ELISA R5 showed a significant decrease in gluten content using split applications of nitrogen (Experiment 2) with 120 mg N compared to Experiment 1. In addition, line E82 ensures that variations in N fertilization will not result in increased gluten content.
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Tuhan H, Işık S, Abacı A, Şimşek E, Anık A, Anal Ö, Böber E. Celiac disease in children and adolescents with Hashimoto Thyroiditis. Turk Arch Pediatr 2016; 51:100-5. [PMID: 27489467 DOI: 10.5152/turkpediatriars.2016.3566] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2015] [Accepted: 02/25/2016] [Indexed: 11/22/2022]
Abstract
AIM The aim of this study was to evaluate clinical and laboratory findings and determine the prevalence of celiac disease (CD) in children with Hashimoto thyroiditis (HT). MATERIAL AND METHODS The data of a total of 80 patients with positive anti-thyroid antibodies who were aged between 6 and 17.9 years were retrospectively studied. Age, gender, complaints at the time of presentation, family history of thyroid disorders, clinical and laboratory findings were recorded. The levels of thyrotropin, free thyroxin, thyroid autoantibodies (thyroid peroxidase and thyroglobulin antibodies), immunoglobulin A (IgA), anti-tissue transglutaminase antibodies (IgA-tTG), and thyroid ultrasonography findings were enrolled. RESULTS Eighty patients (65 females (81.2%) and 15 males (18,8%)) were included in the study. Family history of thyroid disease was present in 38 (47.5%) patients. The most common complaints at the time of presentation were goiter (%30) and weight gain (%25). Forty three (53.8%), 23 (28.7%), and 14 (17.5%) patients presented with euthyroidism, subclinical hypothyroidism and obvious hypothyroidism. Thirty seven (46.2%) patients had goiter. IgA-tTG was found to be positive after a diagnosis of HT was made in only one patient (1.25%) and the diagnosis of CD was confirmed when intestinal biopsy of this patient revealed villus atrophy, crypt hyperplasia and increase in the intraepithelial lymphocyte count. CONCLUSIONS In our study, it was found that the most common complaints at presentation in patients with a diagnosis of hashimoto thyroiditis included goiter, weakness and weight gain and the prevalence of celiac diseases was found to be 1.25% (1/80). This study shows that the prevalence of CD in patients with a diagnosis of HT is higher compared to the prevalence in the healthy pediatric population.
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Affiliation(s)
- Hale Tuhan
- Division of Pediatric Endocrinology, Dokuz Eylül University School of Medicine, İzmir, Turkey
| | - Sakine Işık
- Division of Pediatric Allergy and Immunology, Dokuz Eylül University School of Medicine, İzmir, Turkey
| | - Ayhan Abacı
- Division of Pediatric Endocrinology, Dokuz Eylül University School of Medicine, İzmir, Turkey
| | - Erdem Şimşek
- Division of Pediatric Endocrinology, Dokuz Eylül University School of Medicine, İzmir, Turkey
| | - Ahmet Anık
- Division of Pediatric Endocrinology, Dokuz Eylül University School of Medicine, İzmir, Turkey
| | - Özden Anal
- Division of Pediatric Allergy and Immunology, Dokuz Eylül University School of Medicine, İzmir, Turkey
| | - Ece Böber
- Division of Pediatric Endocrinology, Dokuz Eylül University School of Medicine, İzmir, Turkey
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García-Molina MD, García-Olmo J, Barro F. Effective Identification of Low-Gliadin Wheat Lines by Near Infrared Spectroscopy (NIRS): Implications for the Development and Analysis of Foodstuffs Suitable for Celiac Patients. PLoS One 2016; 11:e0152292. [PMID: 27018786 PMCID: PMC4809495 DOI: 10.1371/journal.pone.0152292] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2015] [Accepted: 03/12/2016] [Indexed: 01/19/2023] Open
Abstract
Scope The aim of this work was to assess the ability of Near Infrared Spectroscopy (NIRS) to distinguish wheat lines with low gliadin content, obtained by RNA interference (RNAi), from non-transgenic wheat lines. The discriminant analysis was performed using both whole grain and flour. The transgenic sample set included 409 samples for whole grain sorting and 414 samples for flour experiments, while the non-transgenic set consisted of 126 and 156 samples for whole grain and flour, respectively. Methods and Results Samples were scanned using a Foss-NIR Systems 6500 System II instrument. Discrimination models were developed using the entire spectral range (400–2500 nm) and ranges of 400–780 nm, 800–1098 nm and 1100–2500 nm, followed by analysis of means of partial least square (PLS). Two external validations were made, using samples from the years 2013 and 2014 and a minimum of 99% of the flour samples and 96% of the whole grain samples were classified correctly. Conclusions The results demonstrate the ability of NIRS to successfully discriminate between wheat samples with low-gliadin content and wild types. These findings are important for the development and analysis of foodstuff for celiac disease (CD) patients to achieve better dietary composition and a reduction in disease incidence.
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Affiliation(s)
- María Dolores García-Molina
- Departamento de Mejora Genética, Instituto de Agricultura Sostenible (IAS), Consejo Superior de Investigaciones Científicas (CSIC), Córdoba, Spain
| | - Juan García-Olmo
- NIR/MIR Spectroscopy Unit, Central Service for Research Support, University of Córdoba, Córdoba, Spain
| | - Francisco Barro
- Departamento de Mejora Genética, Instituto de Agricultura Sostenible (IAS), Consejo Superior de Investigaciones Científicas (CSIC), Córdoba, Spain
- * E-mail:
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Nielsen JA, Weber JJ, Lager DJ. Diarrhoea and duodenal disease. Gut 2014; 63:1736, 1804. [PMID: 25107558 DOI: 10.1136/gutjnl-2014-307924] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Affiliation(s)
| | - James J Weber
- Division of Research, Texas Digestive Disease Consultants, Southlake, Texas, USA
| | - Donna J Lager
- Gastrointestinal Pathology Division, ProPath, Dallas, Texas, USA
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Zanini B, Lanzarotto F, Villanacci V, Carabellese N, Ricci C, Lanzini A. Clinical expression of lymphocytic duodenosis in "mild enteropathy" celiac disease and in functional gastrointestinal syndromes. Scand J Gastroenterol 2014; 49:794-800. [PMID: 24941349 DOI: 10.3109/00365521.2014.919017] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Abnormally high number of duodenal intraepithelial lymphocytes is frequently found in many conditions including mild enteropathy celiac disease (CD) and functional gastrointestinal syndromes, but is unclear whether lymphocytosis affects the clinical phenotype particularly in functional syndromes. MATERIALS AND METHODS We compared clinical characteristics of celiac patients with lymphocytic duodenosis and normal villous structure with those of patients with functional gastrointestinal syndromes with and without lymphocytic duodenosis. We retrospectively identified 3 cohorts among patients referred for suspected CD: (1) "CoelD", 135 patients (age 36 ± 14 years) with mild enteropathy CD; (2) "LymD", 245 patients (38 ± 12 years) with functional gastrointestinal syndromes and lymphocytic duodenosis; and (3) "NorD", 147 patients (37 ± 15 years) with functional syndromes and normal duodenal histology. RESULTS Prevalence of gastrointestinal symptoms was similar in the three cohorts, but prevalence of extra-intestinal manifestations (42% vs. 27% vs. 18%, p < 0.003) and of associated diseases (35% vs. 15% vs. 14%, p < 0.0001) was higher in "CoelD" than in "LymD" and "NorD", respectively. Prevalence of Helicobacter pylori infection was similar in the three cohorts. The proportion of patients with final diagnosis of irritable bowel syndrome-diarrhea (38% vs. 37%), dyspepsia (31% vs. 27%), functional pain (14% vs. 19%), and functional diarrhoea (14% vs. 11%) was virtually the same in the cohorts with (LymD) and without (NorD) lymphocytic duodenosis. CONCLUSIONS Lymphocytic duodenosis has different clinical presentation in patients with mild enteropathy CD than those with functional gastrointestinal syndromes, and is not specific for any particular functional syndrome.
