|
1
|
Gupta M, Graham C, Gupta S. Immune Checkpoint Inhibitor-Associated Celiac Disease: A Retrospective Analysis and Literature Review. Diseases 2024; 12:315. [PMID: 39727645 PMCID: PMC11727056 DOI: 10.3390/diseases12120315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 10/21/2024] [Accepted: 11/16/2024] [Indexed: 12/28/2024] Open
Abstract
INTRODUCTION Immune checkpoint inhibitors (ICI) are used to treat various malignancies. They block the inhibitory signals of tumor cells and enhance the inflammatory cascade, which results in tumor killing. However, this can lead to unchecked inflammation throughout the body, leading to various adverse effects. A rare gastrointestinal adverse effect of ICI therapy is the development of immune-mediated celiac disease. This entity has a similar clinical presentation to the more common ICI-induced enterocolitis. Our study aims to determine the clinical characteristics and optimal treatment strategies for this rare ICI toxicity and differentiate it from ICI-induced enterocolitis. METHODS AND MATERIAL We conducted a retrospective analysis of eight cases of ICI-induced celiac disease and 24 cases of ICI-induced enterocolitis from the literature. Data on patient demographics, clinical history, therapeutic interventions and outcomes were collected. A comparative analysis was performed to identify the key differences between the two groups. RESULTS Patients with ICI-induced celiac disease were more likely to have a pre-existing autoimmune condition and HLA-DQ2 positivity. Significant differences in clinical manifestations, histological findings, and treatment outcomes were observed. Notably, weight loss, nutritional deficiencies and electrolyte abnormalities were more commonly associated with ICI-induced celiac disease. Regarding pathology, duodenal villous blunting was noted more commonly with ICI-induced celiac disease. Initiating a gluten-free diet led to a rapid improvement in patients with ICI-induced celiac disease, while immunosuppressive therapy did not have an impact. CONCLUSION ICI-induced celiac disease is a rare and underrecognized gastrointestinal adverse effect of ICI therapy, often misdiagnosed as ICI-induced enterocolitis. Early recognition and treatment with a gluten-free diet can lead to rapid symptom resolution, sparing patients from unnecessary systemic immunosuppression and the discontinuation of antineoplastic immunotherapy.
Collapse
Affiliation(s)
- Malvika Gupta
- Kasturba Medical College, Manipal Academy of Higher Education, Mangalore 575001, India;
| | - Christopher Graham
- Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN 55455, USA;
| | - Supriya Gupta
- Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN 55455, USA;
| |
Collapse
|
|
2
|
Mollica L, Quaquarini E, Schiepatti A, Travaglino E, Antoci F, Vanoli A, Arpa G, Biagi F, Locati LD. A small bowel adenocarcinoma harboring a DDR2 mutation in a celiac patient. Clin J Gastroenterol 2024; 17:1026-1032. [PMID: 39117782 DOI: 10.1007/s12328-024-02025-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Accepted: 07/23/2024] [Indexed: 08/10/2024]
Abstract
We present the case of a 62-year-old man with a history of celiac disease and IgA deficiency, following a strict gluten-free diet that was admitted to our hospital for recurrent abdominal pain, fatigue and melena. Esophagogastroduodenoscopy and colonoscopy with biopsies were normal. A video-capsule endoscopy was performed and revealed a sub-stenosing, vegetating, and bleeding lesion in the first jejunal loop. He underwent laparotomic surgery with resection of the involved segment with loco-regional lymphadenectomy. The pathological report described a poorly differentiated adenocarcinoma of the jejunum, stage IIIA (pT3pN1). Analysis of next-generation sequencing (NGS) of DNA on the surgical sample revealed a likely pathogenetic variant in exon 15 of the DDR2 gene (c.2003G > A) and a TP53 non-frame-shift deletion (c.585_602del). Considering the risk of recurrence, he was candidate to 6 months of adjuvant chemotherapy with platinum salt and fluoropyrimidine. Thirty-eight months after the diagnosis, the patient is still disease free and in good clinical condition. This is the first described case of SBA with DDR2 mutation. Considering the limited therapeutic options beyond surgery for SBA, molecular analyses could become promising for the search for potential targetable alterations for treatments with new available drugs.
Collapse
Affiliation(s)
- Ludovica Mollica
- Medical Oncology Unit, Istituti Clinici Scientifici Maugeri IRCCS, Via Maugeri, 10 27100, Pavia, Italy
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
| | - Erica Quaquarini
- Medical Oncology Unit, Istituti Clinici Scientifici Maugeri IRCCS, Via Maugeri, 10 27100, Pavia, Italy.
| | - Annalisa Schiepatti
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
- Gastroenterology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
| | - Erica Travaglino
- Anatomic Pathology Unit, Fondazione IRCCS San Matteo Hospital, Pavia, Italy
| | - Francesca Antoci
- Anatomic Pathology Unit, Fondazione IRCCS San Matteo Hospital, Pavia, Italy
| | - Alessandro Vanoli
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Giovanni Arpa
- Anatomical Pathology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
| | - Federico Biagi
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
- Gastroenterology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
| | - Laura Deborah Locati
- Medical Oncology Unit, Istituti Clinici Scientifici Maugeri IRCCS, Via Maugeri, 10 27100, Pavia, Italy
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
| |
Collapse
|
|
3
|
Chalasani A, Ly T, Paramsothy S. A Rare Cause of Abdominal Pain and Weight Loss. Gastroenterology 2024; 167:e9-e13. [PMID: 38331203 DOI: 10.1053/j.gastro.2024.01.047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 01/29/2024] [Accepted: 01/30/2024] [Indexed: 02/10/2024]
Affiliation(s)
- Aashish Chalasani
- Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, New South Wales, Australia.
| | - Theresa Ly
- Department of Anatomical Pathology, NSW Health Pathology, Concord Repatriation General Hospital, Sydney, New South Wales, Australia; Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
| | - Sudarshan Paramsothy
- Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, New South Wales, Australia; Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia; Faculty of Medicine Health and Human Science, Macquarie University, Sydney, New South Wales, Australia
| |
Collapse
|
|
4
|
Falcomer AL, de Lima BR, Farage P, Fabris S, Ritter R, Raposo A, Teixeira-Lemos E, Chaves C, Zandonadi RP. Enhancing life with celiac disease: unveiling effective tools for assessing health-related quality of life. Front Immunol 2024; 15:1396589. [PMID: 38742113 PMCID: PMC11089154 DOI: 10.3389/fimmu.2024.1396589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Accepted: 04/15/2024] [Indexed: 05/16/2024] Open
Abstract
Celiac disease (CD) is an autoimmune chronic enteropathy provoked by gluten ingestion in genetically predisposed individuals. Considering it´s only safe treatment is a lifelong gluten-free diet, the burden of living with the disease becomes evident, as well as the need to assess CD health-related quality of life (HRQOL). This review aims to identify and analyze the instruments used to evaluate the HRQOL of adults with CD. This integrative review using a systematic approach was designed to achieve high scientific standards. Accordingly, the search strategy was developed and executed as recommended by the guideline of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Detailed individual searches were developed to Pubmed, Science Direct, Scopus, Web of Science, and Google Scholar. After careful analysis of the papers, 43 studies were included, in which seven instruments were identified: Celiac Disease Questionnaire (CDQ) (n=21), Celiac Disease Specific Quality of Life Instrument (CD-QOL) (n=17), Celiac Disease Assessment Questionnaire (CDAQ) (n=4), CeliacQ-7 (n=1), CeliacQ-27 (n=1), Black and Orfila´s self-developed instrument (n=1) and the Coeliac Disease Quality of Life Questionnaire (CDQL) (n=1). The CDQ and CD-QOL were the two most applied instruments. Since the first focuses on the physical and mental symptoms related to the disease and the second focuses on the emotional repercussions of adhering to the GFD treatment for life (dysphoria), the CDQ application is an interesting option for countries that struggle with public policies for CD patients and patients with active CD. The CD-QOL could be used for countries with strict regulations for CD and gluten-free products and populations in remission. When comparing results among different populations, it is preferable to utilize culturally validated instruments, which have been applied across multiple countries, providing greater comparability between study findings.
Collapse
Affiliation(s)
- Ana Luísa Falcomer
- Department of Nutrition, Faculty of Health Sciences, University of Brasília, Brasília, Brazil
- Department of Nutrition, Centro Universitário IESB, Brasília, Brazil
| | - Bernardo Romão de Lima
- Department of Nutrition, Faculty of Health Sciences, University of Brasília, Brasília, Brazil
- Department of Nutrition, Centro Universitário IESB, Brasília, Brazil
| | - Priscila Farage
- Faculty of Nutrition (FANUT), Federal University of Goiás, Goiânia, Brazil
| | - Samantha Fabris
- Department of Nutrition, Faculty of Health Sciences, University of Brasília, Brasília, Brazil
| | - Ruth Ritter
- Department of Nutrition, Faculty of Health Sciences, University of Brasília, Brasília, Brazil
| | - António Raposo
- CBIOS (Research Center for Biosciences and Health Technologies), Universidade Lusófona de Humanidades e Tecnologias, Lisboa, Portugal
| | | | - Cláudia Chaves
- ESSV, Centre for Studies in Education and Innovation (CI&DEI), Polytechnic University of Viseu, Viseu, Portugal
| | - Renata Puppin Zandonadi
- Department of Nutrition, Faculty of Health Sciences, University of Brasília, Brasília, Brazil
| |
Collapse
|
|
5
|
Ciacci C, De Micco I, Di Stefano M, Mengoli C. Celiac disease in adult patients. PEDIATRIC AND ADULT CELIAC DISEASE 2024:103-123. [DOI: 10.1016/b978-0-443-13359-6.00001-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
6
|
Schiepatti A, Maimaris S, Raju SA, Green OL, Mantica G, Therrien A, Flores-Marin D, Linden J, Fernández-Bañares F, Esteve M, Leffler D, Biagi F, Sanders DS. Persistent villous atrophy predicts development of complications and mortality in adult patients with coeliac disease: a multicentre longitudinal cohort study and development of a score to identify high-risk patients. Gut 2023; 72:2095-2102. [PMID: 37364982 PMCID: PMC10579485 DOI: 10.1136/gutjnl-2023-329751] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Accepted: 06/01/2023] [Indexed: 06/28/2023]
Abstract
OBJECTIVE Persistent villous atrophy (pVA) in coeliac disease (CD) despite a gluten-free diet (GFD) has unclear meaning. We aimed to (i) study the relationship between pVA and long-term outcomes and (ii) develop a score to identify patients at risk of pVA. DESIGN This is a multicentre retrospective-prospective study consisting of a study cohort (cohort 1) and an external validation cohort (cohort 2) of patients with biopsy-proven CD diagnosed between 2000 and 2021. Cohort 1 was used to (i) compare long-term outcomes between patients with and without pVA (Marsh ≥3a) at follow-up biopsy and (ii) to develop a score to evaluate the risk of pVA, which was validated in cohort 2. RESULTS Of 2211 patients, 694 (31%) underwent follow-up duodenal biopsy and were included in the study cohort (491F, 44±16 years). 157/694 (23%) had pVA. Risk of complications (HR 9.53, 95% CI 4.77 to 19.04, p<0.001) and mortality (HR 2.93, 95% CI 1.43 to 6.02, p<0.01) were increased in patients with pVA. A 5-point score was developed and externally validated (receiver operating characteristic area under the curve 0.78, 95% CI 0.68 to 0.89) to stratify patients by risk of pVA: low (0-1 points, 5% pVA), intermediate (2 points, 16% pVA) and high (3-5 points, 73% pVA). Predictors for pVA used in the score were age at diagnosis ≥45 years (OR 2.01, 95% CI 1.21 to 3.34, p<0.01), classical pattern of CD (OR 2.14, 95% CI 1.28 to 3.58, p<0.01), lack of clinical response to GFD (OR 2.40, 95% CI 1.43 to 4.01, p<0.001) and poor GFD adherence (OR 48.9, 95% CI 26.1 to 91.8, p<0.001). CONCLUSIONS Risk of complications and mortality were increased in patients with pVA. We developed a score to identify patients at risk of pVA and in need of histological reassessment and closer follow-up.
