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Manninen J, Paavola S, Kurppa K, Huhtala H, Salmi T, Kaukinen K, Pasternack C. Prevalence of oral manifestations in coeliac disease and associated factors. BMC Gastroenterol 2025; 25:126. [PMID: 40033185 DOI: 10.1186/s12876-025-03699-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 02/14/2025] [Indexed: 03/05/2025] Open
Abstract
BACKGROUND Various oral manifestations are associated with coeliac disease in children, whereas data on adults are scarce. Moreover, possible individual factors predisposing to these manifestations remain unresolved. The aim of this study was to investigate these issues in a large cohort of adult coeliac disease patients both at diagnosis and while on gluten-free diet (GFD). METHODS This population-based study involved 873 adult patients with coeliac disease and 563 non-coeliac controls. Patients and controls were interviewed and structured questionnaires were used to assess the severity of gastrointestinal symptoms and quality of life at the time of the study. All participants were systematically asked about oral manifestations, including dental enamel defects, recurrent aphthous ulceration and glossodynia. Coeliac disease-related data were collected from medical records. Possible individual factors associated with oral manifestations were studied using logistic regression analysis. RESULTS Dental enamel defects were more common among patients than among non-coeliac controls (27% vs. 4%, p < 0.001). Prior to the coeliac disease diagnosis, 56% of the patients had experienced recurrent aphthous ulceration and GFD brought relief to 69% of them. While on GFD, coeliac disease patients had higher prevalence of recurrent aphthous ulceration than did the controls (17% vs. 13%, p = 0.040), but this significance disappeared after adjusting for gender. Glossodynia on GFD was more prevalent in the coeliac cohort than in the controls (14% vs 6%, p < 0.001). Oral manifestations at diagnosis and on GFD were associated with the presence of abdominal symptoms at the time of coeliac disease diagnosis, long diagnostic delay and female gender. At the time of the study, patients with oral symptoms had more severe gastrointestinal symptoms and poorer quality of life than those without these symptoms. CONCLUSIONS Oral manifestations were more prevalent, at diagnosis and on GFD, in patients with coeliac disease than in the controls, and they were associated with long diagnostic delay, abdominal symptoms, female gender and impaired quality of life. A GFD was shown beneficial in relieving recurrent aphthous ulcerations in patients with coeliac disease.
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Affiliation(s)
- Jani Manninen
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Saana Paavola
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Internal Medicine, Tampere University Hospital, Wellbeing Services County of Pirkanmaa, Tampere, Finland
| | - Kalle Kurppa
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Tampere Center for Child, Adolescent and Maternal Health Research, Tampere University and Tampere University Hospital, Wellbeing Services County of Pirkanmaa, Tampere, Finland
- The University Consortium of Seinäjoki, Seinäjoki, Finland
| | - Heini Huhtala
- Faculty of Social Sciences, Tampere University, Tampere, Finland
| | - Teea Salmi
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Dermatology, Tampere University Hospital, Wellbeing Services County of Pirkanmaa, Tampere, Finland
| | - Katri Kaukinen
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Internal Medicine, Tampere University Hospital, Wellbeing Services County of Pirkanmaa, Tampere, Finland
| | - Camilla Pasternack
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
- Department of Dermatology, Tampere University Hospital, Wellbeing Services County of Pirkanmaa, Tampere, Finland.
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Stroebele-Benschop N, Rau CJ, Dieze A, Bschaden A. Life Challenges and Quality of Life of People Living With Coeliac Disease: Time of Diagnosis Matters. J Hum Nutr Diet 2025; 38. [PMID: 39718414 DOI: 10.1111/jhn.13413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 10/28/2024] [Accepted: 11/27/2024] [Indexed: 12/25/2024]
Abstract
BACKGROUND Previous studies have examined the quality of life of patients with coeliac disease. There is a lack of understanding about potential changes in emotional responses and life challenges after diagnosis. This exploratory study aimed to evaluate the emotional impact, life challenges and quality of life in people living with coeliac disease in Germany. METHODS An online survey was conducted among patients with coeliac disease to assess difficulties in implementing a gluten-free diet in daily life activities, including food shopping and preparation, and eating away from home, as well as additional costs of time and money. Furthermore, the questionnaire assessed the time of diagnosis, emotions felt after diagnosis and today, compliance regarding the gluten-free diet and sociodemographic data. Participants were recruited in 2022 via social media, newsletters and websites. Out of 1286 participants who had taken part in the survey, 766 met the inclusion criteria and were included in the data analysis. RESULTS The majority of the respondents (aged 18-83 years) were female (93%) and almost 50% were diagnosed more than 5 years ago. Negative emotion ratings related to the disease were associated with age at the time of diagnosis and years passed since diagnosis. While compliance was high with 89% of respondents strictly adhering to the gluten-free diet, patients with coeliac disease reported mainly life challenges in social situations involving food such as out-of-home consumption in restaurants, at work and while travelling. These challenges appear to persist over time. CONCLUSIONS Negative emotions and difficulties in implementing a gluten-free diet are negatively impacting individuals with coeliac disease, particularly in the first months after diagnosis. Particularly adolescents and young adults appear to be negatively impacted. The study emphasises the need to improve the quality of life in all impacted areas through better guidance and improved training of health professionals as well as food providers outside of home and through psychological counselling in the first year of diagnosis to better help individuals improve their quality of life.
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Affiliation(s)
- Nanette Stroebele-Benschop
- Department of Applied Nutritional Psychology, University of Hohenheim, Stuttgart, Baden-Wuerttemberg, Germany
| | - Christine J Rau
- Department of Applied Nutritional Psychology, University of Hohenheim, Stuttgart, Baden-Wuerttemberg, Germany
| | - Anastasia Dieze
- Department of Applied Nutritional Psychology, University of Hohenheim, Stuttgart, Baden-Wuerttemberg, Germany
| | - Andreas Bschaden
- Department of Applied Nutritional Psychology, University of Hohenheim, Stuttgart, Baden-Wuerttemberg, Germany
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Sareila H, Kurppa K, Huhtala H, Laurikka P, Arnala S, Koskela T, Kaukinen K, Kivelä L. Patient perceptions of the Finnish guidelines enabling coeliac disease diagnosis without biopsies in adults. Scand J Gastroenterol 2025; 60:20-27. [PMID: 39620385 DOI: 10.1080/00365521.2024.2431628] [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: 09/27/2024] [Revised: 11/09/2024] [Accepted: 11/11/2024] [Indexed: 04/05/2025]
Abstract
OBJECTIVES Diagnosis of coeliac disease based on serology only has been allowed since 2018 in Finland for adults meeting specific criteria. We studied the patient experiences and perceptions of this novel diagnostic option. METHODS Altogether 194 adult patients were questioned on socio-demographic and health-related characteristics, quality of life and various coeliac disease-related issues. The results were compared between patients diagnosed with intestinal biopsy or based on serology only. RESULTS Altogether 69 (36%) of the patients were diagnosed without duodenal biopsies. They were younger (median 43 vs. 51 years, p = 0.046), diagnosed more recently (2021 vs. 2020, p < 0.001) and more often in primary health care (78% vs. 43%, p = 0.001), had fewer esophageal symptoms at diagnosis (17% vs. 30%, p = 0.046) and considered the diagnostic process easier (49% vs. 30%, p = 0.032) than those diagnosed by duodenal biopsy (n = 125). The no-biopsy group received less often dietician follow-up (4% vs. 17%, p = 0.012), reported more persistent symptoms (36% vs. 21%, p = 0.026) and experienced more stress due to the diet (68% vs. 47%, p = 0.039). Symptom persistence or stress were not associated with year of diagnosis or dietician follow-up. The groups were comparable in socio-economic characteristics, general health, quality of life, diagnostic delay, dietician guidance at diagnosis, and dietary adherence. CONCLUSIONS The non-invasive approach resulted in de-centralized diagnosis and easier patient-experienced diagnostic process of coeliac disease, but was associated with increased risk for persistent symptoms and stress due to gluten-free diet. These results highlight the significance of appropriate patient guidance and support regardless of the diagnostic strategy.
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Affiliation(s)
- Hanna Sareila
- Celiac Disease Research Centre, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Hatanpää Health Care Centre, Wellbeing Services County of Pirkanmaa, Tampere, Finland
| | - Kalle Kurppa
- Celiac Disease Research Centre, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Tampere Center for Child, Adolescent and Maternal Health Research, Tampere University, Tampere, Finland
- Department of Paediatrics, Tampere University Hospital, Wellbeing Services County of Pirkanmaa, Tampere, Finland
- The University Consortium of Seinäjoki, Seinäjoki, Finland
| | - Heini Huhtala
- Faculty of Social Sciences, Tampere University, Tampere, Finland
| | - Pilvi Laurikka
- Celiac Disease Research Centre, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Internal Medicine, Kanta-Häme Central Hospital, Wellbeing Services County of Hanta-Häme, Hämeenlinna, Finland
| | - Sanna Arnala
- Celiac Disease Research Centre, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Tuomas Koskela
- Department of General Practice, Faculty of Medicine and Health Technology, University of Tampere, Finland
- Wellbeing Services County of Pirkanmaa, Tampere, Finland
| | - Katri Kaukinen
- Celiac Disease Research Centre, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Internal Medicine, Tampere University Hospital, Wellbeing Services County of Pirkanmaa, Tampere, Finland
| | - Laura Kivelä
- Celiac Disease Research Centre, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Paediatrics, Tampere University Hospital, Wellbeing Services County of Pirkanmaa, Tampere, Finland
- Children's Hospital, Helsinki University Hospital, Helsinki, Finland
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Hanani A, Shaer H, Nairat M, Zeer R, Abdo Q, Damiri B. Mental health well-being and quality of life among celiac, ulcerative colitis and Crohn’s disease patients in Palestine. COGENT PSYCHOLOGY 2024; 11. [DOI: 10.1080/23311908.2024.2369411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 06/08/2024] [Accepted: 06/13/2024] [Indexed: 01/03/2025] Open
Affiliation(s)
- Ahmad Hanani
- Medicine & Health Science Faculty, Public Health Division, An-Najah National University, Nablus, Palestine
| | - Hamza Shaer
- Medicine & Health Science Faculty, Department of Medicine, An-Najah National University, Nablus, Palestine
| | - Mahmoud Nairat
- Medicine & Health Science Faculty, Department of Medicine, An-Najah National University, Nablus, Palestine
| | - Ramadan Zeer
- Medicine & Health Science Faculty, Department of Medicine, An-Najah National University, Nablus, Palestine
| | - Qusai Abdo
- Medicine & Health Science Faculty, Department of Internal Medicine, An-Najah National University Hospital, An-Najah National University, Nablus, Palestine
| | - Basma Damiri
- Medicine & Health Science Faculty, Drug and Toxicology Division, An-Najah National University, Nablus, Palestine
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Hujoel IA, Hujoel MLA, Choung RS, Murray JA. Symptom Outcomes of Celiac Disease in Those on a Gluten-free Diet. J Clin Gastroenterol 2024; 58:781-788. [PMID: 38019078 DOI: 10.1097/mcg.0000000000001946] [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] [Received: 07/21/2023] [Accepted: 10/20/2023] [Indexed: 11/30/2023]
Abstract
GOALS We aimed to evaluate symptom outcomes in those on a gluten-free diet during the 5 years after diagnosis. BACKGROUND Celiac disease is common; however, little is known about long-term symptom outcomes. STUDY We performed a retrospective chart review on individuals with celiac disease followed at a tertiary referral center between 2012 and 2018. To minimize bias, strict inclusion/exclusion criteria were utilized. Only those with definitive biopsy-proven celiac disease, on a gluten-free diet, and with systematic follow-up were included. The standardized care at this center reduced the risk that decisions on testing and follow-up visits were determined by symptom status. Summary statistics were computed and generalized linear models with a logit link were used to associate the proportion of symptomatic visits with various covariates using R statistical programming. RESULTS Of the 1023 records reviewed, 212 met inclusion/exclusion criteria; 146 (69%) were female and the mean age at diagnosis was 43 (range: 11 to 84 y old). During follow-up, over 50% remained symptomatic, with many having the same symptoms that prompted the diagnosis. The only predictors for remaining symptomatic were female sex and younger age at diagnosis. Abnormal serology during follow-up and small bowel normalization were not predictive. CONCLUSIONS In individuals with definitive celiac disease with systematic long-term follow-up in a Celiac Clinic, roughly half remained symptomatic despite a gluten-free diet. Many suffer from the same symptoms that prompted the diagnosis of celiac disease. Small bowel healing and abnormal serology in follow-up were not predictive of remaining symptomatic. These findings stress the importance of long-term care in celiac disease.