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Affiliation(s)
- Barbara Zanini
- Gastroenterology Unit, University and Spedali Civili , Brescia , Italy
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Pimenta-Martins A, Pinto E, Gomes AM. Perceção do estado de saúde e da qualidade de vida numa amostra de celíacos portugueses. GE JORNAL PORTUGUÊS DE GASTRENTEROLOGIA 2014; 21:109-116. [DOI: 10.1016/j.jpg.2013.09.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
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Kratzer W, Kibele M, Akinli A, Porzner M, Boehm BO, Koenig W, Oeztuerk S, Mason RA, Mao R, Haenle MH. Prevalence of celiac disease in Germany: A prospective follow-up study. World J Gastroenterol 2013; 19:2612-2620. [PMID: 23674868 PMCID: PMC3645379 DOI: 10.3748/wjg.v19.i17.2612] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2012] [Revised: 11/28/2012] [Accepted: 02/06/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the prevalence of celiac disease in a randomly selected population sample.
METHODS: A total of 2157 subjects (1036 males; 1121 females) participating in a population-based cross-sectional study underwent laboratory testing for tissue transglutaminase and antibodies to immunoglobulin A, endomysium and antigliadin. In a second step, all subjects who had been examined serologically were surveyed using a questionnaire that included questions specific to celiac disease. Subjects with positive antibody titers and those with histories positive for celiac disease then underwent biopsy. At the first follow up, antibody titers were again determined in these subjects and subjects were questioned regarding symptoms specific for celiac disease and disorders associated with celiac disease. The second follow up consisted of a telephone interview with subjects positive for celiac disease.
RESULTS: Antibody tests consistent with celiac disease were reported in eight subjects, corresponding to an overall prevalence of 1:270 (8/2157). The prevalence among women was 1:224 and 1:518 in men. Classical symptoms were observed in 62.5% of subjects. Atypical celiac disease was present in 25.0%, and transient celiac disease in 12.5%. False-negative test results were returned in three subjects. This yields a sensitivity and specificity of 62.5% and 50.0%, respectively, for tissue transglutaminase immunoglobulin-A antibody; of 62.5% and 71.4% respectively, for endomysium antibody; and of 62.5% and 71.4%, respectively, for antigliadin antibody.
CONCLUSION: The prevalence rate in our collective lies within the middle tertile of comparable studies in Europe. The use of a single antibody test for screening purposes must be called into question.
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Busto Bea V, Crespo Pérez L, Cano Ruiz A. [Update on collagenous sprue: connective tissue as a cause of chronic diarrhea]. Med Clin (Barc) 2013; 140:415-9. [PMID: 23332631 DOI: 10.1016/j.medcli.2012.11.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2012] [Revised: 11/02/2012] [Accepted: 11/08/2012] [Indexed: 12/29/2022]
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Bhattacharya M, Kapoor S, Dubey AP. Celiac disease presentation in a tertiary referral centre in India: current scenario. Indian J Gastroenterol 2013; 32:98-102. [PMID: 22903368 DOI: 10.1007/s12664-012-0240-y] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2012] [Accepted: 07/27/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND Nondiarrheal celiac disease (NDCD) is being increasingly reported but data from India is limited. AIM We undertook this study to compare the clinical spectrum of NDCD with that of diarrheal/classical celiac disease (CCD). METHOD This facility-based retrospective observational study included consecutive patients diagnosed with celiac disease (CD) (as per modified ESPGHAN criteria) from October 2009 to August 2011. RESULTS A total of 381 patients were diagnosed with CD during the study period. NDCD was present in 192 (51.8 %). NDCD had higher mean age at presentation (5.8 ± 2.8 vs. 6.9 ± 2.9 years respectively; p = 0.003) and longer duration of symptoms prior to diagnosis (2.9 ± 1.7 years vs. 3.6 ± 2.2 years; p = 0.02) as compared to CCD. In the NDCD group, the most frequent gastrointestinal (GI) symptoms were recurrent abdominal pain [122 (63.5 %)] and abdominal distension [102 (53.1 %)] followed by constipation [48 (25 %)], vomiting [76 (39.6 %)] and recurrent oral ulcers [89 (46.4 %)]. Vomiting and constipation were more frequently seen in NDCD as compared to CCD (p < 0.001 in both). Commonly enumerated extraintestinal manifestations in NDCD included failure to thrive [109 (56.8 %)], isolated short stature [36 (18.8 %)], persistent anemia [83 (43.2 %)] and hepatomegaly/splenomegaly or both [56 (29.2 %)]. Associated comorbidities included autoimmune thyroiditis [11 (5.7 %)], type 1 diabetes mellitus [8 (4.2 %)], bronchial asthma [23 (11.9 %)], idiopathic pulmonary hemosiderosis [4 (2.1 %)], Down's syndrome [3 (1.6 %)], alopecia areata [6 (3.1 %)], polyarthritis [2 (1.0 %)], dermatitis herpetiformis [6 (3.1 %)] and chronic liver disease [6 (3.1 %)]. The number of patients with a Marsh score IIIb and above of duodenal biopsy was significantly more in the CCD group (p < 0.001). CONCLUSIONS NDCD is not uncommon in India. Long-term follow up is needed to evaluate the impact of the disease and of treatment in these children.
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Affiliation(s)
- Malobika Bhattacharya
- Department of Pediatrics, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi 110 002, India.
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Zanini B, Caselani F, Magni A, Turini D, Ferraresi A, Lanzarotto F, Villanacci V, Carabellese N, Ricci C, Lanzini A. Celiac disease with mild enteropathy is not mild disease. Clin Gastroenterol Hepatol 2013; 11:253-8. [PMID: 23022697 DOI: 10.1016/j.cgh.2012.09.027] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2012] [Revised: 09/12/2012] [Accepted: 09/17/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Patients with celiac disease have varying degrees of damage to the small intestinal mucosa, ranging from lymphocytic duodenosis with normal villous structure to severe villous atrophy. We assessed whether the severity of mucosal lesions was associated with clinical and laboratory features of celiac disease. METHODS We compared demographic, clinical, and laboratory characteristics among patients with celiac disease who were classified based on the severity of duodenal lesions. We analyzed data from 1408 adult patients seen consecutively at a tertiary referral center since 1990. Patients were classified as having villous atrophy (n = 1249) or as having mild enteropathy (n = 159) in the presence or absence of villous atrophy. RESULTS Similar percentages of patients with villous atrophy, vs mild enteropathy, experienced weight loss (17% vs 17%), gastrointestinal manifestations (70% vs 70%), extraintestinal manifestations (66% vs 57%), and other associated conditions (19% vs 23%). More patients with villous atrophy than patients with mild enteropathy developed osteopenia or osteoporosis (22% vs 5%; P = .0005). Greater percentages of patients with villous atrophy than those with mild enteropathy also had anemia (42% vs 29%; P = .002), folate deficiency (75% vs 64%; P = .02), hypocholesterolemia (7% vs 2%; P = .02), hypocalcemia (26% vs 13%; P = .004), or hyperparathyroidism (45% vs 29%; P = .004). CONCLUSIONS Although osteopenia, osteoporosis, and alterations in laboratory parameters are prevalent among patients with celiac disease with mild enteropathy, they are more prevalent and severe in those with villous atrophy. The prevalence of associated conditions is similar between these groups. These results indicate that celiac disease with mild enteropathy is not mild disease, but requires treatment with a gluten-free diet.