Collapse
Affiliation(s)
- Annalisa Schiepatti
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
- Gastroenterology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
| | - Stiliano Maimaris
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
- Gastroenterology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
| | - Suneil A Raju
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK
| | - Olivia L Green
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK
| | - Giulia Mantica
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
| | - Amelie Therrien
- Celiac Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - David Flores-Marin
- Celiac Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Justin Linden
- Celiac Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Fernando Fernández-Bañares
- Department of Gastroenterology, Hospital Universitari Mutua Terrassa, Terrassa, Spain
- Centro de Investigación biomédica en red de enfermedades hepáticas y digestivas (CIBEREHD), Madrid, Spain
| | - Maria Esteve
- Department of Gastroenterology, Hospital Universitari Mutua Terrassa, Terrassa, Spain
- Centro de Investigación biomédica en red de enfermedades hepáticas y digestivas (CIBEREHD), Madrid, Spain
| | - Daniel Leffler
- Celiac Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Federico Biagi
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
- Gastroenterology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
| | - David S Sanders
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK
| |
Collapse
|
|
7
|
Chaves C, Raposo A, Zandonadi RP, Nakano EY, Ramos F, Teixeira-Lemos E. Quality of Life Perception among Portuguese Celiac Patients: A Cross-Sectional Study Using the Celiac Disease Questionnaire (CDQ). Nutrients 2023; 15:2051. [PMID: 37432200 DOI: 10.3390/nu15092051] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 04/21/2023] [Accepted: 04/22/2023] [Indexed: 07/12/2023] Open
Abstract
The aim of this study is to assess Portuguese celiac patients' quality of life (QoL) perception. A cross-sectional study was performed with a non-probability convenience sample of Portuguese celiac patients using an online self-administered celiac disease quality of life questionnaire (CDQ), previously validated for the Portuguese population. The final sample comprised 234 celiac patients, which included the following: primarily women (69.2%); aged between 18 and 49 years old (56.4%); with a partner (60.6%); with a high educational level (58.9%-graduated or post-graduated); following a gluten-free diet (GFD) (55.1%); and not using antidepressants (93.1%). The Portuguese CDQ presented good reliability and responsiveness in this sample of Portuguese celiac patients. In general, the CDQ in Portugal was affected by age at diagnosis (p = 0.017), educational level (p = 0.005), and compliance with GFD (p = 0.034). The emotion domain was affected only by using antidepressants (p = 0.036). The social domain was affected by gender (females had lower rates, p = 0.016), age at diagnosis (p = 0.009), educational level (p = 0.000), and compliance with a GFD (p = 0.002). The worries domain did not differ according to socioeconomic data. The symptoms domain was affected by compliance with GFD (p = 0.000), age at diagnosis (p = 0.000), and educational level (p = 0.014). Data on celiac QoL is essential to support the formulation and implementation of strategies to minimize the issues suffered by celiac patients, lowering their physical, emotional, and social burden. Additionally, data on Portuguese celiac disease patients using the CDQ will allow future comparative research among celiac populations from different countries.
Collapse
Affiliation(s)
- Cláudia Chaves
- ESSV, Centre for Studies in Education and Innovation (CI&DEI), Polytechnic University of Viseu, 3504-510 Viseu, Portugal
| | - António Raposo
- CBIOS (Research Center for Biosciences and Health Technologies), Universidade Lusófona de Humanidades e Tecnologias, Campo Grande 376, 1749-024 Lisboa, Portugal
| | - Renata Puppin Zandonadi
- University of Brasília, Faculty of Health Sciences, Nutrition Department, Campus Universitário Darcy Ribeiro, Brasília 70910-900, Brazil
| | | | - Fernando Ramos
- Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal
- Associated Laboratory for Green Chemistry (LAQV) of the Network of Chemistry and Technology (REQUIMTE), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
| | - Edite Teixeira-Lemos
- CERNAS-IPV, Research Centre, Polytechnic University of Viseu, 3504-510 Viseu, Portugal
| |
Collapse
|
|
8
|
Scalvini D, Schiepatti A, Maimaris S, Cosentini E, Muscia R, Gregorio V, Roda E, Fassio F, Baiardi P, Locatelli CA, Biagi F. Humoral immunogenicity of COVID-19 vaccines in patients with coeliac disease and other noncoeliac enteropathies compared to healthy controls. Eur J Gastroenterol Hepatol 2023; 35:167-173. [PMID: 36574307 DOI: 10.1097/meg.0000000000002484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
OBJECTIVES Data are lacking on the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients affected by coeliac disease, Whipple's disease and other noncoeliac enteropathies (NCE), characterised by primary or drug-related immunosuppression. We aimed to assess humoral response to SARS-CoV-2 vaccination in these patients compared to controls. METHODS Between December 2021 and January 2022, IgG anti-SARS-CoV-2 spike protein antibodies were measured in serum samples of coeliac disease, Whipple's disease and NCE patients attending our gastroenterology outpatient clinic for follow-up, who had received their first SARS-CoV-2 vaccination dose 3-6-9 (±1) months prior. Humoral response was compared with healthy controls (vaccinated healthcare workers undergoing serological screening), matched for gender, age, and time from first vaccine dose at sample collection. RESULTS A total of 120 patients [107 coeliac disease; 10 Whipple's disease; 2 common-variable immunodeficiency (CVID); 1 idiopathic villous atrophy; 77 F, 42 ± 16 years] and 240 matched controls (154 F, 43 ± 14 years) were enrolled. At 3, 6 and 9 months, humoral response in coeliac patients was not impaired compared to controls. Inadequate humoral response to vaccination was significantly more common among Whipple's disease patients than controls ( P < 0.001). Patients on immunosuppressive therapy had markedly lower IgG anti-SARS-CoV-2 antibody titres (median 14 vs. 520 BAU/mL, P < 0.001). As expected, patients with CVID showed no humoral response to vaccination. CONCLUSIONS Humoral immunogenicity of SARS-CoV-2 vaccines was not reduced in coeliac disease patients compared to controls, although it was in Whipple's disease and CVID patients. Post-vaccination humoral response should be monitored in patients with Whipple's disease and chronic enteropathies on immunosuppressive therapy in order to schedule vaccine booster doses.
Collapse
Affiliation(s)
- Davide Scalvini
- Dipartimento di Medicina Interna e Terapia Medica, University of Pavia
- Istituti Clinici Scientifici Maugeri, IRCCS, Gastroenterology Unit of Pavia Institute
| | - Annalisa Schiepatti
- Dipartimento di Medicina Interna e Terapia Medica, University of Pavia
- Istituti Clinici Scientifici Maugeri, IRCCS, Gastroenterology Unit of Pavia Institute
| | - Stiliano Maimaris
- Dipartimento di Medicina Interna e Terapia Medica, University of Pavia
- Istituti Clinici Scientifici Maugeri, IRCCS, Gastroenterology Unit of Pavia Institute
| | - Emanuele Cosentini
- Dipartimento di Medicina Interna e Terapia Medica, University of Pavia
- Istituti Clinici Scientifici Maugeri, IRCCS, Gastroenterology Unit of Pavia Institute
| | - Roberta Muscia
- Dipartimento di Medicina Interna e Terapia Medica, University of Pavia
- Istituti Clinici Scientifici Maugeri, IRCCS, Gastroenterology Unit of Pavia Institute
| | - Virginia Gregorio
- Dipartimento di Medicina Interna e Terapia Medica, University of Pavia
- Istituti Clinici Scientifici Maugeri, IRCCS, Gastroenterology Unit of Pavia Institute
| | - Elisa Roda
- Istituti Clinici Scientifici Maugeri, IRCCS, Toxicology Unit, Poison Centre and National Toxicology Information Centre of Pavia Institute
| | - Federico Fassio
- Department of Public Health, Experimental and Forensic Medicine - Unit of Biostatistics and Clinical Epidemiology - University of Pavia
| | - Paola Baiardi
- Istituti Clinici Scientifici Maugeri, IRCCS, Direzione Scientifica of Pavia Institute, Pavia, Italy
| | - Carlo Alessandro Locatelli
- Istituti Clinici Scientifici Maugeri, IRCCS, Toxicology Unit, Poison Centre and National Toxicology Information Centre of Pavia Institute
| | - Federico Biagi
- Dipartimento di Medicina Interna e Terapia Medica, University of Pavia
- Istituti Clinici Scientifici Maugeri, IRCCS, Gastroenterology Unit of Pavia Institute
| |
Collapse
|
|
9
|
Borrelli DE Andreis F, Schiepatti A, Gibiino G, Fabbri C, Baiardi P, Biagi F. Is it time to rethink the burden of non-coeliac gluten sensitivity? A systematic review. Minerva Gastroenterol (Torino) 2022; 68:442-449. [PMID: 34929997 DOI: 10.23736/s2724-5985.21.03077-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
INTRODUCTION Non-coeliac gluten sensitivity (NCGS) is still a poorly defined clinical condition. This review aims to describe the clinical features of subjects with a symptomatic response to gluten intake, and to estimate the prevalence of NCGS. EVIDENCE ACQUISITION Literature search was conducted in accordance with PRISMA recommendations. The PubMed database was searched for original articles until 1st June 2020. EVIDENCE SYNTHESIS We identified 30 relevant articles, including 14 studies that investigated NCGS through a double-blind, placebo-controlled crossover trial (DBPCC), and 16 that examined the role of gluten in causing symptoms without a DBPCC. We found that regardless of the diagnostic work up, gluten-sensitive patients were predominately middle-aged females complaining of abdominal pain, bloating and diarrhea. The pooled prevalence of NCGS after DBPCC was 24% (5-34%). Subjects with irritable bowel syndrome or self-reporting gluten intolerance accounted for the vast majority of the patients who did not start a DBPCC. A symptomatic response to a gluten-free diet (GFD) occurred in between 7% and 93% of patients. No data on long-term outcomes of NCGS individuals were reported. CONCLUSIONS Clinical features of NCGS patients did not differ among all the included studies, whereas prevalence figures are rather heterogeneous. Long-term benefit of a GFD on these patients still needs to be ascertained.
Collapse
Affiliation(s)
- Federica Borrelli DE Andreis
- Gastroenterology Unit, IRCCS Pavia Institute, Istituti Clinici Scientifici Maugeri, University of Pavia, Pavia, Italy
| | - Annalisa Schiepatti
- Gastroenterology Unit, IRCCS Pavia Institute, Istituti Clinici Scientifici Maugeri, University of Pavia, Pavia, Italy -
| | - Giulia Gibiino
- Gastroenterology and Digestive Endoscopy Unit, Morgagni-Pierantoni Hospital, Forlì, Italy.,M. Bufalini Hospital, AUSL Romagna, Cesena, Italy
| | - Carlo Fabbri
- Gastroenterology and Digestive Endoscopy Unit, Morgagni-Pierantoni Hospital, Forlì, Italy.,M. Bufalini Hospital, AUSL Romagna, Cesena, Italy
| | - Paola Baiardi
- Scientific Direction, Istituti Clinici Scientifici Maugeri, Pavia, Italy
| | - Federico Biagi
- Gastroenterology Unit, IRCCS Pavia Institute, Istituti Clinici Scientifici Maugeri, University of Pavia, Pavia, Italy
| |
Collapse
|
|
10
|
Costantino A, Aversano GM, Lasagni G, Smania V, Doneda L, Vecchi M, Roncoroni L, Pastorello EA, Elli L. Diagnostic management of patients reporting symptoms after wheat ingestion. Front Nutr 2022; 9:1007007. [PMID: 36276818 PMCID: PMC9582535 DOI: 10.3389/fnut.2022.1007007] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Accepted: 09/12/2022] [Indexed: 12/11/2022] Open
Abstract
Many patients report symptoms after wheat ingestion experiencing a wide spectrum of clinical manifestations. Three possible diagnoses have been recognized: celiac disease (CD), wheat allergy (WA), and non-celiac (gluten) wheat sensitivity (NCGS/NCWS). CD is a chronic immune-mediated disease of the small bowel caused by exposure to dietary gluten in genetically predisposed individuals, with a prevalence of approximately 1%. It is characterized by mucosal inflammation and atrophy following exposure to gluten and improvement after gluten withdrawal. Food allergies are immunological responses to a food antigen. WA is the expression of an immunologically mediated process that can be immunoglobulin E (IgE) or non-IgE mediated; its many symptoms include urticaria/angioedema, asthma, rhinitis, and anaphylaxis. NCGS/NCWS is characterized by gastrointestinal and/or extra-intestinal symptoms after ingestion of gluten-containing food in subjects not affected by CD or WA. The aim of this review is to help physicians and nutritionists diagnose the cause of symptoms reported after wheat ingestion, thus avoiding patient frustration, inappropriate testing, and incorrect or missed diagnoses. An algorithm for the diagnostic approach in these patients is provided, to help to diagnose CD, WA, NCGS/NCWS or to identify possible functional disorders as the wheat-sensitive irritable bowel syndrome. A personalized approach, regular follow-up, and the help of a skilled healthcare professional are mandatory for patients with symptoms following wheat ingestion is provided. A gluten-free-diet is often recommended for patients with self-reported gluten/wheat-dependent symptoms; for patients with symptoms similar to those of functional diseases while there is evidence that a low-FODMAP diet could be the first option.