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Affiliation(s)
- Isabel A Hujoel
- Division of Gastroenterology, Department of Internal Medicine University of Washington, Seattle, WA
| | - Margaux L A Hujoel
- Division of Genetics, Department of Medicine Brigham and Women's Hospital and Harvard Medical School, Boston
- Program in Medical and Population Genetics Broad Institute of MIT and Harvard, Cambridge, MA
| | - Rok Seon Choung
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Joseph A Murray
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
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Ciaccio EJ, Lee AR, Lebovits J, Wolf RL, Lewis SK, Ciacci C, Green PHR. Psychological, Psychiatric, and Organic Brain Manifestations of Celiac Disease. Dig Dis 2024; 42:419-444. [PMID: 38861947 DOI: 10.1159/000534219] [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: 04/19/2023] [Accepted: 09/07/2023] [Indexed: 06/13/2024]
Abstract
INTRODUCTION Celiac disease is an autoimmune condition that affects approximately 1% of the population worldwide. Although its main impact often concerns the small intestine, resulting in villous atrophy and nutrient malabsorption, it can also cause systemic manifestations, particularly when undiagnosed or left untreated. METHOD Attention is directed to the possible psychological, psychiatric, and organic brain manifestations of celiac disease. Specific topics related to the influence and risk of such manifestations with respect to celiac disease are defined and discussed. Overall, eighteen main topics are considered, sifted from over 500 references. RESULTS The most often studied topics were found to be the effect on quality of life, organic brain dysfunction and ataxia, epilepsy, Down syndrome, generalized psychological disorders, eating dysfunction, depression, and schizophrenia. For most every topic, although many studies report a connection to celiac disease, there are often one or more contrary studies and opinions. A bibliographic analysis of the cited articles was also done. There has been a sharp increase in interest in this research since 1990. Recently published articles tend to receive more referencing, up to as many as 15 citations per year, suggesting an increasing impact of the topics. The number of manuscript pages per article has also tended to increase, up to as many as 12 pages. The impact factor of the publishing journal has remained level over the years. CONCLUSION This compendium may be useful in developing a consensus regarding psychological, psychiatric, and organic brain manifestations that can occur in celiac disease and for determining the best direction for ongoing research focus.
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Affiliation(s)
- Edward J Ciaccio
- Department of Medicine - Celiac Disease Center, Columbia University Irving Medical Center, New York, New York, USA
| | - Anne R Lee
- Department of Medicine - Celiac Disease Center, Columbia University Irving Medical Center, New York, New York, USA
| | - Jessica Lebovits
- Department of Medicine - Celiac Disease Center, Columbia University Irving Medical Center, New York, New York, USA
| | - Randi L Wolf
- Teachers College, Columbia University, New York, New York, USA
| | - Suzanne K Lewis
- Department of Medicine - Celiac Disease Center, Columbia University Irving Medical Center, New York, New York, USA
| | - Carolina Ciacci
- Department of Medicine, Surgery, and Dentistry, Scuola Medica Salernitana, Università degli Studi di Salerno, Salerno, Italy
| | - Peter H R Green
- Department of Medicine - Celiac Disease Center, Columbia University Irving Medical Center, New York, New York, USA
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Kurppa K, Mulder CJ, Stordal K, Kaukinen K. Celiac Disease Affects 1% of Global Population: Who Will Manage All These Patients? Gastroenterology 2024; 167:148-158. [PMID: 38290622 DOI: 10.1053/j.gastro.2023.12.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 12/19/2023] [Accepted: 12/19/2023] [Indexed: 02/01/2024]
Abstract
Celiac disease is a common gastrointestinal condition with an estimated global prevalence of up to 1%. Adequate long-term surveillance of patients is imperative to ensure strict adherence to treatment with a gluten-free diet and the ensuing clinical and histologic recovery. Traditionally, this has been accomplished by means of regular on-site attendance at specialist health care facilities, accompanied for most patients by follow-up endoscopic and laboratory tests. However, the rapidly increasing prevalence of celiac disease and the limited health care resources challenge the current centralized and nonindividualized follow-up strategies. The improved noninvasive surveillance tools and online health care services are further changing the landscape of celiac disease management. There is a clear need for more personalized and on-demand follow-up based on early treatment response and patient-related factors associated with long-term prognosis. Additional scientific evidence on the optimal implementation of follow-up for pediatric and adulthood celiac disease is nevertheless called for.
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Affiliation(s)
- Kalle Kurppa
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Tampere Center for Child, Adolescent, and Maternal Health Research, Tampere University, Tampere, Finland; Department of Pediatrics, Tampere University Hospital, Tampere, Finland; University Consortium of Seinäjoki, Seinäjoki, Finland.
| | - Chris J Mulder
- Department of Gastroenterology, Amsterdam University Medical Center, Amsterdam, The Netherlands; Location Vrije Universiteit, Amsterdam, The Netherlands
| | - Ketil Stordal
- Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway; Department of Pediatric Research, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Katri Kaukinen
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
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Raju SA, Shiha MG, Penny HA. Monitoring coeliac disease in 2024, time to change practice? Curr Opin Gastroenterol 2024; 40:190-195. [PMID: 38547329 DOI: 10.1097/mog.0000000000001009] [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: 04/04/2024]
Abstract
PURPOSE OF REVIEW Persistent villous atrophy is associated with morbidity in coeliac disease and most commonly due to ongoing gluten ingestion. Current methods for assessing gluten exposure and persisting villous atrophy include dietary questionnaires and repeat duodenal biopsy, which have limited accuracy or are invasive. This review discusses adjunctive and/or novel tests that could be used to overcome these challenges. RECENT FINDINGS Small bowel capsule endoscopy is well tolerated and helps to evaluate for persisting villous atrophy and importantly, complications associated with coeliac disease. Testing for urinary and/or stool gluten immunogenic peptides may help identify recent gluten exposure, but further studies are still warranted to evaluate the accuracy and applicability of this approach. Measuring spikes in circulating Interleukin-2 following gluten challenge has shown promise for coeliac disease diagnosis, and thus may serve as a useful confirmatory test in those with persisting symptoms but provides no information on mucosal inflammation. No specific gut microbial signature has been identified in coeliac disease; however, studies have shown a reduced microbial diversity in active disease, which with future refinement may prove clinically useful. SUMMARY There is no evidence to support alternative methods for assessing persisting villous atrophy in coeliac disease over performing an up-to-date duodenal biopsy. Monitoring for adherence to a gluten-free diet remains clinically challenging and should be a priority for future research.
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Affiliation(s)
- Suneil A Raju
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK
| | - Mohamed G Shiha
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK
| | - Hugo A Penny
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK
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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.
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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
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Soheilian Khorzoghi M, Rostami-Nejad M, Yadegar A, Dabiri H, Hadadi A, Rodrigo L. Impact of probiotics on gut microbiota composition and clinical symptoms of coeliac disease patients following gluten-free diet. Contemp Clin Trials Commun 2023; 35:101201. [PMID: 37680267 PMCID: PMC10480319 DOI: 10.1016/j.conctc.2023.101201] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Revised: 08/03/2023] [Accepted: 08/20/2023] [Indexed: 09/09/2023] Open
Abstract
Coeliac disease (CD) is associated with alterations in gut microbiota composition. This study evaluated the effects of probiotics on gut microbiota composition and clinical symptoms of treated CD patients. In this double-blind, placebo-controlled trial study, 31 CD patients that were randomly classified as probiotics (n = 15) and placebo (n = 16) groups received 109 colony-forming units/capsule for 12 weeks. Fecal samples were collected before and after probiotics, or placebo administration and the changes in intestinal microbiota were assessed by quantitative real-time PCR. Probiotic administration improved the patients' clinical symptoms when compared to the placebo group. Fatigue score was significantly reduced by the intake of probiotic supplements (P = 0.02). Except for Staphylococcus spp., the relative abundances of Bacteroidetes, Lactobacillus spp., Bifidobacterium spp., Clostridium cluster I, Enterobacteriaceae, and Firmicutes were higher in probiotics group. Accordingly, a 12-week multi-strain probiotic treatment regimen may modify the composition of intestinal microbiota and improve GI symptoms in CD patients.
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Affiliation(s)
| | - Mohammad Rostami-Nejad
- Celiac Disease and Gluten Related Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hossein Dabiri
- Department of Microbiology, Faculty of Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azam Hadadi
- Department of Microbiology, Karaj Branch, Islamic Azad University, Karaj, Iran
| | - Luis Rodrigo
- Gastroenterology and Liver Service, Hospital Universitario Central de Asturias, School of Medicine, University of Oviedo, Spain
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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.
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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
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12
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Mulder CJJ, Elli L, Lebwohl B, Makharia GK, Rostami K, Rubio-Tapia A, Schumann M, Tye-Din J, Zeitz J, Al-Toma A. Follow-Up of Celiac Disease in Adults: "When, What, Who, and Where". Nutrients 2023; 15:2048. [PMID: 37432208 DOI: 10.3390/nu15092048] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Revised: 04/14/2023] [Accepted: 04/21/2023] [Indexed: 07/12/2023] Open
Abstract
For patients with celiac disease (CeD), a lifelong gluten-free diet is not a voluntary lifestyle choice-it is a necessity. The key end points in clinical follow-up are symptom resolution, the normalization of weight, prevention of overweight, seroconversion, and negation or minimization of increased long-term morbidity. For the latter, a surrogate endpoint is mucosal healing, which means the normalization of histology to Marsh 0-1. Ideally, celiac follow-up care includes a multidisciplinary approach, effective referral processes, improved access that leverages technological advances, and following guidelines with the identification of measurable quality indicators, ideally informed by evidence-based research. Face-to-face CeD care and telemedicine are considered the standards for this process, although published data are insufficient. Guidelines and statements on diagnosis are readily available. However, data are lacking on optimal clinic visit intervals and outcomes and quality indicators such as improvement of symptoms, function and quality of life, survival and disease control, and how to most effectively use healthcare resources. The results of future research should provide the basis for general recommendations for evidence-based standards of quality of care in CeD.
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Affiliation(s)
- Chris J J Mulder
- Department of Gastroenterology, Amsterdam UMC, Location Vrije Universiteit, 1081 HV Amsterdam, The Netherlands
| | - Luca Elli
- Center for Prevention and Diagnosis of Celiac Disease, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Benjamin Lebwohl
- Department of Medicine, Celiac Disease Center, Columbia University Medical Center, 180 Fort Washington Avenue, Suite 936, New York, NY 10032, USA
| | - Govind K Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India
| | - Kamran Rostami
- Department of Gastroenterology, Palmerston North Hospital, Palmerston North 4442, New Zealand
| | - Alberto Rubio-Tapia
- Division of Gastroenterology, Hepatology, and Nutrition, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Michael Schumann
- Department of Gastroenterology, Infectious Diseases, and Rheumatology, Campus Benjamin Franklin, Charité-University Medicine Berlin, 13125 Berlin, Germany
| | - Jason Tye-Din
- Department of Immunology, The Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia
- Department of Gastroenterology, The Royal Melbourne Hospital, Parkville, VIC 3050, Australia
| | - Jonas Zeitz
- Division of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland
- Swiss Celiac Center, Center of Gastroenterology, Clinic Hirslanden, 8032 Zurich, Switzerland
| | - Abdulbaqi Al-Toma
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, 3435 CM Nieuwegein, The Netherlands
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13
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Dochat C, Afari N, Arigo D. Psychometric validation of the celiac disease-specific quality of life survey (CD-QOL) in adults with celiac disease in the United States. Qual Life Res 2023:10.1007/s11136-023-03380-7. [PMID: 36928648 PMCID: PMC10329069 DOI: 10.1007/s11136-023-03380-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/20/2023] [Indexed: 03/18/2023]
Abstract
PURPOSE Celiac disease and its treatment negatively impact quality of life, indicating potential need for measurement of disease-specific quality of life domains to inform interdisciplinary intervention. The Celiac Disease Quality of Life Survey (CD-QOL) has been used in clinical research; however, its factor structure has not been confirmed and psychometric properties have not been evaluated in English-speaking adults in the U.S. AIMS (1) Confirm the factor structure of the 20-item English CD-QOL; (2) assess psychometric properties including internal consistency reliability, convergent validity, known groups validity, and incremental validity. METHODS 453 adults with self-reported Celiac disease (Mage = 40.57; 88% female; 92% White) completed the CD-QOL and validated measures of generic health-related quality of life (SF-36), gluten-free diet adherence (CDAT), anxiety and depression symptoms (PROMIS), and physical symptoms (CSI) as part of the iCureCeliac® patient-powered research network. RESULTS Confirmatory factor analysis found superior fit for a bifactor structure with one general factor and four group factors. Ancillary bifactor analyses suggest the CD-QOL can be considered primarily unidimensional. Total and three subscale scores demonstrated acceptable internal consistency reliability. Convergent and known groups validity were supported. The CD-QOL demonstrated some incremental validity over the SF-36. CONCLUSION The English CD-QOL can be used as a measure of disease-specific quality of life among adults with Celiac disease in the U.S. Compared to generic instruments, the CD-QOL appears to better capture specific cognitive and affective aspects of living with Celiac disease. Use of a total score is recommended. Its utility as a screening and outcome measurement tool in clinical settings should be examined.
