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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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Bergman D, King J, Lebwohl B, Clements MS, Roelstraete B, Kaplan GG, Green PHR, Murray JA, Ludvigsson JF. Two waves of coeliac disease incidence in Sweden: a nationwide population-based cohort study from 1990 to 2015. Gut 2022; 71:1088-1094. [PMID: 34321220 PMCID: PMC9120400 DOI: 10.1136/gutjnl-2021-324209] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 07/05/2021] [Indexed: 01/21/2023]
Abstract
OBJECTIVES To assess the incidence of biopsy-verified coeliac disease (CD) in Sweden and examine the incidence of duodenal/jejunal biopsies with normal mucosa over time as a proxy for CD awareness and investigation. DESIGN Nationwide population-based cohort study 1990-2015 based on biopsy reports indicating villous atrophy (VA) or normal mucosa in the duodenum/jejunum. RESULTS We identified 44 771 individuals (63% females) with a biopsy report specifying VA and 412 279 (62% females) with a biopsy report indicating normal mucosa (without a prior biopsy indicating VA). The median age at diagnosis of CD was 28 years. The mean age-standardised incidence rate during the study period was 19.0 per 100 000 person-years (95% CI 17.3 to 20.8). The incidence reached a peak in 1994 for both sexes and a second higher peak in 2002-2003 for females and in 2006 for males. The lifetime risk of developing CD was 1.8% (2.3% in females and 1.4% in males).Prior to 2015, there was a parallel rise in rates for biopsies showing normal duodenal/jejunal mucosa. CONCLUSIONS In Sweden, the incidence of CD increased until 2002-2003 in females and until 2006 in males. Since then, the incidence of CD has declined despite increasing duodenal/jejunal biopsies, suggesting that increased awareness and investigation are unlikely to elevate the incidence of the disease in Sweden. Across a lifetime, 1 in 44 females and 1 in 72 males are expected to be diagnosed with CD in Sweden, indicating a relatively high societal burden of disease.
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Affiliation(s)
- David Bergman
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden .,Brommaplans Primary Health Care Center, Stockholm County, Stockholm, Sweden
| | - James King
- Centre for health informatics, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
| | - Benjamin Lebwohl
- Department of Medicine, Celiac Disease Center, Columbia University College of Physicians and Surgeons, New York, New York, USA
| | - Mark S Clements
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
| | - Bjorn Roelstraete
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
| | - Gilaad G Kaplan
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Peter HR Green
- Department of Medicine, Celiac Disease Center, Columbia University College of Physicians and Surgeons, New York, New York, USA
| | - Joseph A Murray
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden,Department of Pediatrics, Örebro University Hospital, Örebro, Sweden
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Di Biase AR, Marasco G, Ravaioli F, Colecchia L, Dajti E, Lecis M, Passini E, Alemanni LV, Festi D, Iughetti L, Colecchia A. Clinical Presentation of Celiac Disease and Diagnosis Accuracy in a Single-Center European Pediatric Cohort over 10 Years. Nutrients 2021; 13:4131. [PMID: 34836386 PMCID: PMC8625284 DOI: 10.3390/nu13114131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Revised: 11/11/2021] [Accepted: 11/16/2021] [Indexed: 11/22/2022] Open
Abstract
(1) Background: Changes in the clinical presentation of celiac disease (CD) in children have been reported. The guidelines of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) allow esophagogastroduodenoscopy (EGD) with biopsies to be avoided under specific circumstances. We aimed to assess the clinical picture of pediatric CD patients at diagnosis and to validate ESPGHAN non-biopsy criteria. (2) Methods: Patients with suspected CD or undergoing screening from 2004 to 2014 at the University Hospital in Modena, Italy were enrolled. The accuracy of ESPGHAN non-biopsy criteria and modified versions were assessed. (3) Results: In total, 410 patients were enrolled, of whom 403 were considered for analysis. Of the patients considered, 45 were asymptomatic and diagnosed with CD (11.2%) while 358 patients (88.2%) were symptomatic, of whom 295 were diagnosed with CD. Among symptomatic CD patients, 57 (19.3%) had gastrointestinal symptoms, 98 (33%) had atypical symptoms and 140 (47.4%) had both. No difference was found for the presence of gastrointestinal symptoms at different ages. The non-biopsy ESPGHAN criteria yielded an accuracy of 59.4% with a positive predictive value (PPV) of 100%; 173 out of 308 EGD (56.2%) could have been avoided. The modified 7× and 5× upper limit of normal cut-offs for IgA anti tissue-transglutaminase reached 60.7% and 64.3% of EGD avoided, respectively. (4) Conclusions: Over 10 years, late age at diagnosis and increased rates of atypical CD presentation were found. ESPGHAN non-biopsy criteria are accurate for CD diagnosis and allow half of unneeded EGD to be avoided. Modified versions allowed sparing a greater number of EGD.
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Affiliation(s)
- Anna Rita Di Biase
- Pediatric Unit, Modena University Hospital, 41124 Modena, Italy; (A.R.D.B.); (M.L.); (E.P.); (L.I.)
| | - Giovanni Marasco
- Department of Digestive Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy; (F.R.); (E.D.); (L.V.A.)
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy; (L.C.); (D.F.)
| | - Federico Ravaioli
- Department of Digestive Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy; (F.R.); (E.D.); (L.V.A.)
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy; (L.C.); (D.F.)
| | - Luigi Colecchia
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy; (L.C.); (D.F.)
| | - Elton Dajti
- Department of Digestive Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy; (F.R.); (E.D.); (L.V.A.)
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy; (L.C.); (D.F.)
| | - Marco Lecis
- Pediatric Unit, Modena University Hospital, 41124 Modena, Italy; (A.R.D.B.); (M.L.); (E.P.); (L.I.)
| | - Erica Passini
- Pediatric Unit, Modena University Hospital, 41124 Modena, Italy; (A.R.D.B.); (M.L.); (E.P.); (L.I.)
| | - Luigina Vanessa Alemanni
- Department of Digestive Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy; (F.R.); (E.D.); (L.V.A.)
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy; (L.C.); (D.F.)
| | - Davide Festi
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy; (L.C.); (D.F.)
| | - Lorenzo Iughetti
- Pediatric Unit, Modena University Hospital, 41124 Modena, Italy; (A.R.D.B.); (M.L.); (E.P.); (L.I.)
| | - Antonio Colecchia
- Gastroenterology Unit, Modena University Hospital, 41124 Modena, Italy;
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Roberts SE, Morrison-Rees S, Thapar N, Benninga MA, Borrelli O, Broekaert I, Dolinsek J, Martin-de-Carpi J, Mas E, Miele E, Pienar C, Ribes-Koninckx C, Thomassen RA, Thomson M, Tzivinikos C, Thorne K, John A, Williams JG. Systematic review and meta-analysis: the incidence and prevalence of paediatric coeliac disease across Europe. Aliment Pharmacol Ther 2021; 54:109-128. [PMID: 34115894 DOI: 10.1111/apt.16337] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2020] [Revised: 09/30/2020] [Accepted: 03/04/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND Coeliac disease is one of the most prevalent immune-mediated gastrointestinal disorders in children. AIM To review the incidence and prevalence of paediatric coeliac disease, and their trends, regionally across Europe, overall and according to age at diagnosis. METHODS Systematic review and meta-analysis from January 1, 1950 to December 31, 2019, based on PubMed, CINAHL and the Cochrane Library, searches of grey literature and websites and hand searching of reference lists. A total of 127 eligible studies were included. RESULTS The prevalence of previously undiagnosed coeliac disease from screening surveys (histology based) ranged from 0.10% to 3.03% (median = 0.70%), with a significantly increasing annual trend (P = 0.029). Prevalence since 2000 was significantly higher in northern Europe (1.60%) than in eastern (0.98%), southern (0.69%) and western (0.60%) Europe. Large increases in the incidence of diagnosed coeliac disease across Europe have reached 50 per 100 000 person-years in Scandinavia, Finland and Spain. The median age at diagnosis increased from 1.9 years before 1990 to 7.6 since 2000. Larger increases in incidence were found in older age groups than in infants and ages <5 years. CONCLUSIONS Paediatric coeliac disease incidence and prevalence have risen across Europe and appear highest in Scandinavia, Finland and Spain. The most recent evidence shows large increases in incidence in most regions, but stabilisation in some (notably Sweden and Finland). Sharp increases in the age at diagnosis may reflect increases in milder and asymptomatic cases diagnosed since reliable serology testing became widely used, through endomysial antibodies after 1990 and tissue transglutaminase antibodies around 2000.
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Diagnosis of celiac disease is being missed in over 80% of children particularly in those from socioeconomically deprived backgrounds. Eur J Pediatr 2021; 180:1941-1946. [PMID: 33569662 DOI: 10.1007/s00431-021-03974-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 01/16/2021] [Accepted: 02/02/2021] [Indexed: 12/20/2022]
Abstract
Population-based screening studies have documented prevalence of celiac disease (CD) at 1% at age 7 years, but 90% of children remain undiagnosed. This prospective cohort study aims to examine whether observed differences in diagnosis rates of CD exist between children from different socioeconomic groups and how this has changed over a 12-year period. All children aged ≤15 years with a postcode within South West of England (SWE) diagnosed with CD during a 12-year period (1999-2010) when all diagnoses were based on endoscopic histology were included in the study. The incidence rates in socioeconomic groups were determined using the Index of Multiple Deprivation Score and Office of National Statistics population data. Four hundred fifteen children were diagnosed with CD; 65 within the City of Bristol (CoB). Diagnosis rate rose 4.2 times in SWE and 3.1 times in CoB between the first and last 4 years of the study. The rate was 1.6 times higher in the least socioeconomically deprived compared to most deprived (2.2 times in CoB), and the gap widened over the 12 years. Missed cases estimates for CoB and SWE are at least 83% and 91%, respectively.Conclusion: These findings suggest that while incidence of diagnosed CD in children has increased over a 12-year period, 83-91% remained undiagnosed. Socioeconomically deprived children are more likely to be underdiagnosed, and the gap between the least and most deprived has widened. To fully address massive underdiagnosis, further strategies including pilot studies using finger prick serological mass screening for CD in children entering primary schools are needed. What is Known: • Epidemiological studies record a 1% prevalence of celiac disease (CD), but up to 90% of children may remain undiagnosed. • Previous studies have documented an increased incidence of CD in higher socioeconomic groups, but proposed reasons remain conflicting. What is New: • Incidence of diagnosed CDhas gone up across all social classes but more so in higher socioeconomic groups and there is an increasing health/wealth gap. • This study estimates that 83-91% of children with CD are still being missed despite improved and easily available serological testing and suggest that population screening should be reconsidered.
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Iorfida D, Valitutti F, Vestri A, Di Rocco A, Cucchiara S, Lubrano R, Montuori M. Dietary Compliance and Quality of Life in Celiac Disease: A Long-Term Follow-Up of Primary School Screening-Detected Patients. Front Pediatr 2021; 9:787938. [PMID: 34993165 PMCID: PMC8724911 DOI: 10.3389/fped.2021.787938] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 11/12/2021] [Indexed: 11/13/2022] Open
Abstract
Background: Whether the diagnostic approach for celiac disease (CD) can really affect quality of life (QoL) and dietary compliance remains controversial. Aims: This study aimed to evaluate QoL and compliance to gluten-free diet (GFD) in adolescents/young adults diagnosed with CD through a screening strategy during childhood compared to age-matched CD patients diagnosed by case-finding and to assess whether follow-up at a referral center for CD influences compliance and QoL. Materials and Methods: Thirty-seven CD patients who were diagnosed by screening programs (SC-group) and 38 age-matched CD patients diagnosed due to symptoms (CF-group) were enrolled. Patients were asked to answer a questionnaire on QoL, dietary compliance, and follow-up care for CD. Results: Twenty-nine patients of the SC-group (median age 18.0 years, interquartile range [IQR] 16.0-19.0) and 31 patients of the CF-group (median age 17.0 years, IQR 15.5-18.0) completed the questionnaire. No significant difference relating adherence to the GFD and QoL was shown between the two groups. The majority (93.5%) of CF-group regularly had annual follow-up at a referral center compared to 37.9% of the SC-group (p < 0.001). Conclusion: The diagnostic strategy does not seem to impact QoL and dietary compliance. However, implementation of follow-up might still be necessary for patients identified through screening.