Collapse
Affiliation(s)
- Andrea Costantino
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy,Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Gloria Maria Aversano
- Department of Internal Medicine, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Giovanni Lasagni
- Department of Allergology and Immunology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Veronica Smania
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Luisa Doneda
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
| | - Maurizio Vecchi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy,Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Leda Roncoroni
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
| | | | - Luca Elli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy,*Correspondence: Luca Elli,
| |
Collapse
|
|
11
|
Zingone F, Maimaris S, Auricchio R, Caio GPI, Carroccio A, Elli L, Galliani E, Montagnani M, Valiante F, Biagi F. Guidelines of the Italian societies of gastroenterology on the diagnosis and management of coeliac disease and dermatitis herpetiformis. Dig Liver Dis 2022; 54:1304-1319. [PMID: 35858884 DOI: 10.1016/j.dld.2022.06.023] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Revised: 05/11/2022] [Accepted: 06/19/2022] [Indexed: 12/29/2022]
Abstract
INTRODUCTION Coeliac disease and dermatitis herpetiformis are immune-mediated diseases triggered by the consumption of gluten in genetically predisposed individuals. These guidelines were developed to provide general practitioners, paediatricians, gastroenterologists, and other clinicians with an overview on the diagnosis, management and follow-up of coeliac patients and those with dermatitis herpetiformis. METHODS Guidelines were developed by the Italian Societies of Gastroenterology. Following a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the certainty of the evidence. Statements and recommendations were developed by working groups consisting of gastroenterologists and a paediatrician with expertise in this field. RESULTS These guidelines provide a practical guidance for the diagnosis, management and follow-up of coeliac patients and dermatitis herpetiformis in children and adults, both in primary care and in specialist settings. We developed four sections on diagnosis, gluten-free diet, follow-up and risk of complications in adults, one section focused on diagnosis and follow-up in children and one on the diagnosis and management of dermatitis herpetiformis. CONCLUSIONS These guidelines may support clinicians to improve the diagnosis and management of patients with coeliac disease.
Collapse
Affiliation(s)
- Fabiana Zingone
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Italy; Gastroenterology Unit, Azienda Ospedale Università, Padova, Italy.
| | - Stiliano Maimaris
- Dipartimento di Medicina Interna e Terapia Medica, Università di Pavia, Italia
| | - Renata Auricchio
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Giacomo Pietro Ismaele Caio
- Department of Morphology, Surgery and Experimental Medicine, St. Anna Hospital, University of Ferrara, Ferrara, Italy
| | - Antonio Carroccio
- Unit of Internal Medicine, "V. Cervello" Hospital, Ospedali Riuniti "Villa Sofia-Cervello", 90146 Palermo, University of Palermo, Italy
| | - Luca Elli
- Gastroenterology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Ermenegildo Galliani
- UOC Gastroenterologia ed Endoscopia Digestiva, AULSS1 Dolomiti Veneto, Ospedale San Martino, Belluno, Italy
| | - Marco Montagnani
- Department of Medical and Surgical Sciences, University of Bologna, Italy; Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy
| | - Flavio Valiante
- UOC Gastroenterologia ed Endoscopia Digestiva, AULSS1 Dolomiti Veneto, Feltre (BL), Italy
| | - Federico Biagi
- Istituti Clinici Maugeri, IRCCS, Unità di Gastroenterologia dell'Istituto di Pavia, Italy
| |
Collapse
|
|
12
|
Caratelli V, Moccia M, Paggioro FR, Fiore L, Avitabile C, Saviano M, Imbriani AL, Dardano P, De Stefano L, Moscone D, Colabufo NA, Ghafir El Idrissi I, Russo F, Riezzo G, Giannelli G, Arduini F. Liquid Biopsy beyond Cancer: A miRNA Detection in Serum with Electrochemical Chip for Non‐Invasive Coeliac Disease Diagnosis. ADVANCED NANOBIOMED RESEARCH 2022. [DOI: 10.1002/anbr.202200015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Affiliation(s)
- Veronica Caratelli
- Department of Chemical Science and Tecnologies University of Rome “Tor Vergata” Via della Ricerca Scientifica 00133 Rome Italy
| | - Maria Moccia
- Institute of Crystallography National Research Council (CNR) Via G. Amendola 122/O 70126 Bari Italy
| | - Francesca R. Paggioro
- Department of Chemical Science and Tecnologies University of Rome “Tor Vergata” Via della Ricerca Scientifica 00133 Rome Italy
| | - Luca Fiore
- Department of Chemical Science and Tecnologies University of Rome “Tor Vergata” Via della Ricerca Scientifica 00133 Rome Italy
| | - Concetta Avitabile
- Institute of Crystallography National Research Council (CNR) Via G. Amendola 122/O 70126 Bari Italy
| | - Michele Saviano
- Institute of Crystallography National Research Council (CNR) Via G. Amendola 122/O 70126 Bari Italy
| | - Anna Lisa Imbriani
- Biochemical Systems International S.p.A. Loc, Palazzo del Pero, 23 52100 Arezzo Italy
| | - Principia Dardano
- Department of Physical Sciences and Matter Technology Institute for Applied Science and Intelligent Systems National Research Council Via Pietro Castellino 111 80131 Napoli Italy
| | - Luca De Stefano
- Department of Physical Sciences and Matter Technology Institute for Applied Science and Intelligent Systems National Research Council Via Pietro Castellino 111 80131 Napoli Italy
| | - Danila Moscone
- Department of Chemical Science and Tecnologies University of Rome “Tor Vergata” Via della Ricerca Scientifica 00133 Rome Italy
| | - Nicola A. Colabufo
- Department of Pharmacy-Pharmaceutical Science University of Bari Aldo Moro Via Orabona 4 70125 Bari Italy
- Biofordrug S.R.L Spin-off of the University of Bari Aldo Moro Via Dante 99, Triggiano 70019 Bari Italy
| | - Imane Ghafir El Idrissi
- Department of Pharmacy-Pharmaceutical Science University of Bari Aldo Moro Via Orabona 4 70125 Bari Italy
- Biofordrug S.R.L Spin-off of the University of Bari Aldo Moro Via Dante 99, Triggiano 70019 Bari Italy
| | - Francesco Russo
- National Institute of Gastroenterology “S. de Bellis” Research Hospital Castellana Grotte 70013 Bari Italy
| | - Giuseppe Riezzo
- National Institute of Gastroenterology “S. de Bellis” Research Hospital Castellana Grotte 70013 Bari Italy
| | - Gianluigi Giannelli
- National Institute of Gastroenterology “S. de Bellis” Research Hospital Castellana Grotte 70013 Bari Italy
| | - Fabiana Arduini
- Department of Chemical Science and Tecnologies University of Rome “Tor Vergata” Via della Ricerca Scientifica 00133 Rome Italy
- SENSE4MED S.R.L. Via della ricerca scientifica 00133 Rome Italy
| |
Collapse
|
|
13
|
Wang M, Kong WJ, Feng Y, Lu JJ, Hui WJ, Liu WD, Li ZQ, Shi T, Cui M, Sun ZZ, Gao F. Epidemiological, clinical, and histological presentation of celiac disease in Northwest China. World J Gastroenterol 2022; 28:1272-1283. [PMID: 35431514 PMCID: PMC8968484 DOI: 10.3748/wjg.v28.i12.1272] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Revised: 11/16/2021] [Accepted: 02/27/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Research on celiac disease (CD) in northwest China is still in its infancy. At present, large-sample data on the epidemiological, clinical, and pathological characteristics of CD are limited.
AIM To investigate the epidemiological, clinical, and pathological characteristics of CD in northwest China.
METHODS The clinical data of 2884 patients with gastrointestinal (GI) symptoms were retrospectively analyzed. Total immunoglobulin A (IgA) and anti-tissue transglutaminase (tTG) IgA levels were examined in all patients. Gastroscopy and colonoscopy were performed in patients with positive anti-tTG IgA and deficient total IgA levels. Atrophy of the duodenal and ileal villi was examined and histopathological examinations were performed. The modified Marsh–Oberhuber classification system was used to grade villous atrophy in the duodenum or distal ileum. The patients’ Helicobacter pylori (H. pylori) infection status was compared in terms of clinical presentation and Marsh grade. Statistical analyses were performed using the t-test or chi-square test.
RESULTS Among the 2884 patients, 73 were positive for serum anti-tTG IgA, and 50 were diagnosed with CD. The CD detection rate was significantly higher in Kazakhs (4.39%) than in Uyghurs (2.19%), Huis (0.71%), and Hans (0.55%). The main symptoms of CD were chronic diarrhea, anorexia, anemia, fatigue, weight loss, sleep disorders, osteopenia, and osteoporosis. The body mass index of patients with CD was significantly lower than that of patients without CD. A total of 69 patients with positive serum anti-tTG IgA and two patients with deficient total IgA levels underwent GI endoscopy. Endoscopy revealed crypt hyperplasia and/or duodenal villous atrophy, mainly manifested as nodular mucosal atrophy, grooves, and fissures. The difference in H. pylori infection rates was not statistically significant between CD and non-CD patients but was significantly different among CD patients with different Marsh grades.
CONCLUSION Among the patients with GI symptoms in northwestern China, the prevalence of CD was more in the Uyghur and Kazakh populations. H. pylori infection may be associated with CD severity.
Collapse
Affiliation(s)
- Man Wang
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Wen-Jie Kong
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Yan Feng
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Jia-Jie Lu
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Wen-Jia Hui
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Wei-Dong Liu
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Zi-Qiong Li
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Tian Shi
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Mei Cui
- Department of Pathology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Zhen-Zhu Sun
- Department of Pathology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Feng Gao
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| |
Collapse
|
|
14
|
Gluten-free diet adherence and implications for the diagnosis of coeliac disease. Pathology 2022; 54:606-610. [PMID: 35337666 DOI: 10.1016/j.pathol.2021.12.297] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Revised: 11/21/2021] [Accepted: 12/06/2021] [Indexed: 12/19/2022]
Abstract
Coeliac disease (CD) is an autoimmune disorder caused by the ingestion of gluten containing foods in genetically susceptible individuals, with a worldwide prevalence of up to 1%. Currently, the only available treatment is a gluten-free diet (GFD). Screening for CD is primarily performed using serum based testing for anti-tissue transglutaminase (tTG) antibodies. Patients must be on a gluten containing diet at the time of testing to ensure an accurate serological result. We investigated the prevalence of a GFD in hospital clinic settings and the general population using survey data to estimate the proportion of CD patients that may be misdiagnosed for CD based on serological tests. Data were collected at clinics of a metropolitan hospital in Sydney, Australia, and the general population. Data from Medicare Benefits Scheme and tTG results from a large Australian private laboratory were reviewed for comparison. Of 778 participants who responded to the survey, 58 (7.5%) were on a GFD. More patients attending the immunology (15.9%) and gastroenterology (12.1%) clinics adopted a GFD than those attending the diabetes (2.6%) or endocrinology (6.1%) clinics, or in the general population (4.3%). More females than males excluded gluten from their diet (p<0.0001). Medicare statistics between 2013 and 2019 demonstrated an increase in CD serological testing; however, tTG data from a private pathology highlighted a stable level of elevated tTG antibodies of 3% of total tests performed. The high number of individuals on a GFD is likely impacting the ability to accurately diagnose CD using serum-based testing.
Collapse
|
|
15
|
20-Year Follow-up Study of Celiac Patients Identified in a Mass School Screening: Compliance to Gluten-Free Diet and Autoimmunity. J Pediatr Gastroenterol Nutr 2022; 74:91-95. [PMID: 34508048 DOI: 10.1097/mpg.0000000000003295] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVES To investigate the compliance to the gluten-free diet in a cohort of adult celiac patients 20 years after the diagnosis, received in childhood through a mass screening. METHODS This is an observational historic cohort follow-up study. It was carried out at the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy. Two matched cohorts of adult celiac patients, diagnosed in childhood through a mass screening or for symptoms were enrolled. Adherence to the gluten free-diet and development of autoimmune diseases were investigated through a questionnaire administrated in the course of a phone interview.The primary study outcome was the adherence to the gluten-free diet, measured through the Biagi questionnaire, in the two cohorts of celiac patients. RESULTS We contacted 25 patients (mean age 28 years, 19 females) diagnosed with screening and 34 patients (mean age 25 years, 26 females) diagnosed in the same period for symptoms. After 20 years, in the cohort diagnosed with screening and in the cohort diagnosed for symptoms the adherence to the gluten-free diet was optimal in 14 (56%) and 26 (81%), improvable in 5 (20%) and 3 (9%), inadequate in 6 (24%) and 3 (9%), respectively. In the two cohorts, four patients (16%) and six patients (18%) developed other autoimmune diseases. CONCLUSIONS Twenty years after the diagnosis, near half of the patients diagnosed in a mass screening, does not have an optimal adherence to the gluten-free diet and a remarkable proportion of them have developed another autoimmune disease.
Collapse
|
|
16
|
Long-Term Adherence to a Gluten-Free Diet and Quality of Life of Celiac Patients After Transition to an Adult Referral Center. Dig Dis Sci 2022; 67:3955-3963. [PMID: 34524598 PMCID: PMC9287197 DOI: 10.1007/s10620-021-07231-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 08/16/2021] [Indexed: 12/09/2022]
Abstract
BACKGROUND Modalities for the transition to adult care of celiac patients diagnosed during childhood/adolescence and their impact on long-term adherence to a gluten-free diet (GFD-A), quality of life (QOL) and maintenance of follow-up in adulthood are unknown. AIMS To evaluate whether timing of transition affects long-term GFD-A, QOL, and continuity of follow-up in adulthood and to identify predictors of long-term GFD-A. METHODS Clinical and demographic data about pediatric care and adult follow-up at our center were retrospectively collected from clinical notes of celiac patients diagnosed during childhood/adolescence and then referred to our tertiary center. QOL and adult long-term GFD-A were prospectively evaluated with validated questionnaires. These parameters were studied by means of univariate and multivariate statistical analysis. RESULTS 183 patients (130F, mean age at diagnosis 7.6 ± 5.8 years) were enrolled. Median age at transition to adult care was 20 years (IQR 17-25). There was no relationship between age at transition to adult care, long-term GFD-A, QOL, and continuity of follow-up. GFD-A tended to improve overall from pediatric care to adult referral (OR 2.92, 95% CI 1.13-7.87, p = 0.02) and also throughout adult follow-up (OR 9.0, 95% CI 4.2-19.7, p < 0.01). On multivariable logistic regression analysis, classical symptoms at diagnosis of celiac disease (p = 0.02) and good GFD-A at adult referral (p < 0.01) predicted good long-term GFD-A, while being lost to follow-up predicted poorer long-term GFD-A (p = 0.02). CONCLUSIONS Clinical characteristics can guide development of personalized strategies for implementing long-term GFD-A and ensure maintenance of regular follow-up in celiac patients diagnosed in childhood/adolescence and transitioning to adult care.