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Affiliation(s)
- Barbara Zanini
- Gastroenterology Unit, University of Brescia, Brescia, Italy
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Porcelli B, Ferretti F, Vindigni C, Scapellato C, Terzuoli L. Detection of autoantibodies against actin filaments in celiac disease. J Clin Lab Anal 2013; 27:21-6. [PMID: 23292801 DOI: 10.1002/jcla.21556] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2012] [Accepted: 10/01/2012] [Indexed: 01/28/2023] Open
Abstract
INTRODUCTION Serum autoantibodies specifically directed toward intracellular cytoskeletal actin filaments (anti-actin antibodies, AAA) were found to be associated with intestinal villous atrophy (IVA) in celiac disease (CD). The aim of this study was to assess IgA-AAA with a commercial test that uses sections of rat intestinal epithelial cells in a well-selected cohort of patients and to evaluate the relationship between the presence of serum IgA-AAA and the severity of intestinal mucosa damage. MATERIALS AND METHODS Serum samples from 70 CD patients and 150 controls subjects were analyzed retrospectively for the presence of IgA-AAA. RESULTS The indirect immunofluorescence test that we used has a specificity of 100%; the sensitivity of the test is not high (25.7%). In this study we also show that serum AAA are more frequently positive in CD patients with total IVA (77.8%) and that this association is significant DISCUSSION IgA-AAA certainly cannot take the place of much more sensitive tests such as a-tTG and EMA in the diagnosis of CD because of their low sensitivity; nonetheless, these antibodies could be determined in a-tTG and/or EMA positive patients who cannot undergo an intestinal biopsy because of a severe contraindication, or in the case of negative consensus regarding endoscopy, or when the histology interpretation is difficult. CONCLUSION In conclusion, the IFI commercial test with intestinal epithelial cells as substrate offers a useful method for IgA-AAA determination. Serum IgA-AAA positivity is indicative of more severe intestinal histology damage and their assay could be a real help to the clinician, especially in the complicated cases.
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Affiliation(s)
- B Porcelli
- Department of Internal Medicine, Endocrine-Metabolic Science and Biochemistry, Biochemistry Section, University of Siena, Siena, Italy.
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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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Harris LA, Park JY, Voltaggio L, Lam-Himlin D. Celiac disease: clinical, endoscopic, and histopathologic review. Gastrointest Endosc 2012; 76:625-40. [PMID: 22898420 DOI: 10.1016/j.gie.2012.04.473] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2012] [Accepted: 04/30/2012] [Indexed: 02/08/2023]
Affiliation(s)
- Lucinda A Harris
- Department of Gastroenterology, Mayo Clinic in Arizona, Scottsdale, Arizona 85259, USA
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Abstract
When investigating a patient with suspected celiac disease (CD), several other conditions must be considered, including potential infection with Giardia lamblia. Although giardiasis is rare, its histopathological and serological picture may resemble that of CD. We report the case of a young man with diabetes mellitus and a family history of CD referred to our hospital because of diarrhoea and weight loss. Investigation showed, among other factors, partial villous atrophy in duodenal biopsies and elevated immunoglobulin A antitissue transglutaminase antibodies. The patient was diagnosed with CD and recommended a gluten-free diet. At the same time, faecal tests were conducted, indicating the presence of G. lamblia. The patient was treated and improved, even after discontinuing the gluten-free diet. Subsequent follow-up after 6 months showed total regression of mucosal histopathology and a normal antitissue transglutaminase antibodies level.
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Affiliation(s)
- Lars Edling
- Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
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Rossi F, Bellini G, Tolone C, Luongo L, Mancusi S, Papparella A, Sturgeon C, Fasano A, Nobili B, Perrone L, Maione S, Miraglia del Giudice E. The Cannabinoid Receptor type 2 Q63R variant increases the risk of celiac disease: Implication for a novel molecular biomarker and future therapeutic intervention. Pharmacol Res 2012; 66:88-94. [DOI: 10.1016/j.phrs.2012.03.011] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2011] [Revised: 03/14/2012] [Accepted: 03/16/2012] [Indexed: 11/26/2022]
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Abstract
UNLABELLED Coeliac disease (CD) is an immune-mediated systemic condition elicited by gluten and related prolamines in genetically predisposed individuals and characterised by gluten-induced symptoms and signs, specific antibodies, a specific human leukocyte antigen (HLA) type and enteropathy. The risk of coeliac disease is increased in first-degree relatives, certain syndromes including Down syndrome and autoimmune disorders. It is thought to occur in 1 in 100-200 individuals, but still only one in four cases is diagnosed. Small-bowel biopsy is no longer deemed necessary in a subgroup of patients, i.e. when all of the following are present: typical symptoms or signs, high titres of and transglutaminase antibodies, endomysial antibodies, and HLA-type DQ2 or DQ8. In all other cases, small-bowel biopsy remains mandatory for a correct diagnosis. Therapy consists of a strictly gluten-free diet. This should result in complete disappearance of symptoms and of serological markers. Adequate follow-up is considered essential. CONCLUSION Although small-bowel biopsy may be omitted in a minority of patients, small-bowel biopsy is essential for a correct diagnosis of CD in all other cases. Diagnostic work-up should be completed before treatment with gluten-free diet instituted.
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Affiliation(s)
- C. M. Frank Kneepkens
- Department of Paediatrics, VU University Medical Centre, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
| | - B. Mary E. von Blomberg
- Department of Pathology, VU University Medical Centre, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
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Ceppi ELM, Brenna OV. Brewing with Rice Malt - A Gluten-free Alternative. JOURNAL OF THE INSTITUTE OF BREWING 2012. [DOI: 10.1002/j.2050-0416.2010.tb00431.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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Kakleas K, Karayianni C, Critselis E, Papathanasiou A, Petrou V, Fotinou A, Karavanaki K. The prevalence and risk factors for coeliac disease among children and adolescents with type 1 diabetes mellitus. Diabetes Res Clin Pract 2010; 90:202-8. [PMID: 20832887 DOI: 10.1016/j.diabres.2010.08.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2010] [Revised: 07/28/2010] [Accepted: 08/09/2010] [Indexed: 11/18/2022]
Abstract
AIMS Our aim was to determine in children with T1DM the prevalence of positive antibodies against tissue transglutaminase (anti-tTG IgA) as indices of coeliac disease (CD), as well as its clinical presentation, its determinants and its association with thyroid (anti-TG, anti-TPO) and pancreatic b-cell autoimmunity (anti-GAD). METHODS The study included 105 children and adolescents with T1DM, aged (mean±SD) 12.44±4.76 years, with a T1DM duration of 4.41±3.70 years. RESULTS Fifty of our patients (47.6%) were positive for anti-GAD, 9/105 (8.6%) for anti-tTG IgA and 21/105(20%) for anti-thyroid antibodies. The anti-tTG IgA (+) children, in comparison with the rest of the study population, were of younger age (9.31 vs. 12.74 years, p=0.038), shorter diabetes duration (2.16 vs. 4.62 years, p=0.056) and had mild growth impairment (height SDS: -0.55 vs. +0.20, p=0.055). Univariate logistic regression analysis revealed that the presence of anti-tTG IgA (+) was associated with younger age and shorter T1DM duration. Only 5/9 (55.6%) children with high titres of anti-tTG IgA developed mild gastrointestinal symptoms or growth retardation and had histological findings typical of CD. CONCLUSIONS The prevalence of anti-tTG IgA positivity among T1DM children was 8.6% and its occurrence was associated with younger age and short diabetes duration. Since CD presents in T1DM patients asymptomatically or with non-specific symptoms, periodic autoantibody screening is necessary for its early diagnosis.
