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Seidita A, Latteri F, Pistone M, Giuliano A, Bertoncello L, Cavallo G, Chiavetta M, Faraci F, Nigro A, Termini A, Verona L, Ammannato A, Accomando S, Cavataio F, Lospalluti ML, Citrano M, Di Liberto D, Soresi M, Mansueto P, Carroccio A. Celiac Disease and Liver Damage: The Gut-Liver Axis Strikes Back (Again)? A Retrospective Analysis in the Light of a Literature Review. Nutrients 2024; 17:85. [PMID: 39796519 PMCID: PMC11722968 DOI: 10.3390/nu17010085] [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: 12/07/2024] [Revised: 12/23/2024] [Accepted: 12/26/2024] [Indexed: 01/13/2025] Open
Abstract
Background/Objectives: An increasing number of studies have reported liver involvement in both children and adults with celiac disease (CD). This often manifests as isolated hypertransaminasemia or hepatic steatosis (HS). The aim of this study was to define the prevalence of hypertransaminasemia and HS in a pediatric population with CD before starting a gluten-free diet (GFD) and to analyze how the introduction of a GFD could modify this condition. We also conducted a state-of-the-art literature review of the association between hypertransaminasemia, metabolic dysfunction-associated steatotic liver disease (MASLD) and CD. Methods: We retrospectively reviewed the clinical charts of pediatric CD patients diagnosed in three different pediatric units of Sicily, analyzing clinical, laboratory, ultrasound, and histology data before and 12 months after the introduction of a GFD. Results: A total of 160 patients (65.0% females, median age 6.4 (0.8-13.2) years) were included; hypertransaminasemia and HS prevalences at diagnosis were 8.1% and 6.1%, respectively. Subjects with hypertransaminasemia were younger (p = 0.01) than those without and had higher frequencies of HS (p = 0.034) and anti-tissue transglutaminase (tTg) immunoglobulin (Ig)G positivity (p = 0.046). Subjects with HS were younger (p = 0.0001) and had a higher frequency of hypertransaminasemia (p = 0.029) compared to non-steatotic ones. After 12 months of a GFD, hypertransaminasemia and HS persisted in 53.8% and 50.0% of patients, respectively. Conclusions: The prevalences of hypertransaminasemia and HS in Sicilian pediatric CD patients seem to be lower than those reported in other geographical areas. A GFD can reverse the trend of liver involvement, although periods of longer than 12 months may be necessary. However, a GFD has been associated with an increased prevalence of HS, and so regular follow-up involving a nutritionist should be recommended to guide physicians in patient management.
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Affiliation(s)
- Aurelio Seidita
- Internal Medicine Unit, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Via Trabucco, 180, 90146 Palermo, Italy; (A.S.)
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
- Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), 90146 Palermo, Italy
| | - Federica Latteri
- Gastroenterology Unit, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Via Trabucco, 180, 90146 Palermo, Italy
| | - Mirco Pistone
- Internal Medicine Unit, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Via Trabucco, 180, 90146 Palermo, Italy; (A.S.)
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
| | - Alessandra Giuliano
- Internal Medicine Unit, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Via Trabucco, 180, 90146 Palermo, Italy; (A.S.)
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
| | - Luca Bertoncello
- Internal Medicine Unit, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Via Trabucco, 180, 90146 Palermo, Italy; (A.S.)
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
| | - Giorgia Cavallo
- Internal Medicine Unit, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Via Trabucco, 180, 90146 Palermo, Italy; (A.S.)
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
| | - Marta Chiavetta
- Internal Medicine Unit, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Via Trabucco, 180, 90146 Palermo, Italy; (A.S.)
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
| | - Francesco Faraci
- Internal Medicine Unit, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Via Trabucco, 180, 90146 Palermo, Italy; (A.S.)
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
| | - Alessia Nigro
- Internal Medicine Unit, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Via Trabucco, 180, 90146 Palermo, Italy; (A.S.)
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
| | - Alessandro Termini
- Internal Medicine Unit, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Via Trabucco, 180, 90146 Palermo, Italy; (A.S.)
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
| | - Laura Verona
- Internal Medicine Unit, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Via Trabucco, 180, 90146 Palermo, Italy; (A.S.)
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
| | - Agnese Ammannato
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
| | - Salvatore Accomando
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
- Department of Pediatrics, University Hospital of Palermo, 90134 Palermo, Italy
| | - Francesca Cavataio
- Pediatric Gastroenterology Unit, “Di Cristina” Hospital, Palermo, 90134 Palermo, Italy
| | | | - Michele Citrano
- Pediatrics Unit, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Via Trabucco, 180, 90146 Palermo, Italy
| | - Diana Di Liberto
- Department of Biomedicine, Neurosciences and Advanced Diagnostics (BIND), Institute of Biochemistry, University of Palermo, 90127 Palermo, Italy
| | - Maurizio Soresi
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
| | - Pasquale Mansueto
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
| | - Antonio Carroccio
- Internal Medicine Unit, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Via Trabucco, 180, 90146 Palermo, Italy; (A.S.)
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
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Pachisia AV, Agarwal A, Mehta S, Kumari A, Dwarakanathan V, Sharma S, Kumar S, Mehra L, Dutta R, Das P, Agarwal S, Shalimar, Ahuja V, Makharia GK. Celiac Disease Is Common in Adults With Cryptogenic Cirrhosis and Responds Favorably to Gluten-Free Diet. Am J Gastroenterol 2024. [DOI: 10.14309/ajg.0000000000003244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 11/07/2024] [Indexed: 01/11/2025]
Abstract
INTRODUCTION:
Liver involvement is common in celiac disease (CeD), and up to 4.6% of patients with cryptogenic cirrhosis have CeD. We investigated the prevalence of CeD in patients with cryptogenic cirrhosis and assessed liver-related outcomes in them on GFD when compared with a propensity score–matched cohort of patients with cryptogenic cirrhosis without CeD.
METHODS:
Consecutive patients with cryptogenic cirrhosis were screened for CeD using IgA anti–tissue transglutaminase antibody (anti-tTG) followed by antiendomysial antibody and duodenal and liver biopsies, on which IgA/anti-tTG colocalization studies were performed. These patients and a cohort of patients with cryptogenic cirrhosis without CeD (1:4 CeD: no CeD matched using propensity score matched for age, sex, Child–Turcotte–Pugh [CTP] and model for end-stage liver disease [MELD]) were initiated on GFD plus standard of care and standard of care, respectively, and followed up for liver-related outcomes for 1 year.
RESULTS:
Of 232 patients with cryptogenic cirrhosis, 14 had high anti-tTG Ab (16.9 ± 10.5 fold rise), with 9 antiendomysial antibody–positive and 11 (4.7%) biopsy-proven CeD. IgA/anti-tTG Ab colocalization was demonstrated in 7/8 liver and 10/11 duodenal biopsies. Patients with cryptogenic cirrhosis with definite CeD (n = 11) and matched cohort without CeD (n = 44) were similar at baseline (age: 31.3 ± 7.7 vs 31.8 ± 9.3 years; 5 [45.5%] vs 15 [34.1%] females; MELDNa 9 [interquartile-range: 8–15.5] vs 12 [9–15]; CTP 7 [6–7.5] vs 6 [5.75–7]). Patients with CeD on GFD improved significantly on follow-up compared with those without CeD (follow-up MELDNa: 9 [7.5–10.5] vs 18.5 [12-20]; P = 0.001 and follow-up CTP: 5 [5-5] vs 8 [7–9]; P < 0.001) with less frequent further decompensations and similar mortality (9.1% vs 18.2%; P = 0.67).
DISCUSSION:
Approximately 4.7% of patients with cryptogenic cirrhosis have biopsy-proven CeD, and their liver-related outcomes improve with GFD.
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Affiliation(s)
| | - Ankit Agarwal
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Shubham Mehta
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Alka Kumari
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Vignesh Dwarakanathan
- Centre for Community Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Sonu Sharma
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Sambuddha Kumar
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Lalita Mehra
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Rimlee Dutta
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Prasenjit Das
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Samagra Agarwal
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Govind K. Makharia
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
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Klugman CM, Levine C. Diagnosing Shosha: literature as a lens to view disease and history. MEDICAL HUMANITIES 2024; 50:450-455. [PMID: 38341273 DOI: 10.1136/medhum-2023-012794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/08/2024] [Indexed: 02/12/2024]
Abstract
In recent decades, physicians have diagnosed fictional and non-fictional characters through portraits, biographies and writing. We argue that such an exercise can be beneficial for a uniquely health humanities reason-better understanding of our current world and the social determinants of health. Drawing on the method of health and social justice studies, we explore the character of Shosha, who appears repeatedly in the writings of Nobel Prize winner Isaac Bashevis Singer. Singer's strong story-telling skill and commitment to writing about the Jewish communities of prewar Poland in vivid detail preserve a slice of history, ensure that future generations will better understand what was destroyed by Nazi extermination policies, and provide lessons for modern political, hunger and war threats to human health. Shosha suffers from a lifelong debilitating disease that neither Singer nor subsequent commentaries ever name. The authors focus first on diagnosing the disease by consulting medical literature and experts. They then examine the value and pitfalls of this exercise and suggest that the lessons of understanding the disease historically, for teaching physicians how to recognise diseases rooted in war and poverty, and for enlightening all of us to the risks faced in human health by a world increasingly taking up arms and sliding towards fascism make diagnosing Shosha necessary and meaningful.
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Affiliation(s)
| | - Carol Levine
- United Hospital Fund of New York, New York, New York, USA
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Haider MB, Al Sbihi A, Reddy SN, Green P. Prevalence of malignant neoplasms in celiac disease patients - a nationwide United States population-based study. World J Clin Oncol 2024; 15:1048-1060. [PMID: 39193153 PMCID: PMC11346075 DOI: 10.5306/wjco.v15.i8.1048] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 06/10/2024] [Accepted: 06/27/2024] [Indexed: 08/16/2024] Open
Abstract
BACKGROUND Celiac disease (CeD) is an autoimmune disorder triggered by the immune response to gluten in genetically predisposed individuals. Recent research has unveiled a heightened risk of developing specific malignant neoplasms (MN) and various malignancies, including gastrointestinal, lymphomas, skin, and others, in individuals with CeD. AIM To investigate the prevalence of MN in hospitalized CeD patients in the United States. METHODS Using data from the National Inpatient Sample spanning two decades, from January 2000 to December 2019, we identified 529842 CeD patients, of which 78128 (14.75%) had MN. Propensity score matching, based on age, sex, race, and calendar year, was employed to compare CeD patients with the general non-CeD population at a 1:1 ratio. RESULTS Positive associations were observed for several malignancies, including small intestine, lymphoma, nonmelanoma skin, liver, melanoma skin, pancreas myelodysplastic syndrome, biliary, stomach, and other neuroendocrine tumors (excluding small and large intestine malignant carcinoid), leukemia, uterus, and testis. Conversely, CeD patients exhibited a reduced risk of respiratory and secondary malignancies. Moreover, certain malignancies showed null associations with CeD, including head and neck, nervous system, esophagus, colorectal, anus, breast, malignant carcinoids, bone and connective tissues, myeloma, cervix, and ovary cancers. CONCLUSION Our study is unique in highlighting the detailed results of positive, negative, or null associations between different hematologic and solid malignancies and CeD. Furthermore, it offers insights into evolving trends in CeD hospital outcomes, shedding light on advancements in its management over the past two decades. These findings contribute valuable information to the understanding of CeD's impact on health and healthcare utilization.
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Affiliation(s)
- Maryam Bilal Haider
- Department of Gastroenterology, Northshore University Health System, Evanston, IL 60201, United States
| | - Ali Al Sbihi
- Department of Hematology/Oncology, University of Miami Miller School of Medicine, Miami, FL 33101, United States
| | - Sushmitha Nanja Reddy
- Department of Hematology/Oncology, Karmanos Cancer Institute/Wayne State University, Detroit, MI 48235, United States
| | - Peter Green
- Celiac Disease Center, Columbia University, New York, NY 10032, United States
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Jang J, Krishnamurthy J, Nylund CM. Association between celiac disease and pneumococcal infections in hospitalized pediatric patients in the United States. J Pediatr Gastroenterol Nutr 2024; 79:335-342. [PMID: 38860336 DOI: 10.1002/jpn3.12250] [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: 08/14/2023] [Revised: 03/01/2024] [Accepted: 03/06/2024] [Indexed: 06/12/2024]
Abstract
OBJECTIVE Celiac disease (CD) is an immune-mediated enteropathy that is associated with pneumococcal infections in adults. The objective of this study is to evaluate the association between CD and pneumococcal infections in hospitalized pediatric patients in the United States (US). STUDY DESIGN The triennial Healthcare Cost and Utilization Project Kids' Inpatient Database was used in a retrospective analysis of children hospitalized in the US from 1997 to 2019. Billing codes were used to define patients with CD who were admitted with Streptococcus pneumoniae speciated infections or an infection commonly caused by S. pneumoniae. A multivariable logistic regression model was used to quantify increased odds of various types of infections for patients with CD. RESULTS Among 55,080,914 pediatric hospital admissions, 15,412 were identified with CD, and 1,722,872 were admitted with the specified infections. CD was associated with both pneumococcus speciated infections (odd ratio [OR], 2.16, 95% confidence interval [CI], 1.38-3.38) and infections commonly caused by S. pneumoniae (OR, 1.78; 95% CI, 1.61-1.96): pneumonia (OR, 1.70; 95% CI, 1.53-1.89), sinusitis (OR, 2.41, 95% CI, 1.76-3.30), and bacteremia (OR, 2.12; 95% CI, 1.56-2.88). Patients with CD had a significantly longer length of stay (p < 0.001) and a greater cost of hospitalization (p < 0.001) with pneumococcus associated infections. CONCLUSIONS CD is associated with an increased risk of both pneumococcus speciated and pneumococcus-associated infections requiring hospitalization. CD admissions are associated with longer hospital stays and higher costs without increased risk of death. Routine pneumococcal vaccinations are strongly recommended for pediatric patients with CD.