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Affiliation(s)
- Donatella Iorfida
- Pediatric Gastroenterology and Liver Unit, Department of Maternal and Child Health, Sapienza-University of Rome, Rome, Italy
| | - Francesco Valitutti
- Pediatric Gastroenterology and Liver Unit, Department of Maternal and Child Health, Sapienza-University of Rome, Rome, Italy.,EBRIS (European Biomedical Research Institute of Salerno), Salerno, Italy
| | - Annarita Vestri
- Department of Public Health and Infectious Disease, Sapienza-University of Rome, Rome, Italy
| | - Arianna Di Rocco
- Department of Public Health and Infectious Disease, Sapienza-University of Rome, Rome, Italy
| | - Salvatore Cucchiara
- Pediatric Gastroenterology and Liver Unit, Department of Maternal and Child Health, Sapienza-University of Rome, Rome, Italy
| | - Riccardo Lubrano
- Pediatrics and Neonatology Unit, Department of Maternal and Child Health, Santa Maria Goretti Hospital, Sapienza-University of Rome, Latina, Italy
| | - Monica Montuori
- Pediatric Gastroenterology and Liver Unit, Department of Maternal and Child Health, Sapienza-University of Rome, Rome, Italy
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Meijer CR, Schweizer JJ, Peeters A, Putter H, Mearin ML. Efficient implementation of the 'non-biopsy approach' for the diagnosis of childhood celiac disease in the Netherlands: a national prospective evaluation 2010-2013. Eur J Pediatr 2021; 180:2485-2492. [PMID: 33856540 PMCID: PMC8285331 DOI: 10.1007/s00431-021-04068-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 03/11/2021] [Accepted: 04/04/2021] [Indexed: 01/11/2023]
Abstract
The aim of this study was (1) to prospectively evaluate the nationwide implementation of the ESPGHAN-guidelines for the diagnosis of celiac disease (CD), (2) to investigate the incidence and clinical presentation of diagnosed childhood CD (0-14 years) in the Netherlands, and (3) to compare the findings with national survey data from 1975 to 1990 and 1993 to 2000 using the same approach. From 2010 to 2013, all practicing paediatricians were invited to report new celiac diagnoses to the Dutch Pediatric Surveillance Unit. Data were collected via questionnaires. A total of 1107 children with newly diagnosed CD were reported (mean age, 5.8 years; range, 10 months-14.9 years; 60.5% female). After the introduction of the non-biopsy approach in 2012, 75% of the diagnoses were made according to the guideline with a significant decrease of 46.3% in biopsies. The use of EMA and HLA-typing significantly increased with 25.8% and 62.1%, respectively. The overall incidence rate of childhood CD was 8.8-fold higher than in 1975-1990 and 2.0-fold higher than in 1993-2000. During the study period, the prevalence of diagnosed CD was 0.14%, far below 0.7% of CD identified via screening in the general Dutch paediatric population. Clinical presentation has shifted towards less severe and extra-intestinal symptoms.Conclusion: ESPGHAN guidelines for CD diagnosis in children were effectively and rapidly implemented in the Netherlands. Incidence of diagnosed CD among children is still significantly rising with a continuous changing clinical presentation. Despite the increasing incidence of diagnoses, significant underdiagnosis still remains. What is Known: • Since 2000 the incidence of diagnosed childhood CD in the Netherlands has shown a steady rise. • The rise in incidence has been accompanied by a changing clinical presentation at diagnosis. What is New: • The ESPGHAN guidelines 2012 for CD diagnosis were effectively and rapidly implemented in the Netherlands. • The incidence of diagnosed childhood CD in the Netherlands has continued to rise significantly during the reported period.
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Affiliation(s)
- Caroline R. Meijer
- Department of Paediatrics, Willem Alexander Children’s Hospital, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - Joachim J. Schweizer
- Department of Paediatrics, Willem Alexander Children’s Hospital, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - Anne Peeters
- Department of Paediatrics, Willem Alexander Children’s Hospital, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - Hein Putter
- Department of Medical Statistics, Leiden University Medical Centre, Leiden, The Netherlands
| | - M. Luisa Mearin
- Department of Paediatrics, Willem Alexander Children’s Hospital, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
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Chrysostomou S, Andreou SN, Andreou C. The development of the gluten free healthy food basket in Cyprus. Is it affordable among low-income adults diagnosed with celiac disease? J Public Health (Oxf) 2020; 42:270-276. [PMID: 31329915 DOI: 10.1093/pubmed/fdz034] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Revised: 02/14/2019] [Accepted: 03/19/2019] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Gluten free (GF) diets are not only restrictive but also costly. The main aim of this study was to evaluate the acceptability, cost and affordability of a Gluten Free Healthy Food Basket (GFHFB) and further examine whether low-income Cypriots diagnosed with celiac disease (CD) experience food stress. METHODS GFΗFBs were constructed for adult women and adult men (±40 years) diagnosed with CD. Feasibility and acceptability was tested through three focus groups. Affordability was defined as the cost of the GFΗFB as a percentage of the Guaranteed Minimum Income (GMI). RESULTS The GFΗFB was 33.6 and 47 euros/month more expensive compared to the HB (Healthy Basket) for women and men, respectively. The total budget for GF-manufactured products were 27.81 and 28.5% of the total food budget, for women and men, respectively. For low-income people receiving the GMI, the proportion of income that would need to be spent on the GFHFB ranges from around 42 to 60%. CONCLUSIONS The GFΗFB is costly and not affordable among low-income Cypriots diagnosed with CD; thus, they are likely to suffer from food stress. As such, the risk of reducing their adherence to a GF diet is high and thus compromises their long-term health.
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Affiliation(s)
- S Chrysostomou
- Department of Life Sciences, European University of Cyprus, 6 Diogenes Street, Engomi, Nicosia, Cyprus
| | - S N Andreou
- Economics Research Center, University of Cyprus, PO Box 20537, CY-1678 Nicosia, Cyprus
| | - Ch Andreou
- Department of Life Sciences, European University of Cyprus, 6 Diogenes Street, Engomi, Nicosia, Cyprus
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Pecora F, Persico F, Gismondi P, Fornaroli F, Iuliano S, de'Angelis GL, Esposito S. Gut Microbiota in Celiac Disease: Is There Any Role for Probiotics? Front Immunol 2020; 11:957. [PMID: 32499787 PMCID: PMC7243837 DOI: 10.3389/fimmu.2020.00957] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Accepted: 04/23/2020] [Indexed: 12/15/2022] Open
Abstract
Celiac disease (CD) is an immune-mediated disorder initiated by the ingestion of gluten in genetically predisposed individuals. Recent data shows that changes in the gut microbiome composition and function are linked with chronic inflammatory diseases; this might also be the case for CD. The main aim of this manuscript is to discuss our present knowledge of the relationships between gut microbiota alterations and CD and to understand if there is any role for probiotics in CD therapy. PubMed was used to search for all of the studies published from November 2009 to November 2019 using key words such as "Celiac Disease" and "Microbiota" (306 articles), "Celiac Disease" and "Gastrointestinal Microbiome" (139), and "Probiotics" and "Celiac Disease" (97 articles). The search was limited to articles published in English that provided evidence-based data. Literature analysis showed that the gut microbiota has a well-established role in gluten metabolism, in modulating the immune response and in regulating the permeability of the intestinal barrier. Promising studies suggest a possible role of probiotics in treating and/or preventing CD. Nevertheless, human trials on the subject are still scarce and lack homogeneity. A possible role was documented for probiotics in improving CD-related symptoms, modulating the peripheral immune response and altering the fecal microbiota, although the results were not consistent in all of the studies. No evidence was found that probiotic administration might prevent CD onset. Knowledge of the role of intestinal bacteria in the development of CD opens new possibilities for its treatment through probiotic administration, even though further studies are needed to better clarify whether probiotics can help treat or prevent the disease and to define which probiotics to use, at what dose and for how long.
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Affiliation(s)
- Francesco Pecora
- Department of Medicine and Surgery, Pediatric Clinic, Pietro Barilla Children's Hospital, University of Parma, Parma, Italy
| | - Federica Persico
- Department of Medicine and Surgery, Pediatric Clinic, Pietro Barilla Children's Hospital, University of Parma, Parma, Italy
| | - Pierpacifico Gismondi
- Department of Medicine and Surgery, Pediatric Clinic, Pietro Barilla Children's Hospital, University of Parma, Parma, Italy
| | - Fabiola Fornaroli
- Unit of Gastroenterology and Digestive Endoscopy, Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Silvia Iuliano
- Unit of Gastroenterology and Digestive Endoscopy, Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Gian Luigi de'Angelis
- Unit of Gastroenterology and Digestive Endoscopy, Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Susanna Esposito
- Department of Medicine and Surgery, Pediatric Clinic, Pietro Barilla Children's Hospital, University of Parma, Parma, Italy
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King JA, Jeong J, Underwood FE, Quan J, Panaccione N, Windsor JW, Coward S, deBruyn J, Ronksley PE, Shaheen AA, Quan H, Godley J, Veldhuyzen van Zanten S, Lebwohl B, Ng SC, Ludvigsson JF, Kaplan GG. Incidence of Celiac Disease Is Increasing Over Time: A Systematic Review and Meta-analysis. Am J Gastroenterol 2020; 115:507-525. [PMID: 32022718 DOI: 10.14309/ajg.0000000000000523] [Citation(s) in RCA: 251] [Impact Index Per Article: 50.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Accepted: 12/05/2019] [Indexed: 12/11/2022]
Abstract
OBJECTIVES To conduct a systematic review and meta-analysis that defines the worldwide incidence of celiac disease (CD) and examines temporal trends. METHODS MEDLINE and EMBASE were searched for population-based studies reporting the incidence of CD in the overall population, children, or adults. No limits were placed on year or language of publication. Studies solely examining at-risk populations (e.g., patients with type 1 diabetes) were excluded. Random-effects models were performed to meta-analyze sex- and age-specific incidence in the 21st century. Temporal trend analyses assessed the average annual percent change in CD incidence over time. RESULTS Of 11,189 citations, 86 eligible studies were identified for inclusion, of which 50 were deemed suitable for analyses. In the 21st century, the pooled female incidence of CD was 17.4 (95% confidence interval [CI]: 13.7, 21.1) (I = 99.5%) per 100,000 person-years, compared with 7.8 (95% CI: 6.3, 9.2) (I = 98.6%) in males. Child-specific incidence was 21.3 per 100,000 person-years (95% CI: 15.9, 26.7) (I = 99.7%) compared with 12.9 (95% CI: 7.6, 18.2) (I = 99.9%) in adults. Pooling average annual percent changes showed the incidence of CD to be increasing by 7.5% (95% CI: 5.8, 9.3) (I = 79.6%) per year over the past several decades. DISCUSSION Incidence of CD is highest in females and children. Overall, the incidence has been significantly rising in the latter half of the 20th century and into the 21st century throughout the Western world. Population-based studies in Africa, Asia, and Latin America are needed to provide a comprehensive picture of the global incidence of CD.