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Affiliation(s)
- Kostas Kakleas
- Second University Department of Pediatrics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
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Turabi E, Regier M, Sumnu G, Sahin S, Rother M. Dielectric and Thermal Properties of Rice Cake Formulations Containing Different Gums Types. INTERNATIONAL JOURNAL OF FOOD PROPERTIES 2010. [DOI: 10.1080/10942910903013365] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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The frequency of histologic lesion variability of the duodenal mucosa in children with celiac disease. World J Pediatr 2010; 6:60-4. [PMID: 20143213 DOI: 10.1007/s12519-010-0008-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2008] [Accepted: 12/29/2008] [Indexed: 10/19/2022]
Abstract
BACKGROUND Celiac disease (CD) may cause changes throughout the gastrointestinal tract. Patchy distribution of duodenal mucosal lesions has been described in adults as well as in children. This study aimed to verify the concept and to evaluate the frequency of histologic lesion variability of the duodenal mucosa in Indian children with CD. METHODS We enrolled 67 children prospectively who underwent upper gastrointestinal endoscopy because of positive tissue transglutaminase antibodies and biopsy as the final evaluation for suspected CD. Four biopsies were taken from the descending duodenum distal to the papilla, and duodenal bulb. The histologic lesions were classified according to the Oberhuber classification with modification proposed by our group. RESULTS Forty-three CD children (64.2%) had a "mixed" type 3 lesion characterized by a different degree of villous atrophy at different biopsy sites. Eight children (11.9%) showed two different types of histologic lesions in the same patient at different biopsy sites. The overall variability of histologic lesion (variability in the grade of villous atrophy [type 3a, 3b, or 3c], and coexistence of villous atrophy and type 2 lesion) was seen in 51 (76.1%) of the CD patients. CONCLUSIONS Children with CD show a high frequency of variability of histologic lesions. Therefore, multiple endoscopic biopsy specimens should be obtained not only from the distal duodenum but also from the bulb.
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Schuppan D, Junker Y, Barisani D. Celiac disease: from pathogenesis to novel therapies. Gastroenterology 2009; 137:1912-1933. [PMID: 19766641 DOI: 10.1053/j.gastro.2009.09.008] [Citation(s) in RCA: 421] [Impact Index Per Article: 26.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2009] [Revised: 09/02/2009] [Accepted: 09/11/2009] [Indexed: 02/08/2023]
Abstract
Celiac disease has become one of the best-understood HLA-linked disorders. Although it shares many immunologic features with inflammatory bowel disease, celiac disease is uniquely characterized by (1) a defined trigger (gluten proteins from wheat and related cereals), (2) the necessary presence of HLA-DQ2 or HLA-DQ8, and (3) the generation of circulating autoantibodies to the enzyme tissue transglutaminase (TG2). TG2 deamidates certain gluten peptides, increasing their affinity to HLA-DQ2 or HLA-DQ8. This generates a more vigorous CD4(+) T-helper 1 T-cell activation, which can result in intestinal mucosal inflammation, malabsorption, and numerous secondary symptoms and autoimmune diseases. Moreover, gluten elicits innate immune responses that act in concert with the adaptive immunity. Exclusion of gluten from the diet reverses many disease manifestations but is usually not or less efficient in patients with refractory celiac disease or associated autoimmune diseases. Based on the advanced understanding of the pathogenesis of celiac disease, targeted nondietary therapies have been devised, and some of these are already in phase 1 or 2 clinical trials. Examples are modified flours that have been depleted of immunogenic gluten epitopes, degradation of immunodominant gliadin peptides that resist intestinal proteases by exogenous endopeptidases, decrease of intestinal permeability by blockage of the epithelial ZOT receptor, inhibition of intestinal TG2 activity by transglutaminase inhibitors, inhibition of gluten peptide presentation by HLA-DQ2 antagonists, modulation or inhibition of proinflammatory cytokines, and induction of oral tolerance to gluten. These and other experimental therapies will be discussed critically.
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Affiliation(s)
- Detlef Schuppan
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
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Venkatesh K, Cohen M, Evans C, Delaney P, Thomas S, Taylor C, Abou-Taleb A, Kiesslich R, Thomson M. Feasibility of confocal endomicroscopy in the diagnosis of pediatric gastrointestinal disorders. World J Gastroenterol 2009; 15:2214-9. [PMID: 19437560 PMCID: PMC2682235 DOI: 10.3748/wjg.15.2214] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the feasibility and utility of confocal laser endomicroscopy (CLE) in the description of normal gastrointestinal (GI) mucosa and in the diagnosis of GI disorders in children, in comparison to histology.
METHODS: Forty-four patients (19 female) median age 10.9 years (range 0.7-16.6 years) with suspected or known GI pathology underwent esophago-gastro-duodenoscopy (OGD) (n = 36) and/or ileocolonoscopy (IC) (n = 31) with CLE using sodium fluorescein and acriflavine as contrast agents. Histological sections were compared with same site confocal images by two experienced pediatric and GI histopathologists and endoscopists, respectively.
RESULTS: Duodenum and ileum were intubated in all but one patient undergoing OGD and IC. The median procedure time was 16.4 min (range 7-25 min) for OGD and 27.9 min (range 15-45 min) for IC. A total of 4798 confocal images were compared with 153 biopsies from the upper GI tract from 36 procedures, and 4661 confocal images were compared with 188 biopsies from the ileocolon from 31 procedures. Confocal images were comparable to conventional histology both in normal and in pathological conditions such as esophagitis, Helicobacter pylori gastritis, celiac disease, inflammatory bowel disease, colonic heterotopia, and graft versus host disease.
CONCLUSION: CLE offers the prospect of targeting biopsies to abnormal mucosa, thereby increasing diagnostic yield, reducing the number of biopsies, decreasing the burden on the histopathological services, and reducing costs.
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Antigliadin immunoglobulin A best in finding celiac disease in children younger than 18 months of age. J Pediatr Gastroenterol Nutr 2008; 47:428-35. [PMID: 18852634 DOI: 10.1097/mpg.0b013e31817d80f4] [Citation(s) in RCA: 64] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES The aim was to investigate age-dependent serum levels and occurrence of elevated celiac disease (CD)-related antibodies in young children, to define the optimal serological procedure when selecting for small intestinal biopsy. PATIENTS AND METHODS Included were 428 children with biopsy verified CD (median age 16 months; range 7.5 months-14 years) and 216 controls (median age 2.7 years; range 8.5 months-14.6 years). Immunoglobulin (Ig) A antibodies against gliadin (AGA-IgA), tissue transglutaminase (tTG-IgA), and endomysium (EMA-IgA) were analysed. RESULTS Increased serum AGA-IgA levels were found in 411 of 428 CD cases, tTG-IgA in 385 of 428, and EMA-IgA in 383 of 428. In the control group, 11 of 216 had increased levels of AGA-IgA, 5 of 216 of tTG-IgA, and 8 of 216 of EMA-IgA. In CD children younger than 18 months, elevated AGA-IgA occurred in 97% and elevated tTG-IgA and EMA-IgA were found in 83% of the cases. Conversely, in CD children older than 18 months, elevated AGA-IgA occurred in 94%, and elevated tTG-IgA and EMA-IgA were found in 99% of the cases. CONCLUSIONS In children older than 18 months, both tTG-IgA and EMA-IgA are sufficiently accurate to be used as a single antibody marker, whereas a large proportion of younger children with CD lack these antibodies. Therefore, when selecting children for small intestinal biopsy, the detection of a combination of AGA-IgA and tTG-IgA is optimal for identifying untreated CD in children younger than 18 months.