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Affiliation(s)
- Janet Jang
- Department of Pediatrics, Madigan Army Medical Center, JBLM, Washington, USA
- Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
| | - Jayasree Krishnamurthy
- Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
| | - Cade M Nylund
- Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
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Maimaris S, Schiepatti A, Biagi F. Systematic review with meta-analysis: Cause-specific and all-cause mortality trends across different coeliac disease phenotypes. Aliment Pharmacol Ther 2024; 59:592-605. [PMID: 38204404 DOI: 10.1111/apt.17867] [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: 07/22/2023] [Revised: 09/07/2023] [Accepted: 12/22/2023] [Indexed: 01/12/2024]
Abstract
BACKGROUND Data on mortality in coeliac disease are contrasting. AIMS To systematically review the literature on all-cause and cause-specific mortality in coeliac disease compared to the general population, and evaluate differences across clinical phenotypes, geographical regions, and over time. METHODS We searched PubMed and Embase from 1 January 1970 to 31 December 2022 for eligible studies reporting on all-cause and cause-specific mortality in coeliac disease compared to the general population or controls. The protocol was registered on Open Science Framework (https://doi.org/10.17605/OSF.IO/852DN). RESULTS We included 25 studies. All-cause mortality (HR 1.16, 95% CI 1.05-1.27, I2 = 89%), mortality due to malignancies (HR 1.21, 95% CI 1.08-1.36, I2 = 65%) and respiratory disease (HR 1.39, 95% CI 1.04-1.86, I2 = 76%) were increased. Mortality due to non-Hodgkin lymphoma (HR 10.14, 95% CI 2.19-46.88, I2 = 96%) was markedly increased. Mortality significantly decreased in recent decades: 1989-2004 (HR 1.61, 95% CI 1.27-2.03, I2 = 91%), 2005-2014 (HR 1.16, 95% CI 0.99-1.36, I2 = 89%), 2015-2022 (HR 1.19, 95% CI 1.05-1.35, I2 = 93%). All-cause mortality was not increased in dermatitis herpetiformis (HR 0.85, 95% CI 0.73-0.99, I2 = 40%) and undiagnosed coeliac disease (HR 1.09, 95% CI 0.95-1.25, I2 = 0%). Mortality was increased in the UK (HR 1.23, 95% CI 1.03-1.47, I2 = 91%) but not Scandinavia (HR 1.01, 95% CI 0.91-1.13, I2 = 81%). Limitations include high heterogeneity and lack of data for many countries. CONCLUSION Mortality in coeliac disease is increased, predominantly due to malignancies-particularly non-Hodgkin lymphoma-although differing significantly across disease phenotypes. Mortality of patients with coeliac disease has significantly decreased in recent decades. These results may influence diagnosis and management.
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Affiliation(s)
- Stiliano Maimaris
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
- Gastroenterology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
| | - Annalisa Schiepatti
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
- Gastroenterology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
| | - Federico Biagi
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
- Gastroenterology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
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Moscatelli OG, Russell AK, Henneken LM, Hardy MY, Mazarakis N, Higgins R, Ekin J, McLeod H, Simkin P, Licciardi PV, Bryant VL, Tye-Din JA. Impaired IgM Memory B Cell Function Is Common in Coeliac Disease but Conjugate Pneumococcal Vaccination Induces Robust Protective Immunity. Vaccines (Basel) 2024; 12:214. [PMID: 38400197 PMCID: PMC10891918 DOI: 10.3390/vaccines12020214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 02/15/2024] [Accepted: 02/16/2024] [Indexed: 02/25/2024] Open
Abstract
Coeliac disease (CD) is associated with hyposplenism, an acquired impairment of spleen function associated with reduced IgM memory B cells and increased susceptibility to serious pneumococcal infection. Little is known about the immune implications of hyposplenism in CD or the optimal pneumococcal vaccination strategy. In this study, the immune effects of hyposplenism in CD, and the accuracy of screening approaches and protective responses induced by two different pneumococcal vaccines were examined. Active and treated CD cohorts, and healthy and surgically splenectomised controls underwent testing for the presence of Howell-Jolly bodies and pitted red cells, spleen ultrasound, and immune assessment of IgM memory B cell frequency and IgM memory B cell responses to T cell-dependent (TD) or T cell-independent (TI) stimulation. Responses following conjugate (TD) and polysaccharide (TI) pneumococcal vaccination were compared using ELISA and opsonophagocytic assays. Although hyposplenism is rare in treated CD (5.1%), functional B cell defects are common (28-61%) and are not detected by current clinical tests. Conjugate pneumococcal vaccination induced superior and sustained protection against clinically relevant serotypes. Clinical practice guidelines in CD should recommend routine pneumococcal vaccination, ideally with a conjugate vaccine, of all patients in lieu of hyposplenism screening.
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Affiliation(s)
- Olivia G. Moscatelli
- Immunology Division, The Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia; (O.G.M.)
- Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia
| | - Amy K. Russell
- Immunology Division, The Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia; (O.G.M.)
- Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia
| | - Lee M. Henneken
- Immunology Division, The Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia; (O.G.M.)
- Department of Gastroenterology, The Royal Melbourne Hospital, Parkville, VIC 3052, Australia
| | - Melinda Y. Hardy
- Immunology Division, The Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia; (O.G.M.)
- Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia
| | - Nadia Mazarakis
- The Murdoch Children’s Research Institute, Parkville, VIC 3052, Australia
| | - Rachel Higgins
- The Murdoch Children’s Research Institute, Parkville, VIC 3052, Australia
| | - Jesse Ekin
- Immunology Division, The Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia; (O.G.M.)
- Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia
| | - Harry McLeod
- Immunology Division, The Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia; (O.G.M.)
- Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia
| | - Paul Simkin
- Department of Radiology, The Royal Melbourne Hospital, Parkville, VIC 3052, Australia
| | - Paul V. Licciardi
- The Murdoch Children’s Research Institute, Parkville, VIC 3052, Australia
- Department of Paediatrics, The University of Melbourne, Parkville, VIC 3052, Australia
| | - Vanessa L. Bryant
- Immunology Division, The Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia; (O.G.M.)
- Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia
- Department of Clinical Immunology, The Royal Melbourne Hospital, Parkville, VIC 3052, Australia
| | - Jason A. Tye-Din
- Immunology Division, The Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia; (O.G.M.)
- Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia
- Department of Gastroenterology, The Royal Melbourne Hospital, Parkville, VIC 3052, Australia
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Yuan S, Leffler D, Lebwohl B, Green PHR, Larsson SC, Söderling J, Sun J, Ludvigsson JF. Older age of celiac disease diagnosis and risk of autoimmune disease: A nationwide matched case-control study. J Autoimmun 2024; 143:103170. [PMID: 38286066 DOI: 10.1016/j.jaut.2024.103170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 01/15/2024] [Accepted: 01/19/2024] [Indexed: 01/31/2024]
Abstract
OBJECTIVES Celiac disease (CeD) has been linked to an increased risk of other autoimmune diseases, yet the impact of delayed CeD diagnosis on risk of developing additional autoimmune diseases remains uncertain. We investigated this through a nationwide matched case-control study. METHODS Using the ESPRESSO cohort with histophatology data from Sweden's 28 pathology departments, we assessed 46,575 biopsy-confirmed CeD cases from 1964 to 2017. We extracted 225,295 matched controls without histopathology information from the Swedish Total Population Register. Autoimmune disease was defined through diagnostic codes in the National Patient Register. Through conditional logistic regression we estimated odds ratio (OR) of autoimmune disease up until CeD diagnosis/matching date comparing CeD cases to controls across different age strata. RESULTS A total of 3059 (6.6 %) CeD patients and 4076 (1.8 %) controls had earlier autoimmune disease. The overall OR for autoimmune disease in CeD was 3.50 (95%CI 3.32-3.70). The risk of autoimmune disease did not escalate with increasing age at CeD diagnosis. Compared with controls, the OR of autoimmune disease in CeD patients was 7.70 (95%CI 4.71-12.57) in those diagnosed with CeD in 0-4 years, 19.02 (95%CI 13.80-26.23) in 5-9 years, 6.18 (95%CI 5.14-7.44) in 10-14 years, 4.80 (95%CI 3.97-5.79) in 15-19 years, 4.24 (95%CI 3.55-5.07) in 20-29 years, 4.65 (95%CI 3.93-5.51) in 30-39 years, 3.67 (95%CI 3.30-4.09) in 40-59 years, and 1.67 (95%CI 1.50-1.85) in ≥60 years. CONCLUSIONS This study revealed an increased risk of autoimmune disease among CeD patients compared with controls. However, older age at CeD diagnosis did not seem to escalate the risk of autoimmune diseases.
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Affiliation(s)
- Shuai Yuan
- Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
| | - Daniel Leffler
- The Celiac Center at Beth Israel Deaconess Medical Center, Harvard Medical School, USA
| | - Benjamin Lebwohl
- Department of Medicine, Celiac Disease Center at Columbia University Medical Center, New York, NY, USA
| | - Peter H R Green
- Departments of Medicine and Surgical Pathology, Columbia University College of Physicians and Surgeons, New York, NY, USA
| | - Susanna C Larsson
- Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Jonas Söderling
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Jiangwei Sun
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Jonas F Ludvigsson
- Department of Medicine, Celiac Disease Center at Columbia University Medical Center, New York, NY, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Orebro University Hospital, Orebro, Sweden
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Hitawala AA, Almomani A, Onwuzo S, Boustany A, Kumar P, Asaad I. Prevalence of autoimmune, cholestatic and nonalcoholic fatty liver disease in celiac disease. Eur J Gastroenterol Hepatol 2023; 35:1030-1036. [PMID: 37395201 DOI: 10.1097/meg.0000000000002599] [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: 07/04/2023]
Abstract
BACKGROUND While there is higher prevalence of autoimmune, cholestatic and fatty liver disease in celiac disease (CeD), most data is from small-scale studies. We evaluated the prevalence and risk factors of the same using large cohort data. METHODS A population-based cross-sectional study was conducted using Explorys, a multi-institutional database. Prevalence and risk factors of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and nonalcoholic fatty liver disease (NAFLD) in CeD were assessed. RESULTS Out of 70 352 325 subjects, 136 735 had CeD (0.19%). The prevalence of AIH (0.32%), PBC (0.15%), PSC (0.004%) and NAFLD (0.7%) were high in CeD. After adjusting for age, gender, Caucasian race and anti-tissue transglutaminase antibody (anti-TTG), CeD subjects had higher odds of AIH [adjusted odds ratio (aOR) 7.06, 95% confidence interval (CI) 6.32-7.89] and PBC (aOR 4.16, 95% CI 3.46-5.0). Even after adjusting for CeD, anti-TTG positivity concurred with higher odds of AIH (aOR 4.79, 95% CI 3.88-5.92) and PBC (aOR 9.22, 95% CI 7.03-12.1). After adjusting for age, gender, Caucasian race, diabetes mellitus (DM), obesity, hypothyroidism and metabolic syndrome, there was higher prevalence of NAFLD in CeD, with the aOR in the presence of DM type 1 being 2.1 (95% CI 1.96-2.25), and in the presence of DM type 2 being 2.92 (95% CI 2.72-3.14). CONCLUSION Subjects with CeD are more likely to have AIH, PBC, PSC and NAFLD. AIH and PBC have higher odds in the presence of anti-TTG. The odds of NAFLD in CeD are high regardless of type of DM.