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Affiliation(s)
- James A King
- Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Jocelyn Jeong
- Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
- Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada
| | - Fox E Underwood
- Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Joshua Quan
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Nicola Panaccione
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Joseph W Windsor
- Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Stephanie Coward
- Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Jennifer deBruyn
- Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada
| | - Paul E Ronksley
- Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Abdel-Aziz Shaheen
- Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Hude Quan
- Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Jenny Godley
- Department of Sociology, University of Calgary, Calgary, Alberta, Canada
| | | | - Benjamin Lebwohl
- Department of Medicine, Celiac Disease Center, Columbia University College of Physicians and Surgeons, New York, New York, USA
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA
| | - Siew C Ng
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China
| | - Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Department of Pediatrics, Örebro University Hospital, Örebro, Sweden
| | - Gilaad G Kaplan
- Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
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Sahin Y, Cakir MD, Isakoca M, Aydin Sahin D. Prevalence of Celiac Disease in Children with Type 1 Diabetes Mellitus in the South of Turkey. IRANIAN JOURNAL OF PEDIATRICS 2019; 30. [DOI: 10.5812/ijp.97306] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/18/2019] [Revised: 10/10/2019] [Accepted: 10/23/2019] [Indexed: 08/29/2023]
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12
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Popp A, Mäki M. Changing Pattern of Childhood Celiac Disease Epidemiology: Contributing Factors. Front Pediatr 2019; 7:357. [PMID: 31555624 PMCID: PMC6727179 DOI: 10.3389/fped.2019.00357] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Accepted: 08/15/2019] [Indexed: 12/14/2022] Open
Abstract
Up until the 1960s and 1970s, diarrhea, malabsorption syndrome, and failure to thrive were the presenting symptoms and signs of celiac disease (CD) in young infants; however this disease was also at the same time reported to be disappearing. Indeed, clinical childhood CD was seen to transform into a milder form, resulting in an upward shift in age at diagnosis during the 1970s (and years later for many countries). This changing pattern of CD presentation then altered the epidemiology of the disease, with major differences between and within countries observed. An awareness of the changing clinical nature of CD and use of case-finding tools to detect even clinically silent CD became an important factor in this changing epidemiology. Countries report both low and high prevalence but it seems to be on the increase resulting in a population-based level of 1-2%. This paper discusses the potential causes and environmental factors behind these observed clinical changes, identifying new clues from different studies published at the time this transformation took place. For instance, it was found that breastfeeding postponed the diagnosis of the disease but did not altogether prevent it. Moreover, gluten introduction at a young age, specifically at the mean age of 2 months, seemed to also have a clear impact in inducing malabsorption syndrome and failure to thrive in young infants in addition to other factors such as gluten intake volume and type of cereal present in the weaning food. Further, the impact of cow's milk and its high osmolarity might have played an important role; humanized milk formulas were not yet invented. Future epidemiological studies on the contributing environmental factors to the shift in CD presentation are thus recommended for countries in which these changing clinical features are still being observed.
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Affiliation(s)
- Alina Popp
- Faculty of Medicine and Health Technology, Tampere Center of Child Health Research, Tampere University and Tampere University Hospital, Tampere, Finland
- National Institute for Mother and Child Health “Alessandrescu-Rusescu”, University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
| | - Markku Mäki
- Faculty of Medicine and Health Technology, Tampere Center of Child Health Research, Tampere University and Tampere University Hospital, Tampere, Finland
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13
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Leinonen H, Kivelä L, Lähdeaho ML, Huhtala H, Kaukinen K, Kurppa K. Daily Life Restrictions are Common and Associated with Health Concerns and Dietary Challenges in Adult Celiac Disease Patients Diagnosed in Childhood. Nutrients 2019; 11:nu11081718. [PMID: 31349675 PMCID: PMC6723871 DOI: 10.3390/nu11081718] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Revised: 07/19/2019] [Accepted: 07/23/2019] [Indexed: 12/20/2022] Open
Abstract
The prevalence and associated factors of daily life restrictions due to a gluten-free diet in adult celiac disease patients diagnosed in childhood are poorly known. We investigated these issues by collecting the medical data of 955 pediatric patients and sending questionnaires evaluating various health outcomes to the 559 patients who had reached adulthood. Of the 231 respondents, 46% reported everyday life restrictions caused by dietary treatment. Compared with those without restrictions, they more often had anemia at diagnosis (37% vs. 22%, p = 0.014), but the groups were comparable in other diagnostic features. In adulthood, patients with restrictions reported more overall symptoms (32% vs. 17%, p = 0.006), although the symptoms measured with the Gastrointestinal Symptom Rating Scale questionnaire were comparable. Despite strict dietary adherence in both groups, the experience of restrictions was associated with dietary challenges (34% vs. 9%, p < 0.001), health concerns (22% vs. 13%, p = 0.050), and lower vitality scores in the Psychological General Well-Being questionnaire. The groups did not differ in their current age, socioeconomic status, family history of celiac disease, general health or health-related lifestyle, the presence of co-morbidities, or regular follow up. Our results encourage healthcare professionals to discuss the possible health concerns and dietary challenges with patients to avoid unnecessary daily life restrictions, especially when young patients start to take responsibility for their treatment.
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Affiliation(s)
- Heini Leinonen
- Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland
- Center for Child Health Research, Tampere University and Department of Pediatrics, Tampere University Hospital, 33014 Tampere, Finland
| | - Laura Kivelä
- Center for Child Health Research, Tampere University and Department of Pediatrics, Tampere University Hospital, 33014 Tampere, Finland.
- Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland.
| | - Marja-Leena Lähdeaho
- Center for Child Health Research, Tampere University and Department of Pediatrics, Tampere University Hospital, 33014 Tampere, Finland
| | - Heini Huhtala
- Faculty of Social Sciences, Tampere University, 33014 Tampere, Finland
| | - Katri Kaukinen
- Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland
- Department of Internal Medicine, Tampere University Hospital, 33014 Tampere, Finland
- Celiac Disease Research Center, Tampere University, 33014 Tampere, Finland
| | - Kalle Kurppa
- Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland
- Center for Child Health Research, Tampere University and Department of Pediatrics, Tampere University Hospital, 33014 Tampere, Finland
- The University Consortium of Seinäjoki, 60320 Seinäjoki, Finland
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Mancuso C, Barisani D. Food additives can act as triggering factors in celiac disease: Current knowledge based on a critical review of the literature. World J Clin Cases 2019; 7:917-927. [PMID: 31119137 PMCID: PMC6509268 DOI: 10.12998/wjcc.v7.i8.917] [Citation(s) in RCA: 9] [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] [Received: 01/13/2019] [Revised: 03/11/2019] [Accepted: 03/16/2019] [Indexed: 02/05/2023] Open
Abstract
Celiac disease (CeD) is an autoimmune disorder, mainly affecting the small intestine, triggered by the ingestion of gluten with the diet in subjects with a specific genetic status. The passage of gluten peptides through the intestinal barrier, the uptake by antigen presenting cells and their presentation to T cells represent essential steps in the pathogenesis of the disease. CeD prevalence varies in different populations, but a tendency to increase has been observed in various studies in recent years. A higher amount of gluten in modern grains could explain this increased frequency, but also food processing could play a role in this phenomenon. In particular, the common use of preservatives such as nanoparticles could intervene in the pathogenesis of CeD, due to their possible effect on the integrity of the intestinal barrier, immune response or microbiota. In fact, these alterations have been reported after exposure to metal nanoparticles, which are commonly used as preservatives or to improve food texture, consistency and color. This review will focus on the interactions between several food additives and the intestine, taking into account data obtained in vitro and in vivo, and analyzing their effect in respect to the development of CeD in genetically predisposed individuals.
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Affiliation(s)
- Clara Mancuso
- Department of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, Monza 20900, Italy
| | - Donatella Barisani
- Department of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
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15
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Prevalence and Clinical Features of Celiac Disease in Healthy School-Aged Children. Dig Dis Sci 2019; 64:173-181. [PMID: 30311156 DOI: 10.1007/s10620-018-5320-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Accepted: 10/03/2018] [Indexed: 12/09/2022]
Abstract
BACKGROUND/AIMS The aim of this study was to determine the prevalence of celiac disease (CD) in healthy school-aged children in the northern region of Cyprus and to investigate the existence of potential markers that may accompany CD. This is the first study to measure the prevalence of CD in the northern region of Cyprus. METHODS This study included 3792 school-aged children who were between the ages of 6 and 10 years between January 2015 and October 2016. CD was screened using total serum IgA, IgA anti-tissue transglutaminase (tTG), and IgA antiendomysial (EMA) antibodies. Subjects with selective IgA deficiency were further tested for IgG-tTG. Small intestinal biopsies were performed on all subjects with tTG antibody positivity. Risk factors and symptoms related to CD were evaluated using questionnaires in both the CD and control groups. RESULTS Of the 3792 subjects, 39 were antibody positive (IgA-tTG was positive only in 14 subjects, IgA-tTG plus IgA-EMA in 21 subjects, and IgG-tTG in 4 subjects). IgA deficiency was detected in 11 subjects (0.29%). IgG-tTG was positive in 4 subjects with IgA deficiency (36.3%). Intestinal biopsies were performed on 28 of the 39 seropositive subjects. The biopsy findings of 15 children were consistent with CD (IgA-tTG positive in 3, IgA-tTG and IgA-EMA positive in 10, and IgG-tTG positive in 2). Thus, biopsies confirmed CD in 1:256 children (0.39%). CONCLUSIONS Our study, which is the first study of school-aged children from the northern region of Cyprus, revealed that CD is a prevalent disease in this region.
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Cristofori F, Indrio F, Miniello VL, De Angelis M, Francavilla R. Probiotics in Celiac Disease. Nutrients 2018; 10:1824. [PMID: 30477107 PMCID: PMC6316269 DOI: 10.3390/nu10121824] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Revised: 11/06/2018] [Accepted: 11/15/2018] [Indexed: 02/06/2023] Open
Abstract
Recently, the interest in the human microbiome and its interplay with the host has exploded and provided new insights on its role in conferring host protection and regulating host physiology, including the correct development of immunity. However, in the presence of microbial imbalance and particular genetic settings, the microbiome may contribute to the dysfunction of host metabolism and physiology, leading to pathogenesis and/or the progression of several diseases. Celiac disease (CD) is a chronic autoimmune enteropathy triggered by dietary gluten exposure in genetically predisposed individuals. Despite ascertaining that gluten is the trigger in CD, evidence has indicated that intestinal microbiota is somehow involved in the pathogenesis, progression, and clinical presentation of CD. Indeed, several studies have reported imbalances in the intestinal microbiota of patients with CD that are mainly characterized by an increased abundance of Bacteroides spp. and a decrease in Bifidobacterium spp. The evidence that some of these microbial imbalances still persist in spite of a strict gluten-free diet and that celiac patients suffering from persistent gastrointestinal symptoms have a desert gut microbiota composition further support its close link with CD. All of this evidence gives rise to the hypothesis that probiotics might play a role in this condition. In this review, we describe the recent scientific evidences linking the gut microbiota in CD, starting from the possible role of microbes in CD pathogenesis, the attempt to define a microbial signature of disease, the effect of a gluten-free diet and host genetic assets regarding microbial composition to end in the exploration of the proof of concept of probiotic use in animal models to the most recent clinical application of selected probiotic strains.
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Affiliation(s)
| | - Flavia Indrio
- Department of Paediatrics, Paediatric Hospital Giovanni XXIII, Via Amendola 207, 70126 Bari, Italy.
| | - Vito Leonardo Miniello
- Department of Paediatrics, Paediatric Hospital Giovanni XXIII, Via Amendola 207, 70126 Bari, Italy.
| | - Maria De Angelis
- Department of Soil, Plant and Food Sciences, University of Bari Aldo Moro, 70126 Bari, Italy.
| | - Ruggiero Francavilla
- Department of Paediatrics, Paediatric Hospital Giovanni XXIII, Via Amendola 207, 70126 Bari, Italy.
- Pediatric Section, Department of Interdisciplinary Medicine, University of Bari Aldo Moro, 70124 Bari, Italy.