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Hurtado-Valenzuela JG, Sotelo-Cruz N, López-Cervantes G, de la Barca AMC. Tetany caused by chronic diarrhea in a child with celiac disease: A case report. CASES JOURNAL 2008; 1:176. [PMID: 18811963 PMCID: PMC2559825 DOI: 10.1186/1757-1626-1-176] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/26/2008] [Accepted: 09/23/2008] [Indexed: 12/02/2022]
Abstract
There is no awareness about celiac disease (CD) in Mexico. A 2.9 year old mestizo boy was admitted to a Mexican hospital with muscle cramps and fine tremors. He suffered chronic diarrhea, abdominal distention, hypotrophic limbs, stunting and wasting, and presented hypocalcemia, anemia and high titers of serological markers. Diagnosis of CD was confirmed by a duodenal biopsy. After replacement of calcium and a gluten-free diet, the symptoms resolved within 6 weeks. After 2-months, serum analyses, anthropometric data as well as antibodies titers were normal after 4 years. CD screening tests are needed in chronic diarrhea for any ethnicity patients.
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Affiliation(s)
- Jaime Gabriel Hurtado-Valenzuela
- Departamento de Medicina Interna, Hospital Infantil del Estado de Sonora, Av, Reforma No, 355 Norte, Colonia Ley 57, Hermosillo 83000, Sonora, México.
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Mangione RA, Patel PN. Caring for patients with celiac disease: The role of the pharmacist. J Am Pharm Assoc (2003) 2008; 48:e125-35; quiz e136-9. [DOI: 10.1331/japha.2008.08014] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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Cassol CA, De Pellegrin CP, Wahys MLC, Pires MMDS, Nassar SM. [Clinical profile of Santa Catarina members of Brazilian Celiac Association]. ARQUIVOS DE GASTROENTEROLOGIA 2007; 44:257-65. [PMID: 18060282 DOI: 10.1590/s0004-28032007000300015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/11/2006] [Accepted: 06/25/2007] [Indexed: 01/29/2023]
Abstract
BACKGROUND Celiac disease is an enteropathy induced by gluten in genetically predisposed individuals. AIM To establish the demographic and clinical characteristics of this disease in Santa Catarina State, Brazil. METHODS A descriptive transversal study was performed involving members of a regional celiac association, to whom a questionnaire focusing various aspects of the disease was sent. RESULTS From a total of 506 members, 145 (28.7%) were enrolled in the study--all of them biopsy-proven celiacs. Their mean age was 30.8 years (range, 3.3-82.5 years). Female to male rate was 2.1:1. The mean age at diagnosis was 16 years for men and 26.7 years for women. Most frequently reported symptoms were: abdominal distention (71.8%), abdominal pain (71%) and diarrhea (65.5%). Anemia, aphthous ulcers and constipation were more related by women, while diarrhea and low weight were more frequent in men. Only 42.1% of the participants had been submitted to biopsies compatible with a correct investigation of the disease (44.2 % had been submitted to biopsy only after gluten exclusion of the diet and 11.7% did not mentioned whether they were in a gluten-free diet when biopsied). Only 61.4% had been submitted to serological tests for diagnostic or dietary control purposes. Associated diseases were related by 65% of the individuals, of which the most common was lactose intolerance (33%). Vitaminic or mineral supplementation was indicated to 45% and only 32.5% have had bone mineral density measured. Of these, 59% had altered results. CONCLUSIONS The results suggest a tendency of diagnosis of celiac disease in older ages, specially among women. This may indicate the necessity of improving public and medical knowledge in Santa Catarina concerning the diagnosis and treatment of this disease.
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Affiliation(s)
- Clarissa Araujo Cassol
- Departamento de Pediatria, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina, Florianópolis, SC.
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Abstract
Serological screening of 5470 children age 7.5 years from a cohort of 13,971 children in the Avon Longitudinal Study of Parents and Children (ALSPAC) suggested the prevalence of celiac disease (CD) to be at least 1%. ALSPAC is an anonymous study, and hence seropositive children could not be individually identified or undergo biopsy. Inasmuch as all children within ALSPAC suspected of having CD are referred to just 1 center, we aimed to identify children with biopsy-confirmed CD who were likely to be in this cohort and to estimate the magnitude of discrepancy between serology-positive cases and biopsy-confirmed cases. The results suggest that more than 90% of CD in children goes undiagnosed.
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Savas N, Akbulut S, Saritas U, Koseoglu T. Correlation of clinical and histopathological with endoscopic findings of celiac disease in the Turkish population. Dig Dis Sci 2007; 52:1299-303. [PMID: 17356915 DOI: 10.1007/s10620-006-9540-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2006] [Accepted: 07/20/2006] [Indexed: 12/12/2022]
Abstract
Endoscopic findings have been described for the diagnosis of celiac disease but the relationship among the clinical presentation, endoscopic markers, and the degree of histopathological findings is not clear. Thirty patients who were thought to have celiac disease were included in this study. Biopsies taken from the duodenum were examined histopathologically. The relationship among the endoscopic, clinical, and histopathological findings were investigated. Partial villous atrophy was seen in 14 patients (46.6%), and subtotal and total villous atrophy were seen in 6 (20%) patients each. Eighty six percent of patients with a mosaic appearance, 76% of patients with the finding of loss of folds, and 90% of patients with scalloping on endoscopy had either partial villous atrophy, subtotal villous atrophy, or total villous atrophy on biopsy. We conclude that endoscopic findings in celiac disease can reveal valuable information both for diagnosis and for demonstration of the severity of the disease state.
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Affiliation(s)
- Nurten Savas
- Department of Gastroenterology, Baskent University Faculty of Medicine, Fevzi Cakmak Cad. 10, Sok No. 45, Bahcelievler, Ankara, 06490, Turkey.
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Vilela EG, de Abreu Ferrari MDL, de Gama Torres HO, Martins FP, Goulart EMA, Lima AS, da Cunha AS. Intestinal permeability and antigliadin antibody test for monitoring adult patients with celiac disease. Dig Dis Sci 2007; 52:1304-9. [PMID: 17356917 DOI: 10.1007/s10620-006-9511-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2006] [Accepted: 07/05/2006] [Indexed: 12/09/2022]
Abstract
Celiac disease causes chronic inflammation of the intestinal mucosa and reduces surface absorption; after the withdrawal of gluten from the diet, there are clinical and histologic improvements. The intestinal permeability test and serologic tests are useful for confirming the diagnosis and monitoring patients. The goal of this study is to compare the antigliadin antibody (AGA) test with the intestinal permeability test for celiac patients on a gluten-free diet. The sample consisted of 22 celiac patients who were antigliadin immunoglobulin A-positive before treatment. After 12 months on a gluten-free diet, AGA testing was repeated and the intestinal permeability test was performed. A control group was composed of 11 healthy individuals. AGA remained positive in 40.9% of celiac patients, and the mean urinary lactulose excretion was 10.27%, that of mannitol was 10.18%, and the lactulose/mannitol ratio was 1.02. In the subgroup in which antigliadin became negative (59.1%), the value for lactulose was 3.79%, that for mannitol was 11.12%, the lactulose/mannitol ratio was 0.38, and the p value was less than 0.0001, 0.66, and less than 0.0001, respectively. When the two celiac subgroups were compared with the control group, the urinary lactulose excretion and the lactulose/mannitol ratio was less in the control group, whereas urinary mannitol excretion was greater. The p values were less than 0.0001 for the three variables, suggesting persistent lesions in mucosa of both subgroups, although to a lesser degree for those that became AGA negative. It is concluded that intestinal permeability allows a more precise clinical physiopathologic correlation than antigliadin and offers more information for the monitoring of these patients.
