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Kowalski MK, Domżał-Magrowska D, Małecka-Wojciesko E. Celiac Disease-Narrative Review on Progress in Celiac Disease. Foods 2025; 14:959. [PMID: 40231983 PMCID: PMC11941517 DOI: 10.3390/foods14060959] [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: 02/03/2025] [Revised: 02/28/2025] [Accepted: 03/09/2025] [Indexed: 04/16/2025] Open
Abstract
Celiac disease is defined as a systemic immunological disorder caused by gluten (gliadin and other prolamin) in genetically predisposed individuals, who present with a variety of gluten-dependent symptoms, specific antibodies, the presence of the HLA DQ2 and DQ8 histocompatibility antigen, and enteropathy. Its prevalence, depending on the studied population and methodology, is estimated at 0.75-1.6% of the general population. During the complex immune reaction it induces, most cells involved in inflammatory processes are activated, which leads to the gradual atrophy of intestinal villi and the proliferation of enterocytes within intestinal crypts. The pathogenesis of celiac disease is extremely complicated and is still the subject of research. According to the current diagnostic guidelines, the following criteria should be taken into account: clinical symptoms (intestinal and extraintestinal), the presence of antibodies against tissue transglutaminase in the IgA class, the level of total IgA, and the presence of typical histological changes in duodenal biopsies. Diet-resistant celiac disease is one of the most important clinical challenges, causing serious complications. Currently, the basic method for treating celiac disease is an elimination diet (i.e., the exclusion of products that may contain gluten from the diet), however, new therapeutic strategies are still being sought, mainly based on supplementation with exogenous endopeptidases, modification of the immune response, and the use of zonulin inhibitors and transglutaminase 2 inhibitors. Clinical trials of new drugs are ongoing. The gradually expanding knowledge about the pathogenesis of celiac disease may allow for the development of new therapeutic strategies for both patients with a mild disease course, as well as those that are diet-resistant.
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Affiliation(s)
| | | | - Ewa Małecka-Wojciesko
- Department of Digestive Tract Diseases, Norbert Barlicki University Hospital, 90-153 Lodz, Poland; (M.K.K.); (D.D.-M.)
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Herrera-Quintana L, Navajas-Porras B, Vázquez-Lorente H, Hinojosa-Nogueira D, Corrales-Borrego FJ, Lopez-Garzon M, Plaza-Diaz J. Celiac Disease: Beyond Diet and Food Awareness. Foods 2025; 14:377. [PMID: 39941971 PMCID: PMC11817883 DOI: 10.3390/foods14030377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Revised: 01/20/2025] [Accepted: 01/23/2025] [Indexed: 02/16/2025] Open
Abstract
Celiac disease is attributable to a combination of genetic predisposition and exposure to dietary gluten, with immune system involvement. The incidence is increasing globally, and the societal economic burden of celiac disease stretches beyond the cost of gluten-free food. This enteropathy that affects the small intestine has been related to different disorders and comorbidities. Thus, the implications of suffering from this disease are multidimensional and need further consideration. Celiac disease is a serious condition that remains under-recognized, resulting in an increased need for programs for better management. This review aims to summarize the current evidence regarding celiac diseases, with special emphasis on clinical implications, diagnosis, dietary management, socioeconomical aspects, and future perspectives.
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Affiliation(s)
- Lourdes Herrera-Quintana
- Department of Physiology, Schools of Pharmacy and Medicine, University of Granada, 18071 Granada, Spain;
| | - Beatriz Navajas-Porras
- Department of Endocrinology and Nutrition, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset, 46017 Valencia, Spain;
| | - Héctor Vázquez-Lorente
- Department of Physiology, Schools of Pharmacy and Medicine, University of Granada, 18071 Granada, Spain;
| | - Daniel Hinojosa-Nogueira
- Unidad de Gestión Clínica de Endocrinología y Nutrición, Laboratorio del Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario de Málaga (Virgen de la Victoria), 29010 Málaga, Spain;
| | | | - Maria Lopez-Garzon
- Biomedical Group (BIO277), Department of Physical Therapy, Health Sciences Faculty, University of Granada, 18171 Granada, Spain;
- Instituto de Investigación Biosanitaria IBS.GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain
| | - Julio Plaza-Diaz
- School of Health Sciences, Universidad Internacional de La Rioja, Avenida de la Paz, 137, 26006 Logroño, Spain;
- Instituto de Investigación Biosanitaria IBS.GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain
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Eklund R, Blackett JW, Lee AR, Green PHR, Lebwohl B. Characteristics of Hospitalized Patients With and Without Celiac Disease on a Gluten-Free Diet. Dig Dis Sci 2024; 69:4116-4123. [PMID: 39395927 DOI: 10.1007/s10620-024-08677-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 09/30/2024] [Indexed: 10/14/2024]
Abstract
BACKGROUND Most people maintaining a gluten-free diet (GFD) do not have celiac disease (CD). Comorbidities and associated conditions in this population are largely unknown. AIMS This study identified demographics, dietary patterns, and diagnoses for patients prescribed a GFD during hospitalization and compared patients with CD to those without CD. METHODS We performed a retrospective cross-sectional study for hospital admissions with a GFD between Jan 1, 2010 and June 30, 2022, while excluding patients missing demographic data (n = 113). We compared patients with and without a CD diagnosis, including multivariable logistic regression to identify characteristics independently associated with a CD diagnosis. RESULTS We analyzed 1527 hospitalized patients of all ages. A minority (n = 467, 30.6%) carried a CD diagnosis. Age, sex, body mass index, and Medicare/Medicaid enrollment and additional diagnoses associated with a GFD (e.g., IBS) were not significantly different. The CD cohort was more predominantly white (66.6% vs 58.4%, p = 0.007) and non-Hispanic (62.5% vs. 52.7%, p = 0.001). While hospitalized, patients with CD had fewer additional dietary restrictions (mean 0.33 vs 0.56, p < 0.001) and more frequent micronutrient supplementation (26.6% vs 21.4%, p = 0.03). CD was independently associated with malnutrition (OR 1.86, 95% CI 1.31-2.65) and inversely associated with a vegetarian diet (OR 0.35, 95% CI 0.15-0.81), reduced lactose diet (OR 0.25, 95% CI 0.13-0.50), and Hispanic ethnicity (OR 0.56, 95% CI 0.35-0.90) while controlling for other covariates. DISCUSSION Two-thirds of hospitalized patients receiving a GFD do not have a diagnosis of CD. Among GFD inpatients, CD is associated with fewer dietary restrictions and independently associated with malnutrition.
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Affiliation(s)
- Rachel Eklund
- Celiac Disease Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, Columbia University, New York, NY, USA
| | - John W Blackett
- Celiac Disease Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, Columbia University, New York, NY, USA
| | - Anne R Lee
- Celiac Disease Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, Columbia University, New York, NY, USA
| | - Peter H R Green
- Celiac Disease Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, Columbia University, New York, NY, USA
| | - Benjamin Lebwohl
- Celiac Disease Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, Columbia University, New York, NY, USA.
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
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DiJoseph K, Weismiller S, Ssentongo P, Dalessio S, Clarke K. Celiac Disease and the Risk of Micronutrient Deficiencies in Ethnic Minority Populations: A Retrospective Cohort Study. Dig Dis 2024; 42:414-418. [PMID: 38838653 DOI: 10.1159/000539179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Accepted: 04/29/2024] [Indexed: 06/07/2024]
Abstract
INTRODUCTION Celiac disease (CD) is a chronic immune-mediated disorder triggered by gluten ingestion in genetically predisposed individuals. Historically, CD was primarily recognized and described as a disease of the Caucasian population. Data from a national survey in 2015 revealed that 0.79% of the population was formally diagnosed with celiac disease, with the non-Hispanic white population having a prevalence of 4-8 times higher than other underrepresented races. Although there is evidence that CD affects minorities at higher than reported rates, there is little data on its effects on minority populations. Our study aimed to characterize celiac-related complications among underrepresented populations in a large health database. METHODS We performed a cohort study among patients aged ≥18, utilizing the TriNetX US Collaborative Network. Two cohorts of patients (minority and non-Hispanic white) with CD were identified between 2016 and 2021. Cohorts were propensity scores matched on demographics and baseline clinical characteristics. Outcomes were assessed up to 1 year after the index event (CD diagnosis), including vitamin/mineral deficiencies and hospital visits. Data were analyzed using the TriNetX Analytics function. RESULTS Each group was matched with 817 patients. Compared to the non-Hispanic white population, the minority group had a similar incidence of iron, vitamin B, and zinc deficiencies. The minority group had a higher risk of vitamin D deficiency, anemia secondary to iron deficiency, inpatient hospital stays, and emergency department visits. CONCLUSION Our results indicate that minority patients with celiac disease have a higher incidence of vitamin D and iron deficiency.