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Affiliation(s)
- Cara Dochat
- San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, 6363 Alvarado Court, San Diego, CA, 92120, USA.
| | - Niloofar Afari
- VA San Diego Healthcare System, San Diego, CA, USA.,University of California San Diego, La Jolla, San Diego, CA, USA
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14
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Oh TY, Hofmekler T, Freeman AJ. Update in Pediatric Gastroenterology and Nutrition. UPDATE IN PEDIATRICS 2023:369-398. [DOI: 10.1007/978-3-031-41542-5_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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15
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Pohjonen JT, Kaukinen KM, Metso MJ, Nurmi RKK, Huhtala HSA, Pörsti IH, Mustonen JT, Mäkelä SM. Presence of gastrointestinal symptoms in IgA nephropathy: a cross-sectional study. BMC Nephrol 2022; 23:395. [PMID: 36482351 PMCID: PMC9733402 DOI: 10.1186/s12882-022-03019-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 11/28/2022] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Gastrointestinal (GI) symptoms are common in end-stage kidney disease. Mounting evidence indicates that the intestine plays an important role in the pathogenesis of IgA nephropathy (IgAN). However, no studies have addressed the obvious question; do IgAN patients suffer from GI symptoms? METHODS Presence of GI symptoms and health-related quality of life were evaluated using the validated Gastrointestinal Symptom Rating Scale (GSRS) and Psychological General Well-Being (PGWB) questionnaires in 104 patients with kidney biopsy-verified IgAN and in 147 healthy controls. A person was regarded to experience 'increased GI symptoms' if the GSRS score exceeded plus 1 standard deviation of the mean of the corresponding score in the healthy controls. RESULTS According to the GSRS total score, the IgAN patients had more GI symptoms than the healthy controls (2.0 vs. 1.7, p < 0.001). Female IgAN patients had higher GSRS total score than male patients (2.2 vs. 1.7, p = 0.001). More IgAN patients with preserved kidney function (eGFR > 60ml/min/1.73m2) suffered from increased symptoms of diarrhoea (76 vs. 25%, p = 0.028), constipation (81 vs. 19%, p = 0.046) and reflux (85 vs. 15%, p = 0.004) than did IgAN patients with reduced kidney function (eGFR < 60ml/min/1.73m2). CONCLUSIONS IgAN patients and especially female IgAN patients experienced more GI symptoms than healthy controls. More prevalent GI symptoms were already observed before kidney function was clearly reduced. Systematic enquiry of GI symptoms might increase the standard of care among IgAN patients. Moreover, GI symptoms may provide clues for future studies that examine the pathophysiology of IgAN.
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Affiliation(s)
- Jussi T. Pohjonen
- grid.502801.e0000 0001 2314 6254Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, FIN-33014 Tampere, Finland ,grid.412330.70000 0004 0628 2985Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
| | - Katri M. Kaukinen
- grid.502801.e0000 0001 2314 6254Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, FIN-33014 Tampere, Finland ,grid.412330.70000 0004 0628 2985Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
| | - Martti J. Metso
- grid.412330.70000 0004 0628 2985Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
| | - Rakel KK. Nurmi
- grid.502801.e0000 0001 2314 6254Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, FIN-33014 Tampere, Finland
| | - Heini SA. Huhtala
- grid.502801.e0000 0001 2314 6254Faculty of Social Sciences, Tampere University, Tampere, Finland
| | - Ilkka H. Pörsti
- grid.412330.70000 0004 0628 2985Department of Internal Medicine, Tampere University Hospital, Tampere, Finland ,grid.502801.e0000 0001 2314 6254Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Jukka T. Mustonen
- grid.412330.70000 0004 0628 2985Department of Internal Medicine, Tampere University Hospital, Tampere, Finland ,grid.502801.e0000 0001 2314 6254Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Satu M. Mäkelä
- grid.412330.70000 0004 0628 2985Department of Internal Medicine, Tampere University Hospital, Tampere, Finland ,grid.502801.e0000 0001 2314 6254Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
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16
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Vuolle S, Laurikka P, Repo M, Huhtala H, Kaukinen K, Kurppa K, Kivelä L. Persistent symptoms are diverse and associated with health concerns and impaired quality of life in patients with paediatric coeliac disease diagnosis after transition to adulthood. BMJ Open Gastroenterol 2022; 9:bmjgast-2022-000914. [PMID: 35820709 PMCID: PMC9277401 DOI: 10.1136/bmjgast-2022-000914] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 05/31/2022] [Indexed: 12/15/2022] Open
Abstract
Objective To investigate the prevalence and associated factors of persistent symptoms despite a strict gluten-free diet in adult patients with coeliac disease diagnosed in childhood. Design Medical data on 239 currently adult patients with paediatric diagnosis were collected from patient records. Also, patients completed structured study questionnaire. All variables were compared between those with and without persistent symptoms. Results Altogether 180 patients reported adhering to a strict gluten-free diet. Of these, 18% experienced persistent symptoms, including various gastrointestinal symptoms (73%), arthralgia (39%), fatigue (39%), skin symptoms (12%) and depression (6%). Those reporting persistent symptoms had more often gastrointestinal comorbidities (19% vs 6%, p=0.023), health concerns (30% vs 12%, p=0.006) and experiences of restrictions on daily life (64% vs 43%, p=0.028) than the asymptomatic subjects. The patients with symptoms had poorer general health (median score 13 vs 14, p=0.040) and vitality (15 vs 18, p=0.015) based on a validated Psychological General Well-Being Questionnaire and more severe symptoms on a Gastrointestinal Symptom Rating Scale scale (total score 2.1 vs 1.7, p<0.001). Except for general health, these differences remained significant after adjusting for comorbidities. The groups were comparable in current sociodemographic characteristics. Furthermore, none of the childhood features, including clinical, serological and histological presentation at diagnosis, and adherence and response to the diet after 6–24 months predicted symptom persistence in adulthood. Conclusion Almost one-fifth of adult patients diagnosed in childhood reported persistent symptoms despite a strict gluten-free diet. The ongoing symptoms were associated with health concerns and impaired quality of life.
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Affiliation(s)
- Satu Vuolle
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.,Tampere Centre for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.,Department of Pediatrics, Tampere University Hospital, Tampere, Finland
| | - Pilvi Laurikka
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.,Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
| | - Marleena Repo
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.,Tampere Centre for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.,Department of Pediatrics, Central Finland Central Hospital, Jyväskylä, Finland
| | - Heini Huhtala
- Faculty of Social Sciences, Tampere University, Tampere, Finland
| | - Katri Kaukinen
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.,Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
| | - Kalle Kurppa
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.,Tampere Centre for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.,Department of Pediatrics, Tampere University Hospital, Tampere, Finland.,The University Consortium of Seinäjoki, Seinäjoki, Finland
| | - Laura Kivelä
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland .,Tampere Centre for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.,Department of Pediatrics, Tampere University Hospital, Tampere, Finland.,Children's Hospital, and Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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17
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Laurikka P, Kivelä L, Kurppa K, Kaukinen K. Review article: Systemic consequences of coeliac disease. Aliment Pharmacol Ther 2022; 56 Suppl 1:S64-S72. [PMID: 35815828 PMCID: PMC9543231 DOI: 10.1111/apt.16912] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 02/08/2022] [Accepted: 03/18/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND The best-known symptoms of coeliac disease are related to the gastrointestinal tract, but the disease may also present with various systemic manifestations outside the intestine. Some of these consequences may remain permanent in undiagnosed individuals or if the diagnostic delay is prolonged. However, for many of the systemic manifestations, the scientific evidence remains scant and contradictory. AIMS AND METHODS We conducted a narrative review of the most thoroughly studied and clinically relevant systemic consequences of coeliac disease, especially those that could be prevented or alleviated by early diagnosis. The review is intended particularly for physicians encountering these patients in daily clinical practice. RESULTS The possible systemic consequences of coeliac disease extend to multiple organ systems, the best studied of which are related to skeletal, reproductive, cardiovascular and neurological systems. Furthermore, the disease is associated with an elevated risk of psychiatric comorbidities, non-Hodgkin lymphomas and intestinal adenocarcinoma. CONCLUSIONS The various systemic consequences of coeliac disease play a significant role in the overall health of patients. Early diagnosis and treatment with a gluten-free diet appear to be beneficial for most, but not all of these conditions. The possible negative metabolic and psychosocial effects of the diet should be acknowledged during follow-up.
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Affiliation(s)
- Pilvi Laurikka
- Celiac Disease Research Center, Faculty of Medicine and Health TechnologyTampere UniversityTampereFinland
- Department of Internal MedicineTampere University HospitalTampereFinland
| | - Laura Kivelä
- Celiac Disease Research Center, Faculty of Medicine and Health TechnologyTampere UniversityTampereFinland
- Children’s Hospital, and Paediatric Research CentreUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland
| | - Kalle Kurppa
- Tampere Center for Child, Adolescent and Maternal Health ResearchTampere University and Tampere University HospitalTampereFinland
- The University Consortium of Seinäjoki and Seinäjoki Central HospitalSeinäjokiFinland
| | - Katri Kaukinen
- Celiac Disease Research Center, Faculty of Medicine and Health TechnologyTampere UniversityTampereFinland
- Department of Internal MedicineTampere University HospitalTampereFinland
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18
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Kivelä L, Eurén A, Repo M, Huhtala H, Kaukinen K, Kurppa K. Coexisting Type 1 Diabetes, Persistent Symptoms, and Financial Issues Associate With Poorer Adherence to a Gluten-Free Diet in Celiac Disease After Transition From Pediatrics to Adult Care. Front Nutr 2022; 9:883220. [PMID: 35719146 PMCID: PMC9200750 DOI: 10.3389/fnut.2022.883220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 04/22/2022] [Indexed: 11/13/2022] Open
Abstract
Purpose We evaluated adherence to a gluten-free diet and associated factors in adult celiac disease patients diagnosed in childhood. Methods Comprehensive medical data on 955 pediatric celiac disease patients was collected and study questionnaires sent to 559 who were now adults. All variables were compared between strictly adherent and non-adherent patients. Results Altogether 237 adults (median age 27 years, 69% women) responded to the questionnaires a median of 18 (range 3-51) years after the childhood diagnosis. Altogether 78% were reportedly adherent and 22% non-adherent. The non-adherent patients had more concomitant type 1 diabetes (18% vs. 4%, p = 0.003), whereas the groups did not differ in demographic data or clinical and histological features at diagnosis, or in short-term dietary adherence. In adulthood, non-adherent patients found gluten-free diet more challenging (39% vs. 17%, p < 0.001) and had higher prevalence (39% vs. 19%, p = 0.004) and severity of symptoms. The main motivation factors for dietary adherence were attempts to avoid symptoms and complications, but these were considered less important and price of gluten-free products more important among non-adherent patients. Adherent and non-adherent patients did not differ in socioeconomic or lifestyle factors, comorbidities other than type 1 diabetes, self-reported general health, health concerns, follow-up, or in quality of life. Conclusion Most originally pediatric celiac disease patients reported strict dietary adherence in adulthood. However, particularly those with concomitant type 1 diabetes, persistent symptoms or financial issues may require attention during the transition from pediatric to adult care.
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Affiliation(s)
- Laura Kivelä
- Celiac Disease Research Center, Tampere University, Tampere, Finland.,Tampere Centre for Child, Adolescent and Maternal Health Research, Tampere University and Department of Pediatrics, Tampere University Hospital, Tampere, Finland.,Children's Hospital and Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Anna Eurén
- Celiac Disease Research Center, Tampere University, Tampere, Finland.,Tampere Centre for Child, Adolescent and Maternal Health Research, Tampere University and Department of Pediatrics, Tampere University Hospital, Tampere, Finland
| | - Marleena Repo
- Celiac Disease Research Center, Tampere University, Tampere, Finland.,Tampere Centre for Child, Adolescent and Maternal Health Research, Tampere University and Department of Pediatrics, Tampere University Hospital, Tampere, Finland
| | - Heini Huhtala
- Faculty of Social Sciences, Tampere University, Tampere, Finland
| | - Katri Kaukinen
- Celiac Disease Research Center, Tampere University, Tampere, Finland.,Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
| | - Kalle Kurppa
- Celiac Disease Research Center, Tampere University, Tampere, Finland.,Tampere Centre for Child, Adolescent and Maternal Health Research, Tampere University and Department of Pediatrics, Tampere University Hospital, Tampere, Finland.,The University Consortium of Seinäjoki and Department of Pediatrics, Seinäjoki Central Hospital, Seinäjoki, Finland
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19
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Simons M, Taft TH, Doerfler B, Ruddy JS, Bollipo S, Nightingale S, Siau K, van Tilburg MAL. Narrative review: Risk of eating disorders and nutritional deficiencies with dietary therapies for irritable bowel syndrome. Neurogastroenterol Motil 2022; 34:e14188. [PMID: 34254719 DOI: 10.1111/nmo.14188] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 04/20/2021] [Accepted: 05/05/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Dietary treatments are growing in popularity as interventions for chronic digestive conditions. Patients with irritable bowel syndrome (IBS) often change their eating behaviors to mitigate symptoms. This can occur under the direction of their physician, a dietitian, or be self-directed. Poorly implemented and monitored diet treatments occur frequently with considerable risks for negative consequences. We aim to review the literature related to dietary treatments and risks associated with nutritional deficiencies and disordered eating. METHODS Searches were conducted from June to December 2020 on PubMed, MEDLINE, EMBASE, DARE and the Cochrane Database of Systematic Reviews using relevant keywords based on the Patient, Intervention, Comparator and Outcome (PICO) format. Studies included both adult and pediatric populations. Results are synthesized into a narrative review. RESULTS While dietary approaches are efficacious in many research studies, their translation to clinical practice has been less clear. Patients with IBS are at risk for nutritional deficiencies, disordered eating, increased anxiety, and decreases in quality of life in both adult and pediatric groups. CONCLUSIONS Physicians prescribing dietary treatment for IBS should be aware of nutritional and psychological risks and implement mitigation measures. These include using a combination of brief, validated questionnaires and clinical history, and collaboration with registered dietitians and/or psychologists. Recommendations for clinical decisions are provided.