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Affiliation(s)
- Eduardo Garcia Vilela
- Instituto Alfa de Gastroenterologia do Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
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Płudowski P, Karczmarewicz E, Socha J, Matusik H, Syczewska M, Lorenc RS. Skeletal and muscular status in juveniles with GFD treated clinical and newly diagnosed atypical celiac disease--preliminary data. J Clin Densitom 2007; 10:76-85. [PMID: 17289529 DOI: 10.1016/j.jocd.2006.10.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2006] [Revised: 10/26/2006] [Accepted: 10/26/2006] [Indexed: 11/30/2022]
Abstract
Undiagnosed and untreated celiac disease (CD) constitutes an increasing skeletal health problem due to its association with low bone density and fractures. Examinations of skeletal status in children using dual-energy X-ray absorptiometry (DXA) are prone to size-related misinterpretation. In contrary, the analysis of muscle-bone relationship seems to limit a possibility of misdiagnosis because skeletal status is evaluated from the functional perspective. The study was aimed to assess skeletal status of children suffering from CD with the use of muscle-bone functional algorithm. The study group comprised 29 celiac patients (13.7yr+/-2.9) on gluten-free diet (GFD), and 24 newly diagnosed atypical celiac patients, including subgroup with normal height (n=14; 12.6yr+/-3.9) and subgroup with short stature (n=10; 12.2yr+/-2.9). Muscular and skeletal status was evaluated by DXA (DPX-L, GE). Anthropometry, total body bone mineral density (TBBMD, g/cm(2)). and total body bone mineral content (TBBMC, g) as well as lean body mass (LBM, g) were evaluated. Muscle-bone interactions were estimated using TBBMC/LBM ratio. Previously established references for healthy controls were used for the calculation of Z-scores (age-matched) and SD-scores (height-matched). GFD treated celiacs and atypical celiacs with normal body height had TBBMD, TBBMC, LBM, and TBBMC/LBM ratio Z-scores and SD-scores within normal range for healthy controls. In contrary, atypical celiacs with short stature had significantly lower Z-scores for TBBMD (-2.3+/-0.4), TBBMC (-2.1+/-0.3), LBM (-1.4+/-0.3). and TBBMC/LBM ratio (-2.3+/-0.6) when compared to respective values observed in GFD treated celiacs (p<0.001, p<0.001, p<0.05, p<0.01) and atypical celiacs with normal height (p<0.01, p<0.01, p<0.05, p<0.01). When body-height matching of DXA data was used to limit the influence of body size, the atypical celiacs with short stature had SD-scores for TBBMD (-1.3+/-0.7), TBBMC (-1.3+/-0.6), and LBM (+0.8+/-0.3) not significantly different from the corresponding SD-scores obtained in the remaining 2 groups. Nevertheless, short stature in atypical celiacs still coincided with significantly lower TBBMC/LBM ratio SD-score of -1.9+/-0.7 when compared to values observed in GFD treated celiacs (+0.04+/-0.2; p<0.05) and atypical celiacs with normal height (-0.4+/-0.2; p<0.05). GFD regime in classic celiacs corresponded with physiological values of DXA assessed indicators of bone and muscle status as well as normal muscle-bone interactions. Untreated atypical celiacs may present a broad spectrum of heterogeneous abnormalities from normal to markedly depressed TBBMC/LBM ratio values pointing on the marked imbalance between TBBMC and LBM.
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Affiliation(s)
- Paweł Płudowski
- Department of Biochemistry, The Children's Memorial Health Institute, Warsaw, Poland
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Bagci S, Ercin CN, Yesilova Z, Ozcan A, Degertekin B, Dagalp K. Levels of serologic markers of celiac disease in patients with reflux esophagitis. World J Gastroenterol 2006; 12:6707-10. [PMID: 17075989 PMCID: PMC4125681 DOI: 10.3748/wjg.v12.i41.6707] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the prevalence of celiac disease serologic markers (antigliadin IgA, IgG, and anti-endomysial IgA) in patients with reflux esophagitis and to detect the relationship between reflux esophagitis and celiac disease (CD).
METHODS: This study was performed prospectively between January 2003 and January 2004. Sixty-eight adult reflux esophagitis patients and 40 people as control group for symptoms related with gastrointestinal system were enrolled in this study. The diagnostic work-up included an accurate medical history with gastrointestinal symptoms, routine laboratory measurements, the detection of antibodies against gliadin (IgA and IgG) and endomysium (IgA), and an upper endoscopy with postbulbar biopsy.
RESULTS: IgA-AGA and IgG-AGA were positive at 8.8% and 10.3% in patients with reflux esophagitis. In control group, it was found that 10% people had positive IgA-AGA, and 7.5% people had positive IgG-AGA. There was no significant relationship between patients and control group regarding positive IgA-AGA and IgG-AGA. The patients and persons in control group had no positive IgA-EMA. On postbulbar biopsies, no finding was detected concerning celiac disease. There were no symptoms and signs for gluten enteropathy in patients and control group.
CONCLUSION: This review supports that an association does not exist between celiac disease and reflux esophagitis. We think these diseases exist independently from each other.
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Affiliation(s)
- Sait Bagci
- Department of Gastroenterology, Gulhane School of Medicine, Etlik 06018 - Ankara, Turkey
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Akbari MR, Mohammadkhani A, Fakheri H, Javad Zahedi M, Shahbazkhani B, Nouraie M, Sotoudeh M, Shakeri R, Malekzadeh R. Screening of the adult population in Iran for coeliac disease: comparison of the tissue-transglutaminase antibody and anti-endomysial antibody tests. Eur J Gastroenterol Hepatol 2006; 18:1181-6. [PMID: 17033439 DOI: 10.1097/01.meg.0000224477.51428.32] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIMS Population-based studies for the prevalence of coeliac disease (CD) in west-Asian countries are scarce. We aimed to determine the prevalence of gluten-sensitive enteropathy (GSE) in the general population of northern and southern Iran, and evaluate the sensitivity and specificity of the anti-endomysial antibody (EMA) immunofluorescent test and the enzyme-linked immunosorbent assay-based test for determination of the IgA anti-tissue transglutaminase antibody (tTG-Ab) using the human recombinant transglutaminase antigen for the detection of CD in screening the asymptomatic adult population. MATERIAL AND METHODS Using a stratified random sampling method we enrolled a total of 2799 individuals (1438 from Sari and 1361 from Kerman). The mean age was 33.7 years (range 18-66), with 1398 men. IgA anti-tissue transglutaminase (tTG) and IgA anti-EMA were determined in the serum of all subjects. Those participants with a positive serology for any of the two tests underwent small intestinal biopsy, and were classified according to revised Marsh criteria histologically. A diagnosis of GSE was based on positive serology and a compatible histopathological finding. The maximum likelihood latent class model was used to estimate the sensitivity and specificity of the two tests. RESULTS Twenty-nine cases showed positive IgA tTG-Ab (15 men and 14 women, mean age 35.4 years, range 18-59), whereas only five were simultaneously positive for EMA. Except for two subjects with normal small bowel histology (Marsh 0), all other subjects were found to have biopsy findings compatible with GSE: 18 Marsh I, five Marsh II, three Marsh IIIa and one Marsh IIIc lesions. he prevalence of GSE was 0.96% or 1:104. The sensitivity and specificity of the human-recombinant IgA tTG-Ab assay were 100 and 99%, respectively, whereas the results for IgA EMA were 19 and 100%, respectively. The IgA EMA was positive in cases with advanced mucosal lesions of the small bowel. The mean serum value of IgA tTG-Ab was higher in patients with severe enteropathy compared with those showing slight mucosal changes (P<0.05). CONCLUSION The minimum prevalence of gluten sensitivity among the general population of northern and southern Iran is 1:104. The best screening test for the detection of GSE in the general population is IgA tTG-Ab.