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Affiliation(s)
- Kara DiJoseph
- Division of Gastroenterology and Hepatology, Department of Medicine, Penn State College of Medicine, Hershey, Pennsylvania, USA
| | - Scott Weismiller
- Department of Medicine, Penn State College of Medicine, Hershey, Pennsylvania, USA
| | - Paddy Ssentongo
- Department of Medicine, Penn State College of Medicine, Hershey, Pennsylvania, USA
| | - Shannon Dalessio
- Division of Gastroenterology and Hepatology, Department of Medicine, Penn State College of Medicine, Hershey, Pennsylvania, USA,
| | - Kofi Clarke
- Division of Gastroenterology and Hepatology, Department of Medicine, Penn State College of Medicine, Hershey, Pennsylvania, USA
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Syage JA, Mäki M, Leffler DA, Silvester JA, Sealey-Voyksner JA, Wu TT, Murray JA. A Composite Morphometric Duodenal Biopsy Mucosal Scale for Celiac Disease Encompassing Both Morphology and Inflammation. Clin Gastroenterol Hepatol 2024; 22:1238-1244.e3. [PMID: 37952751 DOI: 10.1016/j.cgh.2023.10.031] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 09/27/2023] [Accepted: 10/19/2023] [Indexed: 11/14/2023]
Abstract
BACKGROUND & AIMS Villus height to crypt depth ratio (Vh:Cd) and intraepithelial lymphocytes (IEL) are key measures of histology of the small intestine in celiac disease. Although the field of celiac disease has advanced, there remains no broadly accepted measure of mucosal injury. We assessed whether a composite Vh:Cd and IEL scale (VCIEL) can improve accuracy and statistical precision for assessing histology, compared with individual measures. METHODS The formulation of the VCIEL composite histologic scale was based on combining the Vh:Cd and IEL measurements for individual patients with equal weighting, by converting each scale to a fraction of their standard deviation and summing the results. The VCIEL formula was applied to several clinical trials and the results for Vh:Cd and IEL were compared with those for VCIEL with regards to clinical significance (effect size) and statistical significance. RESULTS For the ALV003-1021 trial, we observed an effect size and P value (analysis of covariance) of 1.37 and 0.038 for ΔVh:Cd, 1.17 and 0.005 for ΔIEL, and 1.86 and 0.004 for ΔVCIEL. For the similar gluten-challenge IMGX003-NCCIH-1721 trial, the corresponding results were 0.76 and 0.057 for ΔVh:Cd, 0.98 and 0.018 for ΔIEL, and 1.14 and 0.007 for ΔVCIEL. Similar improvements with the use of VCIEL over individual Vh:Cd and IEL measures were observed for other studies, including a nontherapeutic gluten challenge study. CONCLUSIONS The composite VCIEL scale combining Vh:Cd and IEL values seems to improve accuracy and statistical precision compared with either component alone.
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Affiliation(s)
| | - Markku Mäki
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Daniel A Leffler
- Celiac Disease Research Program, Harvard Medical School, Boston, Massachusetts
| | - Jocelyn A Silvester
- Celiac Disease Research Program, Harvard Medical School, Boston, Massachusetts
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Tran T, Senger S, Baldassarre M, Brosnan RA, Cristofori F, Crocco M, De Santis S, Elli L, Faherty CS, Francavilla R, Goodchild-Michelman I, Kenyon VA, Leonard MM, Lima RS, Malerba F, Montuori M, Morelli A, Norsa L, Passaro T, Piemontese P, Reed JC, Sansotta N, Valitutti F, Zomorrodi AR, Fasano A. Novel Bacteroides Vulgatus strain protects against gluten-induced break of human celiac gut epithelial homeostasis: a pre-clinical proof-of-concept study. Pediatr Res 2024; 95:1254-1264. [PMID: 38177249 PMCID: PMC11035120 DOI: 10.1038/s41390-023-02960-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 11/09/2023] [Accepted: 11/18/2023] [Indexed: 01/06/2024]
Abstract
BACKGROUND AND AIMS We have identified a decreased abundance of microbial species known to have a potential anti-inflammatory, protective effect in subjects that developed Celiac Disease (CeD) compared to those who did not. We aim to confirm the potential protective role of one of these species, namely Bacteroides vulgatus, and to mechanistically establish the effect of bacterial bioproducts on gluten-dependent changes on human gut epithelial functions. METHODS We identified, isolated, cultivated, and sequenced a unique novel strain (20220303-A2) of B. vulgatus found only in control subjects. Using a human gut organoid system developed from pre-celiac patients, we monitored epithelial phenotype and innate immune cytokines at baseline, after exposure to gliadin, or gliadin plus B. vulgatus cell free supernatant (CFS). RESULTS Following gliadin exposure, we observed increases in epithelial cell death, epithelial monolayer permeability, and secretion of pro-inflammatory cytokines. These effects were mitigated upon exposure to B. vulgatus 20220303-A2 CFS, which had matched phenotype gene product mutations. These protective effects were mediated by epigenetic reprogramming of the organoids treated with B. vulgatus CFS. CONCLUSIONS We identified a unique strain of B. vulgatus that may exert a beneficial role by protecting CeD epithelium against a gluten-induced break of epithelial tolerance through miRNA reprogramming. IMPACT Gut dysbiosis precedes the onset of celiac disease in genetically at-risk infants. This dysbiosis is characterized by the loss of protective bacterial strains in those children who will go on to develop celiac disease. The paper reports the mechanism by which one of these protective strains, B. vulgatus, ameliorates the gluten-induced break of gut epithelial homeostasis by epigenetically re-programming the target intestinal epithelium involving pathways controlling permeability, immune response, and cell turnover.
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Affiliation(s)
- Tina Tran
- Mucosal Immunology and Biology Research Center, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital; Department of Pediatrics, Harvard Medical School, Boston, MA, USA
| | - Stefania Senger
- Center for Scientific Review, National Institutes of Health, Bethesda, MD, USA
| | | | - Rachel A Brosnan
- Mucosal Immunology and Biology Research Center, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital; Department of Pediatrics, Harvard Medical School, Boston, MA, USA
| | - Fernanda Cristofori
- Pediatric Unit "Bruno Trambusti", Osp Pediatrico Giovanni XXIII, University of Bari, Bari, Italy
| | - Marco Crocco
- Department of Pediatrics, IRCCS Ospedale Giannina Gaslini, Genova, Italy
| | - Stefania De Santis
- Digestive Health Research Institute, Case Western Reserve University School of Medicine, Cleveland, OH, USA
- Department of Pathology, Case Western University School of Medicine, Cleveland, OH, USA
| | - Luca Elli
- Celiac Disease Referral Center, Ospedale Maggiore Policlinico, Milan, Italy
| | - Christina S Faherty
- Mucosal Immunology and Biology Research Center, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital; Department of Pediatrics, Harvard Medical School, Boston, MA, USA
| | - Ruggero Francavilla
- Pediatric Unit "Bruno Trambusti", Osp Pediatrico Giovanni XXIII, University of Bari, Bari, Italy
| | - Isabella Goodchild-Michelman
- Mucosal Immunology and Biology Research Center, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital; Department of Pediatrics, Harvard Medical School, Boston, MA, USA
| | - Victoria A Kenyon
- Mucosal Immunology and Biology Research Center, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital; Department of Pediatrics, Harvard Medical School, Boston, MA, USA
| | - Maureen M Leonard
- Mucosal Immunology and Biology Research Center, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital; Department of Pediatrics, Harvard Medical School, Boston, MA, USA
- Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, Mass General for Children, Boston, MA, USA
| | - Rosiane S Lima
- Mucosal Immunology and Biology Research Center, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital; Department of Pediatrics, Harvard Medical School, Boston, MA, USA
| | - Federica Malerba
- Department of Pediatrics, IRCCS Ospedale Giannina Gaslini, Genova, Italy
| | - Monica Montuori
- Pediatric Gastroenterology Unit, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Annalisa Morelli
- Pediatric Training Program, University of Salerno School of Medicine, Salerno, Italy
| | - Lorenzo Norsa
- Pediatric Hepatology Gastroenterology and Transplant Unit, Ospedale Papa Giovanni XXIII Bergamo, Bergamo, Italy
| | - Tiziana Passaro
- Celiac Disease Referral Center, "San Giovanni di Dio e Ruggi d'Aragona" University Hospital, Pole of Cava de' Tirreni, Salerno, Italy
| | - Pasqua Piemontese
- NICU, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - James C Reed
- Mucosal Immunology and Biology Research Center, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital; Department of Pediatrics, Harvard Medical School, Boston, MA, USA
- Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, Mass General for Children, Boston, MA, USA
| | - Naire Sansotta
- Pediatric Hepatology Gastroenterology and Transplant Unit, Ospedale Papa Giovanni XXIII Bergamo, Bergamo, Italy
| | - Francesco Valitutti
- Pediatric Gastroenterology and Liver Unit, Santobono-Pausilipon Children's Hospital, Naples, Italy
- European Biomedical Research Institute of Salerno, Salerno, Italy
| | - Ali R Zomorrodi
- Mucosal Immunology and Biology Research Center, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital; Department of Pediatrics, Harvard Medical School, Boston, MA, USA
| | - Alessio Fasano
- Mucosal Immunology and Biology Research Center, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
- Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, Mass General for Children, Boston, MA, USA.
- European Biomedical Research Institute of Salerno, Salerno, Italy.