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Affiliation(s)
- Asif Ali Hitawala
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Ashraf Almomani
- Department of Gastroenterology and Digestive Diseases, Cleveland Clinic Foundation, Weston, Florida
| | - Somtochukwu Onwuzo
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Antoine Boustany
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Prabhat Kumar
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Imad Asaad
- Department of Gastroenterology and Digestive Diseases, Cleveland Clinic Foundation, Cleveland, Ohio, USA
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10
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Wang Y, Chen B, Ciaccio EJ, Jneid H, Virani SS, Lavie CJ, Lebovits J, Green PHR, Krittanawong C. Celiac Disease and the Risk of Cardiovascular Diseases. Int J Mol Sci 2023; 24:9974. [PMID: 37373122 DOI: 10.3390/ijms24129974] [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: 05/16/2023] [Revised: 06/01/2023] [Accepted: 06/07/2023] [Indexed: 06/29/2023] Open
Abstract
Celiac disease (CD) is a chronic autoimmune disorder that affects the small intestine in genetically predisposed individuals. Previous studies have investigated the potential link between CD and cardiovascular disease (CVD); however, the findings have been inconsistent. We aimed to provide an updated review of the literature on the association between CD and CVD. PubMed was searched from inception to January 2023 using keywords including CD, cardiovascular disease, coronary artery disease, cardiac arrhythmia, heart failure, cardiomyopathy, and myocarditis. We summarized the results of the studies, including meta-analyses and original investigations, and presented them according to the different forms of CVD. Meta-analyses published in 2015 provided mixed results regarding the relationship between CD and CVD. However, subsequent original investigations have shed new light on this association. Recent studies indicate that individuals with CD are at a higher risk of developing overall CVD, including an increased risk of myocardial infarction and atrial fibrillation. However, the link between CD and stroke is less established. Further research is needed to determine the link between CD and other cardiac arrhythmias, such as ventricular arrhythmia. Moreover, the relationship between CD and cardiomyopathy or heart failure, as well as myopericarditis, remains ambiguous. CD patients have a lower prevalence of traditional cardiac risk factors, such as smoking, hypertension, hyperlipidemia, and obesity. Therefore, it is important to discover strategies to identify patients at risk and reduce the risk of CVD in CD populations. Lastly, it is unclear whether adherence to a gluten-free diet can diminish or increase the risk of CVD among individuals with CD, necessitating further research in this area. To fully comprehend the correlation between CD and CVD and to determine the optimal prevention strategies for CVD in individuals with CD, additional research is necessary.
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Affiliation(s)
- Yichen Wang
- Mercy Internal Medicine Service, Trinity Health of New England, Springfield, MA 01104, USA
| | - Bing Chen
- Department of Gastroenterology and Nutrition, Geisinger Medical Center, Danville, PA 17821, USA
| | - Edward J Ciaccio
- Department of Medicine, Celiac Disease Center, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
| | - Hani Jneid
- Division of Cardiology, University of Texas Medical Branch, Houston, TX 77030, USA
| | - Salim S Virani
- Section of Cardiology and Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
- Office of the Vice Provost (Research), The Aga Khan University, Karachi 74800, Pakistan
| | - Carl J Lavie
- John Ochsner Heart and Vascular Institute, Ochsner Clinical School, University of Queensland School of Medicine, New Orleans, LA 70121, USA
| | - Jessica Lebovits
- Department of Medicine, Celiac Disease Center, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
| | - Peter H R Green
- Department of Medicine, Celiac Disease Center, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
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Brady RP, Jensen ET, Rigdon J, Crimmins NA, Mallon D, Dolan LM, Imperatore G, Kahkoska AR, Mottl AK, Honor A, Pettitt DJ, Merjaneh L, Dabelea D, Shah AS. The Frequency of Undiagnosed Celiac Disease in Youth with Type 1 Diabetes and Its Association with Diabetic Retinopathy: The SEARCH for Diabetes in Youth Study. Pediatr Diabetes 2023; 2023:9038795. [PMID: 39845332 PMCID: PMC11753297 DOI: 10.1155/2023/9038795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2025] Open
Abstract
Aims Celiac disease (CD) in adults with type 1 diabetes has been associated with increased cardiovascular risk and the earlier occurrence of diabetes-associated complications. In the Search for Diabetes in Youth study, we aimed to assess the frequency of CD and the potential for undiagnosed CD among youth with childhood onset type 1 diabetes. In addition, we assessed the burden of cardiovascular risk factors and diabetes-associated complications in youth with type 1 diabetes by CD status and IgA tissue transglutaminase autoantibody (tTGA) levels. Methods 2,444 youths with type 1 diabetes completed a CD questionnaire and underwent tTGA testing. Integrating the celiac disease questionnaire and tTGA results for this cross-sectional analysis, participants were categorized as follows: (1) reported CD; (2) seropositive for CD (no reported CD and seropositive tTGA); and (3) type 1 diabetes only (comparison group: no reported CD and seronegative tTGA). Subanalyses were performed on those with no reported CD and tTGA ≥10x ULN, designated potentially undiagnosed CD. Cardiovascular risk factors and diabetes-associated complications were evaluated by CD status and tTGA levels utilizing a Poisson model to estimate relative risk. Results Reported CD in youths with type 1 diabetes was 7%. Seropositivity for tTGA with no reported CD was present in 4%, and 1.2% had potentially undiagnosed CD. Youths with potentially undiagnosed CD had a 2.69x higher risk of diabetic retinopathy than comparison group. In addition, CD with tTGA <0.05 (controlled CD) was associated with lower HbA1c. Conclusions Undiagnosed CD is likely present in youths with type 1 diabetes and potentially undiagnosed CD is associated with a higher risk of diabetic retinopathy. These findings indicate the importance of routine screening for CD in type 1 diabetes in youths.
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Affiliation(s)
- Ryan P. Brady
- Department of Pediatrics, Cincinnati Children’s Hospital & University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
| | - Elizabeth T. Jensen
- Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Joseph Rigdon
- Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Nancy A. Crimmins
- Department of Pediatrics, Cincinnati Children’s Hospital & University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
| | - Daniel Mallon
- Department of Pediatrics, Cincinnati Children’s Hospital & University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
| | - Lawrence M. Dolan
- Department of Pediatrics, Cincinnati Children’s Hospital & University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
| | - Giuseppina Imperatore
- Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA
| | - Anna R. Kahkoska
- Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Amy K. Mottl
- Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Ann Honor
- Department of Pediatrics, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | | | - Lina Merjaneh
- Department of Pediatrics, University of Washington, Seattle, WA 98195, USA
| | - Dana Dabelea
- Lifeourse Epidemiology of Adiposity and Diabetes (LEAD) Center, Departments of Epidemiology and Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Amy S. Shah
- Department of Pediatrics, Cincinnati Children’s Hospital & University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
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12
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Prevalence of celiac disease in patients with liver diseases: a systematic review and meta-analyses. Am J Gastroenterol 2022; 118:820-832. [PMID: 36599134 DOI: 10.14309/ajg.0000000000002123] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 11/02/2022] [Indexed: 01/06/2023]
Abstract
OBJECTIVES A subset of patients with celiac disease (CeD) have liver involvement in the form of hypertransaminasemia, liver cirrhosis and autoimmune hepatitis. We conducted a systematic review with meta-analyses to determine pooled prevalence of CeD in patients with cryptogenic cirrhosis, all-cause cirrhosis, cryptogenic hypertransaminasemia, and all-cause hypertransaminasemia. METHODS We searched PubMed and EMBASE up to January 2022. Cross-sectional, case-control and prospective cohort studies performing serological tests and/or intestinal biopsy for CeD on patients with cryptogenic cirrhosis, all-cause cirrhosis, cryptogenic hypertransaminasemia and all-cause hypertransaminasemia were included, to calculate pooled estimates of seroprevalence and prevalence of biopsy-confirmed CeD in these four groups. RESULTS Of 6,871 articles screened, 20 articles were included finally in three meta-analyses for cryptogenic cirrhosis, all-cause cirrhosis and cryptogenic hypertransaminasemia. For the all-cause hypertransaminasemia group, a qualitative review of four studies was done instead of a meta-analysis, due to significant differences in studies. The pooled prevalence (95%CI) of biopsy-confirmed CeD, in cryptogenic cirrhosis was 4.6%(2.2-7.5%) while pooled prevalence of biopsy-confirmed CeD in all-cause cirrhosis was 0.8%(0-3.4%). Pooled prevalence of biopsy-confirmed CeD in cryptogenic hypertransaminasemia was 5.7%(3.2-8.8%). CONCLUSIONS Nearly one in 20 patients each with cryptogenic cirrhosis and cryptogenic hypertransaminasemia have CeD, hence they should both be considered high-risk groups for CeD. While prevalence of CeD in all-cause cirrhosis is similar to that in general population, it may be worth screening them for CeD as liver pathology has potential for reversal in them.
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13
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Koskinen I, Hervonen K, Huhtala H, Pasternack C, Salmi T, Reunala T, Collin P, Kaukinen K. Mortality and causes of death in different celiac disease phenotypes during long-term follow-up. Dig Liver Dis 2022; 54:1502-1507. [PMID: 35589505 DOI: 10.1016/j.dld.2022.04.016] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 04/24/2022] [Accepted: 04/27/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND Celiac disease has been associated with increased mortality, but data on long-term mortality are scarce. AIMS To determine long-term mortality in celiac disease. METHODS The study cohort consisted of all celiac disease patients (n=1,392) diagnosed in Tampere University Hospital catchment area 1960 - 2000. Patients were categorized into subgroups based on demographic (age, gender, decade of diagnosis) and celiac disease characteristics (e.g., phenotype, severity of villous atrophy) collected from medical records. Overall and cause-specific mortality was compared to those of age-, sex-, and place of residence matched reference individuals (n=4,177) over time. RESULTS During the 41 years of follow-up (median 26.5 years), 376 celiac disease patients and 1,155 reference individuals died. All-cause mortality was not increased (hazard ratio (HR) 0.96, 95% confidence intervals (CI) 0.85-1.08). Mortality from lymphoproliferative diseases and diseases of the central nervous system was increased (HR 2.42, 95% CI 1.38-4.24 and HR 2.14, 95% CI 1.05-4.36 respectively) while the risk from alcohol related diseases was decreased (HR 0.31, 95% CI 0.09-1.00). Examination of various celiac disease phenotypes revealed no significant differences in mortality CONCLUSIONS: Overall mortality was not increased in any celiac disease phenotype during a very long-term follow-up.
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Affiliation(s)
- Inka Koskinen
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Internal Medicine, Central Finland Central Hospital, Jyväskylä, Finland.
| | - Kaisa Hervonen
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Dermatology, Tampere University Hospital, Tampere, Finland
| | - Heini Huhtala
- Faculty of Social Sciences, Tampere University, Tampere, Finland
| | - Camilla Pasternack
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, 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, Tampere, Finland
| | - Timo Reunala
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Dermatology, Tampere University Hospital, Tampere, Finland
| | - Pekka Collin
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, 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
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14
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Edwards George JB, Aideyan B, Yates K, Voorhees KN, O’Flynn J, Sweet K, Avery K, Ehrlich A, Bast A, Leffler DA. Gluten-induced Neurocognitive Impairment: Results of a Nationwide Study. J Clin Gastroenterol 2022; 56:584-591. [PMID: 34049371 PMCID: PMC9256899 DOI: 10.1097/mcg.0000000000001561] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 03/25/2021] [Indexed: 01/08/2023]
Abstract
GOALS This study aimed to understand the neurocognitive symptoms associated with gluten exposure in individuals with self-reported celiac disease (CD) and nonceliac gluten sensitivity (NCGS). BACKGROUND While gluten-induced neurocognitive impairment (GINI; eg, "celiac fog" or "brain fog") is commonly described by individuals with CD and NCGS, there are little data regarding the prevalence and symptoms associated with these experiences. STUDY A 9-question online survey was accessed by 1396 individuals (1143 with CD; 253 with NCGS). Forced choice and free-response questions were asked of participants to obtain a description of neurocognitive symptoms experienced after gluten ingestion. Free-response answers were coded using a coding structure developed based on the Health-Related Quality of Life Instrument. RESULTS The majority of survey participants (89% of CD and 95% of NCGS) reported having GINI symptoms. When describing symptoms, the most common word descriptors for both groups were difficulty concentrating, forgetfulness, and grogginess. Timing of symptoms, including onset and symptom peak, were similar across the 2 groups. Coding of free responses found the most common references were to cognitive, physical, psychological, and overall quality of life impacts. CONCLUSIONS This survey suggests that GINI is common and may be severe in both individuals with CD and NCGS. Cognitive impairment and decline in physical functioning may be similar to that occurring in other illnesses, such as lupus. Clinical follow-up with both individuals with CD and NCGS should include assessment of GINI symptoms. Further research is warranted, including the development of a patient-reported outcome measure including neurocognitive effects of gluten exposure.