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Affiliation(s)
- Madison Simons
- Division of Gastroenterology & Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Tiffany H Taft
- Division of Gastroenterology & Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Bethany Doerfler
- Division of Gastroenterology & Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | | | - Steven Bollipo
- School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
| | - Scott Nightingale
- School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia.,Hunter Medical Research Institute, New Lambton, NSW, Australia
| | - Keith Siau
- The Dudley Group, NHS Foundation Trust, Dudley, UK
| | - Miranda A L van Tilburg
- College of Pharmacy & Health Sciences, Campbell University, Buies Creek, NC, USA.,Division of Gastroenterology and Hepatology, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.,School of Social Work, University of Washington, Seattle, WA, USA
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20
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Schiepatti A, Bacchi S, Biagi F, Panelli S, Betti E, Corazza GR, Capelli E, Ciccocioppo R. Relationship between duodenal microbiota composition, clinical features at diagnosis, and persistent symptoms in adult Coeliac disease. Dig Liver Dis 2021; 53:972-979. [PMID: 33741248 DOI: 10.1016/j.dld.2021.02.019] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 02/19/2021] [Accepted: 02/22/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Duodenal dysbiosis has been suggested to possibly influence the clinical manifestations of coeliac disease (CD), both at onset and when symptoms persist despite a gluten-free diet (GFD). AIMS To evaluate the relationship between duodenal microbiota composition and: i) clinical phenotype of untreated CD (UCD); ii) presence and type of persistent symptoms despite a satisfactory serological and histological response to a strict GFD. METHODS Duodenal microbiota was analyzed by 16S rRNA sequencing and compared with i) clinical features in 12 adult UCD patients; ii) presence/absence and type of persistent symptoms (diarrhea-predominant vs. non-diarrhea predominant) in 25 adult treated coeliac patients (TCD) on a strict GFD. RESULTS UCD with iron deficiency anemia (IDA) had a pro-inflammatory shift in their duodenal microbiota (reduction of Firmicutes, p = 0.03; increase of beta-Proteobacteria, p = 0.02) than those without IDA. TCD with persistent diarrhea showed a reduction of Actinobacteria (p = 0.03) and Rothia spp (p = 0.046) compared to TCD suffering from other type of persistent symptoms. CONCLUSION A distinctive duodenal microbiota profile is associated with IDA in UCD, and diarrhea-predominant persistent symptoms in TCD. Clinical interventions may include reconsidering patients presenting with IDA as a specific disease subtype, and dietary rebalancing if diarrhea persists despite histological response to a GFD.
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Affiliation(s)
- Annalisa Schiepatti
- Istituti Clinici Scientifici Maugeri, I.R.C.C.S., Gastroenterology Unit of Pavia Institute, University of Pavia, Pavia, Italy.
| | - Sara Bacchi
- Laboratory of Immunology and Genetic Analysis, Department of Earth and Environmental Science, University of Pavia, Pavia, Italy; Centre for Health Technologies, University of Pavia, Pavia, Italy
| | - Federico Biagi
- Istituti Clinici Scientifici Maugeri, I.R.C.C.S., Gastroenterology Unit of Pavia Institute, University of Pavia, Pavia, Italy
| | - Simona Panelli
- Department of Biomedical and Clinical Sciences "L. Sacco", Pediatric Clinical Research Center "Invernizzi", University of Milan, Milan, Italy
| | - Elena Betti
- First Department of Internal Medicine, I.R.C.C.S. San Matteo Hospital Foundation, University of Pavia, Pavia, Italy
| | - Gino Roberto Corazza
- First Department of Internal Medicine, I.R.C.C.S. San Matteo Hospital Foundation, University of Pavia, Pavia, Italy
| | - Enrica Capelli
- Laboratory of Immunology and Genetic Analysis, Department of Earth and Environmental Science, University of Pavia, Pavia, Italy; Centre for Health Technologies, University of Pavia, Pavia, Italy
| | - Rachele Ciccocioppo
- Gastroenterology Unit, Department of Medicine, A.O.U.I. Policlinico G.B. Rossi and University of Verona, Verona, Italy
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21
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Detection of gluten in duplicate portions to determine gluten intake of coeliac disease patients on a gluten-free diet. Br J Nutr 2021; 125:1051-1057. [PMID: 32723408 DOI: 10.1017/s0007114520002974] [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] [Indexed: 12/31/2022]
Abstract
This study determined the gluten content of foods and meals consumed by coeliac disease (CD) patients who adhere to a gluten-free diet, and to estimate the total daily intake of gluten of these patients. CD patients fulfilling defined inclusion criteria were preselected and approached for participation in the study. Duplicate portions (DP) of foods and mixed dishes were collected from the CD patients for evaluating complete daily food intake during two individual days. Also, for these days, written food records were completed by the participants. From each DP, a laboratory sample was prepared and analysed for its gluten concentration and total daily gluten intake was calculated. Each individual's total daily intakes of energy and macronutrients were calculated using the Dutch food composition database. In total, twenty-seven CD patients participated, seven males and twenty females, aged between 21 and 64 years. In thirty-two (6 %) of 499 food samples collected in total, more than 3 mg/kg gluten was present. In four of these thirty-two samples, the gluten concentration was above the European legal limit of 20 mg/kg and three of the four samples had a gluten-free label. The maximal gluten intake was 3·3 mg gluten/d. The gluten tolerance for sensitive CD patients (>0·75 mg/d) was exceeded on at least six out of fifty-four study days. To also protect these sensitive CD patients, legal thresholds should be re-evaluated and the detection limit of analytical methods for gluten analysis lowered.
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Weiman DI, Mahmud FH, Clarke ABM, Assor E, McDonald C, Saibil F, Lochnan HA, Punthakee Z, Marcon MA. Impact of a Gluten-Free Diet on Quality of Life and Health Perception in Patients With Type 1 Diabetes and Asymptomatic Celiac Disease. J Clin Endocrinol Metab 2021; 106:e1984-e1992. [PMID: 33524131 DOI: 10.1210/clinem/dgaa977] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Indexed: 02/13/2023]
Abstract
CONTEXT Celiac disease (CD) is a common comorbidity seen in patients with type 1 diabetes (T1D) and is frequently asymptomatic. As chronic conditions requiring significant lifestyle changes, there are limited reports assessing changes in health-related quality of life (HRQoL) during transition to a gluten-free diet (GFD) in patients with T1D who are asymptomatic for CD. OBJECTIVE This work aims to prospectively assess HRQoL and health perception in children and adults with T1D and asymptomatic CD after random assignment to GFD vs usual diet. METHODS Patients with T1D aged 8 to 45 years without CD symptoms were serologically screened for CD, with positive results confirmed with intestinal biopsy. Participants were randomly assigned in an open-label fashion to a GFD or gluten-containing diet (GCD) for 12 months. Generic and diabetes-specific HRQoL and self-perceived wellness (SPW) were assessed longitudinally. RESULTS A total of 2387 T1D patients were serologically screened. CD was biopsy-confirmed in 82 patients and 51 participants were randomly assigned to a GFD (N = 27) or GCD (N = 24). Excellent adherence to the assigned diets was observed. Overall, no changes in generic (P = .73) or diabetes-specific HRQoL (P = .30), or SPW (P = .41) were observed between groups over 12 months. Hemoglobin A1c (HbA1c) and gastrointestinal symptoms were consistent predictors of HRQoL and SPW. CONCLUSION HRQoL and SPW were not significantly affected by the adoption of a GFD over 12 months, but worsened with symptom onset and increased HbA1c. Our findings indicate that transition to a GFD can be made successfully in this population without adversely affecting quality of life.
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Affiliation(s)
- Daniel I Weiman
- Division of Endocrinology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Farid H Mahmud
- Division of Endocrinology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Antoine B M Clarke
- Division of Endocrinology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Esther Assor
- Division of Endocrinology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Charlotte McDonald
- Division of Endocrinology and Metabolism, St. Joseph's Health Care, Western University, London, Ontario, Canada
| | - Fred Saibil
- Division of Gastroenterology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
| | - Heather A Lochnan
- Department of Medicine and The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada
| | - Zubin Punthakee
- Division of Endocrinology, McMaster University, Hamilton, Ontario, Canada
| | - Margaret A Marcon
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
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Xhakollari V, Canavari M, Osman M. Why people follow a gluten-free diet? An application of health behaviour models. Appetite 2021; 161:105136. [PMID: 33513415 DOI: 10.1016/j.appet.2021.105136] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Revised: 01/15/2021] [Accepted: 01/18/2021] [Indexed: 02/08/2023]
Abstract
PURPOSE To understand factors affecting adherence to GFD by celiac and non-celiac people through the application of behavioural theories, Integrative Model (IM) and Multi Theory Model (MTM). METHODS Analyses were conducted for a sample of 308 subjects, majority females, celiac and non-celiac. Adherence to GFD was measured considering two scales, self-declared adherence and scored adherence, in order to discern possible inconsistencies between what subjects believe and what they really do. Subsequently, adherence to GFD was modelled by considering constructs of MTM and IM. Moreover, the constructs were designed based on literature review. Ordered logit (OL) model was used to test the IM and MTM theoretical models. RESULTS The findings show that adherence to GFD is affected mainly by attitudes towards GFD, self-efficacy, injunctive norms, knowledge about GFD and health conditions. Between the two models, IM and MTM, results show that all constructs of IM explain the behaviour. Contrary, for MTM, results indicate only some constructs of the MTM explain adherence to GFD. CONCLUSIONS Results of this study should be considered for improving the adherence to GFD for celiac people. Furthermore, it is important to consider the non-celiac people's perceptions for GFD and GF products. In other words an accurate information about the diet and products it is relevant for supporting people to make healthier food choices. Finally, as the results show, IM explain adherence to GFD better than MTM.
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Affiliation(s)
- Vilma Xhakollari
- Department of Agricultural and Food Sciences, Alma Mater Studiorum-University of Bologna, Viale Giuseppe Fanin 50, 40127, Bologna, Italy.
| | - Maurizio Canavari
- Department of Agricultural and Food Sciences, Alma Mater Studiorum-University of Bologna, Viale Giuseppe Fanin 50, 40127, Bologna, Italy.
| | - Magda Osman
- Biological and Experimental Psychology, School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London, E1 4NS, UK.
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24
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Gluten content in labeled and unlabeled gluten-free food products used by patients with celiac disease. Eur J Clin Nutr 2021; 75:1245-1253. [PMID: 33462461 DOI: 10.1038/s41430-020-00854-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 12/12/2020] [Accepted: 12/17/2020] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Gluten-free (GF) diet is the only reliable treatment for patients with celiac disease (CeD), but data on the extent of gluten contamination in GF food available in India is scanty. We evaluated gluten content in labeled, imported, and non-labeled GF food products currently available in the Indian market. METHODS Overall, 794 processed and commercially available packaged GF products (labeled GF (n = 360), imported GF (n = 80), and non-labeled/naturally GF (n = 354)) were collected from supermarkets of National Capital Region of India. Those unavailable in stores were purchased from e-commerce sites or directly from the manufacturers. Gluten level in them was determined by Ridascreen Gliadin sandwich R5 enzyme-linked immunosorbent assay (R-Biopharm AG, Germany). As per Codex Alimentarius and Food Safety and Standard Authority of India, "gluten free" labeled products must not contain > 20 mg/kg of gluten. RESULTS Overall, 10.1% of 794 GF products including 38 (10.8%) of 360 labeled and 42 (11.8%) of 354 non-labeled/naturally GF food products had gluten content > 20 mg/kg (range: 24.43-355 and 23.2-463.8 mg/kg, respectively). None of the imported GF products had gluten more than the recommended limits. Contaminated products most commonly belonged to cereal and their products (flours, coarse grains, pasta/macaroni, snack foods) pulse flours, spices, and bakery items. CONCLUSIONS A substantial proportion (10.1%) of GF food products (both labeled and non-labeled) available in India have gluten content greater than the prescribed limits of <20 mg/kg. Physicians, dietitians, support group, and patients with CeD should be made aware of this fact and regulatory bodies should ensure quality assurance.
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Tan IL, Withoff S, Kolkman JJ, Wijmenga C, Weersma RK, Visschedijk MC. Non-classical clinical presentation at diagnosis by male celiac disease patients of older age. Eur J Intern Med 2021; 83:28-33. [PMID: 33218785 DOI: 10.1016/j.ejim.2020.09.020] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 09/21/2020] [Accepted: 09/21/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND . In a biopsy-proven adult celiac disease (CeD) cohort from the Netherlands, male patients were diagnosed with CeD at significantly older ages than female patients. OBJECTIVES To identify which factors contribute to diagnosis later in life and whether diagnostic delay influences improvement of symptoms after starting a gluten-free diet (GFD). METHODS . We performed a questionnaire study in 211 CeD patients (67:144, male:female) with median age at diagnosis of 41.8 years (interquartile range: 25-58) and at least Marsh 2 histology. RESULTS . Classical symptoms (diarrhea, fatigue, abdominal pain and/or weight loss) were more frequent in women than men, but sex was not significantly associated with age at diagnosis. In a multivariate analysis, a non-classical presentation (without any classical symptoms) and a negative family history of CeD were significant predictors of older age at diagnosis (coefficients of 8 and 12 years, respectively). A delay of >3 years between first symptom and diagnosis was associated with slower improvement of symptoms after start of GFD, but not with sex, presentation of classical symptoms or age at diagnosis. CONCLUSION . Non-classical CeD presentation is more prevalent in men and is associated with a diagnosis of CeD later in life. Recognizing CeD sooner after onset of symptoms is important because a long diagnostic delay is associated with a slower improvement of symptoms after starting a GFD.