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Ching CK, Lyudmer M, Lewis S, Krishnareddy S, Green PHR, Lebwohl B. Predictors of Subsequent Celiac Disease Seropositivity in Patients Diagnosed with Duodenal Villus Atrophy on Upper Endoscopy. Dig Dis Sci 2024; 69:876-883. [PMID: 38112838 DOI: 10.1007/s10620-023-08217-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Accepted: 11/24/2023] [Indexed: 12/21/2023]
Abstract
BACKGROUND The diagnosis of celiac disease (CD) is based on positive IgA autoantibodies to tissue transglutaminase (TTG IgA) and confirmatory histopathology demonstrating duodenal villus atrophy (VA). Diagnostic challenges can occur when VA is found on duodenal biopsies in patients without prior CD serologies. AIMS To characterize the predictors of CD seropositivity in patients with VA on biopsy without prior CD serologies. METHODS We performed a retrospective cohort study of patients found to have duodenal VA on histopathology from 2010 to 2020 who did not have prior CD serologies measured and who had them checked after their biopsy. Patients with known or suspected CD prior to their duodenal biopsy were excluded. RESULTS Of 162 patients with VA and no prior CD serologies, 50 (31%) subsequently had an elevated TTG IgA consistent with CD. Patients with an elevated TTG IgA were more likely to be non-Hispanic (76% vs. 42%; p < 0.001), white (74% vs. 62%; p = 0.025), and younger (ages 18-39, 26% vs. 12%; p = 0.002) compared to those with a negative TTG IgA. By contrast, these patients were less likely to present in middle adulthood (ages 40-59, 6% vs. 29%; p = 0.002). The most common identified etiologies of seronegative VA were Crohn's disease (13%), seronegative CD (8.9%), H. pylori infection (6.3%), tropical sprue (5.4%), and olmesartan-related enteropathy (3.6%). CONCLUSION Age and ethnicity may be helpful when stratifying the likelihood of CD in the absence of supporting serologies. A majority of patients (69%) diagnosed with VA without prior CD serologies have negative serologies, consistent with seronegative CD or the spectrum of non-celiac enteropathies for which further evaluation is needed.
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Affiliation(s)
- Charlotte K Ching
- Department of Medicine, Columbia University Irving Medical Center, 177 Fort Washington Avenue, New York, NY, 10032, USA.
| | - Michael Lyudmer
- Department of Medicine, Columbia University Irving Medical Center, 177 Fort Washington Avenue, New York, NY, 10032, USA
| | - Suzanne Lewis
- Division of Digestive and Liver Diseases, Celiac Disease Center, Columbia University Irving Medical Center, New York, NY, USA
| | - Suneeta Krishnareddy
- Division of Digestive and Liver Diseases, Celiac Disease Center, Columbia University Irving Medical Center, New York, NY, USA
| | - Peter H R Green
- Division of Digestive and Liver Diseases, Celiac Disease Center, Columbia University Irving Medical Center, New York, NY, USA
| | - Benjamin Lebwohl
- Division of Digestive and Liver Diseases, Celiac Disease Center, Columbia University Irving Medical Center, New York, NY, USA
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Dochat C, Afari N, Satherley RM, Coburn S, McBeth JF. Celiac disease symptom profiles and their relationship to gluten-free diet adherence, mental health, and quality of life. BMC Gastroenterol 2024; 24:9. [PMID: 38166645 PMCID: PMC10759532 DOI: 10.1186/s12876-023-03101-x] [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: 04/16/2023] [Accepted: 12/15/2023] [Indexed: 01/05/2024] Open
Abstract
BACKGROUND A subgroup of adults with celiac disease experience persistent gastrointestinal and extraintestinal symptoms, which vary between individuals and the cause(s) for which are often unclear. METHODS The present observational study sought to elucidate patterns of persistent symptoms and the relationship between those patterns and gluten-free diet adherence, psychiatric symptoms, and various aspects of quality of life (QOL) in an online sample of adults with celiac disease. U.S. adults with self-reported, biopsy-confirmed celiac disease (N = 523; Mage = 40.3 years; 88% women; 93.5% White) voluntarily completed questionnaires as part of the iCureCeliac® research network: (a) Celiac Symptoms Index (CSI) for physical symptoms and subjective health; (b) Celiac Dietary Adherence Test for gluten-free diet adherence; (c) PROMIS-29, SF-36, and Celiac Disease Quality of Life Survey for psychiatric symptoms and QOL. Symptom profiles were derived using latent profile analysis and profile differences were examined using auxiliary analyses. RESULTS Latent profile analysis of CSI items determined a four-profile solution fit best. Profiles were characterized by: (1) little to no symptoms and excellent subjective health (37% of sample); (2) infrequent symptoms and good subjective health (33%); (3) occasional symptoms and fair to poor subjective health (24%); (4) frequent to constant symptoms and fair to poor subjective health (6%). Profiles 2 and 3 reported moderate overall symptomology though Profile 2 reported relatively greater extraintestinal symptoms and Profile 3 reported relatively greater gastrointestinal symptoms, physical pain, and worse subjective health. Profiles differed on anxiety and depression symptoms, limitations due to physical and emotional health, social functioning, and sleep, but not clinical characteristics, gluten-free diet adherence, or QOL. Despite Profile 3's moderate symptom burden and low subjective health as reported on the CSI, Profile 3 reported the lowest psychiatric symptoms and highest quality of life on standardized measures. CONCLUSIONS Adults with celiac disease reported variable patterns of persistent symptoms, symptom severity, and subjective health. Lack of profile differences in gluten-free diet adherence suggests that adjunctive dietary or medical assessment and intervention may be warranted. Lower persistent symptom burden did not necessarily translate to better mental health and QOL, suggesting that behavioral intervention may be helpful even for those with lower celiac symptom burden.
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Affiliation(s)
- Cara Dochat
- San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA.
| | - Niloofar Afari
- VA San Diego Healthcare System, San Diego, CA, USA
- University of California San Diego, La Jolla, CA, USA
| | | | - Shayna Coburn
- Children's National Health System, Washington, DC, USA
- George Washington University School of Medicine & Health Sciences, Washington, DC, USA
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Syage J, Ramos A, Loskutov V, Norum A, Bledsoe A, Choung RS, Dickason M, Sealey-Voyksner J, Murray J. Dynamics of Serologic Change to Gluten in Celiac Disease Patients. Nutrients 2023; 15:5083. [PMID: 38140342 PMCID: PMC10746107 DOI: 10.3390/nu15245083] [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: 10/22/2023] [Revised: 11/25/2023] [Accepted: 11/30/2023] [Indexed: 12/24/2023] Open
Abstract
Serologic measures of tissue transglutaminase (tTG) immunoglobulin A (IgA) and deamidated gliadin peptide (DGP) IgA and immunoglobulin G (IgG) are hallmark tests utilized when diagnosing individuals for celiac disease (CeD) and for monitoring adherence to a gluten-free diet (GFD), currently the only available treatment for CeD. We address two issues in this study: (i) the relapse to seropositivity for CeD patients who resume a gluten containing diet and (ii) the correlation between two different tTG-IgA assays near the upper limit of normal (ULN) designated thresholds. Regarding the first issue, often a suspected CeD individual is put back on a gluten diet to return to their serologic levels. However, we show it requires a substantial amount of gluten for serology to return to a positive level. For example, in one study of 22 patients treated with placebo and taking 84 g of gluten over 6 weeks, only two converted from seronegative to seropositive for tTG-IgA. Regarding the second topic, we compare the relationship for different serologic assays, namely tTG-IgA AB (recombinant, ULN = 4 units/mL) vs. tTG-IgA (non-recombinant, ULN = 20 units). There is a strong correlation between both measurements as evidenced by a Pearson coefficient of R = 0.8584; however, we observed that the cross-correlation in terms of sensitivity and specificity improved substantially by using an ULN value of three instead of four for the tTG-IgA AB (recombinant) assay. This result suggests that assay thresholds used for initial diagnosis in patients who have not yet started a GFD may need to be adjusted for monitoring and in the setting of a diagnostic gluten challenge.
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Affiliation(s)
- Jack Syage
- ImmunogenX, Inc., 1600 Dove Street, Suite 330, Newport Beach, CA 92660, USA; (A.R.); (V.L.); (M.D.)
| | - Ana Ramos
- ImmunogenX, Inc., 1600 Dove Street, Suite 330, Newport Beach, CA 92660, USA; (A.R.); (V.L.); (M.D.)
| | - Vasiliy Loskutov
- ImmunogenX, Inc., 1600 Dove Street, Suite 330, Newport Beach, CA 92660, USA; (A.R.); (V.L.); (M.D.)
| | - Anna Norum
- ImmunogenX, Inc., 1600 Dove Street, Suite 330, Newport Beach, CA 92660, USA; (A.R.); (V.L.); (M.D.)
| | - Adam Bledsoe
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA
| | - Rok Seon Choung
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA
| | - Matthew Dickason
- ImmunogenX, Inc., 1600 Dove Street, Suite 330, Newport Beach, CA 92660, USA; (A.R.); (V.L.); (M.D.)
| | - Jennifer Sealey-Voyksner
- ImmunogenX, Inc., 1600 Dove Street, Suite 330, Newport Beach, CA 92660, USA; (A.R.); (V.L.); (M.D.)