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17
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Kivelä L, Kurppa K. Screening for coeliac disease in children. Acta Paediatr 2018; 107:1879-1887. [PMID: 29920762 DOI: 10.1111/apa.14468] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Revised: 05/01/2018] [Accepted: 06/15/2018] [Indexed: 12/12/2022]
Abstract
AIM Coeliac disease is a common but markedly under-diagnosed condition, which may lead to serious long-term complications if untreated. Both the diagnostic yield and true incidence have significantly increased during the last few decades and it is now one of the most common chronic gastrointestinal conditions in children. The aim of this review was to summarise the current concepts on screening for coeliac disease in children and adolescents. METHOD We conducted a non-systematic literature review of papers published about coeliac disease screening since the year 2000. RESULTS Our review showed that the diagnostic yield could be significantly improved by screening for at-risk groups, or even the whole population, but these approaches remain controversial. Evidence suggests that screening for certain high-risk groups could be beneficial, but untargeted mass screening is not currently recommended. However, whether the benefits of an early diagnosis would overcome the challenges of lifelong dietary treatment, especially in asymptomatic individuals who consider themselves healthy, are unclear. CONCLUSION There is moderate evidence that screening certain at-risk groups for coeliac disease could be beneficial, but more studies in different settings are needed before large-scale population screening can be recommended.
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Affiliation(s)
- Laura Kivelä
- Tampere Center for Child Health Research; University of Tampere and Tampere University Hospital; Tampere Finland
- Department of Pediatrics; Hospital District of South Ostrobothnia; Seinäjoki Finland
| | - Kalle Kurppa
- Tampere Center for Child Health Research; University of Tampere and Tampere University Hospital; Tampere Finland
- School of Medicine and Life Sciences; University of Tampere; Tampere Finland
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18
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Burkhardt JG, Chapa-Rodriguez A, Bahna SL. Gluten sensitivities and the allergist: Threshing the grain from the husks. Allergy 2018; 73:1359-1368. [PMID: 29131356 DOI: 10.1111/all.13354] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/08/2017] [Indexed: 12/12/2022]
Abstract
"Gluten sensitivity" has become commonplace among the public. Wheat allergy (WA) and celiac disease (CD) are well-defined entities, but are becoming a fraction of individuals following a gluten-free diet (GFD). Wheat allergy has a prevalence of <0.5%. Wheat, specifically its omega-5 gliadin fraction, is the most common allergen implicated in food-dependent, exercise-induced anaphylaxis. CD is a non-IgE hypersensitivity to certain cereal proteins: gluten in wheat, secalin in rye, hordein in barley, and to a lesser extent avenin in oat. It is a rare disease, with an estimated prevalence that varied widely geographically, being higher in Northern Europe and the African Saharawi region than in South-East Asia. In addition to suggestive symptoms, serologic testing has high diagnostic reliability and biopsy is a confirmatory procedure. Patients with CD have extra-intestinal autoimmune comorbid conditions more frequently than expected. A third entity is nonceliac gluten sensitivity, which has been created because of the increasing number of subjects who claim a better quality of life or improvement of their variety of symptoms on switching to a GFD. The phenomenon is being fueled by the media and exploited by the industry. The lack of a specific objective test has been raising substantial controversy about this entity. Allergists and gastroenterologists need to pay attention to the multitudes of individuals who elect to follow a GFD. Many such subjects might have WA, CD, or another illness. Providing them with appropriate evaluation and specific management would be of great advantages, medically and economically.
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Affiliation(s)
- J. G. Burkhardt
- Allergy & Immunology Section; Louisiana State University Health Sciences Center; Shreveport LA USA
| | - A. Chapa-Rodriguez
- Pediatric Gastroenterology & Nutrition Section; Louisiana State University Health Sciences Center; Shreveport LA USA
| | - S. L. Bahna
- Allergy & Immunology Section; Louisiana State University Health Sciences Center; Shreveport LA USA
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19
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Cabrera CM, Méndez-López IM, Caballero A. Risk variation in celiac disease in a population from Southern Spain: evaluating the influence of the DQB1*02:02 allele frequency. Scand J Gastroenterol 2018; 53:266-272. [PMID: 29361871 DOI: 10.1080/00365521.2018.1430253] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES To date, the greatest genetic risk factor known for celiac disease (CD) is the presence of HLA-DQ2 heterodimers, specifically DQ2.5 in state of homozygosis or heterozygosis. DQ2.2 variants are the second most important risk factor when carried trans to DQ2. This study aimed to determine the prevalence and risk genotypes of HLA-DR-DQ. MATERIAL AND METHODS A total of 196 patients with CD and 206 healthy controls from the Province of Málaga (southern Spain) were included. The corresponding risk gradient in our population was established in accordance with the odds ratios (ORs) found. RESULTS The heterozygous genotype for DR7-DQ2.2/DR3-DQ2.5 presented the highest risk (OR =6.404, p = .0001) followed by the DR3-DQ2.5 homozygous genotype (OR =4.721, p = .001). An intermediate risk was found for the DQ2.5 heterozygous genotype with no other DQ risk variant (DQ8 or DQ2.2). Similarly, these three genotypes had also an increase in the risk of associated-autoimmune diseases. The DQB1*02:01 allele was the most widely represented among patients with CD respect to the control group (f = 0.479, p = .0001), with the second most common being DQB1*02:02 (f = 0.209, p = .0001). CONCLUSIONS In addition to the gene dosage effect confirmed in our report, and in contrast with previous studies, we found a raised risk for those patients with DQ2.2 heterodimers in trans configuration to DQ2.5 compared to DQ2.5 homozygous individuals. Therefore, in our population of patients with CD the frequency of DQ2.2 acts as a factor that increases the genetic risk of developing CD.
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Affiliation(s)
- Carmen M Cabrera
- a Department of Hematology, Immunology Section , Carlos Haya Regional University Hospital , Málaga , Spain
| | - Isabel M Méndez-López
- a Department of Hematology, Immunology Section , Carlos Haya Regional University Hospital , Málaga , Spain
| | - Abelardo Caballero
- a Department of Hematology, Immunology Section , Carlos Haya Regional University Hospital , Málaga , Spain.,b Faculty of Medicine , University of Málaga , Málaga , Spain
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20
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Liester MG, Liester MB. Drought’s potential influence on the increasing prevalence of celiac disease. COGENT MEDICINE 2018. [DOI: 10.1080/2331205x.2018.1529848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022] Open
Affiliation(s)
- Maya G. Liester
- Department of Psychiatry, University of Colorado School of Medicine, Colorado Springs, CO, 80918, USA
| | - Mitchell B. Liester
- Department of Psychiatry, University of Colorado School of Medicine, Colorado Springs, CO, 80918, USA
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21
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Almallouhi E, King KS, Patel B, Wi C, Juhn YJ, Murray JA, Absah I. Increasing Incidence and Altered Presentation in a Population-based Study of Pediatric Celiac Disease in North America. J Pediatr Gastroenterol Nutr 2017; 65:432-437. [PMID: 28151767 PMCID: PMC5538895 DOI: 10.1097/mpg.0000000000001532] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Celiac disease (CD) is a common immune-mediated disorder that affects up to 1% of the general population. Recent reports suggest that the incidence of CD has reached a plateau in many countries. We aim to study the incidence and altered presentation of childhood CD in a well-defined population. METHODS Using the Rochester Epidemiology Project, we retrospectively reviewed Mayo Clinic and Olmsted Medical Center medical records from January 1994 to December 2014. We identified all CD cases of patients ages 18 years or younger at the time of diagnosis. Incidence rates were calculated by adjusting for age, sex, and calendar year and standardizing to the 2010 US white population. RESULTS We identified 100 patients with CD. Incidence of CD has increased from 8.1 per 100,000 person-years (2000-2002) to 21.5 per 100,000 person-years (2011-2014). There was an increase in CD prevalence in children from 2010 (0.10%) to 2014 (0.17%). Thirty-four patients (34%) presented with classical CD symptoms, 43 (43%) had nonclassical CD, and 23 (23%) were diagnosed by screening asymptomatic high-risk patients. Thirty-six patients (36%) had complete villous atrophy, 51 (51%) had partial atrophy, and 11 (11%) had increased intraepithelial lymphocytes. Two patients were diagnosed without biopsy. Most patients (67%) had a normal body mass index, 17% were overweight/obese, and only 9% were underweight. CONCLUSIONS Both incidence and prevalence of CD have continued to increase in children during the past 15 years in Olmsted County, Minnesota. Clinical and pathologic presentations of CD are changing over time (more nonclassical and asymptomatic cases are emerging).
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Affiliation(s)
- Eyad Almallouhi
- Division of Pediatric Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Katherine S. King
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN
| | - Bhavisha Patel
- Division of Allergy, Department of Internal Medicine, Mayo Clinic, Rochester, MN
| | - Chung Wi
- Asthma Epidemiology Research Unit and Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN
| | - Young J. Juhn
- Division of Allergy, Department of Internal Medicine, Mayo Clinic, Rochester, MN
| | - Joseph A. Murray
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Imad Absah
- Division of Pediatric Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
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22
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Jansen MAE, Beth SA, van den Heuvel D, Kiefte-de Jong JC, Raat H, Jaddoe VWV, van Zelm MC, Moll HA. Ethnic differences in coeliac disease autoimmunity in childhood: the Generation R Study. Arch Dis Child 2017; 102:529-534. [PMID: 28052882 DOI: 10.1136/archdischild-2016-311343] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Revised: 12/05/2016] [Accepted: 12/08/2016] [Indexed: 12/15/2022]
Abstract
OBJECTIVE The aim was to identify whether ethnic differences in coeliac disease autoimmunity (CDA) in children at 6 years of age exist, and when present, to evaluate how these differences may be explained by sociodemographic and environmental factors. DESIGN This study was embedded within a multi-ethnic population-based prospective cohort study. SETTING AND PATIENTS 4442 six-year-old children born between 2002 and 2006 were included. Information on ethnicity, environmental and lifestyle characteristics was assessed by questionnaires. Ethnicity was categorised into Western (Dutch, European, Indonesian, American, Oceanian) and non-Western (Turkish, Moroccan, Cape Verdean, Antillean, Surinamese). Serum transglutaminase type 2 antibody (TG2A) levels were measured with fluorescence enzyme immunoassay. Serum IgG levels against cytomegalovirus (CMV) were measured by ELISA. MAIN OUTCOME MEASURES TG2A positivity was defined as TG2A ≥7 U/mL, strong TG2A positivity as TG2A ≥10 upper limit normal (70 U/mL). RESULTS Of 4442 children, 60 (1.4%) children were TG2A positive, of whom 31 were strong positive. 66% of children were Western, 33% non-Western. Western ethnicity, high socioeconomic position and daycare attendance were positively associated with strong TG2A positivity (odds ratio (OR) 6.85 (1.62 to 28.8) p<0.01, OR 3.70 (1.40 to 9.82) p<0.01, OR 3.90 (1.38 to 11.0) p=0.01 resp.), whereas CMV seropositivity was inversely related to strong TG2A positivity (OR 0.32 (0.12 to 0.84) p=0.02). Together, these factors explained up to 47% (-67 to -17; p=0.02) of the ethnic differences in TG2A positivity between Western and non-Western children. CONCLUSIONS Ethnic differences in children with CDA are present in childhood. Socioeconomic position, daycare attendance and CMV seropositivity partly explained these differences, which may serve as targets for prevention strategies for CDA.