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Affiliation(s)
- Ineke L Tan
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands; Department of Genetics, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands
| | - Sebo Withoff
- Department of Genetics, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands
| | - Jeroen J Kolkman
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands; Department of Gastroenterology and Hepatology, Medisch Spectrum Twente, 7500 KA Enschede, the Netherlands
| | - Cisca Wijmenga
- Department of Genetics, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands
| | - Rinse K Weersma
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands; Department of Genetics, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands
| | - Marijn C Visschedijk
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands; Department of Genetics, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands.
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Abstract
BACKGROUND It is not known if genetic background, characteristics at diagnosis, physical and psychological well-being, and adherence to a gluten-free diet are comparable between patients with familial or sporadic celiac disease. These issues were investigated in a follow-up study. METHODS Altogether 1064 patients were analyzed for celiac disease-associated serology, predisposing HLA-DQ, and non-HLA genotypes. Medical data were collected from patient records and supplementary interviews. Current symptoms and quality of life were further evaluated with the Gastrointestinal Symptom Rating Scale (GSRS), the Psychological General Well-Being questionnaire (PGWB), and Short Form 36 (SF-36) questionnaires. RESULTS Familial and sporadic groups differed (P < 0.001) in the reason for diagnosis and clinical presentation at diagnosis, familial patients being more often screen-detected (26% vs. 2%, P < 0.001) and having less often gastrointestinal (49% vs. 69%) and severe symptoms (47% vs. 65%). The groups were comparable in terms of histological damage, frequency of malabsorption, comorbidities, childhood diagnoses, and short-term treatment response. At the time of the study, familial cases reported fewer symptoms (21% vs. 30%, P = 0.004) and lower prevalence of all (78% vs. 86%, P = 0.007), neurological (10% vs. 15%, P = 0.013), and dermatological (9% vs. 17%, P = 0.001) comorbidities. Dietary adherence and GSRS scores were comparable, but familial cases had better quality of life according to PGWB and SF-36. High-risk genotype HLA-DQ2.5/DQ2.5 was more frequent among familial cases, and four non-HLA SNPs were associated with familial celiac disease. CONCLUSIONS Despite the greater proportion of high-risk genotypes, familial cases had milder symptoms at presentation than did sporadic cases. Worse experience of symptoms and poorer quality of life in sporadic disease indicate a need for intensified support.
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Airaksinen L, Laurikka P, Huhtala H, Kurppa K, Salmi T, Saavalainen P, Kaukinen K, Lindfors K. Influence of HLA-DQ2.5 Dose on Clinical Picture of Unrelated Celiac Disease Patients. Nutrients 2020; 12:nu12123775. [PMID: 33317091 PMCID: PMC7764246 DOI: 10.3390/nu12123775] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Accepted: 12/07/2020] [Indexed: 12/13/2022] Open
Abstract
The clinical phenotype of celiac disease varies considerably among patients and the dosage of HLA-DQ2.5 alleles has been suggested to be a contributing factor. We investigated whether HLA-DQ2.5 allele dosage is associated with distinct clinical parameters at the time of diagnosis and with patients’ response to a gluten-free diet. The final cohort included 605 carefully phenotyped non-related Finnish celiac disease patients grouped as having 0, 1 or 2 copies of HLA-DQ2.5. Clinical data at the time of diagnosis and during gluten-free diet were collected systematically from medical records and supplementary interviews. An increasing HLA-DQ2.5 dose effect was detected for celiac disease antibody positivity at diagnosis (p = 0.021) and for the presence of any first-degree relatives with celiac disease (p = 0.011 and p = 0.031, respectively). Instead, DQ2.5-negative patients were suffering most often from classical symptoms at diagnosis (p = 0.007 between HLA groups). In addition, during follow-up they were most often symptomatic despite a gluten-free diet (p = 0.002 between groups). Our results thus suggest that increasing HLA-DQ2.5 dose only has a minor effect on the clinical picture of celiac disease. However, HLA-DQ2.5-negative patients should not be overlooked in clinical practice and particular attention should be paid to this patient group during gluten-free diet.
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Affiliation(s)
- Laura Airaksinen
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland; (L.A.); (P.L.); (T.S.); (K.K.)
| | - Pilvi Laurikka
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland; (L.A.); (P.L.); (T.S.); (K.K.)
| | - Heini Huhtala
- Faculty of Social Sciences, Tampere University, 33520 Tampere, Finland;
| | - Kalle Kurppa
- Tampere Centre for Child Health Research, Tampere University Hospital and Tampere University, 33521 Tampere, Finland;
- Department of Pediatrics, Seinäjoki Central Hospital and University Consortium of Seinäjoki, 60220 Seinäjoki, Finland
| | - Teea Salmi
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland; (L.A.); (P.L.); (T.S.); (K.K.)
- Department of Dermatology, Tampere University Hospital, 33521 Tampere, Finland
| | - Päivi Saavalainen
- Research Programs Unit, Immunobiology, and Haartman Institute, Department of Medical Genetics, University of Helsinki, 00014 Helsinki, Finland;
| | - Katri Kaukinen
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland; (L.A.); (P.L.); (T.S.); (K.K.)
- Department of Internal Medicine, Tampere University Hospital, 33521 Tampere, Finland
| | - Katri Lindfors
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland; (L.A.); (P.L.); (T.S.); (K.K.)
- Correspondence:
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Elwenspoek MMC, Jackson J, Dawson S, Everitt H, Gillett P, Hay AD, Jones HE, Lane DL, Mallett S, Robins G, Sheppard AL, Stubbs J, Thom H, Watson J, Whiting P. Accuracy of potential diagnostic indicators for coeliac disease: a systematic review protocol. BMJ Open 2020; 10:e038994. [PMID: 33020103 PMCID: PMC7537462 DOI: 10.1136/bmjopen-2020-038994] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
INTRODUCTION Coeliac disease (CD) is a systemic immune-mediated disorder triggered by gluten in genetically predisposed individuals. CD is diagnosed using a combination of serology tests and endoscopic biopsy of the small intestine. However, because of non-specific symptoms and heterogeneous clinical presentation, diagnosing CD is challenging. Early detection of CD through improved case-finding strategies can improve the response to a gluten-free diet, patients' quality of life and potentially reduce the risk of complications. However, there is a lack of consensus in which groups may benefit from active case-finding. METHODS AND ANALYSIS We will perform a systematic review to determine the accuracy of diagnostic indicators (such as symptoms and risk factors) for CD in adults and children, and thus can help identify patients who should be offered CD testing. MEDLINE, Embase, Cochrane Library and Web of Science will be searched from 1997 until 2020. Screening will be performed in duplicate. Data extraction will be performed by one and checked by a second reviewer. Disagreements will be resolved through discussion or referral to a third reviewer. We will produce a narrative summary of identified prediction models. Studies, where 2×2 data can be extracted or reconstructed, will be treated as diagnostic accuracy studies, that is, the diagnostic indicators are the index tests and CD serology and/or biopsy is the reference standard. For each diagnostic indicator, we will perform a bivariate random-effects meta-analysis of the sensitivity and specificity. ETHICS AND DISSEMINATION Results will be reported in peer-reviewed journals, academic and public presentations and social media. We will convene an implementation panel to advise on the optimum strategy for enhanced dissemination. We will discuss findings with Coeliac UK to help with dissemination to patients. Ethical approval is not applicable, as this is a systematic review and no research participants will be involved. PROSPERO REGISTRATION NUMBER CRD42020170766.
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Affiliation(s)
- Martha Maria Christine Elwenspoek
- The National Institute for Health Research Applied Research Collaboration West (NIHR ARC West), University Hospitals Bristol NHS Foundation Trust, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Joni Jackson
- The National Institute for Health Research Applied Research Collaboration West (NIHR ARC West), University Hospitals Bristol NHS Foundation Trust, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Sarah Dawson
- The National Institute for Health Research Applied Research Collaboration West (NIHR ARC West), University Hospitals Bristol NHS Foundation Trust, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Hazel Everitt
- Primary Care, Population Sciences and Medical Education, University of Southampton, Southampton, UK
| | - Peter Gillett
- Paediatric Gastroenterology, Hepatology and Nutrition Department, Royal Hospital for Sick Children, Edinburgh, UK
| | - Alastair D Hay
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Hayley E Jones
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | | | - Susan Mallett
- School of Health and Population Sciences, University of Birmingham, Birmingham, West Midlands, UK
| | - Gerry Robins
- Department of Gastroenterology, York Teaching Hospital NHS Foundation Trust, York, North Yorkshire, UK
| | | | - Jo Stubbs
- Patient representative, Patient representative, UK
| | - Howard Thom
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Jessica Watson
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Penny Whiting
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
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Severity of Villous Atrophy at Diagnosis in Childhood Does Not Predict Long-term Outcomes in Celiac Disease. J Pediatr Gastroenterol Nutr 2020; 71:71-77. [PMID: 32097370 DOI: 10.1097/mpg.0000000000002675] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVES Current pediatric guidelines allow noninvasive diagnosis of celiac disease in selected children. We investigated in a large cohort study whether the severity of villous atrophy at diagnosis is associated with clinical characteristics or long-term health outcomes, thus having a prognostic significance. METHODS Comprehensive medical data on 906 children with celiac disease were analyzed. Long-term health outcomes of 503 adult patients diagnosed in childhood were moreover assessed with a specific study questionnaire and validated Gastrointestinal Symptom Rating Scale (GSRS) and Psychological General Well-Being (PGWB) questionnaires. Patients were classified into 3 groups according to the severity of villous atrophy at diagnosis, and all variables were compared. RESULTS Altogether 34% of the patients had partial, 40% subtotal, and 26% total villous atrophy. Children with milder lesions were diagnosed more recently (median year 2007 vs 2006 vs 2001, respectively, P < 0.001), more often by screening (30% vs 25% vs 17%, P < 0.001) and they suffered less often from anemia (16% vs 21% vs 32%, P < 0.001) and growth disturbances (22% vs 36% vs 54%, P < 0.001) and had lower transglutaminase-2 antibody levels (median 64 U/L vs 120 U/L vs 120 U/L, P < 0.001). There was no difference in other disease features.Altogether 212 adults diagnosed in childhood completed the questionnaires. Severity of villous atrophy at childhood diagnosis did not predict presence of complications or comorbidities, persistent symptoms, and self-perceived health, quality of life or adherence to a gluten-free diet in adulthood. CONCLUSION Presence of advanced villous atrophy at diagnosis is associated with more severe clinical characteristics but not with poorer long-term health and treatment outcomes.
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Abstract
Studies show that people with celiac disease have reduced well-being and have persistent symptoms, mainly related to the gastrointestinal tract. The aim of this study was to analyze how persons in a celiac disease member association report their symptoms, health, and life satisfaction. A questionnaire, with both open and closed questions, was distributed to all members (n = 726) of a celiac association in the southeast of Sweden. The response rate was 74.5%, of which 524 (72%) said they had received a celiac disease diagnosis and were thus included in the study. Almost half of the participants (40.7%-42.2%) stated that they had persistent celiac disease symptoms despite following a gluten-free diet. Diarrhea, abdominal pain, and congestion were persistent symptoms reported and could contribute to a lower health status compared with people without persistent symptoms. The life satisfaction scale (LiSat-9) showed differences in 5 of 9 variables between the groups. Living with celiac disease is far from easy when you have persistent symptoms. People with celiac disease require follow-up by healthcare services, and a new treatment needs to be developed because following the gluten-free diet alone does not seem to alleviate symptoms in everyone.
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Kivelä L, Hekkala S, Huhtala H, Kaukinen K, Kurppa K. Lack of long-term follow-up after paediatric-adult transition in coeliac disease is not associated with complications, ongoing symptoms or dietary adherence. United European Gastroenterol J 2020; 8:157-166. [PMID: 32213072 DOI: 10.1177/2050640619900077] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Follow-up of coeliac disease is recommended to prevent complications associated with unsuccessful treatment. OBJECTIVE The objective of this article is to evaluate the implementation and significance of long-term follow-up. METHODS Medical data were collected from 585 and follow-up questionnaires sent to 559 current adult coeliac disease patients diagnosed in childhood. Diagnostic features and adulthood health outcomes were compared between those with and without adulthood follow-up. RESULTS Of paediatric patients, 92% were followed up 6-24 months after diagnosis. A total of 235 adults responded to the questionnaires a median of 18 years after diagnosis, and 25% of them reported regular follow-up. They were diagnosed more recently than those without follow-up (median year 2001 vs 1995, p = 0.001), being otherwise comparable at diagnosis. Those with follow-up were less often smokers (5% vs 16%, p = 0.042) and relatives of coeliac patients (48% vs 66%, p = 0.018), and more often students (48% vs 28%, p = 0.005) and type 1 diabetics (19% vs 4%, p = 0.001). Lack of follow-up was not associated with complications, ongoing symptoms, poorer general health or dietary adherence. All completely non-adherent patients were without follow-up. CONCLUSIONS Most coeliac disease patients diagnosed in childhood were not followed up according to recommendations in adulthood. The individual effect of this on long-term treatment outcomes varied markedly.