| | - Joseph Murray
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA
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10
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Hujoel I. Current Diagnostic Algorithms May Fail to Identify Black Americans With Celiac Disease. GASTRO HEP ADVANCES 2023; 3:134-135. [PMID: 39132190 PMCID: PMC11308727 DOI: 10.1016/j.gastha.2023.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 12/01/2023] [Indexed: 08/13/2024]
Affiliation(s)
- Isabel Hujoel
- Division of Gastroenterology, University of Washington, Seattle, Washington
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11
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Kohli AT, Hersh AO, Ponder L, Chan LHK, Rouster-Stevens KA, Tebo AE, Kugathasan S, Guthery SL, Bohnsack JF, Prahalad S. Prevalence of tissue transglutaminase antibodies and IgA deficiency are not increased in juvenile idiopathic arthritis: a case-control study. Pediatr Rheumatol Online J 2023; 21:110. [PMID: 37798643 PMCID: PMC10557180 DOI: 10.1186/s12969-023-00890-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 09/01/2023] [Indexed: 10/07/2023] Open
Abstract
BACKGROUND The prevalence of Celiac Disease (CD) in Juvenile Idiopathic Arthritis (JIA) has been reported to be 0.1-7% in various small studies. As a result of the limited number of research and their inconclusive results there are no clear recommendations for routine CD screening in asymptomatic patients with JIA. Our aim is to estimate the prevalence of IgA deficiency and tissue transglutaminase (tTG) IgA in a cohort of JIA followed in two large academic medical centers. METHODS Serum was collected and stored from all subjects and analyzed in a reference laboratory for total IgA (Quantitative Nephelometry) and tTG IgA antibody levels (Semi-Quantitative Enzyme-Linked Immunosorbent Assay). Fisher's exact tests were performed for statistical significance. Risk estimates (odds ratios) with 95% confidence intervals were calculated. RESULTS 808 JIA cases and 140 controls were analyzed. Majority were non-Hispanic whites (72% vs. 68% p = 0.309). A total of 1.2% of cases were IgA deficient compared to none of the controls (p = 0.373). After excluding IgA deficient subjects, 2% of cases had tTG IgA ≥ 4u/mL compared to 3.6% of controls (p = 0.216) (OR = 0.5; 95% C.I = 0.1-1.4); and 0.8% of cases had tTG IgA > 10u/mL compared to 1.4% of controls (p = 0.627) (OR = 0.5; 95%C.I = 0.1-2.9). CONCLUSIONS Using the largest JIA cohort to date to investigate prevalence of celiac antibodies, the prevalence of positive tTG IgA was 0.8% and of IgA deficiency was 1.2%. The results did not demonstrate a higher prevalence of abnormal tTG IgA in JIA. The study did not support the routine screening of asymptomatic JIA patients for CD.
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Affiliation(s)
- Angela Taneja Kohli
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
- Children's Healthcare of Atlanta, Atlanta, GA, USA.
| | - Aimee O Hersh
- Department of Pediatrics, Spencer F. Eccles School of Medicine, University of Utah, Salt Lake City, UT, USA
| | - Lori Ponder
- Children's Healthcare of Atlanta, Atlanta, GA, USA
| | - Lai Hin Kimi Chan
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
| | - Kelly A Rouster-Stevens
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
- Children's Healthcare of Atlanta, Atlanta, GA, USA
| | - Anne E Tebo
- University of Utah, Salt Lake City, UT, USA
- ARUP Laboratories, Salt Lake City, USA
| | - Subra Kugathasan
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
- Children's Healthcare of Atlanta, Atlanta, GA, USA
| | - Stephen L Guthery
- Department of Pediatrics, Spencer F. Eccles School of Medicine, University of Utah, Salt Lake City, UT, USA
| | - John F Bohnsack
- Department of Pediatrics, Spencer F. Eccles School of Medicine, University of Utah, Salt Lake City, UT, USA
| | - Sampath Prahalad
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
- Children's Healthcare of Atlanta, Atlanta, GA, USA
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12
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Urbonas V, Sadauskaite J, Varnas D. Population-Based Screening for Coeliac Disease in Lithuanian Children from 2009 to 2014. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1630. [PMID: 37763749 PMCID: PMC10534554 DOI: 10.3390/medicina59091630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 08/17/2023] [Accepted: 09/05/2023] [Indexed: 09/29/2023]
Abstract
Background and Objectives. Coeliac disease is an autoimmune disorder provoked by a dietary group of proteins called gluten in genetically predisposed individuals. Over the past several decades, the prevalence of coeliac disease has been steadily growing and it is now recognized to be occurring worldwide. The prevalence varies greatly between ethnic, racial groups and regionally. Such variability makes local epidemiological studies important for spreading awareness and setting a threshold for suspicion of coeliac disease. We explored the potential application of a quick point-of-care test for the purpose of detecting a presence of IgA class TG2 antibodies for coeliac disease and screening in a Lithuanian pediatric population. Previously, there were no data regarding coeliac disease prevalence in Lithuania. Materials and Methods. Overall, we included 1458 children 11-13 years of age from several Lithuanian schools selected randomly in this study. Utilizing one point-of-care test using a single blood sample taken from a fingertip, we identified the existence of IgA class TG2 antibodies. Only children whose parents gave consent were enrolled in the study. Those with positive IgA class TG2-ab were directed to a tertiary hospital for additional clinical assessment and confirmation of suspected coeliac disease. Results. A total of two (0.14%) of the 1458 enrolled children were detected with the presence of TG2 antibodies and the coeliac disease diagnosis was further confirmed with histological examination of duodenal biopsy samples. Additionally, we checked that patients had not previously reported any clinical symptoms and signs that could suggest coeliac disease or any other disease of the gastrointestinal tract. Conclusions. The detected prevalence of coeliac disease in the Lithuanian pediatric population is 1:729. The rapid finger prick test for the presence of IgA class TG2 antibodies is a reasonable and accurate method to screen for celiac disease in children.
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Affiliation(s)
- Vaidotas Urbonas
- Clinic of Children's Diseases, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Jolita Sadauskaite
- Clinic of Children's Diseases, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Dominykas Varnas
- Clinic of Children's Diseases, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
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13
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Altaffer AL, Weiss P. Clinical features, treatment, and outcomes of celiac-associated arthritis: a retrospective cohort study. Pediatr Rheumatol Online J 2023; 21:43. [PMID: 37131195 PMCID: PMC10152788 DOI: 10.1186/s12969-023-00822-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Accepted: 04/17/2023] [Indexed: 05/04/2023] Open
Abstract
BACKGROUND Although arthritis is recognized as an extra-intestinal manifestation of celiac disease, little is known about the clinical course and outcomes of pediatric celiac-associated arthritis. This study describes clinical characteristics, treatments, and outcomes of children with celiac-associated arthritis. METHODS This was a retrospective cohort study of children with celiac disease seen in pediatric rheumatology clinic between 2004 and 2021 for joint complaints. Data was abstracted from electronic health records. Patient demographics and clinical manifestations were evaluated using standard descriptive statistics. Physician- and patient-reported outcomes were evaluated at the index visit, 6-month follow-up, and last recorded visit, and were compared using Wilcoxon signed-rank tests. RESULTS Twenty-nine patients with celiac disease were evaluated for joint complaints, and 13 were diagnosed with arthritis. Their mean age was 8.9 years (SD 5.9), and 61.5% were female. Celiac disease diagnosis was made before arthritis diagnosis in only 2 cases (15.4%). Initial testing that led to the celiac disease diagnosis was obtained by the rheumatologist in 6 cases (46.2%). Only 8 patients (61.5%) had concomitant GI symptoms, and of these, 3 patients had BMI z-scores <-1.64 and 1 had impaired linear growth. Arthritis presentation was most often oligoarticular (76.9%) and asymmetric (84.6%). Most cases required systemic therapy (n = 11, 84.6%) with DMARDs, biologics, or both. Of the 10 patients who required systemic therapy and reported compliance with the gluten-free diet, 3 (30%) were able to stop systemic medications. Two of 3 patients who cleared celiac serologies came off systemic medications. Statistically significant improvement was noted in the number of joints involved (p = 0.02) and physician global assessment of disease activity (p = 0.03) between the index and final visit. CONCLUSIONS Rheumatologists play an important role in the identification of celiac disease, as arthritis was the presenting symptom in most cases and was not always associated with GI symptoms or poor growth. The arthritis was most often oligoarticular and asymmetric. Most children required systemic therapy. The gluten-free diet may not be sufficient to manage arthritis, but antibody clearance may be an indicator of higher likelihood of disease control off medications. Outcomes are promising with a combination of diet and medical therapy.