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Affiliation(s)
- Jessica B. Edwards George
- Department of Applied Psychology, Bouvé College of Health Sciences, Northeastern University, Boston, MA
| | - Babatunde Aideyan
- Department of Applied Psychology, Bouvé College of Health Sciences, Northeastern University, Boston, MA
| | - Kayla Yates
- Department of Applied Psychology, Bouvé College of Health Sciences, Northeastern University, Boston, MA
| | | | - Jennifer O’Flynn
- Department of Applied Psychology, Bouvé College of Health Sciences, Northeastern University, Boston, MA
| | | | | | - Alan Ehrlich
- Department of Family Medicine and Community Health, University of Massachusetts Medical School, Worcester
| | | | - Daniel A. Leffler
- Takeda, Cambridge
- Celiac Center, Division of Gastroenterology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
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Bernardi N, Sciatti E, Pancaldi E, Alghisi F, Drera A, Falco R, Vizzardi E. Coeliac and cardiovascular disease: a possible relationship between two apparently separate conditions. Monaldi Arch Chest Dis 2022; 93. [PMID: 35872630 DOI: 10.4081/monaldi.2022.2366] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 07/17/2022] [Indexed: 11/23/2022] Open
Abstract
Coeliac disease (CD) is an autoimmune condition with a high prevalence among general population and multisystemic involvement: a more complex scene than a merely gastrointestinal disease. Therefore, an early diagnosis and treatment with a gluten-free diet is mainly important to reduce mortality and comorbidities. Together with autoimmune diseases (as Hashimoto thyroiditis, insulin-dependent diabetes mellitus, autoimmune liver disease and connective tissue diseases), also an accelerated progression of atherosclerosis and a higher prevalence of heart disease have been reported in coeliacs. In the present paper we tried to collect from literature the emergent data on the probable relationship between coeliac and cardiovascular disease, focusing on pathophysiological bases of vascular injury. Data and opinions on the development of cardiovascular risk in patients with CD are conflicting. However, the major evidence supports the theory of an increased cardiovascular risk in CD, due to many mechanisms of myocardial injury, such as chronic malabsorption, abnormalities of intestinal permeability, and direct immune response against self-proteins. The conclusions that come from these data suggest the utility of a careful cardiovascular follow up in coeliac patients.
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Abstract
PURPOSE OF REVIEW This review highlights literature from the past year and explores the impact on current understanding of celiac disease pathogenesis, diagnosis, and management. RECENT FINDINGS In contrast to earlier clinical trials, recent data suggests that early gluten introduction may protect against the development of celiac disease. Celiac disease is underdiagnosed, associated with high burden of disease and linked to excess mortality risk, yet, there remains considerable uncertainty regarding the utility of mass screening in asymptomatic individuals. The gut microbiome is increasingly implicated in celiac disease pathogenesis, although the exact mechanism is undefined. Probiotics have been proposed as a disease-modifying option for celiac disease but most studies assessing efficacy are of low-quality. Patients with celiac disease do not appear to be at increased risk of contracting or developing adverse outcomes from COVID-19. Little is known about the pathogenesis of nonceliac gluten sensitivity; however, recent findings suggest an autoimmune basis for the condition. SUMMARY Current understanding of celiac disease continues to advance, though significant knowledge gaps remain. Large, rigorous, prospectively designed studies are needed to further characterize celiac disease pathogenesis, management and therapeutic options.
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Affiliation(s)
- Eugenia Uche-Anya
- Celiac Disease Center, Department of Medicine, Columbia University, New York, New York, USA
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17
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Pelizzaro F, Marsilio I, Fassan M, Piazza F, Barberio B, D’Odorico A, Savarino EV, Farinati F, Zingone F. The Risk of Malignancies in Celiac Disease-A Literature Review. Cancers (Basel) 2021; 13:cancers13215288. [PMID: 34771450 PMCID: PMC8582432 DOI: 10.3390/cancers13215288] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Revised: 10/15/2021] [Accepted: 10/19/2021] [Indexed: 12/14/2022] Open
Abstract
Celiac disease (CeD) is an immune-mediated enteropathy precipitated by ingestion of gluten in genetically predisposed individuals. Considering that CeD affects approximately 1% of the Western population, it may be considered a global health problem. In the large majority of cases, CeD has a benign course, characterized by the complete resolution of symptoms and a normal life expectancy after the beginning of a gluten-free-diet (GFD); however, an increased risk of developing malignancies, such as lymphomas and small bowel carcinoma (SBC), has been reported. In particular, enteropathy-associated T-cell lymphoma (EATL), a peculiar type of T-cell lymphoma, is characteristically associated with CeD. Moreover, the possible association between CeD and several other malignancies has been also investigated in a considerable number of studies. In this paper, we aim to provide a comprehensive review of the current knowledge about the associations between CeD and cancer, focusing in particular on EATL and SBC, two rare but aggressive malignancies.
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Affiliation(s)
- Filippo Pelizzaro
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Ilaria Marsilio
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Matteo Fassan
- Surgical Pathology and Cytopathology Unit, Department of Medicine (DIMED), University Hospital of Padova, 35128 Padova, Italy;
- Veneto Oncology Institute, IOV-IRCCS, 35128 Padova, Italy
| | - Francesco Piazza
- Department of Medicine, Hematology, University Hospital of Padova, 35128 Padova, Italy;
| | - Brigida Barberio
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Anna D’Odorico
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Edoardo V. Savarino
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Fabio Farinati
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
| | - Fabiana Zingone
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (F.P.); (I.M.); (B.B.); (A.D.); (E.V.S.); (F.F.)
- Correspondence:
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Wang M, Yu M, Kong WJ, Cui M, Gao F. Association between intestinal neoplasms and celiac disease: A review. World J Gastrointest Oncol 2021; 13:1017-1028. [PMID: 34616509 PMCID: PMC8465454 DOI: 10.4251/wjgo.v13.i9.1017] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 06/02/2021] [Accepted: 07/30/2021] [Indexed: 02/06/2023] Open
Abstract
Celiac disease (CD) is a chronic immune-mediated intestinal disease with genetic susceptibility. It is characterized by inflammatory damage to the small intestine after ingestion of cereals and products containing gluten protein. In recent years, the global prevalence rate of CD has been approximately 1%, and is gradually increasing. CD patients adhere to a gluten-free diet (GFD) throughout their entire life. However, it is difficult to adhere strictly to a GFD. Untreated CD may be accompanied by gastrointestinal symptoms, such as diarrhea, abdominal pain, and extraintestinal symptoms caused by secondary malnutrition. Many studies have suggested that CD is associated with intestinal tumors such as enteropathy-associated T-cell lymphoma (EATL), small bowel cancer (SBC), and colorectal cancer. In this study, we reviewed related studies published in the literature to provide a reference for the prevention and treatment of intestinal tumors in patients with CD. Compared with the general population, CD patients had a high total risk of SBC and EATL, but not colorectal cancer. The protective effect of GFD on CD-related malignancies is controversial. Further studies are needed to confirm whether GFD treatment can reduce the risk of intestinal neoplasms in CD.
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Affiliation(s)
- Man Wang
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Ming Yu
- Department of General Practice, Xiangyang Central Hospital, The Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021 Hubei Province, China
| | - Wen-Jie Kong
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Mei Cui
- Department of Pathology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Feng Gao
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
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19
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Alkhayyat M, Saleh MA, Abureesh M, Khoudari G, Qapaja T, Mansoor E, Simons-Linares CR, Vargo J, Stevens T, Rubio-Tapia A, Chahal P. The Risk of Acute and Chronic Pancreatitis in Celiac Disease. Dig Dis Sci 2021; 66:2691-2699. [PMID: 32809104 DOI: 10.1007/s10620-020-06546-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2020] [Accepted: 08/06/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIMS Celiac disease (CD) is a chronic immune-mediated enteropathy that is precipitated by dietary gluten in genetically predisposed individuals. A few studies reported a higher incidence of pancreatitis in the CD population. Using a large US database, we sought to describe the epidemiology, risk, and outcomes of acute pancreatitis (AP) and chronic pancreatitis (CP) in CD patients. METHODS We queried a multiple health system data analytics and research platform (Explorys Inc, Cleveland, OH, USA). A cohort of patients with a diagnosis of CD was identified. Subsequently, individuals who developed a new diagnosis of AP and CP after at least 30 days of being diagnosed with CD were identified. A multivariate regression model was performed to adjust for multiple confounding factors. RESULTS Of the 72,965,940 individuals in the database, 133,400 (0.18%), 362,050 (0.50%), and 95,190 (0.13%) had CD, AP, and CP, respectively. New diagnosis of AP and CP after at least 30 days of CD diagnosis was 1.06%, 0.52%, respectively, compared to non-CD patients with 0.49% for AP and 0.13% for CP, P < .0001. In multivariate regression analysis, patients with CD were at higher risk of developing AP [OR 2.66; 95% CI 2.55-2.77] and CP [OR 2.18; 95% CI 2.04-2.34]. Idiopathic AP was the most common etiology among CD patients [OR 1.54; 95% CI 1.34-1.77]. CONCLUSIONS In this largest US population database and after adjusting for several confounders, patients with CD were at increased risk of developing AP and CP. Celiac disease patients had worse outcomes and higher medical burden compared to non-CD patients. Recurrent abdominal pain that suggests pancreatic etiology, idiopathic pancreatitis, or elevation of pancreatic enzymes should warrant investigation for CD as a potential cause of pancreatic disease.
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Affiliation(s)
- Motasem Alkhayyat
- Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.,Department of Internal Medicine, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Mohannad Abou Saleh
- Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.,Gastroenterology, Hepatology and Nutrition, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue/A30, Cleveland, OH, 44195, USA
| | - Mohammad Abureesh
- Staten Island University Hospital, 475 Seaview Ave, Staten Island, NY, 10305, USA
| | - George Khoudari
- Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Thabet Qapaja
- Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Emad Mansoor
- University Hospitals Cleveland Medical Center, 11100 Euclid Avenue, Cleveland, OH, 44106, USA
| | | | - John Vargo
- Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Tyler Stevens
- Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | | | - Prabhleen Chahal
- Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA. .,Gastroenterology, Hepatology and Nutrition, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
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20
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Behrendt I, Fasshauer M, Eichner G. Gluten Intake and All-Cause and Cause-Specific Mortality: Prospective Findings from the UK Biobank. J Nutr 2021; 151:591-597. [PMID: 33382415 DOI: 10.1093/jn/nxaa387] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Revised: 10/20/2020] [Accepted: 11/11/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Gluten has been linked to adverse effects on metabolic and vascular health. OBJECTIVES The present study determines the association between dietary gluten intake and all-cause (primary objective), as well as cause-specific, mortality in people without celiac disease. METHODS Gluten intake was estimated in 159,265 participants of the UK Biobank which is a large multicenter, prospective cohort study initiated in 2006. Cox proportional hazard regression models were used and HRs were determined for all-cause and cause-specific mortality. All models were adjusted for confounders and multiple testing. RESULTS Median (IQR) age was 57 (49-62) y with 52.1% of participants being female. Gluten intake was 8.5 (5.1-12.4) g/d with significantly higher consumption in males [10.0 (6.3-14.1) g/d] than in females [7.2 (4.6-10.7) g/d] (P < 0.0001). During a median follow-up of 11.1 (10.6-11.9) y and 1.8 million person-years, 6259 deaths occurred. Gluten intake was not significantly associated with all-cause mortality after adjusting for confounders (HR: 1.00; 95% CI: 1.00, 1.01; P = 0.59). Dietary gluten was not significantly associated with cancer (HR: 1.00; 95% CI: 1.00, 1.01; raw P = 0.24) or noncancer (HR: 1.00; 95% CI: 0.99, 1.01; raw P = 0.56) mortality. However, gluten intake was positively associated with ischemic heart disease mortality (HR: 1.02; 95% CI: 1.01, 1.04; raw P = 0.003, Holm-adjusted P = 0.04). CONCLUSIONS Gluten intake is not significantly associated with all-cause and cancer mortality in adults without celiac disease. The findings support the hypothesis that limiting gluten intake is unlikely to provide significant overall survival benefits on a population level. The positive association between gluten intake and ischemic heart disease mortality requires further study.
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Affiliation(s)
- Inken Behrendt
- Institute of Nutritional Science, Justus-Liebig University of Giessen, Giessen, Germany
| | - Mathias Fasshauer
- Institute of Nutritional Science, Justus-Liebig University of Giessen, Giessen, Germany.,Department of Internal Medicine (Endocrinology, Nephrology, and Rheumatology), University of Leipzig, Leipzig, Germany.,Integrated Research and Treatment Center (IFB) AdiposityDiseases, Leipzig University Medical Center, Leipzig, Germany
| | - Gerrit Eichner
- Mathematical Institute, Justus-Liebig University of Giessen, Giessen, Germany
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21
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Contribution of Infectious Agents to the Development of Celiac Disease. Microorganisms 2021; 9:microorganisms9030547. [PMID: 33800833 PMCID: PMC8001938 DOI: 10.3390/microorganisms9030547] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 02/28/2021] [Accepted: 03/02/2021] [Indexed: 02/07/2023] Open
Abstract
The ingestion of wheat gliadin (alcohol-soluble proteins, an integral part of wheat gluten) and related proteins induce, in genetically predisposed individuals, celiac disease (CD), which is characterized by immune-mediated impairment of the small intestinal mucosa. The lifelong omission of gluten and related grain proteins, i.e., a gluten-free diet (GFD), is at present the only therapy for CD. Although a GFD usually reduces CD symptoms, it does not entirely restore the small intestinal mucosa to a fully healthy state. Recently, the participation of microbial components in pathogenetic mechanisms of celiac disease was suggested. The present review provides information on infectious diseases associated with CD and the putative role of infections in CD development. Moreover, the involvement of the microbiota as a factor contributing to pathological changes in the intestine is discussed. Attention is paid to the mechanisms by which microbes and their components affect mucosal immunity, including tolerance to food antigens. Modulation of microbiota composition and function and the potential beneficial effects of probiotics in celiac disease are discussed.