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Affiliation(s)
- Laura Kivelä
- Tampere Center for Child Health Research, Tampere University and Department of Paediatrics, Tampere University Hospital, Tampere, Finland.,University of Helsinki and Helsinki University Hospital, Children's Hospital, and Pediatric Research Center, Helsinki, Finland
| | - Sointu Hekkala
- Tampere Center for Child Health Research, Tampere University and Department of Paediatrics, Tampere University Hospital, Tampere, Finland.,Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Heini Huhtala
- Faculty of Social Sciences, Tampere University, Tampere, Finland
| | - Katri Kaukinen
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.,Department of Internal Medicine, Tampere University Hospital, Tampere, Finland.,Celiac Disease Research Center, Tampere University, Tampere, Finland
| | - Kalle Kurppa
- Tampere Center for Child Health Research, Tampere University and Department of Paediatrics, Tampere University Hospital, Tampere, Finland.,Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.,The University Consortium of Seinäjoki, Seinäjoki, Finland
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Harnett JE, Myers SP. Quality of life in people with ongoing symptoms of coeliac disease despite adherence to a strict gluten-free diet. Sci Rep 2020; 10:1144. [PMID: 31980719 PMCID: PMC6981136 DOI: 10.1038/s41598-020-58236-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Accepted: 01/02/2020] [Indexed: 12/13/2022] Open
Abstract
People with Coeliac disease who suffer persistent symptoms despite adherence to a gluten-free diet are at a greater risk of a reduced health related quality of life. The purpose of this paper is to report the quality of life experienced by this specific group of patients in Australia. A Coeliac Disease Specific Questionnaire (CDQ) was administered to 45 people who were enrolled in a clinical trial and reported persistent symptoms of Coeliac disease despite adherence to a strict gluten free diet. The clinical trial was based in New South Wales, Australia. The instrument used was a subscale and total scores of a CDQ measuring health related quality of life. At baseline the overall mean CDQ score was 147 ± 3.31 (optimum 196) consisting of 4 subscales; gastrointestinal 33 ± 0.88, emotional 32.9 ± 0.99, worries 39.8 ± 0.79 and social 41 ± 6.12 each with a potential score of 49. The health related quality of life of people reporting persistent symptoms of Coeliac disease despite adherence to a gluten free diet is sub-optimal with concerningly low scores for emotional quality.
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Affiliation(s)
- Joanna E Harnett
- School of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
| | - Stephen P Myers
- NatMed-Research, Division of Research, Southern Cross University, Lismore, Australia
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Psychiatric Manifestations of Coeliac Disease, a Systematic Review and Meta-Analysis. Nutrients 2020; 12:nu12010142. [PMID: 31947912 PMCID: PMC7019223 DOI: 10.3390/nu12010142] [Citation(s) in RCA: 61] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Revised: 12/30/2019] [Accepted: 01/03/2020] [Indexed: 12/16/2022] Open
Abstract
Background: Coeliac disease (CD) is increasingly prevalent and is associated with both gastrointestinal (GI) and extra-intestinal manifestations. Psychiatric disorders are amongst extra-intestinal manifestations proposed. The relationship between CD and such psychiatric disorders is not well recognised or understood. Aim: The aim of this systematic review and meta-analysis was to provide a greater understanding of the existing evidence and theories surrounding psychiatric manifestations of CD. Methodology: An online literature search using PubMed was conducted, the prevalence data for both CD and psychiatric disorders was extracted from eligible articles. Meta analyses on odds ratios were also performed. Results: A total of 37 articles were included in this review. A significant increase in risk was detected for autistic spectrum disorder (OR 1.53, 95% CI 1.24–1.88, p < 0.0001), attention deficit hyperactivity disorder (OR 1.39, 95% CI 1.18–1.63, p < 0.0001), depression (OR 2.17, 95% CI 2.17–11.15, p < 0.0001), anxiety (OR 6.03, 95% CI 2.22–16.35, p < 0.0001), and eating disorders (OR 1.62, 95% CI 1.37–1.91, p < 0.00001) amongst the CD population compared to healthy controls. No significant differences were found for bipolar disorder (OR 2.35, 95% CI 2.29–19.21, p = 0.43) or schizophrenia (OR 0.46, 95% CI 0.02–10.18, p = 0.62). Conclusion: CD is associated with an increased risk of depression, anxiety, eating disorders as well as ASD and ADHD. More research is required to investigate specific biological explanations as well as any effect of gluten free diet.
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Clifford S, Taylor AJ, Gerber M, Devine J, Cho M, Walker R, Stefani I, Fidel S, Drahos J, Leffler DA. Concepts and Instruments for Patient-Reported Outcome Assessment in Celiac Disease: Literature Review and Experts' Perspectives. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2020; 23:104-113. [PMID: 31952665 DOI: 10.1016/j.jval.2019.07.018] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 05/28/2019] [Accepted: 07/18/2019] [Indexed: 06/10/2023]
Abstract
BACKGROUND In diseases where there is a large subjective component, such as celiac disease (CD), patient reported-outcomes (PRO) endpoints are highly relevant. However, there is a gap in knowledge about which PRO endpoints and instruments should be used for clinical trials for treatment of celiac disease. OBJECTIVES To identify patient-centered symptom, impact, and health-related quality of life (HRQoL) concepts in CD and relevant PRO instruments, and to gather expert input on concepts and instruments to inform selection of PRO endpoints for use in clinical trials of new CD treatments. METHODS A targeted literature review was conducted to identify symptom, impact, and HRQoL concepts, including those captured in PROs further reviewed against U.S. Food and Drug Administration standards for development and validation as endpoints. US and European clinicians, payers, and a patient advocate (n = 21) were interviewed to assess the identified concepts' relative importance in measuring treatment benefit and to gauge the value of potential PROs as endpoints for market access/reimbursement. RESULTS Thirty-four published studies were identified: 27 elucidated patient-centered concepts and 7 detailed the development or validation of PRO instruments. The Celiac Disease Symptom Diary and Celiac Disease Patient Reported Outcome instrument were deemed most appropriate for use as endpoints; however, each had limitations related to conceptual coverage, evidence for measurement properties, and feasibility for use in clinical trials. Experts reported gastrointestinal symptoms as most important to treat, with extra-intestinal symptoms burdensome from the patient perspective as well. Payers emphasized measuring both frequency and severity of symptoms and targeting patients nonresponsive to the gluten-free diet for treatment. CONCLUSIONS With emerging treatment options for CD, further work is needed to operationalize PRO symptom endpoints that are meaningful to patients, valued by payers, and acceptable to regulators in demonstrating efficacy.
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Affiliation(s)
- Sarah Clifford
- Patient Centered Outcomes, Commercialisation and Outcomes, ICON Clinical Research, Los Angeles, CA, USA
| | | | - Michele Gerber
- Clinical Science, Takeda Pharmaceuticals International, Cambridge, MA, USA
| | - Jacob Devine
- Patient Centered Outcomes, Commercialisation and Outcomes, ICON Clinical Research, South San Francisco, CA, USA
| | - Margaret Cho
- Patient Centered Outcomes, Commercialisation and Outcomes, ICON Clinical Research, South San Francisco, CA, USA.
| | | | - Ioanna Stefani
- Pricing and Market Access, ICON Clinical Research, London, UK
| | | | - Jennifer Drahos
- Global Outcomes Research, Takeda Pharmaceuticals International, Cambridge, MA, USA
| | - Daniel A Leffler
- Clinical Science, Takeda Pharmaceuticals International, Cambridge, MA, USA; Division of Gastroenterology, Beth Israel Deaconness Medical Center, Boston, MA, USA
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Rusanen J, Toivonen A, Hepojoki J, Hepojoki S, Arikoski P, Heikkinen M, Vaarala O, Ilonen J, Hedman K. LFRET, a novel rapid assay for anti-tissue transglutaminase antibody detection. PLoS One 2019; 14:e0225851. [PMID: 31770411 PMCID: PMC6879146 DOI: 10.1371/journal.pone.0225851] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Accepted: 11/13/2019] [Indexed: 12/27/2022] Open
Abstract
The diagnosis of celiac disease (CD) is currently based on serology and intestinal biopsy, with detection of anti-tissue transglutaminase (tTG) IgA antibodies recommended as the first-line test. Emphasizing the increasing importance of serological testing, new guidelines and evidence suggest basing the diagnosis solely on serology without confirmatory biopsy. Enzyme immunoassays (EIAs) are the established approach for anti-tTG antibody detection, with the existing point-of-care (POC) tests lacking sensitivity and/or specificity. Improved POC methods could help reduce the underdiagnosis and diagnostic delay of CD. We have previously developed rapid homogenous immunoassays based on time-resolved Förster resonance energy transfer (TR-FRET), and demonstrated their suitability in serodiagnostics with hanta- and Zika virus infections as models. In this study, we set out to establish a protein L -based TR-FRET assay (LFRET) for the detection of anti-tTG antibodies. We studied 74 patients with biopsy-confirmed CD and 70 healthy controls, with 1) the new tTG-LFRET assay, and for reference 2) a well-established EIA and 3) an existing commercial POC test. IgG depletion was employed to differentiate between anti-tTG IgA and IgG positivity. The sensitivity and specificity of the first-generation tTG-LFRET POC assay in detection of CD were 87.8% and 94.3%, respectively, in line with those of the reference POC test. The sensitivity and specificity of EIA were 95.9% and 91.9%, respectively. This study demonstrates the applicability of LFRET to serological diagnosis of autoimmune diseases in general and of CD in particular.
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Affiliation(s)
- Juuso Rusanen
- University of Helsinki, Medicum, Department of Virology, Helsinki, Finland
- * E-mail:
| | - Anne Toivonen
- Laboratory Services (HUSLAB), Department of Virology and Immunology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Department of Clinical Microbiology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland
| | - Jussi Hepojoki
- University of Helsinki, Medicum, Department of Virology, Helsinki, Finland
- Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
| | - Satu Hepojoki
- University of Helsinki, Medicum, Department of Virology, Helsinki, Finland
| | - Pekka Arikoski
- Department of Pediatrics, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland
| | - Markku Heikkinen
- Department of Gastroenterology, Kuopio University Hospital, Kuopio, Finland
| | - Outi Vaarala
- Clinicum, University of Helsinki, Helsinki, Finland
| | - Jorma Ilonen
- Immunogenetics Laboratory, Institute of Biomedicine, University of Turku and Clinical Microbiology, Turku University Hospital, Turku, Finland
| | - Klaus Hedman
- University of Helsinki, Medicum, Department of Virology, Helsinki, Finland
- Laboratory Services (HUSLAB), Department of Virology and Immunology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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Diagnosing Celiac Disease: Towards Wide-Scale Screening and Serology-Based Criteria? Gastroenterol Res Pract 2019; 2019:2916024. [PMID: 31467522 PMCID: PMC6701393 DOI: 10.1155/2019/2916024] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2019] [Accepted: 07/16/2019] [Indexed: 12/12/2022] Open
Abstract
Celiac disease is one of the most common food-related chronic disorders in children. Unfortunately, this multifaceted disease is challenging to recognize and remains markedly underdiagnosed. Screening of either known at-risk groups or even the whole population could increase the suboptimal diagnostic yield substantially. Many recent guidelines recommend screening of at least selected risk groups, but more wide-scale screening remains controversial. The increasing prevalence of celiac disease and the development of autoantibody assays have also led to a gradual shift in the diagnostics towards less invasive serology-based criteria in a subgroup of symptomatic children. The main open questions concern whether these criteria are applicable to all countries and clinical settings, as well as to adult patients. On the other hand, widening screening and the mistaken practice of initiating a gluten-free diet before the appropriate exclusion of celiac disease increase the number of borderline seropositive cases, which may also challenge the classical histopathological diagnostics. Sophisticated diagnostic methods and a deeper understanding of the natural history of early developing celiac disease may prove useful in these circumstances.
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Dietary Factors and Mucosal Immune Response in Celiac Disease Patients Having Persistent Symptoms Despite a Gluten-free Diet. J Clin Gastroenterol 2019; 53:507-513. [PMID: 29505551 DOI: 10.1097/mcg.0000000000001013] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
GOALS The aim of this study was to investigate the role of dietary factors, distinct small-bowel mucosal immune cell types, and epithelial integrity in the perpetuation of gastrointestinal symptoms in treated celiac disease patients. BACKGROUND For unexplained reasons, many celiac disease patients suffer from persistent symptoms, despite a strict gluten-free diet (GFD) and recovered intestinal mucosa. STUDY We compared clinical and serological data and mucosal recovery in 22 asymptomatic and 25 symptomatic celiac patients on a long-term GFD. The density of CD3 and γδ intraepithelial lymphocytes (IELs), CD25 and FOXP3 regulatory T cells, and CD117 mast cells, and the expression of tight junction proteins claudin-3 and occludin, heat shock protein 60, interleukin 15, and Toll-like receptor 2 and 4 were evaluated in duodenal biopsies. RESULTS All subjects kept a strict GFD and had negative celiac autoantibodies and recovered mucosal morphology. The asymptomatic patients had higher mean fiber intake (20.2 vs. 15.2 g/d, P=0.028) and density of CD3 IELs (59.3 vs. 45.0 cell/mm, P=0.045) than those with persistent symptoms. There was a similar but nonsignificant trend in γδ IELs (17.9 vs. 13.5, P=0.149). There were no differences between the groups in other parameters measured. CONCLUSIONS Low fiber intake may predispose patients to persistent symptoms in celiac disease. There were no differences between the groups in the markers of innate immunity, epithelial stress or epithelial integrity. A higher number of IELs in asymptomatic subjects may indicate that the association between symptoms and mucosal inflammation is more complicated than previously thought.