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Affiliation(s)
- Ana Luiza Altaffer
- Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
- Department of Pediatrics, Division of Rheumatology, Baylor College of Medicine and Texas Children's Hospital, 1102 Bates Ave Suite 330, Houston, 77030, TX, USA.
| | - Pamela Weiss
- Department of Pediatrics, Division of Rheumatology and Clinical Futures, Children's Hospital of Philadelphia and Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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14
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Jansson-Knodell CL, White M, Lockett C, Xu H, Rubio-Tapia A, Shin A. Self-Reported Gluten Intolerance Is Prevalent, but Not All Gluten-Containing Foods Are Equal. Dig Dis Sci 2023; 68:1364-1368. [PMID: 36662341 DOI: 10.1007/s10620-022-07800-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Accepted: 12/16/2022] [Indexed: 01/21/2023]
Abstract
BACKGROUND Celiac disease prevalence approaches 1%; more suffer from non-celiac gluten sensitivity. AIMS Our goal was to estimate the prevalence of gluten intolerance. METHODS We invited US adults (18-80 years) via Amazon's mechanical Turk to complete an online survey. Gluten intolerance was defined as self-reported intolerance to wheat, barley, rye, flour, or pasta. Those with celiac disease were not excluded. RESULTS We collected 2133 responses. Rate of gluten intolerance was 5.1% (95% CI 4.2-6.1%). Each food had different rates: wheat 4.8%, flour 1.2%, pasta 0.9%, barley 0.8%, and rye 0.8%. Among 108 adults reporting any gluten intolerance, 62.0% selected only wheat, 10.2% selected all gluten-containing grains excluding pasta and flour, and 5.6% selected all gluten-containing products. Overall intolerance to any food was 24.8% (95% CI 23.0-26.6%). Wheat was second only to lactose. CONCLUSIONS Self-reported intolerance to wheat, but not all gluten-containing foods, is common. Findings may suggest poor knowledge of gluten-containing foods or that self-perceived non-celiac gluten sensitivity is prevalent.
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Affiliation(s)
- Claire L Jansson-Knodell
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Mattie White
- Internal Medicine, Department of Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Carolyn Lockett
- Roudebush VA Medical Center, 1481 W 10Th St, Indianapolis, IN, 46202, USA
| | - Huiping Xu
- Department of Biostatistics, Indiana University School of Medicine, 410 W 10th Street, Indianapolis, IN, 46202, USA
| | - Alberto Rubio-Tapia
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
| | - Andrea Shin
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA.
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15
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Dochat C, Afari N, Arigo D. Psychometric validation of the celiac disease-specific quality of life survey (CD-QOL) in adults with celiac disease in the United States. Qual Life Res 2023:10.1007/s11136-023-03380-7. [PMID: 36928648 PMCID: PMC10329069 DOI: 10.1007/s11136-023-03380-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/20/2023] [Indexed: 03/18/2023]
Abstract
PURPOSE Celiac disease and its treatment negatively impact quality of life, indicating potential need for measurement of disease-specific quality of life domains to inform interdisciplinary intervention. The Celiac Disease Quality of Life Survey (CD-QOL) has been used in clinical research; however, its factor structure has not been confirmed and psychometric properties have not been evaluated in English-speaking adults in the U.S. AIMS (1) Confirm the factor structure of the 20-item English CD-QOL; (2) assess psychometric properties including internal consistency reliability, convergent validity, known groups validity, and incremental validity. METHODS 453 adults with self-reported Celiac disease (Mage = 40.57; 88% female; 92% White) completed the CD-QOL and validated measures of generic health-related quality of life (SF-36), gluten-free diet adherence (CDAT), anxiety and depression symptoms (PROMIS), and physical symptoms (CSI) as part of the iCureCeliac® patient-powered research network. RESULTS Confirmatory factor analysis found superior fit for a bifactor structure with one general factor and four group factors. Ancillary bifactor analyses suggest the CD-QOL can be considered primarily unidimensional. Total and three subscale scores demonstrated acceptable internal consistency reliability. Convergent and known groups validity were supported. The CD-QOL demonstrated some incremental validity over the SF-36. CONCLUSION The English CD-QOL can be used as a measure of disease-specific quality of life among adults with Celiac disease in the U.S. Compared to generic instruments, the CD-QOL appears to better capture specific cognitive and affective aspects of living with Celiac disease. Use of a total score is recommended. Its utility as a screening and outcome measurement tool in clinical settings should be examined.
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Affiliation(s)
- Cara Dochat
- San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, 6363 Alvarado Court, San Diego, CA, 92120, USA.
| | - Niloofar Afari
- VA San Diego Healthcare System, San Diego, CA, USA.,University of California San Diego, La Jolla, San Diego, CA, USA
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16
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Miller FW. The increasing prevalence of autoimmunity and autoimmune diseases: an urgent call to action for improved understanding, diagnosis, treatment, and prevention. Curr Opin Immunol 2023; 80:102266. [PMID: 36446151 PMCID: PMC9918670 DOI: 10.1016/j.coi.2022.102266] [Citation(s) in RCA: 149] [Impact Index Per Article: 74.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Accepted: 11/04/2022] [Indexed: 11/27/2022]
Abstract
Autoimmunity is characterized by self-reactive immune components and autoimmune disease by autoimmunity plus pathology. Both autoimmunity and autoimmune diseases are dramatically increasing in many parts of the world, likely as a result of changes in our exposures to environmental factors. Current evidence implicates the momentous alterations in our foods, xenobiotics, air pollution, infections, personal lifestyles, stress, and climate change as causes for these increases. Autoimmune diseases have a major impact on the individuals and families they affect, as well as on our society and healthcare costs, and current projections suggest they may soon take their place among the predominant medical disorders. This necessitates that we increase the scope and scale of our efforts, and coordinate our resources and studies, to understand autoimmune disease risk factors and pathogeneses and improve our diagnostic, therapeutic, and preventive approaches, as the costs of inaction will be profound and far greater without such investments.
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Affiliation(s)
- Frederick W Miller
- Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Bldg. 101, Maildrop A2-03, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA.
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17
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Murray JA, Syage JA, Wu TT, Dickason MA, Ramos AG, Van Dyke C, Horwath I, Lavin PT, Mäki M, Hujoel I, Papadakis KA, Bledsoe AC, Khosla C, Sealey-Voyksner JA. Latiglutenase Protects the Mucosa and Attenuates Symptom Severity in Patients With Celiac Disease Exposed to a Gluten Challenge. Gastroenterology 2022; 163:1510-1521.e6. [PMID: 35931103 PMCID: PMC9707643 DOI: 10.1053/j.gastro.2022.07.071] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 07/28/2022] [Accepted: 07/30/2022] [Indexed: 12/07/2022]
Abstract
BACKGROUND & AIMS Gluten ingestion in patients with celiac disease can lead to gastrointestinal symptoms and small intestinal mucosal injury. METHODS This gluten challenge phase 2 trial was double blind and placebo controlled, and it assessed the efficacy and safety of a 1200-mg dose of IMGX003 in patients with celiac disease exposed to 2 g of gluten per day for 6 weeks. The change in the ratio of villus height to crypt depth was the primary endpoint. Secondary endpoints included density of intraepithelial lymphocytes and symptom severity. These endpoints were evaluated by analysis of covariance. Additional endpoints included serology and gluten-immunogenic peptides in urine. RESULTS Fifty patients were randomized, and 43 patients completed the study (IMGX003, n = 21; placebo, n = 22). The mean change in the ratio of villus height to crypt depth (primary endpoint) for IMGX003 vs placebo was -0.04 vs -0.35 (P = .057). The mean change in the density of intraepithelial lymphocytes (secondary endpoint) for IMGX003 vs placebo was 9.8 vs 24.8 cells/mm epithelium (P = .018). The mean change (worsening) in symptom severity in relative units (secondary endpoint) for IMGX003 vs placebo was 0.22 vs 1.63 (abdominal pain, P = .231), 0.96 vs 3.29 (bloating, P = .204), and 0.02 vs 3.20 (tiredness, P = .113). The 3 × 2-week trend line significance values for these symptoms, respectively, were P = .014, .030, and .002. CONCLUSIONS IMGX003 reduced gluten-induced intestinal mucosal damage and symptom severity. (ClinicalTrials.gov, Number: NCT03585478).
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Affiliation(s)
- Joseph A Murray
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
| | | | - Tsung-Teh Wu
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
| | | | | | - Carol Van Dyke
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Irina Horwath
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Philip T Lavin
- Boston Biostatistics Research Foundation, Framingham, Massachusetts
| | - Markku Mäki
- Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland
| | - Isabel Hujoel
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | | | - Adam C Bledsoe
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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18
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Desher KA, Alkalay MJ. Clinical differences among racially diverse children with celiac disease. World J Pediatr 2022; 18:710-714. [PMID: 35960472 DOI: 10.1007/s12519-022-00596-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Accepted: 07/17/2022] [Indexed: 11/29/2022]
Affiliation(s)
- Kaley A Desher
- Department of Pediatric Gastroenterology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
- , Preferred postal address is 6605 Vickery Creek Rd, Cumming, GA, 30040, USA.
| | - Michele J Alkalay
- Department of Pediatric Gastroenterology, University of Texas Southwestern Medical Center, Dallas, TX, USA
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19
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Makharia GK, Singh P, Catassi C, Sanders DS, Leffler D, Ali RAR, Bai JC. The global burden of coeliac disease: opportunities and challenges. Nat Rev Gastroenterol Hepatol 2022; 19:313-327. [PMID: 34980921 DOI: 10.1038/s41575-021-00552-z] [Citation(s) in RCA: 70] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/08/2021] [Indexed: 02/06/2023]
Abstract
Coeliac disease is a systemic disorder characterized by immune-mediated enteropathy, which is caused by gluten ingestion in genetically susceptible individuals. The clinical presentation of coeliac disease is highly variable and ranges from malabsorption through solely extra-intestinal manifestations to asymptomatic. As a result, the majority of patients with coeliac disease remain undiagnosed, misdiagnosed or experience a substantial delay in diagnosis. Coeliac disease is diagnosed by a combination of serological findings of disease-related antibodies and histological evidence of villous abnormalities in duodenal biopsy samples. However, variability in histological grading and in the diagnostic performance of some commercially available serological tests remains unacceptably high and confirmatory assays are not readily available in many parts of the world. Currently, the only effective treatment for coeliac disease is a lifelong, strict, gluten-free diet. However, many barriers impede patients' adherence to this diet, including lack of widespread availability, high cost, cross-contamination and its overall restrictive nature. Routine follow-up is necessary to ensure adherence to a gluten-free diet but considerable variation is evident in follow-up protocols and the optimal disease management strategy is not clear. However, these challenges in the diagnosis and management of coeliac disease suggest opportunities for future research.