Collapse
|
|
17
|
Schiepatti A, Alimenti E, Maimaris S, Nicolardi ML, Manzella La Barbera F, Baiardi P, Biagi F. Prevalence, incidence and clinical features of SARS-CoV-2 infection in adult coeliac patients. Eur J Gastroenterol Hepatol 2021; 33:1361-1366. [PMID: 33399400 PMCID: PMC8492080 DOI: 10.1097/meg.0000000000001969] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 09/29/2020] [Indexed: 01/08/2023]
Abstract
OBJECTIVES Data on SARS-CoV-2 disease (COVID-19) in adult coeliac disease (CD) are lacking. The aim of the present study is to evaluate the epidemiology and clinical features of COVID-19 in adult coeliac patients regularly followed-up at our centre since January 2015. METHODS Data about general health status and clinical features of laboratory-confirmed COVID-19 were prospectively collected over the phone. Data about CD were retrospectively collected from clinical notes. Prevalence and incidence of COVID-19 were compared between the coeliac cohort and the figures in the general population of Lombardy, Northern Italy between 20 February to 5 June 2020 provided by the Italian National Institute of Health (Istituto Superiore di Sanità) and the Lombardy regional government. RESULTS Nine out of 324 patients contracted COVID-19, thus resulting in a prevalence of 2.78% [95% confidence interval (CI) 0.98-4.58] and an incidence rate of 8.15/1000 person-month (95% CI 4.24-15.66). Prevalence of COVID-19 ascertained by means of nasal swab was 1.79% (95% CI 0.22-3.35) and the incidence rate 5.26/1000 person-month (95% CI 2.19-12.63), without difference from the general population. Clinical type of CD, age, sex, duration and adherence to a gluten-free diet, and mucosal healing did not differ between coeliac patients with and without COVID-19. None of the 9 patients with COVID-19 required hospitalization. CONCLUSION Patients with CD do not seem to carry an increased risk of COVID-19 compared to the general population and their disease course is mild.
Collapse
Affiliation(s)
- Annalisa Schiepatti
- Istituti Clinici Scientifici Maugeri, IRCCS, Gastroenterology Unit of Pavia Institute, University of Pavia
| | - Eleonora Alimenti
- Istituti Clinici Scientifici Maugeri, IRCCS, Gastroenterology Unit of Pavia Institute, University of Pavia
| | - Stiliano Maimaris
- Istituti Clinici Scientifici Maugeri, IRCCS, Gastroenterology Unit of Pavia Institute, University of Pavia
| | - Maria Luisa Nicolardi
- Istituti Clinici Scientifici Maugeri, IRCCS, Gastroenterology Unit of Pavia Institute, University of Pavia
| | | | - Paola Baiardi
- Direzione Scientifica Centrale, Fondazione S. Maugeri, IRCCS, Pavia, Italy
| | - Federico Biagi
- Istituti Clinici Scientifici Maugeri, IRCCS, Gastroenterology Unit of Pavia Institute, University of Pavia
| |
Collapse
|
|
18
|
Meijer-Boekel C, van den Akker M, van Bodegom L, Escher J, van Geloven N, van Overveld F, Rings EHH, Smit L, de Vries MC, Mearin ML. Early diagnosis of coeliac disease in the Preventive Youth Health Care Centres in the Netherlands: study protocol of a case finding study (GLUTENSCREEN). BMJ Paediatr Open 2021; 5:e001152. [PMID: 34466665 PMCID: PMC8359518 DOI: 10.1136/bmjpo-2021-001152] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Accepted: 07/02/2021] [Indexed: 01/02/2023] Open
Abstract
Introduction Coeliac disease (CD) occurs in 1% of the population, develops early in life and is severely underdiagnosed. Undiagnosed and untreated disease is associated with short-term and long-term complications. The current healthcare approach is unable to solve the underdiagnosis of CD and timely diagnosis and treatment is only achieved by active case finding. Aim: to perform a case finding project to detect CD children who visit the Youth Health Care Centres (YHCCs) in a well-described region in the Netherlands to evaluate whether it is feasible, cost-effective and well accepted by the population. Methods/analysis Prospective intervention cohort study. Parents of all children aged 12 months and 4 years attending the YHCCs for a regular visit are asked whether their child has one or more CD-related symptoms from a standardised list. If so, they will be invited to participate in the case finding study. After informed consent, a point of care test (POCT) to assess CD-specific antibodies against tissue transglutaminase (TG2A) is performed onsite the YHCCs. If the POCT is positive, CD is highly suspected and the child will be referred to hospital for definitive diagnosis according to the Guideline Coeliac Disease of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition guideline. Main outcomes Incidence rate of new CD diagnoses in the study region in comparison to the one in the same age diagnosed by standard of care in the rest of the Netherlands.Feasibility and cost-effectiveness of active CD case finding at the YHCCs. All costs of active case finding, diagnostics and treatment of CD and the potential short-term and long-term consequences of the disease will be calculated for the setting with and without case finding.Ethical acceptability: by questionnaires on parental and healthcare professionals' satisfaction.A statistical analysis plan was prepared and is published on the GLUTENSCREEN website (Statistical-Analysis-Plan-11-5-2021_def.pdf (glutenscreen.nl) and added as annex 1). Ethics and dissemination The Medical Ethics Committee Leiden approved this study. If we prove that case finding at the YHCC is feasible, cost-effective and well accepted by the population, implementation is recommended. Trial registration number NL63291.058.17.
Collapse
Affiliation(s)
- Caroline Meijer-Boekel
- Paediatric Gastroenterology, Leiden University Medical Center, Leiden, Zuid Holland, The Netherlands
| | - M.Elske van den Akker
- Biomedical Data Sciences, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
| | - Leti van Bodegom
- Biomedical Data Sciences, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
| | - Johanna Escher
- Paediatric Gastroenterology, Erasmus University Rotterdam, Rotterdam, Zuid-Holland, The Netherlands
| | - Nan van Geloven
- Biomedical Data Sciences, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
| | | | - Edmond H H.M Rings
- Paediatric Gastroenterology, Leiden University Medical Center, Leiden, Zuid Holland, The Netherlands
| | - Lucy Smit
- Youth Health Care Centre, Kennemerland, The Netherlands
| | - Martine Charlotte de Vries
- Department of Medical Ethics and Health Law, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
| | - M. Luisa Mearin
- Paediatric Gastroenterology, Leiden University Medical Center, Leiden, Zuid Holland, The Netherlands
| |
Collapse
|
|
19
|
Falcomer AL, Farage P, Pratesi CB, Pratesi R, Gandolfi L, Nakano EY, Raposo A, Zandonadi RP. Health-Related Quality of Life and Experiences of Brazilian Celiac Individuals over the Course of the Sars-Cov-2 Pandemic. Nutrients 2021; 13:nu13051582. [PMID: 34065154 PMCID: PMC8151969 DOI: 10.3390/nu13051582] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 05/05/2021] [Accepted: 05/07/2021] [Indexed: 12/13/2022] Open
Abstract
Since the end of 2019, the world has been facing an unpredicted COVID-19 pandemic with consequences for the economy, environment, society, and health. The COVID-19 pandemic has increased the risk of death, bringing unbearable psychological pressure upon people worldwide. For celiac patients, the pandemic may represent an additional burden concerning the inherent aspects of celiac disease (CD) that compromise these individuals’ quality of life (QoL). Therefore, the objective of this study was to evaluate Brazilian celiac patients’ QoL during the course of the COVID-19 pandemic caused by its outbreak and rapid spread and subsequent restrictive measures in addition to the dietary restrictions and other burdens caused by CD. This country-wide cross-sectional study was conducted using a self-administered instrument previously validated in Brazilian–Portuguese to investigate the QoL of individuals with CD. Data collected through the online self-administration of the Brazilian version of the celiac disease quality of life questionnaire (CDQ) comprised 674 CD individuals’ responses. Although pandemics have historically posed a challenge for Brazilian population, this period was not associated with a negative impact on Brazilian CD individuals’ QoL. During the pandemic, the QoL of Brazilian’s with CD was more affected by gastrointestinal aspects than emotions and social aspects and worries. Gender, age, marital status, having (or not) children, occupation, and a positive test for COVID-19 did not affect CD individuals’ QoL. However, the study revealed a larger burden and diminished QoL for individuals not following a gluten-free diet and those using antidepressants. Additional research is necessary to verify how the length of the pandemic will affect celiac individuals and then compare those outcomes compare to the COVID-19 period and after.
Collapse
Affiliation(s)
- Ana Luísa Falcomer
- Department of Nutrition, School of Health Sciences, University of Brasilia, 70910-900 Brasilia, Brazil;
| | - Priscila Farage
- Faculty of Nutrition, Federal University of Goias, 74605-080 Goiânia, Brazil;
| | - Cláudia B. Pratesi
- Interdisciplinary Laboratory of Biosciences and Celiac Disease Research Center, School of Medicine, University of Brasilia, 70910-900 Brasilia, Brazil; (C.B.P.); (R.P.); (L.G.)
| | - Riccardo Pratesi
- Interdisciplinary Laboratory of Biosciences and Celiac Disease Research Center, School of Medicine, University of Brasilia, 70910-900 Brasilia, Brazil; (C.B.P.); (R.P.); (L.G.)
| | - Lenora Gandolfi
- Interdisciplinary Laboratory of Biosciences and Celiac Disease Research Center, School of Medicine, University of Brasilia, 70910-900 Brasilia, Brazil; (C.B.P.); (R.P.); (L.G.)
| | | | - António Raposo
- CBIOS (Research Center for Biosciences and Health Technologies), Universidade Lusófona de Humanidades e Tecnologias, Campo Grande 376, 1749-024 Lisboa, Portugal
- Correspondence: (A.R.); (R.P.Z.); Tel.: +55-619-8103-3600 (R.P.Z.)
| | - Renata Puppin Zandonadi
- Department of Nutrition, School of Health Sciences, University of Brasilia, 70910-900 Brasilia, Brazil;
- Correspondence: (A.R.); (R.P.Z.); Tel.: +55-619-8103-3600 (R.P.Z.)
| |
Collapse
|
|
20
|
Behrendt I, Fasshauer M, Eichner G. Gluten Intake and All-Cause and Cause-Specific Mortality: Prospective Findings from the UK Biobank. J Nutr 2021; 151:591-597. [PMID: 33382415 DOI: 10.1093/jn/nxaa387] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Revised: 10/20/2020] [Accepted: 11/11/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Gluten has been linked to adverse effects on metabolic and vascular health. OBJECTIVES The present study determines the association between dietary gluten intake and all-cause (primary objective), as well as cause-specific, mortality in people without celiac disease. METHODS Gluten intake was estimated in 159,265 participants of the UK Biobank which is a large multicenter, prospective cohort study initiated in 2006. Cox proportional hazard regression models were used and HRs were determined for all-cause and cause-specific mortality. All models were adjusted for confounders and multiple testing. RESULTS Median (IQR) age was 57 (49-62) y with 52.1% of participants being female. Gluten intake was 8.5 (5.1-12.4) g/d with significantly higher consumption in males [10.0 (6.3-14.1) g/d] than in females [7.2 (4.6-10.7) g/d] (P < 0.0001). During a median follow-up of 11.1 (10.6-11.9) y and 1.8 million person-years, 6259 deaths occurred. Gluten intake was not significantly associated with all-cause mortality after adjusting for confounders (HR: 1.00; 95% CI: 1.00, 1.01; P = 0.59). Dietary gluten was not significantly associated with cancer (HR: 1.00; 95% CI: 1.00, 1.01; raw P = 0.24) or noncancer (HR: 1.00; 95% CI: 0.99, 1.01; raw P = 0.56) mortality. However, gluten intake was positively associated with ischemic heart disease mortality (HR: 1.02; 95% CI: 1.01, 1.04; raw P = 0.003, Holm-adjusted P = 0.04). CONCLUSIONS Gluten intake is not significantly associated with all-cause and cancer mortality in adults without celiac disease. The findings support the hypothesis that limiting gluten intake is unlikely to provide significant overall survival benefits on a population level. The positive association between gluten intake and ischemic heart disease mortality requires further study.