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Ring Jacobsson L, Johansson Stark Å, Eckerblad J. Illness beliefs among people living with treated coeliac disease. Scand J Caring Sci 2019; 34:401-408. [PMID: 31365153 DOI: 10.1111/scs.12741] [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: 02/02/2019] [Accepted: 07/03/2019] [Indexed: 11/29/2022]
Abstract
BACKGROUND Evidence suggests that many people with coeliac disease (CD) suffer from continuing illness despite following a strict gluten-free diet. Beliefs affect how people experience and manage their residual symptoms. Illness beliefs therefore provide a useful framework for understanding these problems. AIM To explore illness beliefs among people living with treated coeliac disease. METHODS The design was qualitative descriptive with semi-structured interviews including 22 adults with coeliac disease. Data were analysed with qualitative content analysis. The study follows the ethical guidelines given in the Declaration of Helsinki and was approved by the local ethical committee (DN 2014/92-31). FINDING The source of experienced continuing illness, despite following a gluten-free diet, was believed to be a bodily imbalance affecting participants' lives in many ways, both private and in contact with the health services. Due to a feeling of exhaustion and lack of energy, this imbalance had prevented them from participating in school, work life and social activities. Since the participants had often been ill for many years before diagnosis, they believed their intestine to be so damaged that it was no longer possible to achieve a bodily balance. CONCLUSIONS Illness beliefs in people diagnosed and treated for CD showed that they explained various continuing conditions, physiological and/or psychological, by a bodily imbalance, originally caused by the CD. By uncovering these illness beliefs, the possibility of finding an adequate and facilitative strategy grows stronger.
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Affiliation(s)
- Lisa Ring Jacobsson
- Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
| | - Åsa Johansson Stark
- Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
| | - Jeanette Eckerblad
- Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
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Leinonen H, Kivelä L, Lähdeaho ML, Huhtala H, Kaukinen K, Kurppa K. Daily Life Restrictions are Common and Associated with Health Concerns and Dietary Challenges in Adult Celiac Disease Patients Diagnosed in Childhood. Nutrients 2019; 11:nu11081718. [PMID: 31349675 PMCID: PMC6723871 DOI: 10.3390/nu11081718] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Revised: 07/19/2019] [Accepted: 07/23/2019] [Indexed: 12/20/2022] Open
Abstract
The prevalence and associated factors of daily life restrictions due to a gluten-free diet in adult celiac disease patients diagnosed in childhood are poorly known. We investigated these issues by collecting the medical data of 955 pediatric patients and sending questionnaires evaluating various health outcomes to the 559 patients who had reached adulthood. Of the 231 respondents, 46% reported everyday life restrictions caused by dietary treatment. Compared with those without restrictions, they more often had anemia at diagnosis (37% vs. 22%, p = 0.014), but the groups were comparable in other diagnostic features. In adulthood, patients with restrictions reported more overall symptoms (32% vs. 17%, p = 0.006), although the symptoms measured with the Gastrointestinal Symptom Rating Scale questionnaire were comparable. Despite strict dietary adherence in both groups, the experience of restrictions was associated with dietary challenges (34% vs. 9%, p < 0.001), health concerns (22% vs. 13%, p = 0.050), and lower vitality scores in the Psychological General Well-Being questionnaire. The groups did not differ in their current age, socioeconomic status, family history of celiac disease, general health or health-related lifestyle, the presence of co-morbidities, or regular follow up. Our results encourage healthcare professionals to discuss the possible health concerns and dietary challenges with patients to avoid unnecessary daily life restrictions, especially when young patients start to take responsibility for their treatment.
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Affiliation(s)
- Heini Leinonen
- Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland
- Center for Child Health Research, Tampere University and Department of Pediatrics, Tampere University Hospital, 33014 Tampere, Finland
| | - Laura Kivelä
- Center for Child Health Research, Tampere University and Department of Pediatrics, Tampere University Hospital, 33014 Tampere, Finland.
- Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland.
| | - Marja-Leena Lähdeaho
- Center for Child Health Research, Tampere University and Department of Pediatrics, Tampere University Hospital, 33014 Tampere, Finland
| | - Heini Huhtala
- Faculty of Social Sciences, Tampere University, 33014 Tampere, Finland
| | - Katri Kaukinen
- Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland
- Department of Internal Medicine, Tampere University Hospital, 33014 Tampere, Finland
- Celiac Disease Research Center, Tampere University, 33014 Tampere, Finland
| | - Kalle Kurppa
- Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland
- Center for Child Health Research, Tampere University and Department of Pediatrics, Tampere University Hospital, 33014 Tampere, Finland
- The University Consortium of Seinäjoki, 60320 Seinäjoki, Finland
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Bittker SS, Bell KR. Potential risk factors for celiac disease in childhood: a case-control epidemiological survey. Clin Exp Gastroenterol 2019; 12:303-319. [PMID: 31308721 PMCID: PMC6615019 DOI: 10.2147/ceg.s210060] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Accepted: 05/08/2019] [Indexed: 12/30/2022] Open
Abstract
Background: Celiac disease (CD) prevalence has increased significantly in recent decades in some developed countries. Yet the environmental factors in the existing literature do not appear to provide a satisfactory explanation for this increase. Objective: To determine whether nine variables are associated with CD in children. These variables are: incidence of ear infection before 2 years old, courses of antibiotics before 2 years old, duration of breastfeeding, vitamin D drop exposure in infancy, vitamin D supplement exposure between 2–3 years old, age at gluten introduction into the diet, fat content of cow’s milk consumed between 2–3 years old, quantity of cow’s milk consumed between 2–3 years old, and type of water consumed at 2 years old. Methods: An Internet-based survey was conducted among parents living in the US with at least one biological child between 3 and 12 years old. Potential participants were informed about the survey through social media, websites, electronic newsletters, and advertisements. Results: After exclusions, there remained 332 responses associated with children with CD (cases), and 241 responses associated with children who do not have CD (controls). In this data set, skim milk as the primary form of liquid cow’s milk consumed between 2–3 years old (adjusted odds ratio [aOR]=3.556, CI=1.430–10.22, P=0.010), vitamin D drops administered for more than 3 months (aOR=1.749, CI=1.079–2.872, P=0.025), courses of antibiotics (aOR=1.133, CI=1.037–1.244, P=0.007), and incidence of ear infection (aOR=1.183, CI=1.041–1.348, P=0.010) are all associated with CD in children. Conclusions: This study is the first to find an association between skim milk consumption and CD and vitamin D drop use for greater than 3 months and CD. It also adds to evidence that early life exposure to antibiotics and early life infection, specifically ear infection, are associated with CD. ![]()
Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/y9aThwSZHoE
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Affiliation(s)
- Seth Scott Bittker
- Interdisciplinary Center for Innovative Theory and Empirics (INCITE), Columbia University, New York, New York, US
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Stocks NP, Gonzalez-Chica D, Hay P. Impact of gastrointestinal conditions, restrictive diets and mental health on health-related quality of life: cross-sectional population-based study in Australia. BMJ Open 2019; 9:e026035. [PMID: 31253614 PMCID: PMC6609067 DOI: 10.1136/bmjopen-2018-026035] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Revised: 06/04/2019] [Accepted: 06/06/2019] [Indexed: 12/17/2022] Open
Abstract
OBJECTIVES To assess the relationship between gastrointestinal conditions, restrictive diets, mental health and health-related quality of life (HRQoL). DESIGN Cross-sectional population-based face-to-face survey. SETTING South Australia. PARTICIPANTS A representative sample of 2912 consenting adults (48.9±18.1 years; 50.9% females) investigated in 2015. PRIMARY AND SECONDARY OUTCOME MEASURES Participants self-reported diagnosis of gastrointestinal conditions, mental health and current use of restrictive diets. The physical component score (PCS) and mental component score (MCS) of HRQoL were investigated (Study Short Form 12 V.1 questionnaire). Linear regression models were used to test the associations, adjusting for (1) sociodemographic variables, (2) mental health status and (3) lifestyle and body mass index. RESULTS The prevalence of restrictive diets (36.1%; 95% CI 33.9 to 38.3) was higher among those with any self-reported gastrointestinal condition (60.7% vs 31.3% for those without these conditions; p<0.001). PCS was lower among those with a gastrointestinal condition (mean difference=-3.4; 95% CI -4.5 to -2.4) or on a restrictive diet (mean difference=-1.9; 95% CI -2.7 to -1.1), with a similar pattern, but with a smaller effect, observed for MCS. Being on a restrictive diet did not modify the relationship between having a gastrointestinal condition and reduced HRQoL. However, having a gastrointestinal condition was associated with a 2.4 points lower PCS (95% CI -3.5 to -1.3) among those without a mental health problem, while for those affected by a mental health condition this reduction was greater (mean difference=-5.9; 95% CI -8.7 to -3.1). For MCS, there was no evidence of interaction between mental health and gastrointestinal conditions. CONCLUSIONS One-third of Australian adults are restricting their diet, and this is associated with lower HRQoL. Being on a restrictive diet was not associated with a better HRQoL among individuals with a gastrointestinal condition. Mental health problems were associated with a stronger adverse relationship between gastrointestinal diseases and physical HRQoL. Health professionals should be alert to these associations when trying to improve health outcomes for patients.
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Affiliation(s)
- Nigel P Stocks
- General Practice, University of Adelaide, Adelaide, South Australia, Australia
| | - David Gonzalez-Chica
- Discipline of General Practice, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia
| | - Phillipa Hay
- Translational Health Research Institute, School of Medicine, Western Sydney University, Sydney, New South Wales, Australia
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Martínez-Martinez MI, Alegre-Martínez A, García-Ibánez J, Cauli O. Quality of Life in People with Coeliac Disease: Psychological and Socio- Economic Aspects. Endocr Metab Immune Disord Drug Targets 2019; 19:116-120. [PMID: 30033882 DOI: 10.2174/1871530318666180723100003] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Revised: 06/22/2018] [Accepted: 07/02/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND OBJECTIVE Coeliac disease (CD) is a chronic autoimmune intestinal disorder characterized by intolerance to gluten, a protein contained in certain cereals. The main physiopathological basis of CD is the progressive destruction of intestinal villi caused by gluten ingestion by genetically-susceptible individuals. Patients who receive a diagnosis of CD must make significant changes to their daily habits and this can affect their quality of life. The objective of this review is to summarize the evidence regarding the economic, physical and social limitations which can affect the quality of life in patients with CD. RESULTS Different factors such as physical changes, psychological effects, interpersonal relationships, emotions and economic difficulties can affect the quality of life of these patients. Observations suggest that, in general, women with CD experience a greater deterioration in their quality of life than men. Lastly, complications in daily life are also associated with the reduced availability of gluten-free products which also usually cost more than standard products. CONCLUSIONS Continuous health education and care regarding socio-economic issues should be continuously developed and provided to people with CD.
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Affiliation(s)
- Maria Isabel Martínez-Martinez
- Departamento de Enfermeria. Facultad de Enfermeria y Podologia, Universidad de Valencia. C/ Jaume Roig, s/n, 46001 Valencia, Spain
| | - Antoni Alegre-Martínez
- Departamento de Ciencias Biomédicas, Universidad Cardenal Herrera CEU. Avenida Seminario, s/n, 46113 Montcada, Valencia, Spain
| | - Jessica García-Ibánez
- Departamento de Enfermeria. Facultad de Enfermeria y Podologia, Universidad de Valencia. C/ Jaume Roig, s/n, 46001 Valencia, Spain
| | - Omar Cauli
- Departamento de Enfermeria. Facultad de Enfermeria y Podologia, Universidad de Valencia. C/ Jaume Roig, s/n, 46001 Valencia, Spain
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Relevance of HLA-DQB1*02 Allele in the Genetic Predisposition of Children with Celiac Disease: Additional Cues from a Meta-Analysis. ACTA ACUST UNITED AC 2019; 55:medicina55050190. [PMID: 31121940 PMCID: PMC6571594 DOI: 10.3390/medicina55050190] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Revised: 04/26/2019] [Accepted: 05/14/2019] [Indexed: 12/12/2022]
Abstract
Background and Objectives: Celiac disease (CD) is a multifactorial immune-mediated disorder, triggered by the ingestion of gluten in genetically-predisposed subjects carrying MHC-DQ2 and -DQ8 heterodimers, which are encoded by four HLA-DQ allelic variants, overall. This meta-analysis aims at providing further epidemiological support to the predominant relevance of one specific allele, namely HLA-DQB1*02, in the predisposition and genetic risk of CD. Materials and Methods: We performed a search of MEDLINE/PubMed, Embase, Web of Science, and Scopus, retrieving all publications (case-control study, cross-sectional, and retrospective cohort study) on the association between HLA class II polymorphisms and first-degree relatives (FDRs) of children with CD. After a critical reading of the articles, two investigators independently performed data extraction according to the following inclusion criteria: HLA class II genes, any DQ and DR molecules, and CD diagnosed following the current clinical guidelines. A third participant was consulted for discussion to reach an agreement concerning discrepancies. Results: Our search strategy selected 14 studies as being eligible for inclusion, and those were submitted for data extraction and analysis. These studies were published between 1999 and 2016 and, collectively, enrolled 3063 FDRs. Positive and negative likelihood ratios (LR+ and LR-, respectively) for CD diagnosis, according to the presence of the HLA-DQ genotype coding a complete MHC-DQ2 and/or MHC-DQ8 molecules, were 1.449 (CI 1.279-1.642) and 0.187 (CI 0.096-0.362), respectively. If only the isolated presence of HLA-DQB1*02 allele is considered, the pooled estimation of LR+ was 1.659 (CI 1.302-2.155) and, importantly, the LR- still showed a very good discriminatory power of 0.195 (CI 0.068-0.558). Conclusions: Through our differential meta-analysis, comparing the presence of the genotype coding the full MHC-DQ2 and/or DQ8 molecules with the isolated presence of HLA-DQB1*02 allelic variant, we found that the LR- of the latter analysis maintained the same value. This observation, along with previous evidences, might be useful to consider potential cost-effective widened screening strategies for CD in children.