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Affiliation(s)
- Michelle A E Jansen
- The Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.,Department of Paediatrics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.,Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Sytske A Beth
- The Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.,Department of Paediatrics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Diana van den Heuvel
- Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Jessica C Kiefte-de Jong
- Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.,Department of Global Public Health, Leiden University College, The Hague, The Netherlands
| | - Hein Raat
- Department of Public Health, University Medical Center, Rotterdam, The Netherlands
| | - Vincent W V Jaddoe
- The Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.,Department of Paediatrics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.,Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Menno C van Zelm
- Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Australia
| | - Henriette A Moll
- The Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.,Department of Paediatrics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
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Holmes GKT, Muirhead A. Epidemiology of coeliac disease in a single centre in Southern Derbyshire 1958-2014. BMJ Open Gastroenterol 2017; 4:e000137. [PMID: 28761688 PMCID: PMC5508802 DOI: 10.1136/bmjgast-2017-000137] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2017] [Revised: 03/09/2017] [Accepted: 03/24/2017] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVE To determine trends in diagnosis of coeliac disease (CD) in patients attending a single centre 1958-2014 and provide figures for prevalence and incidence in those born in Derby city over 4 decades. To explore a link between deprivation and prevalence and characteristics of CD in Asians. DESIGN An unselected, consecutive series of 2410 adult patients with CD diagnosed in the catchment area of the Derby hospitals was identified. 1077 born within Derby city identified by postcodes was used to determine changes in prevalence and incidence over 4 decades. 191 patients were Asian. Population numbers were obtained from National Census information. RESULTS In the quinquennium 2010-2014, 20 times more patients were diagnosed than during 1975-1979. 27% were diagnosed at ≥60 years. A paucity of diagnoses in young men was observed. Women were diagnosed most often in age band ≥35<45, 15 years earlier than men. The largest increase in diagnosis rates occurred in young women and the elderly. In 2014, overall prevalence was 1:188; women 1:138. 4.6% of the variation was attributed to deprivation. Diagnosis rates in Asians increased markedly although only 5% were diagnosed at ≥60 years, much lower than for whites. CONCLUSIONS The dramatic increase in number of patients with CD presents challenges for follow-up and new models of care need to be explored. Healthcare workers should be alert to the diagnosis in young men and elderly Asians. A dedicated coeliac clinic is an excellent facility to increase diagnosis rates.
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Affiliation(s)
| | - A Muirhead
- Department of Public Health, Derby City Council, Derby, UK
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24
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Symptoms and Mucosal Changes Stable During Rapid Increase of Pediatric Celiac Disease in Norway. J Pediatr Gastroenterol Nutr 2017; 64:586-591. [PMID: 27299421 DOI: 10.1097/mpg.0000000000001307] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
OBJECTIVES We aimed to study whether the incidence of pediatric celiac disease (CD) in South-Eastern Norway changed from 2000 to 2010. We also examined whether there was a change in symptoms and histopathological morphology in the duodenal biopsies during the same period. METHODS In 3 hospitals in South-Eastern Norway, records from pediatric patients (0-14.9 years) diagnosed with CD during two 3-year periods (2000-2002 and 2008-2010) were reviewed. Only cases with a duodenal biopsy diagnosis of CD classified as Marsh grade 2 and 3a-c were included. Frequencies of symptoms, anthropometric data, and laboratory results were compared, in addition to re-examinations of histological sections from one of the hospitals. RESULTS A total of 400 cases were diagnosed with a female to male ratio of 1.5:1. The incidence rate for 2000 to 2002 was 15.9 cases per 100,000 person-years (95% confidence interval 12.8-19.4), compared with 45.5 cases per 100,000 person-years during 2008 to 2010 (95% confidence interval 40.5-50.9), P < 0.001. The relative frequencies of symptoms and the distribution of histopathological changes were similar in the 2 periods, whereas weight z scores and hemoglobin levels were significantly lower in the first period. CONCLUSIONS We found a 3-fold increase in the incidence rate for CD in the Norwegian pediatric population during the decade 2000 to 2010. Slightly higher weight and hemoglobin levels at diagnosis in the latter period may be due to improved CD awareness. Unaltered relative frequencies of symptoms and histopathological changes in the gut, however, suggest a true increase of CD in Norwegian children.
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25
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Greuter T, Schmidlin S, Lattmann J, Stotz M, Lehmann R, Zeitz J, Scharl M, Misselwitz B, Pohl D, Fried M, Tutuian R, Fasano A, Schoepfer AM, Rogler G, Biedermann L, Vavricka SR. The perspective of celiac disease patients on emerging treatment options and non-celiac gluten sensitivity. Dig Liver Dis 2017; 49:268-272. [PMID: 28034662 DOI: 10.1016/j.dld.2016.11.016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2016] [Revised: 11/27/2016] [Accepted: 11/27/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Non-celiac gluten sensitivity (NCGS) and emerging treatment options are hot topics in the celiac disease (CeD) scientific literature. However, very little is known about the perspective on these issues of CeD patients. METHODS We performed a large patient survey among unselected CeD patients in Switzerland. RESULTS A total of 1689 patients were analyzed. 57.5% have previously heard of NCGS. 64.5% believe in the existence of this entity. Regarding a potential influence of NCGS on CeD awareness, 31.7% show a positive and 27.5% a negative perception. Patients with prior use of alternative medicine and women more often have heard of and believe in the existence of NCGS vs. those never having used alternative methods and men, respectively (66.9 vs. 56.9%, p=0.001 and 78.5 vs. 69.0%, p=0.001; 60.7 vs. 44.2%, p<0.001 and 71.0 vs. 60.8%, p=0.002). Women and patients ≥30 years more often show a negative attitude towards NCGS (32.2% vs. 24.8%, p=0.024 and 32.2% vs. 24.2%, p=0.018). With regard to emerging treatment options for CeD, 43.3% have previously heard of novel agents, more women than men (46.0 vs. 38.0%, p=0.019). CONCLUSIONS Perception of and attitude towards NCGS differ depending on sex, age and prior use of alternative medicine. Knowledge of the progress towards emerging treatment options is currently limited.
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Affiliation(s)
- Thomas Greuter
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Sandra Schmidlin
- Division of Gastroenterology and Hepatology, Triemli Hospital Zurich, Zurich, Switzerland
| | - Jaqueline Lattmann
- Division of Gastroenterology and Hepatology, Triemli Hospital Zurich, Zurich, Switzerland
| | - Matthias Stotz
- Division of Gastroenterology and Hepatology, Triemli Hospital Zurich, Zurich, Switzerland
| | - Romina Lehmann
- Division of Gastroenterology and Hepatology, Triemli Hospital Zurich, Zurich, Switzerland
| | - Jonas Zeitz
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Michael Scharl
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Benjamin Misselwitz
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Daniel Pohl
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Michael Fried
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Radu Tutuian
- Division of Gastroenterology and Hepatology, Spital Tiefenau, Bern, Switzerland
| | - Alessio Fasano
- Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Boston, MA, USA
| | - Alain M Schoepfer
- Division of Gastroenterology and Hepatology, University Hospital Lausanne-CHUV, Lausanne, Switzerland
| | - Gerhard Rogler
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Luc Biedermann
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Stephan R Vavricka
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland; Division of Gastroenterology and Hepatology, Triemli Hospital Zurich, Zurich, Switzerland.
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Cameron RL, Ahmed S, Pollock KGJ. Adverse event monitoring of the human papillomavirus vaccines in Scotland. Intern Med J 2017; 46:452-7. [PMID: 26765074 DOI: 10.1111/imj.13005] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Revised: 12/08/2015] [Accepted: 12/21/2015] [Indexed: 01/09/2023]
Abstract
BACKGROUND Human papillomavirus (HPV) vaccines are currently utilised globally in national immunisation programmes. While evidence from clinical trials and epidemiological studies suggest that the HPV vaccines are both effective and safe, concerns about the safety of the vaccine and scientifically unproven associations with severe adverse events following immunisation have led to dramatic decreases in vaccine uptake in Japan and acceptance issues in other countries. AIM In Scotland, we utilised hospital admissions data to assess the impact of the HPV immunisation programme on the incidence of 60 diagnoses between 2004 and 2014 in both girls and boys; with boys acting as a comparator group. METHODS Tabular and graphical outputs of the number of admissions, the incidence and the incidence ratio of 59 diagnoses were created to assess trends before and after the introduction of the HPV vaccine. Data linkage was utilised to investigate further the increase in Bell palsy diagnoses. RESULTS Fifty-four diagnoses showed no change in incidence following the introduction of the national immunisation programme, and while small increases in incidence were observed for Bell palsy, coeliac disease, ovarian dysfunction, juvenile onset of type 1 diabetes, demyelinating disease and juvenile rheumatoid arthritis, none was statistically significant. CONCLUSIONS Consistent with previous evidence, we present disaggregate data that reiterate the safety of both HPV vaccines.
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Affiliation(s)
- R L Cameron
- Vaccine Preventable Diseases, Health Protection Scotland, Glasgow, UK
| | - S Ahmed
- Vaccine Preventable Diseases, Health Protection Scotland, Glasgow, UK
| | - K G J Pollock
- Vaccine Preventable Diseases, Health Protection Scotland, Glasgow, UK
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27
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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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Belsha D, Bremner R, Thomson M. Indications for gastrointestinal endoscopy in childhood. Arch Dis Child 2016; 101:1153-1160. [PMID: 27246069 DOI: 10.1136/archdischild-2014-306043] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2015] [Revised: 04/18/2016] [Accepted: 05/02/2016] [Indexed: 12/11/2022]
Abstract
Endoscopic examination of the gastrointestinal tract (GIT) for diagnostics and therapy in children has evolved markedly over the last 20 or so years and is now usually undertaken by paediatric endoscopists. Updated diagnostic and management guidelines for common disorders including coeliac disease, gastro-oesophageal reflux disease, eosinophilic oesophagitis and inflammatory bowel disease highlight the central role of endoscopy. Therapeutic endoscopic approaches are also now widely available and further broaden the referral spectrum to include treatment of GIT bleeding, gastrostomy insertion, dilation of strictures and polypectomy. Lastly, the advent of newer technologies allows the examination of hitherto inaccessible areas of the GIT such as the mid-small bowel by wireless capsule video-endoscopy and enteroscopy. We summarise recent current practice and clinical guidelines, focussing on the key indications for referrals that are likely to require endoscopic assessment.
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Affiliation(s)
- D Belsha
- Centre for Paediatric Gastroenterology, Sheffield Children's Hospital, Sheffield, UK
| | - R Bremner
- Centre for Paediatric Gastroenterology, Birmingham Children's Hospital, Birmingham, UK
| | - M Thomson
- Centre for Paediatric Gastroenterology, Sheffield Children's Hospital, Sheffield, UK
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29
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Herpesvirus Infections and Transglutaminase Type 2 Antibody Positivity in Childhood: The Generation R Study. J Pediatr Gastroenterol Nutr 2016; 63:423-30. [PMID: 26881413 DOI: 10.1097/mpg.0000000000001163] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
OBJECTIVES Persistent viral infections have been implicated in the etiology of autoimmune diseases in adulthood, but it is not known whether herpesviruses are associated with the development of celiac disease autoimmunity in childhood. We assessed whether herpesvirus infections are associated with transglutaminase type 2 antibody (TG2A) concentrations in children at 6 years of age. METHODS The present study was embedded within a population-based prospective cohort study. Serum immunoglobulin G levels against Epstein-Barr virus, cytomegalovirus (CMV), and herpes simplex virus type 1 were measured by enzyme-linked immunosorbent assay , and TG2A concentrations with fluorescence enzyme immunoassay in 4420 children at 6 years of age. Children were categorized based on TG2A concentrations into negative (<7 U/mL), positive (≥7-70 U/mL), and strongly positive (≥70 U/mL), that is, 10 times upper limit normal. RESULTS Fifty-nine children (1.3%) were TG2A positive, and of these 31 (53%) had concentrations 70 U/mL or more. Children with TG2A concentrations 70 U/mL or more were less often infected with CMV (adjusted odds ratio (aOR) 0.38, 95% CI 0.14-0.98, P = 0.04) and with any of the 3 viruses (aOR 0.38, 95% CI 0.18-0.78, P < 0.01) than children with TG2A negative concentrations. In addition, children with TG2A concentrations 70 U/mL or more were less often infected with 2 or more viruses than children with TG2A negative concentrations (aOR 0.15, 95% CI 0.03-0.65, P = 0.01). CONCLUSIONS Both CMV single infection and combined CMV, Epstein-Barr virus and/or herpes simplex virus type 1 infections are inversely associated with strongly TG2A positivity. This may indicate a protective effect of herpesvirus infections in the pathogenesis of celiac disease autoimmunity.