Collapse
Affiliation(s)
- Inken Behrendt
- Institute of Nutritional Science, Justus-Liebig University of Giessen, Giessen, Germany
| | - Mathias Fasshauer
- Institute of Nutritional Science, Justus-Liebig University of Giessen, Giessen, Germany.,Department of Internal Medicine (Endocrinology, Nephrology, and Rheumatology), University of Leipzig, Leipzig, Germany.,Integrated Research and Treatment Center (IFB) AdiposityDiseases, Leipzig University Medical Center, Leipzig, Germany
| | - Gerrit Eichner
- Mathematical Institute, Justus-Liebig University of Giessen, Giessen, Germany
| |
Collapse
|
|
21
|
Cellular and molecular bases of refractory celiac disease. INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY 2021; 358:207-240. [PMID: 33707055 DOI: 10.1016/bs.ircmb.2020.12.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Refractory celiac disease (RCD) encompasses biologically heterogeneous disorders that develop in a small proportion (0.3%) of individuals with celiac disease that are associated with high morbidity. Two broad categories are currently recognized, type I (RCD I) and type II (RCD II), based on immunophenotypic and molecular features of the intraepithelial lymphocytes (IELs). RCD I is characterized by a polyclonal expansion of IELs displaying a normal immunophenotype, while RCD II represents a clonal proliferation of immunophenotypically "aberrant" IELs, and is considered a low-grade lymphoproliferative disorder. The pathogenesis of RCD I has not been clarified, but limited studies suggest multifactorial etiology. On the other hand, recent immunologic, molecular and immunophenotypic analyses have proposed lineage-negative innate IELs to be the cell of origin of a proportion of RCD II cases. Furthermore, sequencing studies have identified frequent, recurrent, activating mutations in members of the JAK-STAT pathway in RCD II. This finding, in conjunction with prior in vitro experimental observations, suggests roles of deregulated cytokine signaling in disease pathogenesis. In this review, we describe current understanding of environmental, immune and genetic factors associated with the development of RCD and briefly discuss diagnostic and therapeutic considerations.
Collapse
|
|
22
|
Dias R, Pereira CB, Pérez-Gregorio R, Mateus N, Freitas V. Recent advances on dietary polyphenol's potential roles in Celiac Disease. Trends Food Sci Technol 2021. [DOI: 10.1016/j.tifs.2020.10.033] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|
|
23
|
Abstract
INTRODUCTION Diagnosed celiac disease (CD) is associated with lymphoproliferative malignancy and gastrointestinal cancer, but little is known about the long-term consequences of undiagnosed CD. We aimed to investigate long-term consequences of undiagnosed CD for mortality and incidence of cancer and other chronic diseases. METHODS We screened biobank serum samples for immunoglobulin (Ig) A and IgG tissue transglutaminase (TTG) and IgG deamidated gliadin peptide in a study of 8 population-based cohort studies comprising 16,776 participants examined during 1976-2012 and followed with >99% complete follow-up in Danish nationwide registries until December 31, 2017, regarding vital status and incidence of diseases. Undiagnosed CD was defined as antibody positivity (IgA-TTG or IgG-TTG ≥ 7 U/mL and/or IgG deamidated gliadin peptide ≥ 10 U/mL) in individuals without a diagnosis of CD recorded in the National Patient Register. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated by Cox regression analyses with age as the underlying time scale. RESULTS The prevalence of undiagnosed CD was 1.0% with no statistically significant increase over time. Undiagnosed CD was associated with increased risk of cancer overall (HR, 1.57; 95% CI, 1.16-2.11), gastrointestinal cancer (HR, 2.33; 95% CI, 1.35-4.04), cancer of the uterus (HR, 3.95; 95% CI, 1.46-10.69), breast cancer (HR, 1.98; 95% CI, 1.02-3.82), head and neck cancer (HR, 3.12; 95% CI, 1.15-8.43), and cardiovascular disease (HR, 1.37; 95% CI, 1.01-1.85). We found no statistically significant association between undiagnosed CD and mortality (HR, 1.19; 95% CI, 0.87-1.61). DISCUSSION Undiagnosed CD was associated with increased risk of cardiovascular disease and cancer suggesting that untreated CD has serious long-term health consequences not only affecting the gastrointestinal tract (see Visual Abstract, Supplementary Digital Content, http://links.lww.com/AJG/B566).
Collapse
|
|
24
|
Demirkesen I, Ozkaya B. Recent strategies for tackling the problems in gluten-free diet and products. Crit Rev Food Sci Nutr 2020; 62:571-597. [DOI: 10.1080/10408398.2020.1823814] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Ilkem Demirkesen
- Department of Animal Health, Food and Feed Research, General Directorate of Agricultural Research and Policies, Ministry of Agriculture and Forestry, Ankara, Turkey
| | - Berrin Ozkaya
- Department of Food Engineering, Ankara University, Ankara, Turkey
| |
Collapse
|
|
25
|
Schiepatti A, Savioli J, Vernero M, Borrelli de Andreis F, Perfetti L, Meriggi A, Biagi F. Pitfalls in the Diagnosis of Coeliac Disease and Gluten-Related Disorders. Nutrients 2020; 12:nu12061711. [PMID: 32517378 PMCID: PMC7352902 DOI: 10.3390/nu12061711] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Revised: 05/30/2020] [Accepted: 06/02/2020] [Indexed: 02/07/2023] Open
Abstract
The spectrum of gluten-related disorders (GRD) has emerged as a relevant phenomenon possibly impacting on health care procedures and costs worldwide. Current classification of GRD is mainly based on their pathophysiology, and the following categories can be distinguished: immune-mediated disorders that include coeliac disease (CD), dermatitis herpetiformis (DH), and gluten ataxia (GA); allergic reactions such as wheat allergy (WA); and non-coeliac gluten sensitivity (NCGS), a condition characterized by both gastrointestinal and extra-intestinal symptoms subjectively believed to be induced by the ingestion of gluten/wheat that has recently gained popularity. Although CD, DH, and WA are well-defined clinical entities, whose diagnosis is based on specific diagnostic criteria, a diagnosis of NCGS may on the contrary be considered only after the exclusion of other organic disorders. Neither allergic nor autoimmune mechanisms have been found to be involved in NCGS. Mistakes in the diagnosis of GRD are still a relevant clinical problem that may result in overtreatment of patients being unnecessary started on a gluten-free diet and waste of health-care resources. On the basis of our clinical experience and literature, we aim to identify the main pitfalls in the diagnosis of CD and its complications, DH, and WA. We provide a practical methodological approach to guide clinicians on how to recognize and avoid them.
Collapse
Affiliation(s)
- Annalisa Schiepatti
- Gastroenterology Unit of IRCCS Pavia Institute, Istituti Clinici Scientifici Maugeri, University of Pavia, 27100 Pavia, Italy; (M.V.); (F.B.d.A.); (F.B.)
- Correspondence: ; Tel.: +39-0382-592331
| | - Jessica Savioli
- Allergy and Immunology Unit of Pavia IRCCS Institute, Istituti Clinici Scientifici Maugeri, 27100 Pavia, Italy; (J.S.); (L.P.); (A.M.)
- First Department of Internal Medicine, Fondazione IRCCS San Matteo Hospital, University of Pavia, 27100 Pavia, Italy
| | - Marta Vernero
- Gastroenterology Unit of IRCCS Pavia Institute, Istituti Clinici Scientifici Maugeri, University of Pavia, 27100 Pavia, Italy; (M.V.); (F.B.d.A.); (F.B.)
- First Department of Internal Medicine, Fondazione IRCCS San Matteo Hospital, University of Pavia, 27100 Pavia, Italy
| | - Federica Borrelli de Andreis
- Gastroenterology Unit of IRCCS Pavia Institute, Istituti Clinici Scientifici Maugeri, University of Pavia, 27100 Pavia, Italy; (M.V.); (F.B.d.A.); (F.B.)
- First Department of Internal Medicine, Fondazione IRCCS San Matteo Hospital, University of Pavia, 27100 Pavia, Italy
| | - Luca Perfetti
- Allergy and Immunology Unit of Pavia IRCCS Institute, Istituti Clinici Scientifici Maugeri, 27100 Pavia, Italy; (J.S.); (L.P.); (A.M.)
| | - Antonio Meriggi
- Allergy and Immunology Unit of Pavia IRCCS Institute, Istituti Clinici Scientifici Maugeri, 27100 Pavia, Italy; (J.S.); (L.P.); (A.M.)
| | - Federico Biagi
- Gastroenterology Unit of IRCCS Pavia Institute, Istituti Clinici Scientifici Maugeri, University of Pavia, 27100 Pavia, Italy; (M.V.); (F.B.d.A.); (F.B.)
| |
Collapse
|
|
26
|
Elli L, Bascuñán K, di Lernia L, Bardella MT, Doneda L, Soldati L, Orlando S, Ferretti F, Lombardo V, Barigelletti G, Scricciolo A, Fabiano S, Vecchi M, Roncoroni L. Safety of occasional ingestion of gluten in patients with celiac disease: a real-life study. BMC Med 2020; 18:42. [PMID: 32172690 PMCID: PMC7075003 DOI: 10.1186/s12916-020-1511-6] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Accepted: 02/05/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Gluten-free diet (GFD) decreases the quality of life of celiac disease (CD) patients, who frequently ask to occasionally ingest gluten-containing food. We evaluated CD patients reporting voluntary and occasional transgressions to their GFD. METHODS From October 2017 to September 2018, the patients reporting occasional and voluntary gluten ingestion (GFD-noncompliant) were prospectively enrolled. These patients underwent clinical examination, blood tests, duodenal biopsy, capsule enteroscopy (CE), and a validated food-frequency questionnaire (FFQ) assessing the frequency and quantity of gluten intake. Mortality was calculated and compared to the general population. A group of patients on strict GFD (GFD-adherent) acted as controls. RESULTS One thousand three hundred seventy-eight CD patients were evaluated during the study period. One hundred nine (8%) reported occasional (weekly or monthly) voluntary ingestion of gluten. The mean gluten intake was 185.2 ± 336.9 g/year, and the duration of their incorrect GFD was 8.6 ± 6.9 years. Among the noncompliant patients, 57% did not present any histological alteration; furthermore, the Marsh score profile was not different between compliant and noncompliant patients. Seventy percent did not present any alteration at CE. Seventy-five percent of patients reported no gastrointestinal symptoms after gluten ingestion. Twenty-three percent of patients in the GFD-noncompliant group presented positive tTG-IgA. No association was found between gluten intake, clinical symptoms, and biomarkers. Mortality was not different between the groups and the general population. CONCLUSIONS Our results are that in a real-life scenario, a group of CD patients on long-term gluten intake showed no significant clinical symptoms or small bowel damage, thus suggesting that a degree of tolerance towards gluten consumption can be reached.
Collapse
Affiliation(s)
- Luca Elli
- Center for Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Via F. Sforza 28, 20122, Milan, Italy.
| | - Karla Bascuñán
- Center for Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Via F. Sforza 28, 20122, Milan, Italy
- Department of Nutrition, School of Medicine, University of Chile, Santiago, Chile
| | | | - Maria Teresa Bardella
- Center for Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Via F. Sforza 28, 20122, Milan, Italy
| | - Luisa Doneda
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
| | - Laura Soldati
- Department of Health Sciences, University of Milan, Milan, Italy
| | - Stefania Orlando
- Center for Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Via F. Sforza 28, 20122, Milan, Italy
| | - Francesca Ferretti
- Center for Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Via F. Sforza 28, 20122, Milan, Italy
| | - Vincenza Lombardo
- Center for Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Via F. Sforza 28, 20122, Milan, Italy
| | - Giulio Barigelletti
- Cancer Registry Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Alice Scricciolo
- Center for Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Via F. Sforza 28, 20122, Milan, Italy
| | - Sabrina Fabiano
- Cancer Registry Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Maurizio Vecchi
- Center for Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Via F. Sforza 28, 20122, Milan, Italy
| | - Leda Roncoroni
- Center for Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Via F. Sforza 28, 20122, Milan, Italy
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
| |
Collapse
|
|
27
|
Abstract
Gluten-related disorders, including celiac disease, wheat allergy, and nonceliac gluten sensitivity (NCGS), are increasingly reported worldwide. Celiac disease is caused by an immune-mediated reaction to ingested gluten in genetically susceptible persons. NCGS is largely a diagnosis of exclusion when other causes of symptoms have been ruled out. All patients with celiac disease should be referred to a registered dietitian nutritionist with expertise in celiac disease and a gastroenterologist who specializes in celiac disease and malabsorptive disorders, and they should remain on a strict gluten-free diet indefinitely. This article provides an overview of gluten- and wheat-related disorders.