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22
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Naaraayan A, Nimkar A, Jesmajian S, Gitler B, Acharya P. Atherosclerotic Cardiovascular Disease Prevalence Among Patients With Celiac Disease in the United States: An Observational Study. Mayo Clin Proc 2021; 96:666-676. [PMID: 33673917 DOI: 10.1016/j.mayocp.2020.04.051] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Revised: 04/07/2020] [Accepted: 04/14/2020] [Indexed: 11/21/2022]
Abstract
OBJECTIVE To assess the prevalence of atherosclerotic cardiovascular disease (ASCVD) by age and sex in patients with celiac disease and to determine associations between ASCVD and celiac disease. PATIENTS AND METHODS This is a retrospective cohort study which included adults (>18 years old) who had hospitalizations recorded in the National Inpatient Sample database in the United States from January 1, 2005, to December 31, 2014. Patients with celiac disease were matched (1:5) by age, sex, race, and calendar year to patients without celiac disease. Prevalence of ASCVD was calculated in patients with celiac disease and controls, and compared by sex and age groups. Associations between celiac disease and ASCVD were determined after adjustment for common cardiovascular risk factors. RESULTS Among 371,776,860 patients hospitalized in the United States between 2005 and 2014, 227,172 adults with celiac disease were matched to 1,133,701 controls. Young women with celiac disease (age <40 years) had a higher prevalence of ASCVD and higher adjusted odds (aOR) of ASCVD when compared with controls (aged 18 to 29 years aOR, 2.22 [95% CI 1.41 to 3.5]; P<.001; and aged 30 to 39 years aOR 1.54 [95% CI 1.19 to 1.99]; P<.001). Adults with celiac disease of all ages and sexes had increased adjusted odds of death if they had ASCVD (aOR aged <40 years 7.31 [95% CI 2.49 to 21.46]; P<.001; and aOR aged ≥40 years 2.02 [95% CI 1.68 to 2.42]; P<.001). CONCLUSION We found significantly higher prevalence and adjusted odds of ASCVD in young women with celiac disease when compared with matched controls. ASCVD was associated with significant mortality among patients with celiac disease.
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23
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Pitchumoni CS. Celiac Disease. GERIATRIC GASTROENTEROLOGY 2021:1597-1616. [DOI: 10.1007/978-3-030-30192-7_69] [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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24
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Pinto-Sanchez MI, Seiler CL, Santesso N, Alaedini A, Semrad C, Lee AR, Bercik P, Lebwohl B, Leffler DA, Kelly CP, Moayyedi P, Green PH, Verdu EF. Association Between Inflammatory Bowel Diseases and Celiac Disease: A Systematic Review and Meta-Analysis. Gastroenterology 2020; 159:884-903.e31. [PMID: 32416141 DOI: 10.1053/j.gastro.2020.05.016] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Revised: 04/23/2020] [Accepted: 05/02/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS There is controversy over the association between celiac disease (CeD) and inflammatory bowel diseases (IBD). We performed a systematic review and meta-analysis to assess evidence for an association between CeD and IBD. METHODS We searched databases including MEDLINE, EMBASE, CENTRAL, Web of Science, CINAHL, DARE, and SIGLE through June 25, 2019 for studies assessing the risk of CeD in patients with IBD, and IBD in patients with CeD, compared with controls of any type. We used the Newcastle-Ottawa Scale to evaluate the risk of bias and GRADE to assess the certainty of the evidence. RESULTS We identified 9791 studies and included 65 studies in our analysis. Moderate certainty evidence found an increased risk of CeD in patients with IBD vs controls (risk ratio [RR] 3.96; 95% confidence interval [CI] 2.23-7.02) and increased risk of IBD in patients with CeD vs controls (RR 9.88; 95% CI 4.03-24.21). There was low-certainty evidence for the risk of anti-Saccharomyces antibodies, a serologic marker of IBD, in patients with CeD vs controls (RR 6.22; 95% CI 2.44-15.84). There was low-certainty evidence for no difference in risk of HLA-DQ2 or DQ8 in patients with IBD vs controls (RR 1.04; 95% CI 0.42-2.56), and very low-certainty evidence for an increased risk of anti-tissue transglutaminase in patients with IBD vs controls (RR 1.52; 95% CI 0.52-4.40). Patients with IBD had a slight decrease in risk of anti-endomysial antibodies vs controls (RR 0.70; 95% CI 0.18-2.74), but these results are uncertain. CONCLUSIONS In a systematic review and meta-analysis, we found an increased risk of IBD in patients with CeD and increased risk of CeD in patients with IBD, compared with other patient populations. High-quality prospective cohort studies are needed to assess the risk of CeD-specific and IBD-specific biomarkers in patients with IBD and CeD.
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Affiliation(s)
- Maria Ines Pinto-Sanchez
- Department of Medicine, Farncombe Family Digestive Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Caroline L Seiler
- Department of Medicine, Farncombe Family Digestive Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Nancy Santesso
- Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada
| | - Armin Alaedini
- Celiac Disease Center at Columbia University, New York, New York
| | - Carol Semrad
- Celiac Disease Center at University of Chicago Medicine, Chicago, Illinois
| | - Anne R Lee
- Celiac Disease Center at Columbia University, New York, New York
| | - Premysl Bercik
- Department of Medicine, Farncombe Family Digestive Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Benjamin Lebwohl
- Celiac Disease Center at Columbia University, New York, New York
| | - Daniel A Leffler
- Department of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Ciaran P Kelly
- Department of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Paul Moayyedi
- Department of Medicine, Farncombe Family Digestive Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Peter H Green
- Celiac Disease Center at Columbia University, New York, New York
| | - Elena F Verdu
- Department of Medicine, Farncombe Family Digestive Research Institute, McMaster University, Hamilton, Ontario, Canada.
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25
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Koskinen I, Virta LJ, Huhtala H, Ilus T, Kaukinen K, Collin P. Overall and Cause-Specific Mortality in Adult Celiac Disease and Dermatitis Herpetiformis Diagnosed in the 21st Century. Am J Gastroenterol 2020; 115:1117-1124. [PMID: 32618663 DOI: 10.14309/ajg.0000000000000665] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION We assessed whether celiac disease-associated mortality is increased in Finland among patients diagnosed in the 21st century, given recent improvements in diagnostic and treatment facilities. METHODS Biopsy-proven patients with celiac disease (Marsh III) and dermatitis herpetiformis aged 20-79 years (median 50 years) diagnosed 2005-2014 (n = 12,803) were identified from the national dietary grant registry. Dates and causes of death were obtained from Statistics Finland. Overall mortality and causes of death were compared with reference individuals (n = 38,384) matched for age, sex, and area of residence (at the time of celiac disease diagnosis) selected from the Population Information System. RESULTS During a mean follow-up of 7.7 years (SD ±3.0 years), 884 (6.9%) and 2,613 (6.8%) deaths occurred among the celiac cohort and reference group, respectively. Overall mortality (hazard ratio [HR] 1.01, 95% confidence intervals [CIs] 0.94-1.09), mortality from all malignancies (HR 1.11, 95% CI 0.96-1.27), gastrointestinal tract malignancies (HR 1.21, 95% CI 0.56-1.71), or cardiovascular diseases (HR 0.91, 95% CI 0.77-1.07) were not increased among patients with celiac disease. Overall, mortality from lymphoproliferative diseases (HR 2.36, 95% CI 1.65-3.39) and nonmalignant digestive diseases (HR 2.19, 95% CI 1.40-3.43) was increased, but HRs decreased after the exclusion of the first 2 years of follow-up (HR 1.71, 95% CI 1.10-2.66 and HR 1.75, 95% CI 1.01-3.05, respectively). DISCUSSION The overall mortality in adult celiac disease diagnosed 2005-2014 was not increased. Mortality from lymphoproliferative diseases was increased but lower than previously reported.
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Affiliation(s)
- Inka Koskinen
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Internal Medicine, Central Finland Central Hospital, Jyväskylä, Finland
| | - Lauri J Virta
- Research Department, Social Insurance Institution of Finland, Turku, Finland
| | - Heini Huhtala
- Faculty of Social Sciences, Tampere University, Tampere, Finland
| | - Tuire Ilus
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, 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
| | - Pekka Collin
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland
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26
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Marafini I, Monteleone G, Stolfi C. Association Between Celiac Disease and Cancer. Int J Mol Sci 2020; 21:ijms21114155. [PMID: 32532079 PMCID: PMC7312081 DOI: 10.3390/ijms21114155] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 06/08/2020] [Accepted: 06/09/2020] [Indexed: 02/06/2023] Open
Abstract
Celiac disease (CD) is a chronic enteropathy that develops in genetically susceptible individuals after the ingestion of gluten. There has been a substantial increase in CD prevalence in the last 50 years, and it is now estimated that this disease affects approximately 1% of the population in the Western world. In the large majority of cases, CD is a benign disease, characterized by the complete resolution of symptoms and a normal life expectancy after the onset of a gluten-free diet (GFD). However, failure to adhere to a strict GFD bears the risk of adverse events and increases mortality. A considerable number of studies have considered the possible association between CD and neoplasms. In particular, an increased risk of malignancies, such as cancers of the gastrointestinal tract and intestinal lymphomas, has been reported. In this review, we summarize and discuss the current evidence on the possible association between CD and cancer.
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Affiliation(s)
- Irene Marafini
- Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy; (I.M.); (G.M.)
- Gastroenterology Unit, Policlinico Tor Vergata, 00133 Rome, Italy
| | - Giovanni Monteleone
- Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy; (I.M.); (G.M.)
- Gastroenterology Unit, Policlinico Tor Vergata, 00133 Rome, Italy
| | - Carmine Stolfi
- Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy; (I.M.); (G.M.)
- Division of Clinical Biochemistry and Clinical Molecular Biology, University of Rome “Tor Vergata”, 00133 Rome, Italy
- Correspondence: ; Tel.: +39-06-72596163
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Maluf SW, Wilhelm Filho D, Parisotto EB, Medeiros GDSD, Pereira CHJ, Maraslis FT, Dornelles Schoeller CC, Rosa JSD, Fröde TS. DNA damage, oxidative stress, and inflammation in children with celiac disease. Genet Mol Biol 2020; 43:e20180390. [PMID: 32555942 PMCID: PMC7288666 DOI: 10.1590/1678-4685-gmb-2018-0390] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2019] [Accepted: 07/12/2019] [Indexed: 02/07/2023] Open
Abstract
The objective of this study was to evaluate the level of genomic instability in patients with celiac disease and to establish a relationship between inflammation, oxidative stress, and DNA damage in these patients. Myeloperoxidase (MPO) activity, adenosine deaminase, nitric oxide (NOx), thiobarbituric acid, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and DNA damage were evaluated in peripheral blood samples from 47 celiac disease patients and 31 controls. Patients with celiac disease presented higher levels of DNA damage in comparison to controls (p=0.023). This difference was also observed for markers of oxidative stress, such as CAT (p=0.011) and SOD (p=0.013), and inflammatory markers such as MPO (p < 0.001) and NOx (p=0.009). Positive correlations were found between DNA damage levels and the values of CAT (r=0.405; p=0.009) and SOD (r=0.516; p < 0.001). Positive correlations were also found between GPx and NOx (r=0.349; p=0.030) and MPO and NOx (r=0.239; p=0.039). CAT and NOx showed a negative correlation (r= −0.315; p=0.042). In conclusion, intestinal inflammation can have systemic effects, causing an imbalance between oxidant and antioxidant markers, which may promote increased levels of DNA damage.