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Affiliation(s)
- Govind K Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.
| | - Prashant Singh
- Department of Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Carlo Catassi
- Department of Paediatrics, Università Politecnica delle Marche, Ancona, Italy
| | - David S Sanders
- Royal Hallamshire Hospital, Sheffield, UK
- University of Sheffield, Sheffield, UK
| | - Daniel Leffler
- Celiac Center, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Raja Affendi Raja Ali
- Department of Medicine, Faculty of Medicine, The National University of Malaysia (UKM), Kuala Lumpur, Malaysia
| | - Julio C Bai
- Universidad del Salvador, Buenos Aires, Argentina
- Dr C. Bonorino Udaondo Gastroenterology Hospital, Buenos Aires, Argentina
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20
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Thompson JS, Mannon P. Celiac disease and the surgeon. Am J Surg 2022; 224:332-338. [PMID: 35221098 DOI: 10.1016/j.amjsurg.2022.02.048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 02/14/2022] [Accepted: 02/16/2022] [Indexed: 11/16/2022]
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21
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Pourhoseingholi MA. Epidemiology and burden of gluten-related disorders. GLUTEN-RELATED DISORDERS 2022:59-81. [DOI: 10.1016/b978-0-12-821846-4.00011-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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22
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Poyrazoglu OB, Dulger AC. Celiac disease is increased in esophageal squamous cell Carcinoma. Pak J Med Sci 2021; 37:1445-1450. [PMID: 34475928 PMCID: PMC8377909 DOI: 10.12669/pjms.37.5.2757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 04/05/2021] [Accepted: 04/29/2021] [Indexed: 11/20/2022] Open
Abstract
Background and Objective: The intercourse between Esophageal squamous cell carcinoma etc. (ESC) and Celiac disease (CD) is still a complicated subject. The purpose of this research was to define the relationship between CD and ESC, and the factors associated with CD in patients with ESC. Methods: This research was conducted by Van University Medical Center in Turkey from 2012 to 2016.CD was identified by analyzing duodenal biopsy materials from 63 ESC patients via histopathologic examinations. Serum samples from the patients were also serologically tested to identify CD. A control group was selected from among subjects who underwent gastroduodenoscopy due to dyspepsia. Distinctions between case characteristics were evaluated with chi-square tests and t-tests for categorical and continuous factors, respectively. Results: Of the 63 study cases, 6 (9.5%) were both histological and serological positive for CD. Of the 290 control group, 8 (2.8%) had histopathological CD and tested positive for celiac antibodies. The patients with ESC had a significantly higher prevalence of CD compared to the dyspeptic patients (p<0.001). In addition, the mean creatinine levels of ESC patients with histopathological-proven CD were higher than those without CD (p=0.026). Furthermore, ESC patients who tested positive for tTg IgA had significantly higher levels of glucose and AST than those who were negative for tTg IgA (p=0.032) and (p=0.008), respectively. Conclusion: The present study demonstrated a statistically significant positive correlation between ESC and CD. Most remarkably, higher creatinine, glucose, and AST levels may predict CD in patients with ESC. These evidences may lead novel approaches for preventing ESC in patients with CD.
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Affiliation(s)
- Omer Bilgehan Poyrazoglu
- Omer Bilgehan Poyrazoglu, MD Assistant Professor of General Surgery Nigde University Medical School, Omer Halisdemir State Hospital Department of General Surgery, Nigde, Turkey
| | - Ahmet Cumhur Dulger
- Ahmet Cumhur Dulger, MD Professor of Gastroenterology, Giresun University Medical School State Hospital, Department of Gastroenterology, Giresun, Turkey
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23
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Gandini A, Gededzha MP, De Maayer T, Barrow P, Mayne E. Diagnosing coeliac disease: A literature review. Hum Immunol 2021; 82:930-936. [PMID: 34462157 DOI: 10.1016/j.humimm.2021.07.015] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 07/14/2021] [Accepted: 07/30/2021] [Indexed: 12/14/2022]
Abstract
Coeliac disease (CD) is an autoimmune gastroenteropathy triggered by gliadin and gliadin-tissue transglutaminase (tTG) complexes. CD is one of the few autoimmune diseases with an accurate, non-invasive serological test. Anti-endomysial, anti-tTG and anti-deaminated gliadin peptides (DGP) antibodies are currently used for serological tests with tTG ELISAs being the superior test. Duodenal biopsy, although invasive, is the gold standard for CD diagnosis. HLA genotyping and flow cytometry can also be used as supplementary tests. The incidence of CD is rising globally although the reasons for this remain unclear. In addition, the true incidence of coeliac disease in African populations remains unknown although recent work suggests that South African populations express the alleles associated with this disease. This review examines the pathogenesis and diagnosis of coeliac disease and considers novel and innovative biomarkers in its diagnosis specifically in an African population.
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Affiliation(s)
- Anastasia Gandini
- University of Witwatersrand, South Africa; National Health Laboratory Service, South Africa; Department of Immunology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
| | - Maemu P Gededzha
- University of Witwatersrand, South Africa; National Health Laboratory Service, South Africa; Department of Immunology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Tim De Maayer
- University of Witwatersrand, South Africa; Rahima Moosa Mother and Child Hospital, South Africa
| | - Peter Barrow
- University of Witwatersrand, South Africa; Wits University Donald Gordon Medical Centre, South Africa
| | - Elizabeth Mayne
- University of Witwatersrand, South Africa; National Health Laboratory Service, South Africa; Department of Immunology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
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Abstract
Objective: To assess the prevalence of gluten-free diet (GFD) among school-age children in Olmsted County, Minnesota, and compare it with the prevalence of celiac disease (CD) in the same age group. Methods: We performed a population-based study in Olmsted County using a survey to collect information from the six school districts in the county for the academic year 2014–2015. The survey contained questions to (1) assess the prevalence of GFD among school-age children in the public schools of Olmsted County; (2) assess the prevalence of CD among school-age children in Olmsted County; and (3) determine the indications for GFD in these children. We used the infrastructure of the Rochester Epidemiology Project (REP) to calculate the prevalence of CD in children aged 4–18 years in December 2014. Results: Using the REP data, we identified sixty patients with CD in the county aged 4–18 years; the prevalence of CD among school students in 2014 was 193.6/100,000. The prevalence of GFD in Olmsted County children, however, was higher, at 265/100,000 according to the survey from the school districts. The prevalence of GFD was highest in Rochester, the largest city. GFD was more common among children in secondary schools. Conclusion: According to our study, there are more children on GFD than the actual cases of CD in Olmsted County during the study period. This finding could be related to an increased number of children without CD who are following GFD for other indications.
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Affiliation(s)
- Eyad Almallouhi
- Division of Pediatric Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.,Department of Neurology, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Imad Absah
- Division of Pediatric Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.,Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
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25
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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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26
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Tovo PA, Opramolla A, Pizzol A, Calosso G, Daprà V, Galliano I, Calvi C, Pinon M, Cisarò F, Rigazio C, Calvo PL, Bergallo M. Overexpression of endogenous retroviruses in children with celiac disease. Eur J Pediatr 2021; 180:2429-2434. [PMID: 33772337 DOI: 10.1007/s00431-021-04050-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 03/16/2021] [Accepted: 03/21/2021] [Indexed: 11/30/2022]
Abstract
Human endogenous retroviruses (HERVs) represent 8% of our genome. Although no longer infectious, they can regulate transcription of adjacent cellular genes, produce retroviral RNAs, and encode viral proteins that can modulate both innate and adaptive immune responses. Based on this, HERVs have been studied and proposed as contributing factors in various autoimmune disorders. Celiac disease (CD) is considered an autoimmune disease, but HERV expression has not been studied in celiac patients. The aim of this study is to assess the transcription levels of pol genes of HERV-H, -K, and -W and of their TRIM28 repressor in WBCs from celiac children and age-matched control subjects. A PCR real-time TaqMan amplification assay was used to evaluate HERV and TRIM28 transcripts with normalization of the results to glyceraldehyde-3-phosphate dehydrogenase. The RNA levels of pol genes of the three HERV families were significantly higher in WBCs from 38 celiac patients than from 51 control subjects. TRIM28 transcription was comparable between the two study populations.Conclusion: Present results show, for the first time, that pol genes of HERV-H, -K, and -W are overexpressed in patients with CD. Given their proinflammatory and autoimmune properties, this suggests that HERVs may contribute to the development of CD in susceptible individuals. What is Known: • Based on this, HERVs have been studied and proposed as contributing factors in various autoimmune disorders. What is New: • Present results show, for the first time, that pol genes of HERV-H, -K, and -W are overexpressed in patients with CD.