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Affiliation(s)
- Mohammad Reza Akbari
- Digestive Disease Research Centre, Tehran University of Medical Sciences, Tehran, Iran
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Sood A, Midha V, Sood N, Avasthi G, Sehgal A. Prevalence of celiac disease among school children in Punjab, North India. J Gastroenterol Hepatol 2006; 21:1622-5. [PMID: 16928227 DOI: 10.1111/j.1440-1746.2006.04281.x] [Citation(s) in RCA: 104] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Celiac disease, as of today, is said to exist in almost all parts of the world, although it is rare among people of purely African-Caribbean, Japanese and Chinese background. The disease has also been considered uncommon in India until recently. Hospital records have revealed an increasing trend of the disease in predominantly wheat-eating areas of North India. The aim of the present study was to determine the prevalence of celiac disease among school children in Punjab, North India. METHODS The study was carried out in the Ludhiana district of Punjab, Northern India. A total of 4347 children aged 3-17 years attending different schools were enrolled. A structured questionnaire was used to collect sociodemographic data and symptoms and signs related to celiac disease and various sociodemographic factors. The screening for celiac disease for the suspected celiacs was done by testing for antitissue transglutaminase (anti-tTG) by indirect solid-phase immunometric assay (ELISA). All children with high anti-tTG whose parents consented underwent upper gastrointestinal endoscopy for small bowel biopsy from the second part of the duodenum. Histopathology was expressed according to the Marsh classification of 1992. Follow up was carried out among children who were put on a gluten-restricted diet, at monthly intervals for 3 months and every 3 months thereafter. The diagnosis of celiac disease was established on the basis of the revised European Society of Paediatric Gastroenterologists and Nutritionists (ESPGAN) criteria (confirmed cases). RESULTS A total of 4347 school children (1967 girls, 2380 boys, age range 3-17 years) were screened for celiac disease. Out of these, 198 suspected children were identified for further evaluation. Twenty-one children tested positive for anti-tTG assay (10.6%, 95% confidence interval: 16.91-34.79). Seventeen of these 21 children agreed to undergo biopsy; of these, 14 had histological changes consistent with celiac disease and all these 14 children had clinical response to gluten restriction. Three children with high anti-tTG had normal mucosa on duodenal biopsy and were not labelled as being in the celiac disease group. In the final analysis the disease prevalence was one in 310 children. CONCLUSIONS This is the first study on celiac disease prevalence among school children from India. Although this disease frequency of one in 310 is thought to be an under-assessment, it clearly shows that celiac disease is not rare in wheat-eating areas of North India.
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Affiliation(s)
- Ajit Sood
- Department of Medicine, Dayanand Medical College and Hospital, Ludhiana, Punjab, India.
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Reinton N, Helgheim A, Shegarfi H, Moghaddam A. A one-step real-time PCR assay for detection of DQA1*05, DQB1*02 and DQB1*0302 to aid diagnosis of celiac disease. J Immunol Methods 2006; 316:125-32. [PMID: 17020762 DOI: 10.1016/j.jim.2006.08.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2006] [Revised: 08/21/2006] [Accepted: 08/23/2006] [Indexed: 11/17/2022]
Abstract
Celiac disease is an autoimmune disorder that develops after dietary exposure of the small intestine to gluten peptides in cereals. Celiac disease has a strong genetic component associated with HLA-DQ2 and HLA-DQ8, and testing for absence of these genetic markers is useful when serological tests and biopsies are indeterminate, as it renders celiac disease highly unlikely. We have developed a new real-time PCR assay, using sequence-specific primers (PCR-SSP) and TaqMan probes, for detection of DQB1*05, DQB1*02 (coding for DQ2) and DQB1*0302 (coding for DQ8). PCR amplification and detection of DQ2 and DQ8 was accurately and unambiguously performed from genomic DNA isolated from cell lines and human DNA. Amplification was scored digitally, without laboratory manipulation of amplified PCR products and with a higher accuracy than PCR-SSP. This assay should increase accuracy and throughput, and reduce risks of contamination in laboratories where testing for HLA DQ2 and DQ8 is performed as part of diagnosis of celiac disease.
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Affiliation(s)
- Nils Reinton
- Fürst Medisinsk Laboratorium, Søren Bulls vei 25, N-1051 Oslo, Norway
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Abstract
Celiac disease is a life-long enteropathy caused by an intolerance to gluten. The pathologic lesion of the small intestinal mucosa is characterized by the loss of absorptive villi, crypt cell hyperplasia, and infiltration of the lamina propria with inflammatory cells. The clinical presentation of celiac disease varies greatly depending on patient's age, duration and extent of the disease, and the presence of extraintestinal manifestations. The classical symptoms like diarrhea, weight loss and abdominal pain are seen less common. Unfortunately, most patients with celiac disease have either silent or atypical presentations, thus escaping diagnosis for several years. The pathologic changes and symptoms resolve when gluten is excluded from the diet for a sustained period. Untreated celiac disease is associated with significant risk of the development of enteropathy-associated intestinal lymphoma.
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Affiliation(s)
- J Stein
- Schwerpunkt Gastroenterologie/Ernährungsmedizin, Medizinische Klinik I-ZAFES am Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt.
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Lanzini A, Magni P, Petroni ML, Motta M, Lanzarotto F, Villanacci V, Amato M, Mora A, Bertolazzi S, Benini F, Ricci C. Circulating ghrelin level is increased in coeliac disease as in functional dyspepsia and reverts to normal during gluten-free diet. Aliment Pharmacol Ther 2006; 23:907-13. [PMID: 16573793 DOI: 10.1111/j.1365-2036.2006.02852.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND It is controversial whether serum ghrelin concentration is altered in coeliac disease and whether this alteration is related to nutritional impairment or to inflammatory changes of duodenal mucosa. AIM To investigate clinical and histopathological variables affecting circulating ghrelin in coeliac patients by comparison with dyspeptic patients and with healthy controls. METHODS We measured serum ghrelin and obtained gastric and duodenal biopsies in 44 coeliac patients before and after 1-year gluten-free diet, in 39 dyspeptic patients and 53 healthy controls. RESULTS Serum ghrelin concentration was significantly higher in coeliac (531 +/- 29 pg/mL, P < 0.05) and in dyspeptic patients (526 +/- 14 pg/mL, P < 0.01) than in healthy controls (451 +/- 8 pg/mL), and body mass index was significantly lower in coeliac (20 +/- 1) and in dyspeptic patients (20 +/- 1) than in healthy controls (22 +/- 1, P < 0.05). In coeliac patients serum ghrelin concentration was not related to the severity of duodenal lesions. Serum ghrelin reverted to normal (399 +/- 30 pg/mL) and body mass index increased significantly (0.6 +/- 0.1 kg/m(2) increase, P < 0.05) during gluten-free diet despite persistent duodenal lymphocytic infiltration. CONCLUSIONS Ghrelin concentration is increased and body mass index is decreased in coeliac and in dyspeptic patients irrespective of presence and severity of duodenal inflammation. Nutritional impairment is a key factor in elevating plasma ghrelin levels in coeliac disease.