Collapse
Affiliation(s)
- Joshua Elliott Rubin
- University of California, San Diego School of Medicine, La Jolla, California (J.E.R., S.E.C.)
| | - Sheila E Crowe
- University of California, San Diego School of Medicine, La Jolla, California (J.E.R., S.E.C.)
| |
Collapse
|
|
28
|
van Vliet C, Spagnolo DV. T- and NK-cell lymphoproliferative disorders of the gastrointestinal tract: review and update. Pathology 2019; 52:128-141. [PMID: 31727264 DOI: 10.1016/j.pathol.2019.10.001] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2019] [Revised: 10/08/2019] [Accepted: 10/08/2019] [Indexed: 12/13/2022]
Abstract
T- and NK-cell lymphoproliferative disorders of the gastrointestinal (GI) tract are uncommon, but are important to recognise as there may be morphological and immunophenotypic overlap between lymphoid lesions with vastly different clinical outcomes. Recent data have led to the reclassification of some lymphomas and inclusion of new entities in the 2016 revision of World Health Organization (WHO) classification of lymphoid neoplasms. It has become clear that enteropathy associated T-cell lymphoma (EATL), formerly thought to be composed of two subtypes known as type I and type II, are distinct entities. Type I EATL is now simply classified as EATL; it is strongly associated with coeliac disease and occurs mainly in Western populations. Type II EATL has been renamed monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL); it shows no definite association with coeliac disease and occurs worldwide with a predominance in Asian populations. There is also a group of aggressive intestinal T-cell lymphomas which do not meet criteria for EATL, MEITL, extranodal NK/T-cell lymphoma of nasal type or anaplastic large cell lymphoma. These neoplasms are now designated intestinal T-cell lymphoma, not otherwise specified. Indolent T-cell lymphoproliferative disorder of the GI tract has been included as a provisional entity in the most recent WHO classification. It is a clonal T-cell lymphoproliferative disorder (CD4+ or CD8+) with an indolent clinical course. Finally, benign NK-cell proliferations of the GI tract, variably designated 'NK-cell enteropathy' and 'lymphomatoid gastropathy' have also been recognised in the last two decades but have not been included in the WHO classification as their neoplastic nature is not established. This review covers the aforementioned lymphoid proliferations, emphasising their salient clinicopathological features and genetic abnormalities. It also provides practical insights into resolving difficult differential diagnoses in daily surgical pathology practice.
Collapse
Affiliation(s)
- Chris van Vliet
- Anatomical Pathology, PathWest Laboratory Medicine, QEII Medical Centre, Nedlands, WA, Australia.
| | - Dominic V Spagnolo
- Anatomical Pathology, PathWest Laboratory Medicine, QEII Medical Centre, Nedlands, WA, Australia; University of Western Australia, School of Pathology and Laboratory Medicine, Nedlands, WA, Australia
| |
Collapse
|
|
29
|
Malamut G, Cording S, Cerf-Bensussan N. Recent advances in celiac disease and refractory celiac disease. F1000Res 2019; 8:F1000 Faculty Rev-969. [PMID: 31297187 PMCID: PMC6600866 DOI: 10.12688/f1000research.18701.1] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/14/2019] [Indexed: 12/21/2022] Open
Abstract
Celiac disease (CeD), defined as gluten-induced enteropathy, is a frequent and largely underdiagnosed disease. Diagnosis relies on the detection of highly specific serum IgA anti-transglutaminase auto-antibodies and on the demonstration of duodenal villous atrophy. Treatment necessitates a strict gluten-free diet, which resolves symptoms and enables histological recovery. However, regular follow-up is necessary to assess mucosal healing, which emerges as an important prognostic factor. Recent work on CeD pathogenesis has highlighted how the cross-talk between gluten-specific CD4 + T cells and interleukin-15 can activate cytotoxic intraepithelial lymphocytes and trigger epithelial lesions. Moreover, acquisition by a subset of intraepithelial lymphocytes of somatic gain-of-function mutations in the JAK-STAT pathway was shown to be a decisive step in the progression toward lymphomas complicating CeD, thus opening new therapeutic perspectives for these rare but life-threatening complications.
Collapse
Affiliation(s)
- Georgia Malamut
- Gastroenterology, Hôpital Cochin APHP, Paris, France
- Université Paris Descartes, Paris, France
- Inserm, UMR1163 and Institut Imagine, Laboratory Intestinal Immunity, Paris, France
| | - Sascha Cording
- Université Paris Descartes, Paris, France
- Inserm, UMR1163 and Institut Imagine, Laboratory Intestinal Immunity, Paris, France
| | - Nadine Cerf-Bensussan
- Université Paris Descartes, Paris, France
- Inserm, UMR1163 and Institut Imagine, Laboratory Intestinal Immunity, Paris, France
| |
Collapse
|
|
30
|
Lindfors K, Ciacci C, Kurppa K, Lundin KEA, Makharia GK, Mearin ML, Murray JA, Verdu EF, Kaukinen K. Coeliac disease. Nat Rev Dis Primers 2019; 5:3. [PMID: 30631077 DOI: 10.1038/s41572-018-0054-z] [Citation(s) in RCA: 259] [Impact Index Per Article: 43.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Coeliac disease is an immune-mediated enteropathy against dietary gluten present in wheat, rye and barley and is one of the most common lifelong food-related disorders worldwide. Coeliac disease is also considered to be a systemic disorder characterized by a variable combination of gluten-related signs and symptoms and disease-specific antibodies in addition to enteropathy. The ingestion of gluten leads to the generation of harmful gluten peptides, which, in predisposed individuals, can induce adaptive and innate immune responses. The clinical presentation is extremely variable; patients may have severe gastrointestinal symptoms and malabsorption, extraintestinal symptoms or have no symptoms at all. Owing to the multifaceted clinical presentation, diagnosis remains a challenge and coeliac disease is heavily underdiagnosed. The diagnosis of coeliac disease is achieved by combining coeliac disease serology and small intestinal mucosal histology during a gluten-containing diet. Currently, the only effective treatment for coeliac disease is a lifelong strict gluten-free diet; however, the diet is restrictive and gluten is difficult to avoid. Optimizing diagnosis and care in coeliac disease requires continuous research and education of both patients and health-care professionals.
Collapse
Affiliation(s)
- Katri Lindfors
- Celiac Disease Research Center, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
| | - Carolina Ciacci
- Coeliac Center at Department of Medicine and Surgery, Scuola Medica Salernitana, University of Salerno, Salerno, Italy
| | - Kalle Kurppa
- Tampere Center for Child Health, University of Tampere and Tampere University Hospital, Tampere, Finland
| | - Knut E A Lundin
- Institute of Clinical Medicine and K.G. Jebsen Coeliac Disease Research Centre, Faculty of Medicine, University of Oslo, and Department of Gastroenterology, Oslo University Hospital, Oslo, Norway
| | - Govind K Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - M Luisa Mearin
- Department of Pediatrics, Leiden University Medical Center, Leiden, Netherlands
| | | | - Elena F Verdu
- Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Katri Kaukinen
- Department of Internal Medicine, Tampere University Hospital and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
| |
Collapse
|
|
31
|
Gluten-Free Diet in Celiac Disease-Forever and for All? Nutrients 2018; 10:nu10111796. [PMID: 30453686 PMCID: PMC6267495 DOI: 10.3390/nu10111796] [Citation(s) in RCA: 80] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Revised: 11/04/2018] [Accepted: 11/15/2018] [Indexed: 12/23/2022] Open
Abstract
The gluten-free diet is the only effective treatment available for celiac disease. However, it is difficult to adhere to and a closer look on the diet’s implementation and indications reveals several ambiguities: Not only is there controversy on the threshold of gluten that can be tolerated in the frame of a strict gluten-free diet, but it is also unclear whether the gluten-free diet is an appropriate treatment in patient subgroups with asymptomatic or potential celiac disease. Reports from a number of research groups suggest that a certain proportion of patients may effectively develop tolerance to gluten and thus become suitable for gluten reintroduction over time. In this review, we set out to create an overview about the current state of research as regards the definition of a strict gluten-free diet in terms of the gluten thresholds considered tolerable and the indication for a gluten-free diet in the absence of histological abnormalities or symptoms. Furthermore, we discuss the concept that a gluten-free diet must be followed for life by all patients.
Collapse
|
|
32
|
A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults. Nat Commun 2018; 9:4630. [PMID: 30425247 PMCID: PMC6234216 DOI: 10.1038/s41467-018-07019-x] [Citation(s) in RCA: 128] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2017] [Accepted: 10/05/2018] [Indexed: 12/31/2022] Open
Abstract
Adherence to a low-gluten diet has become increasingly common in parts of the general population. However, the effects of reducing gluten-rich food items including wheat, barley and rye cereals in healthy adults are unclear. Here, we undertook a randomised, controlled, cross-over trial involving 60 middle-aged Danish adults without known disorders with two 8-week interventions comparing a low-gluten diet (2 g gluten per day) and a high-gluten diet (18 g gluten per day), separated by a washout period of at least six weeks with habitual diet (12 g gluten per day). We find that, in comparison with a high-gluten diet, a low-gluten diet induces moderate changes in the intestinal microbiome, reduces fasting and postprandial hydrogen exhalation, and leads to improvements in self-reported bloating. These observations suggest that most of the effects of a low-gluten diet in non-coeliac adults may be driven by qualitative changes in dietary fibres. Gluten-free diets are increasingly common in the general population. Here, the authors report the results of a randomised cross-over trial involving middle-aged, healthy Danish adults, showing evidence that a low-gluten diet leads to gut microbiome changes, possibly due to variations in dietary fibres.
Collapse
|
|
33
|
Wimmer G, Vécsei A, Häfner M, Uhl A. Fisher encoding of convolutional neural network features for endoscopic image classification. J Med Imaging (Bellingham) 2018; 5:034504. [PMID: 30840751 PMCID: PMC6152583 DOI: 10.1117/1.jmi.5.3.034504] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Accepted: 08/21/2018] [Indexed: 12/14/2022] Open
Abstract
We propose an approach for the automated diagnosis of celiac disease (CD) and colonic polyps (CP) based on applying Fisher encoding to the activations of convolutional layers. In our experiments, three different convolutional neural network (CNN) architectures (AlexNet, VGG-f, and VGG-16) are applied to three endoscopic image databases (one CD database and two CP databases). For each network architecture, we perform experiments using a version of the net that is pretrained on the ImageNet database, as well as a version of the net that is trained on a specific endoscopic image database. The Fisher representations of convolutional layer activations are classified using support vector machines. Additionally, experiments are performed by concatenating the Fisher representations of several layers to combine the information of these layers. We will show that our proposed CNN-Fisher approach clearly outperforms other CNN- and non-CNN-based approaches and that our approach requires no training on the target dataset, which results in substantial time savings compared with other CNN-based approaches.
Collapse
Affiliation(s)
- Georg Wimmer
- University of Salzburg, Department of Computer Sciences, Salzburg, Austria
| | | | | | - Andreas Uhl
- University of Salzburg, Department of Computer Sciences, Salzburg, Austria
| |
Collapse
|
|
34
|
Ludvigsson JF, Ciacci C, Green PH, Kaukinen K, Korponay-Szabo IR, Kurppa K, Murray JA, Lundin KEA, Maki MJ, Popp A, Reilly NR, Rodriguez-Herrera A, Sanders DS, Schuppan D, Sleet S, Taavela J, Voorhees K, Walker MM, Leffler DA. Outcome measures in coeliac disease trials: the Tampere recommendations. Gut 2018; 67:1410-1424. [PMID: 29440464 PMCID: PMC6204961 DOI: 10.1136/gutjnl-2017-314853] [Citation(s) in RCA: 81] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Revised: 12/19/2017] [Accepted: 01/08/2018] [Indexed: 12/12/2022]
Abstract
OBJECTIVE A gluten-free diet is the only treatment option of coeliac disease, but recently an increasing number of trials have begun to explore alternative treatment strategies. We aimed to review the literature on coeliac disease therapeutic trials and issue recommendations for outcome measures. DESIGN Based on a literature review of 10 062 references, we (17 researchers and 2 patient representatives from 10 countries) reviewed the use and suitability of both clinical and non-clinical outcome measures. We then made expert-based recommendations for use of these outcomes in coeliac disease trials and identified areas where research is needed. RESULTS We comment on the use of histology, serology, clinical outcome assessment (including patient-reported outcomes), quality of life and immunological tools including gluten immunogenic peptides for trials in coeliac disease. CONCLUSION Careful evaluation and reporting of outcome measures will increase transparency and comparability of coeliac disease therapeutic trials, and will benefit patients, healthcare and the pharmaceutical industry.