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Affiliation(s)
- Sharbel Weidner Maluf
- Universidade Federal de Santa Catarina, Hospital Universitário, Laboratório de Genética, Florianópolis, SC, Brazil
| | - Danilo Wilhelm Filho
- Universidade Federal de Santa Catarina, Departamento de Ecologia e Zoologia, Florianópolis, SC, Brazil
| | - Eduardo Benedetti Parisotto
- Universidade Federal de Mato Grosso do Sul, Faculdade de Ciências Farmacêuticas, Alimentos e Nutrição, Campo Grande, MS, Brazil
| | | | | | - Flora Troina Maraslis
- Universidade Federal de Santa Catarina, Hospital Universitário, Laboratório de Genética, Florianópolis, SC, Brazil
| | | | - Julia Savan da Rosa
- Universidade Federal de Santa Catarina, Centro de Ciências de Saúde, Departamento de Análises Clínicas, Florianópolis, SC, Brazil
| | - Tânia Silvia Fröde
- Universidade Federal de Santa Catarina, Centro de Ciências de Saúde, Departamento de Análises Clínicas, Florianópolis, SC, Brazil
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28
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Evaluation of nasal mucociliary clearance time in children with celiac disease. Int J Pediatr Otorhinolaryngol 2020; 133:109936. [PMID: 32088546 DOI: 10.1016/j.ijporl.2020.109936] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2019] [Revised: 01/10/2020] [Accepted: 02/06/2020] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Celiac disease is an autoimmune disorder that develops because of sensitivity to gluten-containing grains in genetically disposed individuals. Nasal mucociliary clearance is the most important protective factor that protects the upper and lower airways from foreign particulates. This study aimed to investigate the effect of celiac disease on nasal mucociliary clearance. METHODS The study included patients with celiac disease and healthy children. Nasal mucociliary clearance time was measured using the saccharin test. The children's saccharin taste time was recorded in seconds. RESULTS Overall, 65 children were included: 43 patients with celiac disease (66.2%) and 22 healthy children (33.8%). Of all the children, 42 (64.6%) were female, and the average age was 11.8 ± 4 years. Nasal mucociliary clearance time of patients with celiac disease (531 ± 155 s) was significantly prolonged in comparison to that of healthy children (448 ± 80 s) (p = 0.006). No relationships were found between the diagnosis age, celiac type, and histopathological phase and compliance with the gluten-free diet and nasal mucociliary clearance time of patients with celiac disease. CONCLUSIONS This study showed that nasal mucociliary clearance was prolonged in patients with celiac disease. A defect in nasal mucociliary clearance increases the risk of infection and inflammation in small airways. Studies reported a high prevalence of respiratory tract infection in patients with celiac disease, which was associated with malnutrition, vitamin deficiency, and hyposplenism. The findings of the present study indicated that impairment of nasal mucociliary clearance could play a role in the development of frequent lung infections in patients with celiac disease.
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Fabian E, Tinchon C, Lueger A, Bauer PK, Mayer-Pickel KI, Raggam RB, Hammer HF, Langner C, Krejs GJ. Clinical-Pathological Conference Series from the Medical University of Graz : Case No 169: A 32-year-old woman with anemia in pregnancy. Wien Klin Wochenschr 2020; 132:322-331. [PMID: 32468113 PMCID: PMC7297834 DOI: 10.1007/s00508-020-01679-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Accepted: 05/07/2020] [Indexed: 11/01/2022]
Affiliation(s)
- Elisabeth Fabian
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Christoph Tinchon
- Division of Hematology and Oncology, Department of Internal Medicine, State Hospital Hochsteiermark, Leoben, Austria
| | - Andreas Lueger
- Division of Emergency Medicine, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Philipp K Bauer
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
| | | | - Reinhold B Raggam
- Division of Angiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Heinz F Hammer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria
| | - Cord Langner
- Department of Pathology, Medical University of Graz, Graz, Austria
| | - Guenter J Krejs
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.
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Brickley MB, Kahlon B, D'Ortenzio L. Using teeth as tools: Investigating the mother-infant dyad and developmental origins of health and disease hypothesis using vitamin D deficiency. AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY 2020; 171:342-353. [PMID: 31709512 PMCID: PMC7004071 DOI: 10.1002/ajpa.23947] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Revised: 09/20/2019] [Accepted: 10/01/2019] [Indexed: 12/12/2022]
Abstract
OBJECTIVES With a growing interest in the mother-infant dyad and the Developmental Origins of Health and Disease hypothesis among biological and medical anthropologists, this study set out to provide all the information required to evaluate if mineralization defects in dentine might be caused by vitamin D deficiency in the critical first 1000 days of life. MATERIALS AND METHODS Information was compiled on dentine formation in utero to approximately 18 years, and a method for determining the location of the neonatal line in dentine was devised, allowing the assessment of the prenatal and early life period. Re-evaluation of previously analyzed teeth (n = 61) was undertaken with detailed examination of n = 5/22 first permanent molars forming in the prenatal and critical early life periods. RESULTS First permanent molars and all deciduous teeth give information on intrauterine development and on the first 1000 days postnatally providing a direct window on maternal and fetal health. Three archaeological individuals had interglobular dentine that formed prenatally suggesting that their mothers experienced vitamin D deficiency at the time dentine was forming and all other individuals had a deficiency during the first 1000 days of life. Conditions that could cause systemic mineralization defects were determined, and in each, case they were found to be consistent with vitamin D deficiency. DISCUSSION The neonatal line serves as a clear baseline for determining prenatal and postnatal events, particularly those related to vitamin D, calcium, and phosphate metabolism, and can be used to investigate the maternal-infant dyad for both past and present communities.
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Affiliation(s)
| | - Bonnie Kahlon
- Department of AnthropologyMcMaster UniversityHamiltonOntarioCanada
| | - Lori D'Ortenzio
- Department of AnthropologyMcMaster UniversityHamiltonOntarioCanada
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Prevalance of Celiac Disease in Patients with Inflammatory Bowel Disease in Turkish Population. Gastroenterol Res Pract 2019; 2019:6272098. [PMID: 31885543 PMCID: PMC6927052 DOI: 10.1155/2019/6272098] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Revised: 11/04/2019] [Accepted: 11/26/2019] [Indexed: 12/16/2022] Open
Abstract
Background Celiac disease (CD) and inflammatory bowel disease (IBD) involve inflammation of the gastrointestinal lumen, which environmental, genetic, and immunological factors have a role in their pathogenesis. The prevalence of celiac disease in IBD ranges from 0% to 14%. In this study, our aim was to determine the prevalence of CD in IBD patients followed by us who are attending the hospital or outpatient clinic over a period of time of seven years. Methods Seven hundred and fifty nine patients (425 M, 334 F, mean age: 46.75, 396 ulcerative colitis (UC), 363 Crohn's disease (CrD)) diagnosed and followed up for IBD between January 2009 and July 2016 were evaluated retrospectively, and clinical, demographic, laboratory, and endoscopic data were collected. Results CD was investigated in 79 (%10.4) inflammatory bowel disease patients according to symptoms, and in 5.06% (n = 4) of them, we diagnosed CD. The most common indication for investigating for CD was iron deficiency anemia unreponsive to iron supplementation. Conclusions We did not find an increased prevalance of celiac disease in Turkish IBD patients in this study. In the presence of refractory iron deficiency anemia without any other cause in IBD patients, investigations for celiac disease should be considered.
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Cirrhose hépatique au cours de la maladie cœliaque : prévalence, caractéristiques et évolution sous régime sans gluten. Rev Med Interne 2019. [DOI: 10.1016/j.revmed.2019.10.187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Abstract
GOAL The aim of this analysis was to assess in patients with inflammatory bowel disease (IBD) the risk of celiac disease and in celiac disease patients the risk of IBD. BACKGROUND Previous studies report a possible association between IBD and celiac disease; however, this link is controversial. STUDY Using the search terms "inflammatory bowel disease" and "celiac disease," we identified initially 1525 publications. In total 27 studies met inclusion criteria. Proportions and 95% confidence intervals (CIs) for the prevalence of IBD in celiac disease and vice versa were compared with published prevalence rates for the respective geographic regions. RESULTS We included 41,482 adult IBD patients (20,357 with Crohn's disease; 19,791 with ulcerative colitis; and 459 patients with celiac disease). Overall, in IBD patients the prevalence of celiac disease was 1110/100,000 (95% CI, 1010-1210/100,000) as compared with a prevalence of 620/100,000 (95% CI, 610-630/100,000) in the respective populations (odds ratio, 2.23; 95% CI, 1.99-2.50). In contrast, in patients with celiac disease, 2130/100,000 had IBD (95% CI, 1590-2670/100,000) as compared with 260/100,000 (95% CI, 250/100,000-270/100,000) in the respective populations (odds ratio, 11.10; 95% CI, 8.55-14.40). This effect was not different for ulcerative colitis and Crohn's disease. Although there was no evidence for publication bias for celiac disease in IBD, the funnel plot suggested that the association between IBD in celiac disease might be influenced by publication bias. CONCLUSIONS The data are consistent with the notion that celiac disease is a risk factor for IBD and to lesser degree patients with IBD have an increased risk of celiac disease.
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Wijarnpreecha K, Panjawatanan P, Corral JE, Lukens FJ, Ungprasert P. Celiac disease and risk of sarcoidosis: A systematic review and meta-analysis. J Evid Based Med 2019; 12:194-199. [PMID: 31218829 DOI: 10.1111/jebm.12355] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Accepted: 05/12/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND/OBJECTIVES Several epidemiologic studies have suggested that patients with celiac disease may be at an increased risk of sarcoidosis but the results were inconsistent. This systematic review and meta-analysis was conducted with the aim to better characterize this risk by summarizing all available data. METHODS A literature review was performed using MEDLINE and EMBASE database from inception to February 2019. Studies that compared the risk of sarcoidosis among patients with celiac disease versus individuals without celiac disease were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS Of 426 retrieved studies, four studies with 693 639 participants met the eligibility criteria and were included in meta-analysis. The risk of sarcoidosis among patients with celiac disease was higher than individuals without celiac disease with the pooled OR of 7.16 (95% CI, 1.48-34.56). The statistical heterogeneity of this study was high (I2 = 95%). CONCLUSIONS This systematic review and meta-analysis found a significantly higher risk of sarcoidosis among patients with celiac disease.
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Affiliation(s)
- Karn Wijarnpreecha
- Department of Internal Medicine, Bassett Medical Center, Cooperstown, New York
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, Jacksonville, Florida
| | | | - Juan E Corral
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, Jacksonville, Florida
| | - Frank J Lukens
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, Jacksonville, Florida
| | - Patompong Ungprasert
- Clinical Epidemiology Unit, Faculty of Medicine Siriraj Hospital, Department of Research and Development, Mahidol University, Bangkok, Thailand
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Casella G, Ingravalle F, Abbate G, Monti C, Bonetti F, Bassotti G, Mansueto P, Villanacci V, Carroccio A. Pneumococcal vaccination in celiac disease. Expert Rev Gastroenterol Hepatol 2019; 13:541-546. [PMID: 30987472 DOI: 10.1080/17474124.2019.1607295] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Celiac disease (CD) is an immune-mediated disorder associated with gluten exposure in genetically predisposed subjects. Areas covered: Infectious disease is one of the causes of morbidity and mortality in CD patients. Invasive streptococcus pneumoniae (pneumococcus) is a particularly dangerous morbid condition in both the general population and celiac patients. Pneumococcal vaccination is the most effective means for its prevention. Expert opinion: In CD, evaluation of spleen function should be useful to select patients who may benefit from vaccination to reduce the risk of pneumococcal disease. Different strategies could be employed: physicians could search for signs of hyposplenism on peripheral blood smear or abdominal ultrasound. However, the best strategy to identify which patients will benefit from pneumococcal vaccination has not yet been defined.
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Affiliation(s)
| | | | - Giorgio Abbate
- c Prevention and Vaccination Center , Corberi-Antonini Hospital - ASST Monza , Limbiate (Monza Brianza) , Italy
| | - Claudio Monti
- a ATS Lecco-Brianza , Limbiate (Monza Brianza) , Italy
| | | | - Gabrio Bassotti
- d Gastroenterology, Hepatology and Digestive Endoscopy Section, Department of Medicine , University of Perugia - Medicine , Perugia , Italy
| | - Pasquale Mansueto
- e Dipartimento Biomedico di Medicina Interna e Specialistica (DiBiMIS) , University of Palermo , Palermo , Italy
| | | | - Antonio Carroccio
- e Dipartimento Biomedico di Medicina Interna e Specialistica (DiBiMIS) , University of Palermo , Palermo , Italy.,g Internal Medicine , Giovanni Paolo II Hospital, Sciacca (ASP Agrigento) , Italy
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Abstract
Celiac disease is a multisystem disorder. Celiac hepatitis characterized by gluten-responsive mild elevation of transaminases is the more common liver manifestation of celiac disease. Celiac disease may also be associated or coexist with other chronic liver disorders. Shared genetic risk and increased intestinal permeability have been suggested to be the most relevant events in the pathogenesis of liver injury in celiac disease. The aim of this article is to review the full spectrum of liver disorders in patients with celiac disease.
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Affiliation(s)
- Alberto Rubio-Tapia
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905
| | - Joseph A. Murray
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905
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Faye AS, Lebwohl B. Celiac Disease: Diagnosis, Screening, and Prognosis. EVIDENCE‐BASED GASTROENTEROLOGY AND HEPATOLOGY 4E 2019:139-149. [DOI: 10.1002/9781119211419.ch9] [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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Abstract
Celiac disease is a common, chronic inflammatory disorder of the small intestine triggered by exposure to gluten in individuals with certain genetic types. This disorder affects people of any age or gender. Although often thought to be European in origin, it is now global in extent. Presentations are variable, from asymptomatic patients to severe malnutrition. Initial detection usually relies on celiac-specific serology, and confirmation often requires intestinal biopsy. There have been substantial increases in prevalence and incidence over the last 2 decades for reasons that are almost certainly environmental but for which there is no clarity as to cause.