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30
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Namatovu F, Olsson C, Lindkvist M, Myléus A, Högberg U, Ivarsson A, Sandström O. Maternal and perinatal conditions and the risk of developing celiac disease during childhood. BMC Pediatr 2016; 16:77. [PMID: 27267234 PMCID: PMC4897811 DOI: 10.1186/s12887-016-0613-y] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Accepted: 06/01/2016] [Indexed: 02/06/2023] Open
Abstract
Background Celiac disease (CD) is increasing worldwide, which might be due to the changing environmental and lifestyle exposures. We aimed to explore how conditions related to maternity, delivery and the neonatal period influence CD onset during childhood. Methods Using Sweden’s national registers we had access to information on 1 912 204 children born between 1991 and 2009, 6 596 of whom developed CD before 15 years of age. Logistic regression analyses were performed to determine how CD is associated with maternity, delivery and the neonatal period. Results Regardless of sex, a reduction in CD risk was observed in children born to mothers aged ≥35 years (odds ratio [OR] 0.8; 95 % confidence interval [CI] 0.7–0.9) and with high maternal income (OR 0.9; 95 % CI 0.8–0.9). Being a second-born child, however, was positively associated with CD. Among boys, elective caesarean delivery increased the risk of CD (OR 1.2; 95 % CI 1.0–1.4), while maternal overweight (OR 0.9; 95 % CI 0.8-0.9), premature rupture of the membrane (OR 0.4; 95 % CI 0.2–0.8) and low birth weight showed a negative association. Girls had an increased CD risk compared to boys and in girls the risk was increased by repeated maternal urinary tract infections (OR 1.1; 95 % CI 1.0–1.2). Conclusions Elective caesarean delivery and repeated maternal urinary tract infections during pregnancy are associated with increased risk of CD onset during childhood, suggesting the role of dysbiosis during early life. High maternal age and high income reduced the risk of CD, which might be due to infant-feeding practices and life style.
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Affiliation(s)
- Fredinah Namatovu
- Department of Public Health and Clinical Medicine, Epidemiology and Global Health, Umeå University, SE-901 87, Umeå, Sweden.
| | - Cecilia Olsson
- Department of Food and Nutrition, Umeå University, Umeå, Sweden
| | - Marie Lindkvist
- Department of Public Health and Clinical Medicine, Epidemiology and Global Health, Umeå University, SE-901 87, Umeå, Sweden
| | - Anna Myléus
- Department of Public Health and Clinical Medicine, Epidemiology and Global Health, Umeå University, SE-901 87, Umeå, Sweden
| | - Ulf Högberg
- Department of Public Health and Clinical Medicine, Epidemiology and Global Health, Umeå University, SE-901 87, Umeå, Sweden.,Department of Women's and Children's Health, Obstetrics and Gynaecology, Uppsala University, Uppsala, Sweden
| | - Anneli Ivarsson
- Department of Public Health and Clinical Medicine, Epidemiology and Global Health, Umeå University, SE-901 87, Umeå, Sweden
| | - Olof Sandström
- Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden
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Fok CY, Sara Holland K, Gil-Zaragozano E, Prosad Paul S. The role of nurses and dietitians in managing paediatric coeliac disease. ACTA ACUST UNITED AC 2016; 25:449-55. [DOI: 10.12968/bjon.2016.25.8.449] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Chi-Yee Fok
- 4th Year Medical Student, University of Bristol
| | | | - Elena Gil-Zaragozano
- Clinical Nurse Specialist in Paediatric Gastroenterology, Bristol Royal Hospital for Children
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Kivelä L, Kaukinen K, Lähdeaho ML, Huhtala H, Ashorn M, Ruuska T, Hiltunen P, Visakorpi J, Mäki M, Kurppa K. Presentation of Celiac Disease in Finnish Children Is No Longer Changing: A 50-Year Perspective. J Pediatr 2015; 167:1109-15.e1. [PMID: 26316370 DOI: 10.1016/j.jpeds.2015.07.057] [Citation(s) in RCA: 67] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2015] [Revised: 07/07/2015] [Accepted: 07/29/2015] [Indexed: 12/23/2022]
Abstract
OBJECTIVES To chart trends in the presentation of celiac disease in a large cohort of Finnish children diagnosed over a period of 48 years. STUDY DESIGN Clinical and serologic data, severity of small-bowel mucosal damage, and presence of associated conditions were gathered from 596 children diagnosed with celiac disease in 1966-2013. The children were divided into 4 groups based on the year of diagnosis (before 1980, 1980-1999, 2000-2009, and 2010-2013), and the variables were compared between the periods. The incidence of celiac disease autoimmunity in 2001-2013 was calculated based on the number of new antibody-positive cases in each year. RESULTS Age at diagnosis rose from median 4.3 years before 1980 to between 7.6 and 9.0 years in the later periods. The severity of clinical presentation, in general, became milder and poor growth less common during the entire study period of 50 years. Percentages of children with classical gastrointestinal presentation decreased, and those with atypical or subclinical presentation increased after the 1990s, these changes leveling off in 2000-2013. Similarly, the severity of small-bowel mucosal damage was milder after the 1990s. The incidence of celiac disease autoimmunity increased in the early 2000s but then fluctuated without a clear trend. There were no significant secular changes in sex distribution, presence of anemia, levels of celiac antibodies, or celiac disease-associated conditions. CONCLUSIONS The clinical and histologic presentation of celiac disease in children became milder, especially in the 1980s and 1990s. However, most of these changes have reached a plateau in recent years.
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Affiliation(s)
- Laura Kivelä
- Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland
| | - Katri Kaukinen
- Department of Internal Medicine, Tampere University Hospital and School of Medicine, University of Tampere, Tampere, Finland
| | - Marja-Leena Lähdeaho
- Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland
| | - Heini Huhtala
- Tampere School of Health Sciences, University of Tampere, Tampere, Finland
| | - Merja Ashorn
- Department of Pediatrics, Lappeenranta Central Hospital, Lappeenranta, Finland
| | - Tarja Ruuska
- Department of Pediatrics, Tampere University Hospital, Tampere, Finland
| | - Pauliina Hiltunen
- Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland
| | - Jarmo Visakorpi
- Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland
| | - Markku Mäki
- Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland
| | - Kalle Kurppa
- Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland.
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Hansen R, Russell RK, Muhammed R. Recent advances in paediatric gastroenterology. Arch Dis Child 2015; 100:886-90. [PMID: 25710546 DOI: 10.1136/archdischild-2014-307089] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2014] [Accepted: 01/28/2015] [Indexed: 12/26/2022]
Abstract
Over the last few years, many changes have been introduced in the diagnosis and management of paediatric gastrointestinal problems. This review highlights the recent developments in Helicobacter pylori infection, eosinophilic oesophagitis, coeliac disease and inflammatory bowel disease.
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Affiliation(s)
- Richard Hansen
- Department of Paediatric Gastroenterology, Hepatology and Nutrition, Royal Hospital for Sick Children, Glasgow, UK
| | - Richard K Russell
- Department of Paediatric Gastroenterology, Hepatology and Nutrition, Royal Hospital for Sick Children, Glasgow, UK
| | - Rafeeq Muhammed
- Department of Paediatric Gastroenterology and Nutrition, Birmingham Children's Hospital, Birmingham, UK
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Verdu EF, Galipeau HJ, Jabri B. Novel players in coeliac disease pathogenesis: role of the gut microbiota. Nat Rev Gastroenterol Hepatol 2015; 12:497-506. [PMID: 26055247 PMCID: PMC5102016 DOI: 10.1038/nrgastro.2015.90] [Citation(s) in RCA: 143] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Several studies point towards alteration in gut microbiota composition and function in coeliac disease, some of which can precede the onset of disease and/or persist when patients are on a gluten-free diet. Evidence also exists that the gut microbiota might promote or reduce coeliac-disease-associated immunopathology. However, additional studies are required in humans and in mice (using gnotobiotic technology) to determine cause-effect relationships and to identify agents for modulating the gut microbiota as a therapeutic or preventative approach for coeliac disease. In this Review, we summarize the current evidence for altered gut microbiota composition in coeliac disease and discuss how the interplay between host genetics, environmental factors and the intestinal microbiota might contribute to its pathogenesis. Moreover, we highlight the importance of utilizing animal models and long-term clinical studies to gain insight into the mechanisms through which host-microbial interactions can influence host responses to gluten.
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Tran TH, Smith C, Mangione RA. Theoretical pharmacokinetic drug alterations in pediatric celiac disease. Expert Opin Drug Metab Toxicol 2015; 11:1539-1550. [PMID: 26155875 DOI: 10.1517/17425255.2015.1065813] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
INTRODUCTION The incidence of pediatric celiac disease has risen and many of these children will receive medications at some time in their life. However, the absorption of drugs in pediatric patients with celiac disease has never been studied. The few studies that do exist have only been performed in adults and indicate that drug concentrations can be altered for some drugs. It is also noteworthy that few researchers have conducted studies to determine if the distribution, metabolism, and excretion of drugs are altered in celiac disease. AREAS COVERED The pharmacokinetics of drugs greatly differ between children and adults. Combined with the pathophysiological changes known to occur with celiac disease, there is compelling evidence to support that drug exposure in pediatric celiac disease may be altered. Relevant characteristics of celiac disease that may affect drug disposition include intestinal atrophy, hypoalbuminemia, reduced CYP3A enzymes, and thyroid dysfunction. EXPERT OPINION The safety and efficacy of drug dosing in children with celiac disease can be enhanced with additional pharmacokinetic studies of commonly prescribed drugs in this population. Ideally, these studies should include drugs that have high bioavailability, are highly protein bound, undergo extensive CYP3A enzyme metabolism, and/or have a narrow therapeutic range.
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Affiliation(s)
- Tran H Tran
- a 1 St. John's University, College of Pharmacy and Health Sciences , 8000 Utopia Parkway, St. Albert Hall, Room 114, Queens, NY 11439, USA +1 202 957 4306 ; +1 718 990 1986 ;
- b 2 Clinical Pharmacy Manager,NewYork-Presbyterian Hospital/Columbia University Medical Center , New York, NY, USA
| | - Candace Smith
- c 3 St. John's University College of Pharmacy and Health Sciences, Chair, Clinical Pharmacy Practice Department , Queens, NY 11439, USA
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Lerner A, Matthias T. Possible association between celiac disease and bacterial transglutaminase in food processing: a hypothesis. Nutr Rev 2015; 73:544-52. [PMID: 26084478 PMCID: PMC4502714 DOI: 10.1093/nutrit/nuv011] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The incidence of celiac disease is increasing worldwide, and human tissue transglutaminase has long been considered the autoantigen of celiac disease. Concomitantly, the food industry has introduced ingredients such as microbial transglutaminase, which acts as a food glue, thereby revolutionizing food qualities. Several observations have led to the hypothesis that microbial transglutaminase is a new environmental enhancer of celiac disease. First, microbial transglutaminase deamidates/transamidates glutens such as the endogenous human tissue transglutaminase. It is capable of crosslinking proteins and other macromolecules, thereby changing their antigenicity and resulting in an increased antigenic load presented to the immune system. Second, it increases the stability of protein against proteinases, thus diminishing foreign protein elimination. Infections and the crosslinked nutritional constituent gluten and microbial transglutaminase increase the permeability of the intestine, where microbial transglutaminases are necessary for bacterial survival. The resulting intestinal leakage allows more immunogenic foreign molecules to induce celiac disease. The increased use of microbial transglutaminase in food processing may promote celiac pathogenesis ex vivo, where deamidation/transamidation starts, possibly explaining the surge in incidence of celiac disease. If future research substantiates this hypothesis, the findings will affect food product labeling, food additive policies of the food industry, and consumer health education.