Collapse
Affiliation(s)
- Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Department of Pediatrics, Örebro University Hospital, Örebro, Sweden
| | - Carolina Ciacci
- Coeliac Center at Department of Medicine and Surgery, Scuola Medica Salernitana, University of Salerno, Salerno, Italy
| | - Peter Hr Green
- Celiac Disease Center at Columbia University, New York, USA
| | - Katri Kaukinen
- Celiac Disease Research Center, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
- Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
| | - Ilma R Korponay-Szabo
- Coeliac Disease Centre, Heim Pál Children's Hospital, Budapest, Hungary
- Department of Paediatrics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Kalle Kurppa
- Celiac Disease Research Center, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
- Department of Paediatrics, Tampere University Hospital, Tampere, Finland
| | | | - Knut Erik Aslaksen Lundin
- Institute of Clinical Medicine and K.G. Jebsen Coeliac Disease Research Centre, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Oslo University Hospital, Oslo, Norway
| | - Markku J Maki
- Science Center, Tampere University Hospital, Tampere, Finland
- Tampere Centre for Child Health Research, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
| | - Alina Popp
- Institute for Mother and Child Health Bucharest, University of Medicine and Pharmacy 'Carol Davila', Bucharest, Romania
- Tampere Centre for Child Health Research, University of Tampere, Tampere University Hospital, Tampere, Finland
| | - Norelle R Reilly
- Division of Pediatric Gastroenterology, Columbia University Medical Center, New York, USA
- Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, USA
| | | | - David S Sanders
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, University of Sheffield, Sheffield, UK
| | - Detlef Schuppan
- Celiac Center, University Medical Center, Johannes-Gutenberg University, Mainz, Germany
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | | | - Juha Taavela
- Tampere Centre for Child Health Research, University of Tampere, Tampere University Hospital, Tampere, Finland
| | | | - Marjorie M Walker
- Faculty of Health and Medicine, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia
| | - Daniel A Leffler
- Celiac Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| |
Collapse
|
|
35
|
Biagi F, Schiepatti A, Maiorano G, Fraternale G, Agazzi S, Zingone F, Ciacci C, Volta U, Caio G, Tortora R, Klersy C, Corazza GR. Risk of complications in coeliac patients depends on age at diagnosis and type of clinical presentation. Dig Liver Dis 2018; 50:549-552. [PMID: 29277481 DOI: 10.1016/j.dld.2017.12.001] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Revised: 11/07/2017] [Accepted: 12/03/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND Coeliac disease is characterised by an increased mortality mostly due to its complications. AIMS To study the risk of developing complications according to clinical presentation and age at diagnosis, a combined retrospective-prospective longitudinal study was performed in three Italian centres. METHODS Incidence of complications and mortality rates were calculated using type and age at diagnosis of coeliac disease, sex, and centre of diagnosis as predictors. Patients referred after being found to suffer from coeliac disease elsewhere were excluded. RESULTS Between 01/1999 and 06/2015, 2225 adult coeliac patients were directly diagnosed in our centres. 17 of them developed a complication and 29 died. In patients older than 60 years at diagnosis of coeliac disease, the risk of complication is 18 times higher than in patients diagnosed at 18-40 years and 9 times higher than in patients diagnosed at 40-60 years. Classical presentation increases the risk of complications by 7 times compared to non-classical presentation; in asymptomatic patients the risk of complication is virtually absent. CONCLUSIONS The risk of developing complications in coeliac patients is linked to age at diagnosis of coeliac disease and type of clinical presentation. Follow-up methods of coeliac patients should be tailored according to these parameters.
Collapse
Affiliation(s)
- Federico Biagi
- Coeliac Centre/First Dept. of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Italy.
| | - Annalisa Schiepatti
- Coeliac Centre/First Dept. of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Italy
| | - Gregorio Maiorano
- Coeliac Centre/First Dept. of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Italy
| | - Giacomo Fraternale
- Coeliac Centre/First Dept. of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Italy
| | - Simona Agazzi
- Coeliac Centre/First Dept. of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Italy
| | - Fabiana Zingone
- Celiac Center at Gastrointestinal Unit, AOU S. Giovanni di Dio e Ruggi d'Aragona, University of Salerno, Italy
| | - Carolina Ciacci
- Celiac Center at Gastrointestinal Unit, AOU S. Giovanni di Dio e Ruggi d'Aragona, University of Salerno, Italy
| | - Umberto Volta
- Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Giacomo Caio
- Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Raffaella Tortora
- Department of Clinical and Experimental Medicine, Unit of Gastroenterology, University of Naples Federico II, Naples, Italy
| | - Catherine Klersy
- Biometry and Clinical Epidemiology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Italy
| | - Gino R Corazza
- Coeliac Centre/First Dept. of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Italy
| |
Collapse
|
|
36
|
Simmons JH, Foster NC, Riddlesworth TD, DuBose SN, Redondo MJ, Liu E, Freemark M. Sex- and age-dependent effects of celiac disease on growth and weight gain in children with type 1 diabetes: Analysis of the type 1 diabetes Exchange Clinic Registry. Pediatr Diabetes 2018; 19:741-748. [PMID: 29271067 DOI: 10.1111/pedi.12629] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Revised: 11/03/2017] [Accepted: 11/27/2017] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Celiac disease (CD) is common in patients with type 1 diabetes (T1D) and effects of CD on growth in children with T1D remain unclear. METHODS We analyzed heights, weights, and body mass index (BMI) in 215 matched pediatric CD/control pairs in the T1D Exchange Clinic Registry. CD was defined by a clinic-reported diagnosis and positive celiac serology (n = 80) and/or positive small bowel biopsy (n = 135). Cases and controls were matched by age (mean: 14 years), diabetes duration (median: 7 years), sex (57% female), and clinic site. There were 5569 height/weight measurements. RESULTS Gluten was restricted for varying periods of time in 61% of females and 51% of males with CD. Females with CD were shorter than female controls at all ages (P = 0.01). Weight z-scores were initially lower in preschool females with CD but similar to controls by middle childhood. Males with CD were initially shorter but adult heights were similar. Height in both sexes and weight in males were lower in CD participants diagnosed at younger age. Growth in T1D children with biopsy-proven CD, 76% of them were gluten-restricted, was comparable to that of T1D controls. CONCLUSION Concurrent CD impairs linear growth in T1D females at all stages of development and in young T1D males. Young females with CD have lower weights, but both sexes have similar weights by middle childhood. Children younger at CD onset remain shorter throughout childhood; males younger at CD onset have persistently lower weights. Long-term gluten restriction may restore weight gain and linear growth in children with CD and T1D.
Collapse
Affiliation(s)
- Jill H Simmons
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN
| | | | | | | | - Maria J Redondo
- Department of Pediatrics-Diabetes Endocrinology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
| | - Edwin Liu
- Department of Pediatric Gastroenterology, Children's Hospital Colorado, Aurora, CO
| | - Michael Freemark
- Department of Pediatric Endocrinology and Diabetes, Duke University Medical Center, Durham, North Carolina
| | | |
Collapse
|
|
37
|
Clerx E, Kupfer SS, Leffler DA. Disparities Among Gastrointestinal Disorders in Research Funding From the National Institutes of Health. Gastroenterology 2017; 153:877-880. [PMID: 28867278 DOI: 10.1053/j.gastro.2017.08.051] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Affiliation(s)
- Emma Clerx
- Harvard University, Boston, Massachusetts
| | - Sonia S Kupfer
- Celiac Disease Center at University of Chicago Medicine, Chicago, Illinois
| | - Daniel A Leffler
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | -
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| |
Collapse
|
|
38
|
Pace LA, Crowe SE. Duodenal Bulb Biopsies Remain Relevant in the Diagnosis of Adult Celiac Disease. Clin Gastroenterol Hepatol 2016; 14:1589-1592. [PMID: 27565522 PMCID: PMC5941945 DOI: 10.1016/j.cgh.2016.08.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2016] [Revised: 08/17/2016] [Accepted: 08/17/2016] [Indexed: 02/07/2023]
Affiliation(s)
- Laura A Pace
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Utah, Salt Lake City, Utah
| | - Sheila E Crowe
- Department of Medicine, Division of Gastroenterology, University of California San Diego, La Jolla, California
| |
Collapse
|
|
39
|
Leffler D, Kupfer SS, Lebwohl B, Bugin K, Griebel D, Lathrop JT, Lee JJ, Mulberg AE, Papadopoulos E, Tomaino J, Crowe SE. Development of Celiac Disease Therapeutics: Report of the Third Gastroenterology Regulatory Endpoints and Advancement of Therapeutics Workshop. Gastroenterology 2016; 151:407-11. [PMID: 27456385 DOI: 10.1053/j.gastro.2016.07.025] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Affiliation(s)
- Daniel Leffler
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Sonia S Kupfer
- Department of Medicine, University of Chicago, Chicago, Illinois
| | | | - Kevin Bugin
- US Food and Drug Administration, Silver Spring, Maryland
| | - Donna Griebel
- US Food and Drug Administration, Silver Spring, Maryland
| | | | - Jessica J Lee
- US Food and Drug Administration, Silver Spring, Maryland
| | | | | | - Juli Tomaino
- US Food and Drug Administration, Silver Spring, Maryland
| | - Sheila E Crowe
- Department of Medicine, University of California San Diego, La Jolla, California.
| |
Collapse
|
|
40
|
Zanella S, De Leo L, Nguyen-Ngoc-Quynh L, Nguyen-Duy B, Not T, Tran-Thi-Chi M, Phung-Duc S, Le-Thanh H, Malaventura C, Vatta S, Ziberna F, Mazzocco M, Volpato S, Phung-Tuyet L, Le-Thi-Minh H, Borgna-Pignatti C. Cross-sectional study of coeliac autoimmunity in a population of Vietnamese children. BMJ Open 2016; 6:e011173. [PMID: 27329441 PMCID: PMC4916638 DOI: 10.1136/bmjopen-2016-011173] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE The prevalence of coeliac disease (CD) in Vietnam is unknown. To fill this void, we assessed the prevalence of serological markers of CD autoimmunity in a population of children in Hanoi. SETTING The outpatient blood drawing laboratory of the largest paediatric hospital in North Vietnam was used for the study, which was part of an international project of collaboration between Italy and Vietnam. PARTICIPANTS Children having blood drawn for any reason were included. Exclusion criteria were age younger than 2 years, acquired or congenital immune deficiency and inadequate sample. A total of 1961 children (96%) were enrolled (838 females, 1123 males, median age 5.3 years). OUTCOMES Primary outcome was the prevalence of positive autoimmunity to both IgA antitransglutaminase antibodies (anti-tTG) assessed with an ELISA test and antiendomysial antibodies (EMA). Secondary outcome was the prevalence of CD predisposing human leucocyte antigens (HLA) (HLA DQ2/8) in the positive children and in a random group of samples negative for IgA anti-tTG. RESULTS The IgA anti-tTG test was positive in 21/1961 (1%; 95% CI 0.61% to 1.53%); however, EMA antibodies were negative in all. HLA DQ2/8 was present in 7/21 (33%; 95% CI 14.5% to 56.9%) of the anti-tTG-positive children and in 72/275 (26%; 95% CI 21% to 32%) of those who were negative. CONCLUSIONS Coeliac autoimmunity is rare in Vietnam, although prevalence of HLA DQ2/8 is similar to that of other countries. We hypothesise that the scarce exposure to gluten could be responsible for these findings.
Collapse
Affiliation(s)
- Sara Zanella
- Department of Medical Sciences/Pediatrics, University of Ferrara, Ferrara, Italy
| | - Luigina De Leo
- Institute for Maternal and Child Health—IRCCS “Burlo Garofolo”, Trieste, Italy
| | | | | | - Tarcisio Not
- Institute for Maternal and Child Health—IRCCS “Burlo Garofolo”, Trieste, Italy
| | | | | | | | - Cristina Malaventura
- Department of Medical Sciences/Pediatrics, University of Ferrara, Ferrara, Italy
| | - Serena Vatta
- Institute for Maternal and Child Health—IRCCS “Burlo Garofolo”, Trieste, Italy
| | - Fabiana Ziberna
- Institute for Maternal and Child Health—IRCCS “Burlo Garofolo”, Trieste, Italy
| | - Martina Mazzocco
- Department of Medical Sciences/Pediatrics, University of Ferrara, Ferrara, Italy
| | - Stefano Volpato
- Department of Medical Sciences/Pediatrics, University of Ferrara, Ferrara, Italy
| | | | | | | |
Collapse
|
|
41
|
Abstract
Celiac disease (CD) is characterized by small intestinal damage, which is mediated by a gluten-driven inflammatory response. Establishing a robust diagnosis is critical for improved quality of life and prevention of co-morbidities, although treatment is associated with a substantial life-long burden of care for patients and families. Unfortunately, CD remains a challenging diagnosis. As awareness of the disease increases, more diagnoses of CD are being made by primary care physicians. In fact, many patients may not present to a gastroenterologist because their symptoms are not clearly linked to a gastrointestinal pathology. Also, many patients are starting a gluten-free diet without prior testing, a circumstance that leads to even more confusion. Lastly, the number of serologic and genetic tests, and the role of endoscopy, can be confusing. The purpose of this review is to examine diagnostic testing strategies, focusing on published guidelines, for the evaluation of patients with suspected CD.