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Elli L, Ferretti F, Orlando S, Vecchi M, Monguzzi E, Roncoroni L, Schuppan D. Management of celiac disease in daily clinical practice. Eur J Intern Med 2019; 61:15-24. [PMID: 30528262 DOI: 10.1016/j.ejim.2018.11.012] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2018] [Revised: 11/06/2018] [Accepted: 11/27/2018] [Indexed: 02/06/2023]
Abstract
Celiac disease (CD) is the most common autoimmune enteropathy worldwide. In CD, dietary gluten triggers a T cell driven small intestinal inflammation in a subset of genetically predisposed subjects, expressing the HLA DQ2 and/or DQ8 genes on their antigen presenting cells. HLA DQ2/DQ8 can bind gluten peptides after their prior modification by the CD autoantigen, tissue transglutaminase (TG2). This process leads to the activation of gluten reactive T cells, small bowel villous atrophy, crypt hyperplasia and intraepithelial lymphocytosis, the histological hallmarks of CD. The clinical picture of CD is extremely heterogeneous including intestinal (especially diarrhea, abdominal pain, bloating) and extraintestinal (especially associated autoimmune diseases, anemia, osteoporosis) manifestations. The prevalence of CD in most parts of the world is estimated at 1:100-1:150 and its diagnosis is based on the presence of circulating autoantibodies (anti-TG2) and the histological detection of villous atrophy. Treatment is a lifelong gluten free diet but adjunctive therapies are in development. Although CD is a well-characterized disease, it is grossly underdiagnosed, despite the severe consequences of long-term gluten ingestion in CD, such as enhanced autoimmunity, refractory CD and intestinal T cell lymphoma. The aim of the presented review is to provide a clinical guide and to summarize the most recent clinical progress in CD research.
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Affiliation(s)
- Luca Elli
- Center for Prevention and Diagnosis of Celiac Disease, Division of Gastroenterology and Endoscopy, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milano, Italy.
| | - Francesca Ferretti
- Center for Prevention and Diagnosis of Celiac Disease, Division of Gastroenterology and Endoscopy, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milano, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Via Festa del Perdono, 20122 Milano, Italy
| | - Stefania Orlando
- Center for Prevention and Diagnosis of Celiac Disease, Division of Gastroenterology and Endoscopy, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milano, Italy
| | - Maurizio Vecchi
- Center for Prevention and Diagnosis of Celiac Disease, Division of Gastroenterology and Endoscopy, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milano, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Via Festa del Perdono, 20122 Milano, Italy
| | - Erika Monguzzi
- Center for Prevention and Diagnosis of Celiac Disease, Division of Gastroenterology and Endoscopy, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milano, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Via Festa del Perdono, 20122 Milano, Italy; Institute for Translational Immunology, Research Center for Immunotherapy (FZI), Johannes Gutenberg University (JGU) Medical Center, 55101 Mainz, Germany
| | - Leda Roncoroni
- Center for Prevention and Diagnosis of Celiac Disease, Division of Gastroenterology and Endoscopy, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milano, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Via Festa del Perdono, 20122 Milano, Italy; Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Via Festa del Perdono, 20122 Milano, Italy
| | - Detlef Schuppan
- Institute for Translational Immunology, Research Center for Immunotherapy (FZI), Johannes Gutenberg University (JGU) Medical Center, 55101 Mainz, Germany; Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
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Quarpong W, Card TR, West J, Solaymani-Dodaran M, Logan RF, Grainge MJ. Mortality in people with coeliac disease: Long-term follow-up from a Scottish cohort. United European Gastroenterol J 2018; 7:377-387. [PMID: 31019706 DOI: 10.1177/2050640618814662] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2018] [Accepted: 10/29/2018] [Indexed: 01/08/2023] Open
Abstract
Background Few studies have determined the very long-term mortality risks in adult and childhood-diagnosed coeliac disease. Objective We quantified mortality risks in coeliac disease and determined whether age at diagnosis, or time following diagnosis, modified these risks. Methods Standardised mortality ratios were determined using data from a cohort of 602 coeliac patients assembled between 1979-1983 from Lothian, Scotland, and followed up from 1970-2016. Results All-cause mortality was 43% higher than in the general population. Excess deaths were primarily from haematological malignancies (standardised mortality ratio, 4.77) and external causes (standardised mortality ratio, 2.62) in adult and childhood-diagnosed cases respectively. Mortality risks declined steadily with time in adult-diagnosed cases (standardised mortality ratio, 4.85 in first year compared to 0.97, 25 years post-diagnosis). Beyond 15 years, this group had a significantly reduced risk of any malignancy (standardised mortality ratio, 0.57 (95% confidence interval: 0.33-0.92)). In contrast, for childhood-diagnosed cases an increased risk existed beyond 25 years (standardised mortality ratio, 2.24). Conclusions Adult-diagnosed coeliac patients have a temporarily increased mortality risk mainly from malignant lymphomas and a decreased risk of any malignancy beyond 15 years post-diagnosis. In contrast, childhood-diagnosed cases are at an increased risk of mortality mainly from external causes, and have long-term mortality risks that requires further investigation.
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Affiliation(s)
- Wilhemina Quarpong
- School of Medicine, Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK
| | - Timothy R Card
- School of Medicine, Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK.,National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre, Nottingham, UK
| | - Joe West
- School of Medicine, Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK.,National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre, Nottingham, UK
| | - Masoud Solaymani-Dodaran
- School of Medicine, Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK.,Minimally Invasive Surgery Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Richard Fa Logan
- School of Medicine, Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK
| | - Matthew J Grainge
- School of Medicine, Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK
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Abstract
Small bowel adenocarcinoma is a clinically and anatomically distinct gastrointestinal cancer that lacks prospective data to support its optimal management. Patients with inflammatory bowel disease and inherited conditions that cause gastrointestinal polyps are at especially high risk. Due to a lack of effective surveillance programs resulting in missed or delayed diagnoses only when symptoms develop, this disease is generally discovered at an advanced stage. Surgical resection is the only treatment modality with a chance of cure. Currently accepted treatment considerations are often generalized from large bowel and pancreatic-biliary cancers, due to some anatomic and clinical parallels. Additional research, however, is desperately needed to characterize the unique molecular differences of this disease to better prognosticate patients and establish rational clinical trials that would improve their outcomes.
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Affiliation(s)
- Emerson Y Chen
- Division of Hematology and Medical Oncology, Department of Medicine, Knight Cancer Institute, Oregon Health & Sciences University, Portland, Oregon
| | - Gina M Vaccaro
- Division of Hematology and Medical Oncology, Department of Medicine, Knight Cancer Institute, Oregon Health & Sciences University, Portland, Oregon
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Tovoli F, Negrini G, Farì R, Guidetti E, Faggiano C, Napoli L, Bolondi L, Granito A. Increased risk of nonalcoholic fatty liver disease in patients with coeliac disease on a gluten-free diet: beyond traditional metabolic factors. Aliment Pharmacol Ther 2018; 48:538-546. [PMID: 29984415 DOI: 10.1111/apt.14910] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 04/27/2018] [Accepted: 06/24/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND A gluten-free diet (GFD) is known to be associated with altered macronutrient intake and metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) is the hepatic hallmark of metabolic syndrome. The risk of NAFLD in patients with coeliac disease (CD) adhering to a GFD remains to be fully investigated; in particular, data from real-life clinical settings are lacking. AIM To assess the prevalence and relative risk of NAFLD in CD patients treated with a GFD. METHODS Case-control study, with prospective enrolment of CD outpatients following a GFD and controls. Patients were matched for demographic characteristics (age and gender) and metabolic risk factors (overweight, diabetes mellitus, total cholesterol, and triglycerides) using a 1:1 ratio. NAFLD was diagnosed according to the European Association for the Study of the Liver criteria. RESULTS 202 CD patients and 202 controls were compared. The raw prevalence of NAFLD was 34.7% and 21.8% in the CD and control group, respectively (P = 0.006). Binary logistic regression confirmed an increased risk of NAFLD in the CD group (adjusted odds ratio = 2.90, 95% confidence interval: 1.64-5.15, P < 0.001). Additionally, the relative risk for NAFLD was notably higher in non-overweight CD patients (adjusted odds ratio = 5.71, 95% confidence interval: 2.30-14.19, P < 0.001). CONCLUSIONS More than one-third of CD patients adhering to a GFD had concurrent NAFLD, accounting for a three-fold increased risk compared to the general population. Dietary advice provided using a patient-tailored approach should assist CD patients with NAFLD in achieving an appropriate nutritional intake whilst reducing the risk of long-term liver-related events.
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Affiliation(s)
- F Tovoli
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - G Negrini
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - R Farì
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - E Guidetti
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - C Faggiano
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - L Napoli
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - L Bolondi
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - A Granito
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
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Creanza A, Lupoli R, Lembo E, Tecce N, Della Pepa G, Lombardi G, Riccardi G, Di Bonito P, Capaldo B. Glycemic control and microvascular complications in adults with type 1 diabetes and long-lasting treated celiac disease: A case-control study. Diabetes Res Clin Pract 2018; 143:282-287. [PMID: 30075178 DOI: 10.1016/j.diabres.2018.07.031] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Revised: 07/09/2018] [Accepted: 07/30/2018] [Indexed: 02/07/2023]
Abstract
AIMS To investigate whether in type 1 diabetes (T1DM) patients the concomitance of long-lasting celiac disease (CD) treated with a gluten free diet (GFD) impacts glycaemic control and the prevalence/severity of microvascular complications. METHODS A case-control, observational study was performed in 34 patients with T1DM and GFD-treated CD and 66 patients with T1DM alone matched for age, gender, and T1DM duration. Anthropometric parameters, glucose control (HbA1c), status of chronic complications and concomitant autoimmune diseases were evaluated. RESULTS HbA1c level was similar in T1DM + CD and T1DM alone (7.8 ± 1.0 vs 7.7 ± 1.1%, P = 0.57); insulin requirement was significantly higher in T1DM + CD compared with T1DM (P = 0.04). There were no differences in systolic blood pressure while diastolic blood pressure was significantly lower in T1DM + CD (P = 0.003). The prevalence/severity of microvascular complications was similar between the two groups. Glomerular filtration rate (eGFR) was significantly lower in T1DM + CD (100 ± 20 vs 110 ± 16 ml/min/1.73 m2, P = 0.007). CONCLUSIONS In patients with T1DM, the co-occurrence of long-term GFD-treated CD neither worsens glycemic control nor negatively impacts chronic microvascular complications. However, patients with T1DM + CD have lower eGFR values than those with T1DM alone.
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Affiliation(s)
- Annalisa Creanza
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Roberta Lupoli
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy
| | - Erminia Lembo
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Nicola Tecce
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Giuseppe Della Pepa
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Gianluca Lombardi
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Gabriele Riccardi
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Procolo Di Bonito
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Brunella Capaldo
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
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Crocker H, Jenkinson C, Peters M. Quality of life in coeliac disease: qualitative interviews to develop candidate items for the Coeliac Disease Assessment Questionnaire. PATIENT-RELATED OUTCOME MEASURES 2018; 9:211-220. [PMID: 30013408 PMCID: PMC6038864 DOI: 10.2147/prom.s149238] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Background Coeliac-specific measures have been criticized for not complying with current guidance on the development of patient-reported outcome measures (PROMs). The aim of this study was to develop a measure to assess health-related quality of life in adults with coeliac disease (CD), in accordance with current guidance for PROM development. Methods In-depth qualitative interviews were conducted with adults with CD. A thematic analysis was undertaken to develop a coding framework. All interviews were analyzed according to this framework. Interviewing continued until data saturation was achieved. Candidate items were developed on the basis of the interview findings. Results The analysis revealed 6 themes: 1) symptoms, 2) gluten-free diet, 3) emotional health, 4) impact on activities, 5) relationships, and 6) financial issues. Data saturation was reached after 8 interviews, but a total of 23 interviews were conducted to include a wide enough range of diverse participants. From the themes, 64 candidate items (9 for symptoms, 15 for emotional health, 16 for gluten-free diet, 7 for relationships, 12 for impact on activities, and 5 for financial issues) were developed to form the first draft of the Coeliac Disease Assessment Questionnaire (CDAQ). Conclusion The 64 items reflect all the issues of importance to people with CD. Next, these items will be pretested and refined to lead to a shorter draft version of the CDAQ before it is administered in a survey to produce a final version with subscales.