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Affiliation(s)
- Aaron Lerner
- A. Lerner is with the Pediatric Gastroenterology and Nutrition Unit, Carmel Medical Center, B. Rappaport School of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. T. Matthias is with the Aesku.Kipp Institute, Wendelsheim, Germany.
| | - Torsten Matthias
- A. Lerner is with the Pediatric Gastroenterology and Nutrition Unit, Carmel Medical Center, B. Rappaport School of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. T. Matthias is with the Aesku.Kipp Institute, Wendelsheim, Germany
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Lionetti E, Gatti S, Pulvirenti A, Catassi C. Celiac disease from a global perspective. Best Pract Res Clin Gastroenterol 2015; 29:365-379. [PMID: 26060103 DOI: 10.1016/j.bpg.2015.05.004] [Citation(s) in RCA: 117] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Revised: 04/28/2015] [Accepted: 05/07/2015] [Indexed: 01/31/2023]
Abstract
Celiac disease (CD) is one of the commonest lifelong disorders in countries populated by individuals of European origin, affecting approximately 1% of the general population. This is a common disease also in North Africa, Middle East and India. The widespread diffusion of CD is not surprising given that its causal factors (HLA predisposing genotypes and consumption of gluten-containing cereals) show a worldwide distribution. Further studies are needed to quantify the incidence of CD in apparently "celiac-free" areas such as Sub-Saharan Africa and Far East. Several reports have shown that CD is increasing in frequency in different geographic areas. Genetic factors do not explain the rising incidence during the last decades; environmental or lifestyle factors may be responsible for these changes over time. The majority of patients with CD are still undiagnosed all over the world, leading to debate about the need of screening program.
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Affiliation(s)
- Elena Lionetti
- Department of Paediatrics, University of Catania, Via S. Sofia 78, 95124 Catania, Italy.
| | - Simona Gatti
- Department of Paediatrics, Marche Polytechnic University, Ancona, Via Corridoni 11, 60123 Ancona, Italy.
| | - Alfredo Pulvirenti
- Department of Clinical and Molecular Biomedicine, University of Catania, Via S. Sofia 78, 95124 Catania, Italy.
| | - Carlo Catassi
- Department of Paediatrics, Marche Polytechnic University, Ancona, Via Corridoni 11, 60123 Ancona, Italy; The Division of Paediatric Gastroenterology and Nutrition, Center for Celiac Research, MassGeneral Hospital for Children, 55 Fruit Street, Boston, MA 02114, USA.
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Al-Ajlan AS. Screening of coeliac disease in undetected adults and patients diagnosed with irritable bowel syndrome in Riyadh, Saudi Arabia. Saudi J Biol Sci 2015; 23:462-6. [PMID: 27298578 PMCID: PMC4890252 DOI: 10.1016/j.sjbs.2015.04.015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2015] [Revised: 04/21/2015] [Accepted: 04/27/2015] [Indexed: 12/11/2022] Open
Abstract
The present study is to determine the prevalence and implication of coeliac disease (CD) among adult Saudis and compared to those with diagnosed irritable bowel syndrome. This prospective study was conducted among 980 adults. Out of that, 482 subjects (staff and students of Riyadh Health Science College) were designated as control cohorts for undetected coeliac disease. Furthermore, another contingent of 498 subjects diagnosed with irritable bowel syndrome (IBS) at Prince Salman Hospital and Al-Iman General Hospital also constituted a segment of the overall initial 1020 subjects. Both cases and control were tested for serological markers of coeliac disease (tissues transglutaminase (tTGAs) and endomysial autoantibody (EMAs) and were confirmed by histopathology test. All the positive for cases of coeliac disease were screened for iron deficiency anaemia, Vitamin D deficiency, and osteoporosis and weight assessment. The percentage of coeliac disease in control subjects and patients diagnosed with irritable bowel syndrome (IBS) were found to be 1.9% and 9.6% respectively, about 38% of the total coeliac disease patients are among females of middle age (20–39-years) and 16% of the males in the same age range. Whereas, 20% and 25% of all coeliac disease cases with ages of 40–59 were remarked as females and males respectively. The identical nature and overlap of symptoms of the two conditions could possibly result in misdiagnosis of coeliac diseases or over-diagnosis of irritable bowel syndrome. The findings of the study might also give considerable implications of the disease in the nutritional level which is noticeable.
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Affiliation(s)
- Abdulrahman S Al-Ajlan
- College of Applied Medical Sciences, Department of Clinical Laboratory Sciences, King Saud University, Riyadh, P.O. Box 10219, Riyadh 11433, Saudi Arabia
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Zingone F, West J, Crooks CJ, Fleming KM, Card TR, Ciacci C, Tata LJ. Socioeconomic variation in the incidence of childhood coeliac disease in the UK. Arch Dis Child 2015; 100:466-73. [PMID: 25613988 PMCID: PMC4413865 DOI: 10.1136/archdischild-2014-307105] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2014] [Accepted: 11/21/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND Serological studies indicate that evidence of coeliac disease (CD) exists in about 1% of all children, but we lack estimates of current diagnostic patterns among children and how they vary by socioeconomic group. METHODS We identified all children aged 0-18 years between 1993 and 2012 who were registered with general practices across the UK that contribute to a large population-based general practice database. The incidence of CD was evaluated in each quintile of the Townsend index of deprivation and stratified by age, sex, country and calendar year. RESULTS Among 2,063,421 children, we identified 1247 CD diagnoses, corresponding to an overall CD incidence of 11.9 per 100,000 person-years, which was similar across the UK countries and higher in girls than in boys. We found a gradient of CD diagnosis across socioeconomic groups, with the rate of diagnosis being 80% higher in children from the least-deprived areas than in those from the most-deprived areas (incident rate ratio 1.80, 95% CI 1.45 to 2.22). This pattern held for both boys and girls and across all ages. Across all four countries of the UK, we found similar associations between CD and socioeconomic status. While CD incidence up to age 2 remained stable over the study period, diagnoses at older ages have almost tripled over the past 20 years. CONCLUSIONS Children living in less socioeconomically deprived areas in the UK are more likely to be diagnosed with CD. Increased implementation of diagnostic guidelines could result in better case identification in more-deprived areas.
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Affiliation(s)
- Fabiana Zingone
- Division of Epidemiology and Public Health, City Hospital Campus, University of Nottingham, Nottingham, UK,Department of Medicine and Surgery, University of Salerno, Salerno, Italy
| | - Joe West
- Division of Epidemiology and Public Health, City Hospital Campus, University of Nottingham, Nottingham, UK
| | - Colin J Crooks
- Division of Epidemiology and Public Health, City Hospital Campus, University of Nottingham, Nottingham, UK
| | - Kate M Fleming
- Division of Epidemiology and Public Health, City Hospital Campus, University of Nottingham, Nottingham, UK
| | - Timothy R Card
- Division of Epidemiology and Public Health, City Hospital Campus, University of Nottingham, Nottingham, UK
| | - Carolina Ciacci
- Department of Medicine and Surgery, University of Salerno, Salerno, Italy
| | - Laila J Tata
- Division of Epidemiology and Public Health, City Hospital Campus, University of Nottingham, Nottingham, UK
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Abstract
In Europe and the USA, the mean frequency of celiac disease (CD) in the general population is approximately 1%, with some regional differences, the reasons for which remain elusive. A similar disease prevalence has been found in other countries mostly populated by individuals of European origin, e.g. Australia and Argentina. In Western countries, a true rise in overall CD prevalence of CD has been documented. CD is a common disorder in North Africa, the Middle East and India; however, the diagnostic rate is low in these countries due to low availability of diagnostic facilities and poor disease awareness. The highest CD prevalence in the world (5.6%) has been described in an African population originally living in Western Sahara, the Saharawi, of Arab-Berber origin. The reasons for this high CD frequency are unclear but could be primarily related to recent dietary changes and genetic factors, given the high level of consanguinity of this population. Further studies are needed to quantify the incidence of the celiac condition in apparently 'celiac-free' areas such as Sub-Saharan Africa and the Far East. In many developing countries, the frequency of CD is likely to increase in the near future given the diffuse tendency to adopt Western, gluten-rich dietary patterns. As most cases currently escape diagnosis all over the world, an effort should be made to increase the awareness of CD polymorphism. A cost-effective case-finding policy and new strategies of mass CD screening could significantly reduce the morbidity and mortality associated with untreated disease. The current high prevalence of CD is just the last link in a chain of events started about 10,000 years ago after wheat domestication and diffusion from the Middle East. We hypothesize different mechanisms to explain the so-called evolutionary celiac paradox of co-localization of gluten consumption and HLA CD-predisposing genotypes.
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Zingone F, West J, Auricchio R, Maria Bevilacqua R, Bile G, Borgheresi P, Erminia Bottiglieri M, Caldore M, Capece G, Cristina Caria M, Crudele A, Cuomo R, Lucia Garofano M, Giardullo N, Gerarda Gravina A, Greco L, Iannotta P, Kosova P, Lamanda R, Malamisura B, Marmo R, Napoli G, Nardone G, Pacelli M, Pascarella F, Riccio E, Riegler G, Rispo A, Rocco A, Romano M, Saffiotti O, Saviano P, Sorrentini I, Speranza P, Tolone C, Tortora R, Troncone R, Ciacci C. Incidence and distribution of coeliac disease in Campania (Italy): 2011-2013. United European Gastroenterol J 2015; 3:182-189. [PMID: 25922679 PMCID: PMC4406904 DOI: 10.1177/2050640615571021] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2014] [Accepted: 12/17/2014] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND There exists a wide variation in the reported incidence of coeliac disease in recent decades. We aimed to evaluate the incidence rate of coeliac diagnoses performed in an Italian region, Campania, between 2011 and 2013 and its variation therein. METHODS All coeliac diagnoses made from 2011 to 2013 and registered within the Campania coeliac disease register (CeliacDB) were identified. Incidence rates were analysed by sex, age and province of residence, with a Poisson model fitted to determine incidence rate ratios. RESULTS We found 2049 coeliac disease diagnoses registered in the CeliacDB between 2011 and 2013; 1441 of these patients were female (70.4%) and 1059 were aged less than 19 years (51.7%). The overall incidence of coeliac disease in Campania was 11.8 per 100,000 person-years (95% CI 11.3-12.3) during the study period, with marked variation by age [27.4 per 100,000 person-years (95% CI 25.8-29.1) in children under 19 years of age and 7.3 per 100,000 (95% CI 6.8-7.8) in adults] and sex [16.1 per 100,000 person-years in females (95% CI 15.3-16.9) and 7.2 per 100,000 person-years in males (95% CI 6.6-7.8)]. Coeliac disease incidence was roughly similar in Naples, Salerno, Caserta and Avellino, but about half in Benevento. More than 80% of our study population was diagnosed by the combination of positive antitransglutaminase IgA and Marsh 3. More than half of the patients were symptomatic at the time of coeliac disease diagnosis (39.7% had a classical presentation and 21.1% a non-classical one according to the Oslo definition). CONCLUSIONS Coeliac disease incidence was roughly similar among Campania provinces, except in Benevento where it was about half, probably due to less awareness of coeliac disease in this area. The incidence of coeliac disease in Campania appears to be lower than that reported by most of the previous literature, suggesting the necessity of new coeliac awareness programmes.