Collapse
Affiliation(s)
- Melissa R Snyder
- a Division of Clinical Biochemistry and Immunology, Department of Laboratory Medicine and Pathology , Mayo Clinic , Rochester , MN , USA
| | - Joseph A Murray
- b Division of Gastroenterology and Hepatology, Department of Medicine , Mayo Clinic , Rochester , MN , USA
| |
Collapse
|
|
42
|
Emilsson L, Lebwohl B, Sundström J, Ludvigsson JF. Cardiovascular disease in patients with coeliac disease: A systematic review and meta-analysis. Dig Liver Dis 2015; 47:847-52. [PMID: 26160499 DOI: 10.1016/j.dld.2015.06.004] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 06/05/2015] [Accepted: 06/08/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Coeliac disease has been associated with an increased risk of cardiovascular disease in some studies, whereas other studies have shown no association. We performed a systematic review and meta-analysis of cardiovascular disease in celiac disease. METHODS Pubmed, Cinahl, EMBASE and Medline via Ovid were searched for relevant articles published until January 5, 2015. English-language articles on studies with more than 20 patients were included, and were quality rated using the GRADE risk of bias tool. We used random-effects models and assessed heterogeneity using the I(2) statistic. RESULTS Ten studies were relevant, reporting the risk of myocardial infarction, cardiovascular death and stroke in 33,128/32,903/32,466 coeliac disease patients respectively. Only one study examined celiac disease and a composite measure of cardiovascular disease and this study found a hazard ratio of 1.10 (95%CI 1.03-1.28). In a meta-analysis, we observed an increased risk of stroke (OR 1.11; 95%CI 1.02-1.20). The risks of myocardial infarction (OR 1.12; 95%CI 0.83-1.40) and cardiovascular death (OR 1.12; 95%CI 0.96-1.29) were similar but were estimated with less certainty. Heterogeneity was low for all outcomes except for myocardial infarction where it was moderate. CONCLUSION Coeliac disease was associated with a modestly increased risk of cardiovascular disease, but the evidence base is limited.
Collapse
Affiliation(s)
- Louise Emilsson
- Primary Care Research Unit, Vårdcentralen Värmlands Nysäter, Värmland County, Sweden; Department of Health Management and Health Economy, Institute of Health and Society, University of Oslo, Oslo, Norway.
| | - Benjamin Lebwohl
- Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Johan Sundström
- Department of Medical Sciences, Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
| | - Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden
| |
Collapse
|
|
43
|
Biagi F, Corazza GR. Do different patients with coeliac disease have different mortality rates? Gut 2015; 64:1187-8. [PMID: 25480310 DOI: 10.1136/gutjnl-2014-308567] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2014] [Accepted: 11/20/2014] [Indexed: 12/08/2022]
Affiliation(s)
- Federico Biagi
- Coeliac Centre/First Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Gino Roberto Corazza
- Coeliac Centre/First Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| |
Collapse
|
|
44
|
Mearin ML. The prevention of coeliac disease. Best Pract Res Clin Gastroenterol 2015; 29:493-501. [PMID: 26060113 DOI: 10.1016/j.bpg.2015.04.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Revised: 04/22/2015] [Accepted: 04/26/2015] [Indexed: 01/31/2023]
Abstract
Primary prevention of coeliac disease is currently not possible. Previously, a 'window of opportunity' was suggested for primary prevention, by introducing gluten between four and six months of age. However, results from recent prospective studies establish that the timing of gluten introduction and the duration or maintenance of breastfeeding do not influence the development of the disease. Secondary prevention is possible through early diagnosis and treatment. Since coeliac disease is severely underdiagnosed, the only way to achieve large-scale secondary prevention is by mass screening. Prospective studies indicate that important health problems, such as reduced foetal growth and birth weight, delayed growth in height and weight in children, and reduced bone mineral density in both children and adults can be prevented by mass screening. Adherence to a strict gluten-free diet may be considered as tertiary prevention.
Collapse
Affiliation(s)
- M Luisa Mearin
- Dept. of Paediatrics, Leiden University Medical Center, Leiden, The Netherlands.
| |
Collapse
|
|
45
|
Mearin ML. Celiac disease: prevention in children. Dig Dis 2015; 33:162-166. [PMID: 25925918 DOI: 10.1159/000369539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Several studies have suggested a protective role of breastfeeding and/or the timing and quantity of gluten introduction in the subsequent development of celiac disease. Especially, prolonged breastfeeding during the introduction of gluten-containing feeding has been associated with a reduced risk of developing celiac disease in infancy. The mentioned results suggest the existence of a 'window of opportunity' between 4 and 6 months of age in which gluten can be introduced in small amounts. Therefore, the European Society for Pediatric Gastroenterology Hepatology and Nutrition recommends avoiding gluten introduction before the age of 4 months and after the age of 7 months and that gluten should be preferably introduced during ongoing breastfeeding. However, the influence of breastfeeding in the development of celiac disease is not clear, since some studies report prevention and others do not, and the studies reporting a protective effect of breastfeeding do not make clear if it concerns prevention of the disease or delays the onset of symptoms. In addition, most of the studies on this topic have been observational and retrospective. For these reasons, prospective studies are needed to understand the relationship between early nutrition in particular and environmental factors in general, concerning the development and possible prevention of celiac disease. Some of these studies are ongoing. One example is the European multicenter PreventCD project (www.preventcoeliacdisease.com) among infants with a first-degree family member with celiac disease carrying HLA-DQ2 and/or -DQ8, randomized to a double-blind dietary intervention with 100 mg of gluten daily or placebo between the age of 4-6 months. All included children are already 3 years old, and the first analyses are being prepared (http://www.trialregister.nl).
Collapse
Affiliation(s)
- M Luisa Mearin
- Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands
| |
Collapse
|
|
46
|
Hegenbart S, Uhl A, Vécsei A. Survey on computer aided decision support for diagnosis of celiac disease. Comput Biol Med 2015; 65:348-58. [PMID: 25770906 PMCID: PMC4593300 DOI: 10.1016/j.compbiomed.2015.02.007] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2014] [Revised: 02/10/2015] [Accepted: 02/11/2015] [Indexed: 12/13/2022]
Abstract
Celiac disease (CD) is a complex autoimmune disorder in genetically predisposed individuals of all age groups triggered by the ingestion of food containing gluten. A reliable diagnosis is of high interest in view of embarking on a strict gluten-free diet, which is the CD treatment modality of first choice. The gold standard for diagnosis of CD is currently based on a histological confirmation of serology, using biopsies performed during upper endoscopy. Computer aided decision support is an emerging option in medicine and endoscopy in particular. Such systems could potentially save costs and manpower while simultaneously increasing the safety of the procedure. Research focused on computer-assisted systems in the context of automated diagnosis of CD has started in 2008. Since then, over 40 publications on the topic have appeared. In this context, data from classical flexible endoscopy as well as wireless capsule endoscopy (WCE) and confocal laser endomicrosopy (CLE) has been used. In this survey paper, we try to give a comprehensive overview of the research focused on computer-assisted diagnosis of CD.
The state-of-the-art research in automated diagnosis of celiac disease is presented. A systematic review of methods and techniques used in this field is given. Specific issues and challenges in the field are identified and discussed.
Collapse
Affiliation(s)
- Sebastian Hegenbart
- Department of Computer Sciences, University of Salzburg, Jakob-Haringer Strasse, 5020 Salzburg, Austria.
| | - Andreas Uhl
- Department of Computer Sciences, University of Salzburg, Jakob-Haringer Strasse, 5020 Salzburg, Austria.
| | - Andreas Vécsei
- St. Anna Children׳s Hospital, Medical University Vienna, 1090 Vienna, Austria.
| |
Collapse
|
|
47
|
Abstract
The advent of highly reliable noninvasive celiac diagnostic tests has transformed the field of celiac disease, from diagnosis, to evaluation of epidemiology, to clinical and translational research. Serologic tests in their modern forms are highly sensitive and specific for diagnosis, allowing for consideration of avoidance of diagnostic intestinal biopsy in some settings. On the other hand, as predictors of intestinal damage and for use in monitoring disease activity, currently available noninvasive tests have been disappointing. Serologic tests, while a measure of disease activity, do not correlate well with histology or symptomatology, and it is unclear if they predict long-term risk. Additionally, while the many clinically available tests have improved accessibility, they can have widely different cutoff levels and overall performance, making the comparison of levels in individual patients over time and across populations quite difficult. In the future, we can expect to see improvement in the currently available serologic tests including tissue transglutaminase and deamidated gliadin peptide with expansion of the dynamic range of the tests, and the celiac care community should push for a standardization of assays that would simplify research and patient care. Additionally, current serologic tests are measures of the adaptive immune response in celiac disease but do not directly measure intestinal inflammation. Promising work on intestinal fatty acid-binding protein and other assays which directly measure intestinal damage may complement traditional serologic tests and further improve our ability to noninvasively diagnose and monitor celiac disease. The coming years hold promise for the continuing evolution of serum-based tests in celiac disease with the possibility of substantial improvement of patient care and clinical research.
Collapse
|
|
48
|
Vriezinga SL, Auricchio R, Bravi E, Castillejo G, Chmielewska A, Crespo Escobar P, Kolaček S, Koletzko S, Korponay-Szabo IR, Mummert E, Polanco I, Putter H, Ribes-Koninckx C, Shamir R, Szajewska H, Werkstetter K, Greco L, Gyimesi J, Hartman C, Hogen Esch C, Hopman E, Ivarsson A, Koltai T, Koning F, Martinez-Ojinaga E, te Marvelde C, Pavic A, Romanos J, Stoopman E, Villanacci V, Wijmenga C, Troncone R, Mearin ML. Randomized feeding intervention in infants at high risk for celiac disease. N Engl J Med 2014; 371:1304-15. [PMID: 25271603 DOI: 10.1056/nejmoa1404172] [Citation(s) in RCA: 300] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
BACKGROUND A window of opportunity has been suggested for reducing the risk of celiac disease by introducing gluten to infants at 4 to 6 months of age. METHODS We performed a multicenter, randomized, double-blind, placebo-controlled dietary-intervention study involving 944 children who were positive for HLA-DQ2 or HLA-DQ8 and had at least one first-degree relative with celiac disease. From 16 to 24 weeks of age, 475 participants received 100 mg of immunologically active gluten daily, and 469 received placebo. Anti-transglutaminase type 2 and antigliadin antibodies were periodically measured. The primary outcome was the frequency of biopsy-confirmed celiac disease at 3 years of age. RESULTS Celiac disease was confirmed by means of biopsies in 77 children. To avoid underestimation of the frequency of celiac disease, 3 additional children who received a diagnosis of celiac disease according to the 2012 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition diagnostic criteria (without having undergone biopsies) were included in the analyses (80 children; median age, 2.8 years; 59% were girls). The cumulative incidence of celiac disease among patients 3 years of age was 5.2% (95% confidence interval [CI], 3.6 to 6.8), with similar rates in the gluten group and the placebo group (5.9% [95% CI, 3.7 to 8.1] and 4.5% [95% CI, 2.5 to 6.5], respectively; hazard ratio in the gluten group, 1.23; 95% CI, 0.79 to 1.91). Rates of elevated levels of anti-transglutaminase type 2 and antigliadin antibodies were also similar in the two study groups (7.0% [95% CI, 4.7 to 9.4] in the gluten group and 5.7% [95% CI, 3.5 to 7.9] in the placebo group; hazard ratio, 1.14; 95% CI, 0.76 to 1.73). Breast-feeding, regardless of whether it was exclusive or whether it was ongoing during gluten introduction, did not significantly influence the development of celiac disease or the effect of the intervention. CONCLUSIONS As compared with placebo, the introduction of small quantities of gluten at 16 to 24 weeks of age did not reduce the risk of celiac disease by 3 years of age in this group of high-risk children. (Funded by the European Commission and others; PreventCD Current Controlled Trials number, ISRCTN74582487.).
Collapse
|
|
49
|
Affiliation(s)
- Daniel A Leffler
- Department of Medicine, Harvard Medical School and Celiac Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Ciarán P Kelly
- Department of Medicine, Harvard Medical School and Celiac Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
| |
Collapse
|
|
50
|
Biagi F, Marchese A, Ferretti F, Ciccocioppo R, Schiepatti A, Volta U, Caio G, Ciacci C, Zingone F, D'Odorico A, Carroccio A, Ambrosiano G, Mansueto P, Gasbarrini A, Piscaglia AC, Andrealli A, Astegiano M, Segato S, Neri M, Meggio A, de Pretis G, De Vitis I, Gobbi P, Corazza GR. A multicentre case control study on complicated coeliac disease: two different patterns of natural history, two different prognoses. BMC Gastroenterol 2014; 14:139. [PMID: 25103857 PMCID: PMC4127435 DOI: 10.1186/1471-230x-14-139] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2014] [Accepted: 07/28/2014] [Indexed: 12/14/2022] Open
Abstract
Background Coeliac disease is a common enteropathy characterized by an increased mortality mainly due to its complications. The natural history of complicated coeliac disease is characterised by two different types of course: patients with a new diagnosis of coeliac disease that do not improve despite a strict gluten-free diet (type A cases) and previously diagnosed coeliac patients that initially improved on a gluten-free diet but then relapsed despite a strict diet (type B cases). Our aim was to study the prognosis and survival of A and B cases. Methods Clinical and laboratory data from coeliac patients who later developed complications (A and B cases) and sex- and age-matched coeliac patients who normally responded to a gluten-free diet (controls) were collected among 11 Italian centres. Results 87 cases and 136 controls were enrolled. Complications tended to occur rapidly after the diagnosis of coeliac disease and cumulative survival dropped in the first months after diagnosis of complicated coeliac disease. Thirty-seven cases died (30/59 in group A, 7/28 in group B). Type B cases presented an increased survival rate compared to A cases. Conclusions Complicated coeliac disease is an extremely serious condition with a high mortality and a short survival. Survival depends on the type of natural history.
Collapse
Affiliation(s)
- Federico Biagi
- Coeliac Centre/First Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, P,le Golgi, 19, I-27100, Pavia, Italy.
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|