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Affiliation(s)
- Helen Crocker
- Health Services Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK,
| | - Crispin Jenkinson
- Health Services Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK,
| | - Michele Peters
- Health Services Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK,
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Hoffmanová I, Sánchez D, Tučková L, Tlaskalová-Hogenová H. Celiac Disease and Liver Disorders: From Putative Pathogenesis to Clinical Implications. Nutrients 2018; 10:nu10070892. [PMID: 30002342 PMCID: PMC6073476 DOI: 10.3390/nu10070892] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 07/04/2018] [Accepted: 07/10/2018] [Indexed: 12/12/2022] Open
Abstract
Immunologically mediated liver diseases belong to the common extraintestinal manifestations of celiac disease. We have reviewed the current literature that addresses the association between celiac disease and liver disorders. We searched relevant articles on MEDLINE/PubMed up to 15 June 2018. The objective of the article is to provide a comprehensive and up-to-date review on the latest hypotheses explaining the pathogenetic relationship between celiac disease and liver injury. Besides the involvement of gut–liver axis, tissue transglutaminase antibodies, and impairment of intestinal barrier, we integrate the latest achievements made in elucidation of the role of gut microbiota in celiac disease and liver disorders, that has not yet been sufficiently discussed in the literature in this context. The further objective is to provide a complete clinical overview on the types of liver diseases frequently found in celiac disease. In conclusion, the review highlights the clinical implication, recommend a rational approach for managing elevated transaminases in celiac patients, and underscore the importance of screening for celiac disease in patients with associated liver disease.
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Affiliation(s)
- Iva Hoffmanová
- Centre for Research on Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Ruska 87, 100 00 Prague, Czech Republic.
- Second Department of Internal Medicine, Third Faculty of Medicine, Charles University, Ruska 87, 100 00 Prague, Czech Republic.
| | - Daniel Sánchez
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, v.v.i., Videnska 1083, 142 20 Prague, Czech Republic.
| | - Ludmila Tučková
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, v.v.i., Videnska 1083, 142 20 Prague, Czech Republic.
| | - Helena Tlaskalová-Hogenová
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, v.v.i., Videnska 1083, 142 20 Prague, Czech Republic.
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Holmes GKT, Muirhead A. Mortality in coeliac disease: a population-based cohort study from a single centre in Southern Derbyshire, UK. BMJ Open Gastroenterol 2018; 5:e000201. [PMID: 29686881 PMCID: PMC5911148 DOI: 10.1136/bmjgast-2018-000201] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Revised: 03/13/2018] [Accepted: 03/29/2018] [Indexed: 12/13/2022] Open
Abstract
Objective With the advent of screening tests, it was hypothesised that milder cases of coeliac disease coming to diagnosis might have reduced risk of mortality. An earlier publication did not support this view. We have re-examined this issue employing a larger number of patients followed for a further 8 years. Design Patients with coeliac disease from Southern Derbyshire, UK, were followed prospectively from 1978 to 2014 and included those diagnosed by biopsy and serology. Causes of death were ascertained. Standardised mortality ratios were calculated for all deaths, cardiovascular disease, malignancy, accidents and suicides, respiratory and digestive disease. Ratios were calculated for individual causes. Analysis centred on the postdiagnosis period that included follow-up time beginning 2 years from the date of coeliac disease diagnosis to avoid ascertainment bias. Patients were stratified according to date of diagnosis to reflect increasing use of serological methods. Results All-cause mortality increase was 57%. Mortality in the serology era declined overall. Mortality from cardiovascular disease, specifically, decreased significantly over time. Death from respiratory disease significantly increased in the postdiagnosis period. The standardised mortality ratio for non-Hodgkin’s lymphoma was 6.32, for pneumonia 2.58, for oesophageal cancer 2.80 and for liver disease 3.10. Survival in those who died after diagnosis increased by three times over the past three decades. Conclusions Serological testing has impacted on the risk of mortality in coeliac disease. There is an opportunity to improve survival by implementing vaccination programmes for pneumonia and more prompt, aggressive treatments for liver disease.
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Nobel YR, Axelrad J, Lewis SK, Whittier S, Lawlor G, Lichtiger S, Green PHR, Lebwohl B. Stool PCR for Gastrointestinal Pathogens in Patients With and Without Immune-Mediated Intestinal Diseases. Dig Dis Sci 2018; 63:996-1002. [PMID: 29411208 DOI: 10.1007/s10620-018-4959-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Accepted: 01/30/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Patients with celiac disease and inflammatory bowel disease, two immune-mediated luminal conditions, have higher rates of certain infections than healthy counterparts. The prevalence of many gastrointestinal infections in these patients, however, is unknown. AIMS Using a novel clinical stool pathogen PCR test, we investigated the hypothesis that patients with celiac disease/inflammatory bowel disease had different distributions of diarrheal pathogens than other patients. METHODS We performed a retrospective cohort study of outpatients who underwent stool pathogen testing with the FilmArray Gastrointestinal PCR Panel (BioFire Diagnostics, Salt Lake City, UT) at our institution from January 1 to December 31, 2015. Rates of pathogens were measured in patients with or without celiac disease/inflammatory bowel disease. RESULTS Of 955 patients, 337 had positive test for any pathogen, with 465 bacterial, parasitic, or viral pathogens identified. One hundred and twenty-seven patients (13.3%) had celiac disease or inflammatory bowel disease, of which 29/127 (22.8%) had a positive test, compared to 308/828 other patients (37.2%) (p = 0.002). Patients with celiac disease/inflammatory bowel disease had significantly fewer viruses (1.6 vs. 8.1% of patients; p = 0.008) and parasites (0 vs. 3.3%; p = 0.039), with nonsignificant trend toward fewer bacteria (21.3 vs. 29.2%; p = 0.063). Escherichia coli species were most common in both populations. CONCLUSIONS Stool PCR identified numerous pathogens in patients with or without celiac disease/inflammatory bowel disease. Patients with celiac disease/inflammatory bowel disease were significantly less likely to have any pathogen identified, and had significantly fewer viruses and parasites. In this population, knowledge of common pathogens can guide diagnostic evaluation and offer opportunities for treatment.
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Affiliation(s)
- Yael R Nobel
- Department of Medicine, Columbia University Medical Center, New York, NY, USA
| | - Jordan Axelrad
- Division of Digestive and Liver Diseases, Columbia University College of Physicians and Surgeons, New York, NY, USA
| | - Suzanne K Lewis
- Division of Digestive and Liver Diseases, Columbia University College of Physicians and Surgeons, New York, NY, USA
| | - Susan Whittier
- Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY, USA
| | - Garrett Lawlor
- Division of Digestive and Liver Diseases, Columbia University College of Physicians and Surgeons, New York, NY, USA
| | - Simon Lichtiger
- Division of Digestive and Liver Diseases, Columbia University College of Physicians and Surgeons, New York, NY, USA
| | - Peter H R Green
- Division of Digestive and Liver Diseases, Columbia University College of Physicians and Surgeons, New York, NY, USA
| | - Benjamin Lebwohl
- Division of Digestive and Liver Diseases, Columbia University College of Physicians and Surgeons, New York, NY, USA.
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
- The Celiac Disease Center at Columbia University, 180 Fort Washington Avenue, Suite 936, New York, NY, 10032, USA.
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Abstract
BACKGROUND/OBJECTIVE Recent epidemiologic studies have suggested that patients with celiac disease might be at an increased risk of schizophrenia. However, the data on this risk remain inconclusive. This meta-analysis was conducted with the aim to summarize all available evidence. METHODS A literature search was carried out using MEDLINE and Embase database from inception to June 2017. Studies that compared the risk of schizophrenia among patients with celiac disease versus individuals without celiac disease were included. Pooled odds ratio and 95% confidence interval were calculated using a random-effect, generic inverse-variance method. RESULTS Of the 284 retrieved studies, four met our eligibility criteria and were included in the analysis. We found a higher risk of schizophrenia among patients with celiac disease compared with individuals without celiac disease with the pooled odds ratio of 2.03 (95% confidence interval: 1.45-2.86). The statistical heterogeneity of this study was insignificant (I=0%). CONCLUSION This systematic review and meta-analysis found a significantly higher risk of schizophrenia among patients with celiac disease.
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Potter MDE, Brienesse SC, Walker MM, Boyle A, Talley NJ. Effect of the gluten-free diet on cardiovascular risk factors in patients with coeliac disease: A systematic review. J Gastroenterol Hepatol 2018; 33:781-791. [PMID: 29105146 DOI: 10.1111/jgh.14039] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2017] [Revised: 10/23/2017] [Accepted: 10/25/2017] [Indexed: 12/30/2022]
Abstract
BACKGROUND AND AIMS A gluten-free diet (GFD), the mainstay of treatment for celiac disease, is being increasingly adopted by people without this condition. The long-term health effects of this diet, apart from its beneficial effect on enteropathy in celiac disease, are unclear. Concerns exist that the GFD may result in micronutrient deficiencies, increased exposure to toxins such as arsenic, and an increased cardiovascular risk. This systematic review addresses the effect of the GFD on several modifiable cardiovascular risk factors. METHODS A systematic search of the literature addressing the GFD and blood pressure, glycaemia, body mass index, waist circumference, and serum lipids in patients before and after adoption of a GFD was conducted using the MEDLINE, EMBASE, PSYCInfo, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases. Two authors performed abstract and full text screening, and quality assessment. RESULTS A total of 5372 articles were identified, from which 27 were included. Lack of control groups in all but one study prevented meta-analysis of results. Overall study quality was low and restricted to patients with celiac disease. Consistent findings across studies included an increase in total cholesterol, high density lipoprotein, fasting glycaemia, and body mass index (while remaining within the healthy weight range). Significant changes in low density lipoprotein, triglycerides, and blood pressure were not consistently reported. CONCLUSIONS A GFD alters certain cardiovascular risk factors in patients with celiac disease, but the overall effect on cardiovascular risk is unclear. Further studies are warranted.
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Affiliation(s)
- Michael D E Potter
- Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia.,John Hunter Hospital, Newcastle, New South Wales, Australia
| | - Stephen C Brienesse
- Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia.,John Hunter Hospital, Newcastle, New South Wales, Australia
| | - Marjorie M Walker
- Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia.,John Hunter Hospital, Newcastle, New South Wales, Australia
| | - Andrew Boyle
- Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia.,John Hunter Hospital, Newcastle, New South Wales, Australia
| | - Nicholas J Talley
- Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia.,John Hunter Hospital, Newcastle, New South Wales, Australia
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Kucukseymen S, Cekin AH, Bayar N, Arslan S, Uygur Kucukseymen E, Mercan T, Ozdemir S. A novel biomarker for prediction of atrial fibrillation susceptibility in patients with celiac disease. PLoS One 2018; 13:e0190382. [PMID: 29315324 PMCID: PMC5760044 DOI: 10.1371/journal.pone.0190382] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2017] [Accepted: 12/13/2017] [Indexed: 12/13/2022] Open
Abstract
Background Celiac disease (CD), a serious autoimmune disorder that occurs in people who are genetically predisposed, is induced by dietary gluten intake and affects primarily the small intestine. Many studies have identified an increased risk of cardiovascular problems in patients with CD. Moreover, these patients are susceptible to certain liver diseases, as well as fibrosis. Objective The aim of this study was to assess the presence of fibrosis using the De Ritis ratio, determining its effect on the electromechanical features of the left atrium and its susceptibility to atrial fibrillation (AF) in patients with CD. Methods A total of 97 patients diagnosed with CD by antibody test and biopsy were included in this prospective study. Two groups were created from these patients, a fibrosis-prone (FP) group and a non-fibrosis-prone (NFP) group, according to the cut-off value, as defined in previously published reports, for the AST/ALT ratio. Electrocardiographic and echocardiographic examinations were performed as part of the study. Results There were no differences in the baseline characteristics and conventional echocardiographic parameters of the defined groups. However, the patients in the FP group, as compared to those in the NFP group, had significantly increased PWD (56.68±6.48 ms vs. 37.49±6.22 ms, P<0.001). Additionally, significantly higher interatrial (60.50±13.05 ms vs. 29.40±11.55 ms, P<0.001), intra-left atrial (44.18±14.12 ms vs. 21.02±11.99 ms, P<0.001), and intra-right atrial (15.61±8.91 ms vs. 8.38±4.50 ms, P<0.001) EMD was found among the patients in the FP group compared to that of the NFP group. Conclusion It is believed that the susceptibility to AF cited in previous studies may be related to fibrosis. Our study is the first to examine the possible effects of fibrosis on AF susceptibility in patients with CD, whereby we propose a new biomarker for prediction of AF susceptibility of these patients.
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Affiliation(s)
- Selcuk Kucukseymen
- Department of Cardiology, University of Health Sciences, Antalya Education and Research Hospital, Antalya, Turkey
- Department of Biophysics, Akdeniz University Faculty of Medicine, Antalya, Turkey
- * E-mail:
| | - Ayhan Hilmi Cekin
- Department of Gastroenterology, University of Health Sciences, Antalya Education and Research Hospital, Antalya, Turkey
| | - Nermin Bayar
- Department of Cardiology, University of Health Sciences, Antalya Education and Research Hospital, Antalya, Turkey
| | - Sakir Arslan
- Department of Cardiology, University of Health Sciences, Antalya Education and Research Hospital, Antalya, Turkey
| | - Elif Uygur Kucukseymen
- Department of Neurology, University of Health Sciences, Antalya Education and Research Hospital, Antalya, Turkey
| | - Tanju Mercan
- Department of Biophysics, Akdeniz University Faculty of Medicine, Antalya, Turkey
| | - Semir Ozdemir
- Department of Biophysics, Akdeniz University Faculty of Medicine, Antalya, Turkey
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