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Affiliation(s)
- Pier-Angelo Tovo
- Department of Public Health and Pediatric Sciences, University of Turin, Piazza Polonia, 96 10126, Turin, Italy
| | - Anna Opramolla
- Pediatric Gastroenterology Unit, Regina Margherita Children's Hospital, Azienda Ospedaliera-Universitaria Città della Salute e della Scienza, Turin, Italy
| | - Antonio Pizzol
- Pediatric Gastroenterology Unit, Regina Margherita Children's Hospital, Azienda Ospedaliera-Universitaria Città della Salute e della Scienza, Turin, Italy
| | - Giulia Calosso
- Pediatric Gastroenterology Unit, Regina Margherita Children's Hospital, Azienda Ospedaliera-Universitaria Città della Salute e della Scienza, Turin, Italy
| | - Valentina Daprà
- Pediatric Laboratory, Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy
| | - Ilaria Galliano
- Pediatric Laboratory, Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy
| | - Cristina Calvi
- Pediatric Laboratory, Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy
| | - Michele Pinon
- Pediatric Gastroenterology Unit, Regina Margherita Children's Hospital, Azienda Ospedaliera-Universitaria Città della Salute e della Scienza, Turin, Italy
| | - Fabio Cisarò
- Pediatric Gastroenterology Unit, Regina Margherita Children's Hospital, Azienda Ospedaliera-Universitaria Città della Salute e della Scienza, Turin, Italy
| | - Caterina Rigazio
- Pediatric Gastroenterology Unit, Regina Margherita Children's Hospital, Azienda Ospedaliera-Universitaria Città della Salute e della Scienza, Turin, Italy
| | - Pier Luigi Calvo
- Pediatric Gastroenterology Unit, Regina Margherita Children's Hospital, Azienda Ospedaliera-Universitaria Città della Salute e della Scienza, Turin, Italy
| | - Massimiliano Bergallo
- Department of Public Health and Pediatric Sciences, University of Turin, Piazza Polonia, 96 10126, Turin, Italy. .,Pediatric Laboratory, Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy.
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27
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Sahin Y. Celiac disease in children: A review of the literature. World J Clin Pediatr 2021; 10:53-71. [PMID: 34316439 PMCID: PMC8290992 DOI: 10.5409/wjcp.v10.i4.53] [Citation(s) in RCA: 92] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 03/23/2021] [Accepted: 05/22/2021] [Indexed: 02/06/2023] Open
Abstract
Celiac disease is an immune-mediated systemic disease triggered by intake of gluten in genetically susceptible individuals. The prevalence of celiac disease in the general population is estimated to be 1% in the world. Its prevalence differs depending on geographical and ethnic variations. The prevalence of celiac disease has increased significantly in the last 30 years due to the increased knowledge and awareness of physicians and the widespread use of highly sensitive and specific diagnostic tests for celiac disease. Despite increased awareness and knowledge about celiac disease, up to 95% of celiac patients still remain undiagnosed. The presentations of celiac disease have significantly changed in the last few decades. Classical symptoms of celiac disease occur in a minority of celiac patients, while older children have either minimal or atypical symptoms. Serologic tests for celiac disease should be done in patients with unexplained chronic or intermittent diarrhea, failure to thrive, weight loss, delayed puberty, short stature, amenorrhea, iron deficiency anemia, nausea, vomiting, chronic abdominal pain, abdominal distension, chronic constipation, recurrent aphthous stomatitis, and abnormal liver enzyme elevation, and in children who belong to specific groups at risk. Early diagnosis of celiac disease is very important to prevent long-term complications. Currently, the only effective treatment is a lifelong gluten-free diet. In this review, we will discuss the epidemiology, clinical findings, diagnostic tests, and treatment of celiac disease in the light of the latest literature.
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Affiliation(s)
- Yasin Sahin
- Pediatric Gastroenterology-Hepatology and Nutrition, Medical Park Gaziantep Hospital, Gaziantep 27560, Turkey
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28
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Jansson-Knodell CL, Rubio-Tapia A. The fashionable gluten-free diet-wear with caution. Am J Clin Nutr 2021; 113:491-492. [PMID: 33515028 DOI: 10.1093/ajcn/nqaa371] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
- Claire L Jansson-Knodell
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Alberto Rubio-Tapia
- Division of Gastroenterology, Hepatology, and Nutrition; Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
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29
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Fujisawa M, Matsushima M, Ueda T, Kaneko M, Fujimoto R, Sano M, Teramura E, Monma M, Mizukami H, Nakahara F, Suzuki H, Suzuki T. Celiac Disease Complicated by Rhabdomyolysis. Intern Med 2021; 60:217-222. [PMID: 32921688 PMCID: PMC7872804 DOI: 10.2169/internalmedicine.5358-20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
At 37 years old, a patient developed chronic watery diarrhea, generalized pain, severe hypokalemia and elevated creatine kinase levels. She was thought to have rhabdomyolysis due to hypokalemia from chronic diarrhea. No organic cause was found. Her symptoms subsided with potassium correction, but hypokalemia persisted; she visited our hospital at 44 years old. Endoscopy detected prominent atrophy of the intestinal villi. Histology indicated Marsh-Oberhuber type-3b disease. Anti-gliadin and anti-tissue transglutaminase IgA antibody tests were positive. She was diagnosed with celiac disease and started on a gluten-free diet, which improved her symptoms. This report is only the tenth of its kind worldwide.
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Affiliation(s)
- Mia Fujisawa
- Divisions of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University, School of Medicine, Japan
| | - Masashi Matsushima
- Divisions of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University, School of Medicine, Japan
| | - Takashi Ueda
- Divisions of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University, School of Medicine, Japan
| | - Motoki Kaneko
- Divisions of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University, School of Medicine, Japan
| | - Ryutaro Fujimoto
- Divisions of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University, School of Medicine, Japan
| | - Masaya Sano
- Divisions of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University, School of Medicine, Japan
| | - Erika Teramura
- Divisions of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University, School of Medicine, Japan
| | - Makiko Monma
- Divisions of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University, School of Medicine, Japan
| | - Hajime Mizukami
- Divisions of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University, School of Medicine, Japan
| | - Fumio Nakahara
- Divisions of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University, School of Medicine, Japan
| | - Hidekazu Suzuki
- Divisions of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University, School of Medicine, Japan
| | - Takayoshi Suzuki
- Divisions of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University, School of Medicine, Japan
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30
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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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31
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Lebwohl B, Rubio-Tapia A. Epidemiology, Presentation, and Diagnosis of Celiac Disease. Gastroenterology 2021; 160:63-75. [PMID: 32950520 DOI: 10.1053/j.gastro.2020.06.098] [Citation(s) in RCA: 180] [Impact Index Per Article: 45.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 04/22/2020] [Accepted: 06/06/2020] [Indexed: 12/16/2022]
Abstract
The incidence of celiac disease is increasing, partly because of improved recognition of, and testing for, the disease. The rise in incidence is also due to a real increase of this immune-based disorder, independent of disease detection. The reasons for this true rise in recent decades are unknown but may be related to environmental factors that may promote loss of tolerance to dietary gluten. Strategies to reduce the development of celiac disease have not been proven successful in randomized trials, but the quantity of early-life gluten exposure has been a major focus of prevention efforts. The criteria for the diagnosis of celiac disease are changing, but in adults, diagnosis still depends on the presence of duodenal villous atrophy while the patient is on a gluten-containing diet, along with findings from serology analysis. Although guidelines in the United States continue to mandate a biopsy at all ages, some children receive a diagnosis of celiac disease without a biopsy. If proven accurate and scalable, assays that detect gluten-HLA tetramer complexes might be used in diagnosis to be made in the context of a gluten-free diet without intestinal biopsy.
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Affiliation(s)
- Benjamin Lebwohl
- Department of Medicine, Columbia University Irving Medical Center, New York, New York; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
| | - Alberto Rubio-Tapia
- Department of Gastroenterology, Hepatology, and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, Ohio
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32
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Koumbi L, Giouleme O, Vassilopoulou E. Non-Celiac Gluten Sensitivity and Irritable Bowel Disease: Looking for the Culprits. Curr Dev Nutr 2020; 4:nzaa176. [PMID: 33442571 PMCID: PMC7788486 DOI: 10.1093/cdn/nzaa176] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Revised: 11/02/2020] [Accepted: 12/02/2020] [Indexed: 12/13/2022] Open
Abstract
During the last 30 y, a gluten-free diet has been classified among the most popular fad diets mainly due to the ambiguous notion that gluten avoidance promotes health. Gluten intolerance has been implicated in non-celiac gluten sensitivity (NCGS) and irritable bowel syndrome (IBS), 2 disorders with overlapping symptoms and increasing trend. Together with gluten, other wheat components; fermentable oligo-, di-, monosaccharide, and polyols (FODMAPs); and amylase trypsin inhibitors (ATIs), are implicated in the pathogenesis of both disorders. Gut microflora alterations in IBS and NCGS have been described, while microbiota manipulations have been shown to be promising in some IBS cases. This literature review summarizes our current knowledge on the impact of wheat ingredients (gluten, FODMAPs, and ATIs) in IBS and NCGS. In both disorders, FODMAPs and ATIs trigger gut dysbiosis, suggesting that gluten may not be the culprit, and microbiota manipulations can be applied in diagnostic and intervention approaches.