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Affiliation(s)
- Fabiana Zingone
- Department of Medicine and Surgery, University of Salerno, Salerno, Italy
- Division of Epidemiology and Public Health, City Hospital Campus, University of Nottingham, Nottingham, UK
- Campania Region Celiac Network, Campania, Italy
| | - Joe West
- Division of Epidemiology and Public Health, City Hospital Campus, University of Nottingham, Nottingham, UK
| | | | | | - Guido Bile
- Campania Region Celiac Network, Campania, Italy
| | | | | | | | | | | | | | | | | | | | | | - Luigi Greco
- Campania Region Celiac Network, Campania, Italy
| | | | | | | | | | | | | | | | | | | | | | | | | | - Alba Rocco
- Campania Region Celiac Network, Campania, Italy
| | | | | | | | | | | | | | | | | | - Carolina Ciacci
- Department of Medicine and Surgery, University of Salerno, Salerno, Italy
- Campania Region Celiac Network, Campania, Italy
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Abstract
Immediately following birth, the gastrointestinal tract is colonized with a complex community of bacteria, which helps shape the immune system. Under conditions of health, the immune system is able to differentiate between innocuous antigens, including food protein and commensals, and harmful antigens such as pathogens. However, patients with celiac disease (CD) develop an intolerance to gluten proteins which results in a pro-inflammatory T-cell mediated immune response with production of anti-gluten and anti-tissue transglutaminase antibodies. This adaptive immune response, in conjunction with activation of innate inflammatory cells, lead to destruction of the small intestinal mucosa. Overall 30% of the global population has genetic risk to develop CD. However, only a small proportion develop CD, suggesting that additional environmental factors must play a role in disease pathogenesis. Alterations in small intestinal microbial composition have recently been associated with active CD, indicating a possible role for the microbiota in CD. However, studies demonstrating causality are lacking. This review will highlight the recent data on the potential role of the microbiota in CD pathogenesis, the potential mechanisms, and discuss future research directions.
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Key Words
- CD, celiac disease
- CTL, cytotoxic T lymphocytes
- DC, dendritic cell
- EC, epithelial cell.
- FISH, fluorescence in situ hybridization
- GALT, gut associated lymphoid tissue
- GFD, gluten-free diet
- GRD, gluten related disorders
- IBD, inflammatory bowel disease
- IEL, intraepithelial lymphocyte
- MLN, mesenteric lymph node
- PBMC, peripheral blood mononuclear cell
- SCFA, short chain fatty acids
- SFB, segmented filamentous bacteria
- TG2, tissue transglutaminase
- Tregs, regulatory T cells
- WT, wild-type
- celiac disease
- gluten related disorders
- immune homeostasis
- microbiota
- oral tolerance
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Affiliation(s)
- Heather J Galipeau
- Farncombe Family Digestive Health Research Institute; McMaster
University; Hamilton, Canada
| | - Elena F Verdu
- Farncombe Family Digestive Health Research Institute; McMaster
University; Hamilton, Canada,Correspondence to: Elena F
Verdu;
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Abstract
PURPOSE OF REVIEW To summarize the recent advances in celiac disease in children. RECENT FINDINGS New clues to the pathogenesis of celiac disease continue to emerge that may implicate the role of microbiome changes, antirotavirus VP7 antibodies, and the Parkinson's disease seven gene in celiac disease. Updated guidelines in pediatrics no longer support biopsies in all patients with celiac disease who have been identified by serology, clinical signs, and genetics. Serology screening of total immunoglobulin A in all patients may not be necessary in select patients. Prevalence and additional diseases associated with celiac disease continue to be elucidated. SUMMARY Our knowledge of celiac disease continues to grow with increasing evidence of the pathogenesis, genetics, diagnosis, and risk factors of the disease. Major changes have been made with respect to the guidelines for pediatric celiac disease, and potential improvements to simplify the algorithms for diagnosis and elimination of unessential testing have been proposed by new studies.
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Abstract
OBJECTIVES The aim of this study was to assess the incidence and clinical pattern of celiac disease (CD) presently diagnosed in Spanish children. METHODS A prospective, multicenter, nationwide registry of new cases of CD in children <15 years was conducted from June 1, 2006 to May 31, 2007. The parameters studied were age at diagnosis, sex, clinical symptoms, associated diseases, nutritional status, CD serology, histological lesions, and HLA-DQ2/-DQ8. The crude incidence rate of CD was calculated as new cases per 1000 live births and as new cases per 100,000 person-years <15 years of age. RESULTS A total of 974 new cases of CD were included. The median age at diagnosis was 2.3 years; 39.5% of CD diagnoses occurred in the first 2 years, 42% between 2 and 6, and 18.4% from 6 to 15. Total number of cases in each age group was 385, 409, and 180, respectively. Regarding clinical presentation 70.9% showed classical symptoms, 21.9% were nonclassical, and 7% were asymptomatic. A total of 95.7% of 931, 94.7% of 611, and 86.7% of 651 children tested positive, respectively, for immunoglobulin A (IgA) anti-transglutaminase type 2 antibodies, IgA endomysial antibodies, and IgA anti-gliadin antibodies. Villous atrophy was observed in 92.4% and increased intraepithelial lymphocytes with crypt hyperplasia in 3.3%. Of the children, 55% had normal growth, and 3.4% were overweight. The HLA phenotype was DQ2: 88.3%, DQ2/DQ8: 8.4%, and DQ8: 2.3%. The incidence rate was 7.9 cases of CD per 1000 live births and 54 cases per 100,000 person-years. CONCLUSIONS In Spain, the most frequent clinical presentation of CD is the classical form, mainly diagnosed during the first 2 years of life. The observed incidence of CD in Spanish children is much higher than the present CD incidence rates observed in other European countries.
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Mooney PD, Hadjivassiliou M, Sanders DS. Emerging drugs for coeliac disease. Expert Opin Emerg Drugs 2014; 19:533-44. [DOI: 10.1517/14728214.2014.959490] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Burger JPW, Roovers EA, Drenth JPH, Meijer JWR, Wahab PJ. Rising incidence of celiac disease in the Netherlands; an analysis of temporal trends from 1995 to 2010. Scand J Gastroenterol 2014; 49:933-41. [PMID: 24873994 DOI: 10.3109/00365521.2014.915054] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE According to screening studies, celiac disease (CD) is prevalent in Western Europe. Actual prevalence tends to be much lower. The width of this actual gap is determined by the balance between disease symptoms and the "case-finding" capabilities of the healthcare system. Therefore, we conducted a nationwide study to determine the temporal trends in the incidence in the Netherlands including a focus on demographic aspects. MATERIALS AND METHODS We performed a nationwide search in the Dutch Pathology Registry (PALGA) to identify all biopsy-proven cases of CD in five different years between 1995 and 2010. Furthermore, demographic profiles and socioeconomic status (SES) of patients were studied. RESULTS The overall incidence of CD increased from 2.72 (confidence interval [CI] 2.46-2.99) in 1995 to 6.65 (CI 6.27-7.06) per 100,000 inhabitants in 2010. No significant regional differences were noticed. In men, rates increased from 2.28 (CI 1.95-2.65) to 4.71 (CI 4.25-5.20) per 100,000 in 2010. In women, the increase was from 3.27 (CI 2.88-3.70) to 8.66 (CI 8.04-9.31) per 100,000 in 2010. A trend toward leveling of incidence was observed from 2008 to 2010. Patients diagnosed during childhood live in areas with a higher SES compared with patients diagnosed at adult age. CONCLUSION The incidence of biopsy-proven CD in the Netherlands increased almost threefold between 1995 and 2010. In areas with a higher SES, relatively more children were diagnosed.
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Affiliation(s)
- Jordy P W Burger
- Department of Gastroenterology and Hepatology, Rijnstate Hospital , Arnhem , The Netherlands
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47
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Abstract
The prevalence of celiac disease (CD) varies greatly, but several reports have shown that CD is increasing in frequency in different geographic areas. The increase in prevalence can be partially attributed to the improvement in diagnostic techniques and disease awareness; however the equally well documented rise in incidence in the last 30-40 years cannot be so easily explained. The new epidemiology of CD is now characterized by an increase of new cases in the historical CD areas (northern Europe and the United States) and more interestingly in a spread of the disease in new regions (Asian countries). A significant change in diet habits, particularly in gluten consumption as well as in infant feeding patterns are probably the main factors that can account for these new trends in CD epidemiology.
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Affiliation(s)
- Carlo Catassi
- *Department of Pediatrics, Università Politecnica delle Marche, 60121, Ancona, Italy †Center for Celiac Research, Massachustetts General Hospital for Children and Celiac Program at Harvard Medical School, Boston, MA
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Dixit R, Lebwohl B, Ludvigsson JF, Lewis SK, Rizkalla-Reilly N, Green PHR. Celiac disease is diagnosed less frequently in young adult males. Dig Dis Sci 2014; 59:1509-12. [PMID: 24445731 DOI: 10.1007/s10620-014-3025-6] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2013] [Accepted: 01/01/2014] [Indexed: 12/13/2022]
Abstract
BACKGROUND The female predominance in celiac disease is difficult to explain because population-based screening studies reveal similar rates for celiac disease-specific autoantibodies in males and females. AIM The aim of this study was to explore the role of age and gender in the presentation of celiac disease. METHODS The frequency of presentation according to age, gender and mode of presentation was determined by analysis of a prospectively maintained database of children and adults seen at a tertiary medical center. RESULTS Of 1,682 patients (68 % female) aged 3 months to 86 years who were diagnosed with celiac disease, age at diagnosis in females peaked at 40-45 years, whereas the age at diagnosis for males had two peaks: 10-15 and 35-40 years. A significantly lower percentage of males in early adulthood were diagnosed compared with males in all other age groups (P < 0.0001). The young and elderly had a more even gender distribution. CONCLUSIONS Based on our analysis, males are diagnosed with celiac disease less frequently than females, especially in early adulthood. There should be more emphasis on the diagnosis of celiac disease among young adult males.
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Affiliation(s)
- Rohit Dixit
- Department of Medicine, Celiac Disease Center, Columbia University College of Physicians and Surgeons, Columbia University, New York, NY, USA
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Affiliation(s)
- Siba P Paul
- Specialty Trainee Year 7 in Paediatric Gastroenterology
| | - Christine Spray
- Consultant in Paediatric Gastroenterology in the Department of Paediatric Gastroenterology, Bristol Royal Hospital for Children, Bristol BS2 8BJ
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Incidence and prevalence of celiac disease and dermatitis herpetiformis in the UK over two decades: population-based study. Am J Gastroenterol 2014; 109:757-68. [PMID: 24667576 PMCID: PMC4012300 DOI: 10.1038/ajg.2014.55] [Citation(s) in RCA: 182] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2013] [Accepted: 02/17/2014] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Few studies have quantified the incidence and prevalence of celiac disease (CD) and dermatitis herpetiformis (DH) nationally and regionally by time and age groups. Understanding this epidemiology is crucial for hypothesizing about causes and quantifying the burden of disease. METHODS Patients with CD or DH were identified in the Clinical Practice Research Datalink between 1990 and 2011. Incidence rates and prevalence were calculated by age, sex, year, and region of residence. Incidence rate ratios (IRR) adjusted for age, sex, and region were calculated with Poisson regression. RESULTS A total of 9,087 incident cases of CD and 809 incident cases of DH were identified. Between 1990 and 2011, the incidence rate of CD increased from 5.2 per 100,000 (95% confidence interval (CI), 3.8-6.8) to 19.1 per 100,000 person-years (95% CI, 17.8-20.5; IRR, 3.6; 95% CI, 2.7-4.8). The incidence of DH decreased over the same time period from 1.8 per 100,000 to 0.8 per 100,000 person-years (average annual IRR, 0.96; 95% CI, 0.94-0.97). The absolute incidence of CD per 100,000 person-years ranged from 22.3 in Northern Ireland to 10 in London. There were large regional variations in prevalence for CD but not DH. CONCLUSIONS We found a fourfold increase in the incidence of CD in the United Kingdom over 22 years, with large regional variations in prevalence. This contrasted with a 4% annual decrease in the incidence of DH, with minimal regional variations in prevalence. These contrasts could reflect differences in diagnosis between CD (serological diagnosis and case finding) and DH (symptomatic presentation) or the possibility that diagnosing and treating CD prevents the development of DH.
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