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Violato M, Gray A. The impact of diagnosis on health-related quality of life in people with coeliac disease: a UK population-based longitudinal perspective. BMC Gastroenterol 2019; 19:68. [PMID: 31046685 PMCID: PMC6498641 DOI: 10.1186/s12876-019-0980-6] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Accepted: 04/08/2019] [Indexed: 12/17/2022] Open
Abstract
Background Before diagnosis, people with coeliac disease suffer reduced quality of life, which improves substantially after the disease has been diagnosed. Delayed diagnosis is common. The aim of this study was to assess changes over time in prevalence of coeliac disease symptoms/associated medical conditions, time to diagnosis, quality of life and its determinants before and after diagnosis in the United Kingdom. Methods A postal questionnaire was designed in 2015 and sent to 4000 individuals with diagnosed coeliac disease, requesting information on respondents’ socio-demographic and clinical characteristics, and their quality of life pre- and post-diagnosis using the EQ-5D instrument. Data were analysed and compared with results from a survey conducted in 2006 using descriptive analyses, univariate and multivariable regression methods. Results The survey response rate was 40%. Sixty-five percent of respondents reported at least 4 symptoms pre-diagnosis, a significant reduction by 13 percentage points (95% CI: -16.9, − 9.4; p-value: < 0.001) compared to 2006. Pre-diagnosis mean duration of symptoms was 12.8 years (SD: 15.3), a non-significant reduction of 0.6 years (95% CI: -2, 0.8; p-value: 0.426) compared to 2006. There was a significant improvement of 0.20 (95% CI: 0.18, 0.22; p-value: < 0.001) in quality of life from pre- (0.65) to post-diagnosis (0.85). Pre-diagnosis values were significantly higher by 0.09 (95% CI: 0.06, 0.12; p-value: < 0.001) than in 2006. Number of symptoms and low income were associated with decreased quality of life. Conclusions Undiagnosed coeliac disease is associated with a substantial decrement in quality of life. Time to diagnosis has not significantly shortened over the decade 2006–2015, but symptoms are less severe when diagnosis occurs. Harmonising clinical guidelines for intensified active case finding will help improve quality of life of people with coeliac disease. Electronic supplementary material The online version of this article (10.1186/s12876-019-0980-6) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Mara Violato
- Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Old Road Campus, Headington, Oxford, OX3 7LF, UK.
| | - Alastair Gray
- Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Old Road Campus, Headington, Oxford, OX3 7LF, UK
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Kauma S, Kaukinen K, Huhtala H, Kivelä L, Pekki H, Salmi T, Saavalainen P, Lindfors K, Kurppa K. The Phenotype of Celiac Disease Has Low Concordance between Siblings, Despite a Similar Distribution of HLA Haplotypes. Nutrients 2019; 11:nu11020479. [PMID: 30823533 PMCID: PMC6412523 DOI: 10.3390/nu11020479] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Revised: 02/20/2019] [Accepted: 02/22/2019] [Indexed: 12/12/2022] Open
Abstract
The factors determining the presentation of celiac disease are unclear. We investigated the phenotypic concordance and the distribution of human leukocyte antigen (HLA) risk haplotypes in affected siblings. One hundred sibling pairs were included. Clinical and histological parameters and HLA haplotypes were compared between the first diagnosed indexes and their siblings. The phenotype was categorized into gastrointestinal, extra-intestinal, malabsorption/anemia, and asymptomatic. The phenotype was fully concordant in 21 pairs. The most common concordant phenotype was gastrointestinal (14 pairs). Indexes had more anemia/malabsorption and extra-intestinal symptoms than siblings (45% vs. 20%, p < 0.001 and 33% vs. 12%, p < 0.001, respectively). Twenty siblings and none of the indexes were asymptomatic. The indexes were more often women (81% vs. 63%, p = 0.008). They were also more often seronegative (11% vs. 0%, p = 0.03) and younger (37 vs. 43 year, p < 0.001), and had more severe histopathology (total/subtotal atrophy 79% vs. 58%, p = 0.047) at diagnosis. The indexes and siblings were comparable in other disease features. Pairs with discordant presentation had similar HLA haplotypes more often than the concordant pairs. The phenotype was observed to vary markedly between siblings, with the indexes generally having a more severe presentation. HLA did not explain the differences, suggesting that non-HLA genes and environmental factors play significant roles.
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Affiliation(s)
- Saana Kauma
- Celiac Disease Research Centre, Faculty of Medicine and Life Sciences, Tampere University, 33520 Tampere, Finland.
| | - Katri Kaukinen
- Celiac Disease Research Centre, Faculty of Medicine and Life Sciences, Tampere University, 33520 Tampere, Finland.
- Department of Internal Medicine, Tampere University Hospital, 33521 Tampere, Finland.
| | - Heini Huhtala
- Faculty of Social Sciences, Tampere University, 33520 Tampere, Finland.
| | - Laura Kivelä
- Tampere Centre for Child Health Research, Tampere University and Tampere University Hospital, 33521 Tampere, Finland.
| | - Henna Pekki
- Celiac Disease Research Centre, Faculty of Medicine and Life Sciences, Tampere University, 33520 Tampere, Finland.
| | - Teea Salmi
- Celiac Disease Research Centre, Faculty of Medicine and Life Sciences, Tampere University, 33520 Tampere, Finland.
- Department of Dermatology, Tampere University Hospital, 33521 Tampere, Finland.
| | - Päivi Saavalainen
- Research Program Unit, Immunobiology, and Department of Medical and Clinical Genetics, University of Helsinki, 00014 Helsinki, Finland.
| | - Katri Lindfors
- Celiac Disease Research Centre, Faculty of Medicine and Life Sciences, Tampere University, 33520 Tampere, Finland.
| | - Kalle Kurppa
- Tampere Centre for Child Health Research, Tampere University and Tampere University Hospital, 33521 Tampere, Finland.
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Fuchs V, Kurppa K, Huhtala H, Laurila K, Mäki M, Collin P, Salmi T, Luostarinen L, Saavalainen P, Kaukinen K. Serology-based criteria for adult coeliac disease have excellent accuracy across the range of pre-test probabilities. Aliment Pharmacol Ther 2019; 49:277-284. [PMID: 30592070 DOI: 10.1111/apt.15109] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Revised: 10/25/2018] [Accepted: 12/02/2018] [Indexed: 12/19/2022]
Abstract
BACKGROUND The revised paediatric criteria for coeliac disease allow omission of duodenal biopsies in symptomatic children who have specific serology and coeliac disease-associated genetics. It remains unclear whether this approach is also applicable for adults with various clinical presentations. AIM To evaluate the accuracy of serology-based criteria in adults with variable pre-test probabilities for coeliac disease. METHODS Three study cohorts comprised adults with high-risk clinical coeliac disease suspicion (n = 421), moderate-risk family members of coeliac disease patients (n = 2357), and low-risk subjects from the general population (n = 2722). Serological and clinical data were collected, and "triple criteria" for coeliac disease comprised transglutaminase 2 antibodies >10× the upper limit of normal, positive endomysium antibodies, and appropriate genetics without requirement of symptoms. The diagnosis was based on intestinal biopsy. RESULTS The diagnosis of coeliac disease was established in 274 subjects. Of these, 59 high-risk subjects, 17 moderate-risk subjects, and 14 low-risk subjects fulfilled the "triple criteria". All had histologically proven coeliac disease, giving the criteria a positive predictive value of 100%. Altogether, 90 (33%) of all 274 newly diagnosed patients could have avoided biopsy, including 37% among high-risk, 20% among moderate-risk, and 48% among low-risk patients. No histological findings other than coeliac disease were found in the biopsies of "triple positive" subjects. CONCLUSIONS Coeliac disease can reliably and safely be diagnosed without biopsy in adults fulfilling the "triple criteria" regardless of the pre-test probability. Revised criteria would enable the number of endoscopies to be reduced by one-third.
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Affiliation(s)
- Valma Fuchs
- Celiac Disease Research Center, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
| | - Kalle Kurppa
- Tampere Center for Child Health Research, University of Tampere, and Department of Paediatrics, Tampere University Hospital, Tampere, Finland
| | - Heini Huhtala
- Tampere Faculty of Social Sciences, University of Tampere, Tampere, Finland
| | - Kaija Laurila
- Celiac Disease Research Center, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
| | - Markku Mäki
- Tampere Center for Child Health Research, University of Tampere, and Department of Paediatrics, Tampere University Hospital, Tampere, Finland
| | - Pekka Collin
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland
| | - Teea Salmi
- Celiac Disease Research Center, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.,Department of Dermatology, Tampere University Hospital, Tampere, Finland
| | - Liisa Luostarinen
- Department of Neurology, Päijät-Häme Central Hospital, Lahti, Finland
| | - Päivi Saavalainen
- Research Programs Unit, Immunobiology, and Haartman Institute, Department of Medical Genetics, University of Helsinki, Helsinki, Finland
| | - 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
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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.
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Kivelä L, Kurppa K. Screening for coeliac disease in children. Acta Paediatr 2018; 107:1879-1887. [PMID: 29920762 DOI: 10.1111/apa.14468] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Revised: 05/01/2018] [Accepted: 06/15/2018] [Indexed: 12/12/2022]
Abstract
AIM Coeliac disease is a common but markedly under-diagnosed condition, which may lead to serious long-term complications if untreated. Both the diagnostic yield and true incidence have significantly increased during the last few decades and it is now one of the most common chronic gastrointestinal conditions in children. The aim of this review was to summarise the current concepts on screening for coeliac disease in children and adolescents. METHOD We conducted a non-systematic literature review of papers published about coeliac disease screening since the year 2000. RESULTS Our review showed that the diagnostic yield could be significantly improved by screening for at-risk groups, or even the whole population, but these approaches remain controversial. Evidence suggests that screening for certain high-risk groups could be beneficial, but untargeted mass screening is not currently recommended. However, whether the benefits of an early diagnosis would overcome the challenges of lifelong dietary treatment, especially in asymptomatic individuals who consider themselves healthy, are unclear. CONCLUSION There is moderate evidence that screening certain at-risk groups for coeliac disease could be beneficial, but more studies in different settings are needed before large-scale population screening can be recommended.
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Affiliation(s)
- Laura Kivelä
- Tampere Center for Child Health Research; University of Tampere and Tampere University Hospital; Tampere Finland
- Department of Pediatrics; Hospital District of South Ostrobothnia; Seinäjoki Finland
| | - Kalle Kurppa
- Tampere Center for Child Health Research; University of Tampere and Tampere University Hospital; Tampere Finland
- School of Medicine and Life Sciences; University of Tampere; Tampere Finland
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All that a physician should know about gluten-free diet. Indian J Gastroenterol 2018; 37:392-401. [PMID: 30367395 DOI: 10.1007/s12664-018-0895-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Accepted: 09/19/2018] [Indexed: 02/06/2023]
Abstract
Gluten-free diet (GFD) is the only definitive treatment for patients with celiac disease (CeD). Strict adherence to GFD improves the symptoms, nutritional deficiencies, and the overall well-being of the patients. The management of CeD is truly different and unique from the treatment of other medical or surgical diseases. While prescribing a GFD is easy, the key to the success lies in the dietary counseling by a nutrition specialist/physician and maintenance of adherence to the prescribed diet by the patient. When restricting gluten from all possible sources, it is pertinent to recommend a diet that is healthy and balanced for patients with celiac disease. Those following GFD must be counseled properly on the ways of balancing their diets and of avoiding cross contamination. They should be taught how to read food labels properly and given tips for dining out or during traveling. Regular follow up with patients is required for assessing the compliance and monitoring growth and the status of recovery. In this review article, we have compiled, for the physicians and gastroenterologists, the relevant information about GFD including counseling, adherence, nutritional adequacy, and many other related issues.
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