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Affiliation(s)
- A Lanzini
- Gastroenterology Unit, University and Spedali Civili, Brescia, Italy.
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Karinen H, Kärkkäinen P, Pihlajamäki J, Janatuinen E, Heikkinen M, Julkunen R, Kosma VM, Naukkarinen A, Laakso M. Gene dose effect of the DQB1*0201 allele contributes to severity of coeliac disease. Scand J Gastroenterol 2006; 41:191-9. [PMID: 16484124 DOI: 10.1080/00365520500206277] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Coeliac disease (CD) susceptibility has been shown to be associated with the HLA alleles DQA1*0501 and DQB1*0201. This HLA-associated risk has been estimated to account for 29-40% of the genetic component of CD. Conflicting data have been published on the gene dose effect of these HLA alleles on the risk and severity of CD. In this study the aim was to investigate the association between the number of HLA risk alleles and the severity of CD. MATERIAL AND METHODS Fifty-four Finnish CD families, including 144 CD patients mainly diagnosed in adulthood (94.4%), were enrolled in the study. The association between the number of DQA1*0501 and DQB1*0201 alleles and villous atrophy, symptoms and laboratory parameters at the time of diagnosis, and the association with villous atrophy after one year of treatment on a gluten-free diet were studied. RESULTS The homozygosity for the DQB1*0201 allele was associated with a more severe form of CD assessed by more severe villous atrophy (p=0.011), younger age (p=0.036), more severe diarrhoea (p=0.048) and a lower level of blood haemoglobin at the time of diagnosis (p=0.010). Furthermore, the homozygosity for the DQB1*0201 allele was associated with a slower recovery of villous atrophy after a gluten-free diet (p=0.041). In contrast, the DQA1*0501 allele did not have a significant association with the severity of CD. CONCLUSIONS Our results demonstrate a gene dose effect of the DQB1*0201 allele on the clinical heterogeneity of CD and on the rate of recovery from villous atrophy in patients on a gluten-free diet.
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Affiliation(s)
- Hannele Karinen
- Department of Medicine, University of Kuopio, Kuopio, Finland
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Abstract
Celiac disease is a complex autoimmune enteropathy that affects the small bowel in genetically predisposed individuals. It is thought that celiac disease is the result of an inappropriate T cell-mediated immune response against ingested gluten protein. The characteristic lesion of the small intestinal mucosa includes loss of absorptive villi and infiltration of the lamina propria with inflammatory cells. The clinical presentation of celiac disease varies greatly depending on patient's age, duration and extent of the disease, and the presence of extraintestinal manifestations. Unfortunately, most patients with celiac disease have either silent or atypical presentations, thus escaping diagnosis for several years. Medical nutrition therapy with lifelong adherence to a strict gluten-free diet is the only accepted treatment of celiac disease. Individuals at risk for this entity should undergo appropriate serologic testing, but there is no evidence to support mass screening.
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Affiliation(s)
- Nisha Chand
- Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University Medical Center, and the Division of Gastroenterology, Hepatology and Nutrition, Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, VA 23249, USA
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Abstract
Secondary osteoporosis occurs as a consequence of various lifestyle factors (eg, eating disorders, smoking, alcoholism), disease processes (eg, endocrinopathies, gastrointestinal tract disease, hepatobiliary disease), and treatment regimens that comprise corticosteroids or chemotherapeutic agents. Some of the disease entities underlying secondary osteoporosis may be clinically silent and identified only during evaluation for documented osteoporosis. The pathogenesis of osteoporosis in these settings is typically multifactorial. The loss of bone may be direct or indirect but ultimately is related to altered osteoblast or osteoclast function. Causes of secondary osteoporosis should especially be investigated in men at all ages and in premenopausal women with atraumatic fractures. In addition, patients with known risk factors should be evaluated. Early recognition and intervention are essential to prevent further loss of bone mass and to prevent fragility fractures.
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Affiliation(s)
- Kimberly Templeton
- Department of Orthopaedic Surgery, University of Kansas Medical Center, Kansas City, KS 66160, USA
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Borowitz D, Durie PR, Clarke LL, Werlin SL, Taylor CJ, Semler J, De Lisle RC, Lewindon P, Lichtman SM, Sinaasappel M, Baker RD, Baker SS, Verkade HJ, Lowe ME, Stallings VA, Janghorbani M, Butler R, Heubi J. Gastrointestinal outcomes and confounders in cystic fibrosis. J Pediatr Gastroenterol Nutr 2005; 41:273-85. [PMID: 16131979 DOI: 10.1097/01.mpg.0000178439.64675.8d] [Citation(s) in RCA: 109] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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50
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Lanzini A, Villanacci V, Apillan N, Lanzarotto F, Pirali F, Amato M, Indelicato A, Scarcella C, Donato F. Epidemiological, clinical and histopathologic characteristics of celiac disease: results of a case-finding population-based program in an Italian community. Scand J Gastroenterol 2005; 40:950-7. [PMID: 16165709 DOI: 10.1080/00365520510023107] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Celiac disease (CD) is underdiagnosed mainly because of lack of awareness of its heterogeneous clinical presentation. The Center for Surveillance and Control of Celiac Disease (CCD) was set up in June 2000 in the province of Brescia, Northern Italy (1,016,426) inhabitants to enhance case-finding, to standardize diagnostic criteria and to collect epidemiological data. MATERIAL AND METHODS The CCD has prompted an educational "celiac awareness program" in the primary-care setting focusing on selective serological screening of high-risk groups, and has reviewed by standardized criteria all diagnoses made in the province since 1984. RESULTS A total of 1437 CD patients have been identified by the CCD, 508 of them diagnosed after June 2000 during the 3 years of activity of the Center (M:F 2:1). Annual incidence was 0.11/1000 before and increased to 0.17/1000 during CCD activity, and this increase was greater for adult (from 0.07/1000 to 0.12/1000) than for pediatric CD (from 0.04/1000 to 0.05/1000). Mean age at diagnosis also increased from 20.2+/-17.7 years to 27.2+/-19.3 years (p<0.0001) as did the proportion of asymptomatic patients (8% versus 15%) before and during CCD activity. There was a linear trend towards increasing proportions of symptomatic patients with increasing severity of histopathologic lesions (p<0.03). CONCLUSIONS Our results indicate that educational programs promoting serological screening of CD in high-risk groups are effective for case-finding in large communities, particularly among the adult population, and suggest that primary-care doctors caring for adults should be particularly targeted by "celiac awareness programs".
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Affiliation(s)
- Alberto Lanzini
- Department of Gastroenterology, Spedali Civili and University of Brescia, Brescia, Italy.
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