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Affiliation(s)
- Lemonica Koumbi
- Department of Nutritional Sciences and Dietetics, International Hellenic University (IHU), Thessaloniki, Greece
| | - Olga Giouleme
- Medical School, Aristotle University, Thessaloniki, Greece
| | - Emilia Vassilopoulou
- Department of Nutritional Sciences and Dietetics, International Hellenic University (IHU), Thessaloniki, Greece
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33
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Yerushalmi B, Vosko S, Ling G, Raanan R, Cohen DL, Shirin H, Shalem T, Matalon S, Broide E. Bedouin Children With Celiac Disease: Less Symptoms but More Severe Histological Features at Presentation. Front Pediatr 2020; 8:580240. [PMID: 33117763 PMCID: PMC7550736 DOI: 10.3389/fped.2020.580240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Accepted: 08/27/2020] [Indexed: 11/13/2022] Open
Abstract
Background: The prevalence of celiac disease (CD) has dramatically increased with wide variability in clinical presentations between different geographical areas. However, the contribution of ethnic disparities in pediatric celiac disease is still unclear, especially in patients of Bedouin origin. Objective: We aimed to compare the clinical presentation and histological severity of celiac disease between Bedouin and Jewish children in southern Israel. Methods: This is a retrospective study in which we collected the demographic and clinical data, laboratory results, and histological severity of CD in two ethnic groups: Bedouins and Jews. The study included patients who were diagnosed between 1997 and 2015 in a tertiary hospital in southern Israel. Results: Data from 844 children with CD (271 Jewish and 573 Bedouins), 505 females (59.8%), were analyzed. Gastrointestinal symptoms and diabetes were more prevalent among the Jewish population (p < 0.001 and p = 0.008, respectively), while family history, failure to thrive, iron deficiency anemia, and histological severity were significantly more prevalent among the Bedouin group. Upon multivariate logistic regression analysis, only the presence of iron deficiency anemia and Bedouin origin were associated with more advanced histological disease (OR of 2.03 (95% C.I 1.31; 4.308) (P < 0.009) and OR 1.78 (95% C.I 1.31; 4.308) (P < 0.003) respectively). Conclusion: The clinical presentation of celiac disease in Bedouin children is characterized by anemia with less gastrointestinal symptoms, but more severe histological damage. These differences might be explained either by a delay in the diagnosis of the disease in this population or by variable environmental, cultural, and nutritional factors unique to this ethnic group.
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Affiliation(s)
- Baruch Yerushalmi
- Pediatric Gastroenterology Unit, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva, Israel
| | - Sergei Vosko
- The Gonczarowski Family Institute of Gastroenterology and Liver Disease, Shamir (Assaf Harofeh) Medical Center, Zerifin, Israel
| | - Galina Ling
- Pediatric Gastroenterology Unit, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva, Israel
| | - Ronit Raanan
- Pediatric Gastroenterology Unit, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva, Israel
| | - Daniel L. Cohen
- The Gonczarowski Family Institute of Gastroenterology and Liver Disease, Shamir (Assaf Harofeh) Medical Center, Zerifin, Israel
| | - Haim Shirin
- The Gonczarowski Family Institute of Gastroenterology and Liver Disease, Shamir (Assaf Harofeh) Medical Center, Zerifin, Israel
| | - Tzipora Shalem
- The Jecheskiel Sigi Gonczarowski Pediatric Gastroenterology Unit, Shamir (Assaf Harofeh) Medical Center, Zerifin, Israel
| | - Shay Matalon
- The Gonczarowski Family Institute of Gastroenterology and Liver Disease, Shamir (Assaf Harofeh) Medical Center, Zerifin, Israel
| | - Efrat Broide
- The Gonczarowski Family Institute of Gastroenterology and Liver Disease, Shamir (Assaf Harofeh) Medical Center, Zerifin, Israel
- The Jecheskiel Sigi Gonczarowski Pediatric Gastroenterology Unit, Shamir (Assaf Harofeh) Medical Center, Zerifin, Israel
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34
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Abstract
Celiac disease (CD) is an immune-mediated enteropathy triggered by dietary ingestion of gluten in genetically susceptible patients. CD is often diagnosed by a "case-finding" approach of symptomatic patients. In recent times, the diagnostic paradigm has shifted to investigate patients who may be asymptomatic, but are at high risk of developing CD due to shared genetic susceptibilities. These high-risk groups include first-degree relatives of CD patients and patients with Type 1 diabetes mellitus, autoimmune thyroid disease, Down's syndrome, and Turner syndrome. Moreover, CD is often diagnosed as the cause of iron deficiency anemia or unexplained chronic diarrhea. Although screening for CD with serological tests is not recommended for the general population, it should be considered in these special populations. In this review, we explore screening for CD among high-risk groups in light of recent research and development in the CD arena.
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Affiliation(s)
- Dennis Kumral
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Virginia, 1215 Lee Street, PO Box 800708, Charlottesville, VA, 22908, USA.
| | - Sana Syed
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, School of Medicine, University of Virginia, MR-4 Bldg, 409 Lane Rd., Charlottesville, VA, 22908, USA
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35
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Azimi T, Nasser A, Shariati A, Shiadeh SMJ, Safari H, Alizade-Sani M, Taghipour A, Dehghan A. The Possible Role of Pathogenic and Non-Pathogenic Bacteria in Initiation and Exacerbation of Celiac Disease; A Comprehensive Review. Curr Pharm Biotechnol 2020; 21:452-466. [PMID: 31858910 DOI: 10.2174/1389201021666191219160729] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Revised: 10/29/2019] [Accepted: 11/22/2019] [Indexed: 02/08/2023]
Abstract
Celiac Disease (CD) is an immune-mediated enteropathy, generally of the proximal intestine, that occurs in genetically susceptible individuals triggered by the ingestion of gluten. The incidence and frequency of CD are increasing, and it is predicted that CD affects approximately 1% of the people worldwide. The common clinical manifestations of CD are divided in two sections, including classic and non-classic symptoms that can be created in childhood and adulthood. The relationship between pathogenic and non-pathogenic bacteria with CD is complex and multidirectional. In previous published studies, results demonstrated the triggering impact of bacteria, viruses, and parasites on initiation and development of Inflammatory Bowel Disease (IBD) and Irritable Bowel Syndrome (IBS). Different studies revealed the inducing effect of pathogenic and non-pathogenic bacteria on CD. However, increasing evidence proposes that some of these microorganisms can also play several positive roles in CD process. Although information of the pathogenesis of the CD is quickly expanding, the possible role of bacteria needs further examination. In conclusion, with respect to the possible correlation between different bacteria in CD, the current review-based study aims to discuss the possible relationship between CD and pathogenic and non-pathogenic bacteria and to show various and significant aspects of mechanisms involved in the CD process.
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Affiliation(s)
- Taher Azimi
- Pediatric Infections Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Students Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Ahmad Nasser
- Clinical Microbiology Research Center, Ilam University of Medical Science, Ilam, Iran.,Department of Medical Microbiology, School of Medicine, Ilam University of Medical Science, Ilam, Iran
| | - Aref Shariati
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.,Student Research Committee, Iran University of Medical Sciences, Tehran, Iran
| | - Seyedeh M J Shiadeh
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hossein Safari
- Health Promotion Research Center, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Mahmood Alizade-Sani
- Students Research Committee, Department of Food Sciences and Technology, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ali Taghipour
- Department of Parasitology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Amin Dehghan
- Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
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Affiliation(s)
- James J Ashton
- Department of Paediatric Gastroenterology, Southampton Children's Hospital, Southampton SO16 6YD, UK
- Department of Human Genetics and Genomics, University of Southampton, Southampton, UK
| | - Rebecca Smith
- Department of Gastroenterology, University Hospital Southampton, Southampton, UK
| | - Trevor Smith
- Department of Gastroenterology, University Hospital Southampton, Southampton, UK
| | - R Mark Beattie
- Department of Paediatric Gastroenterology, Southampton Children's Hospital, Southampton SO16 6YD, UK
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Zhou C, Gao F, Gao J, Yuan J, Lu J, Sun Z, Xu M, Engel J, Hui W, Gilissen L, Chen H. Prevalence of coeliac disease in Northwest China: heterogeneity across Northern Silk road ethnic populations. Aliment Pharmacol Ther 2020; 51:1116-1129. [PMID: 32363620 DOI: 10.1111/apt.15737] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 12/27/2019] [Accepted: 03/28/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Epidemiological data of coeliac disease are lacking from the central Asian region. AIMS To verify the occurrence of coeliac disease amongst four major ethnic groups of Xinjiang Uyghur Autonomus Region, China. METHODS 2277 in-patients with gastrointestinal symptoms (1391 Han, 608 Uyghur, 146 Kazakh and 132 Hui; mean age: 54 ± 12.8 years) were included. Total IgA, anti-deamidated gliadin peptide (DGP)-IgG, and anti-tissue transglutaminase (anti-tTG)-IgA were analysed. All antibody-positive subjects were further tested for endomysial (EMA) antibodies and were HLA genotyped. All subjects with antibody positivity were asked to undergo intestinal biopsy. In addition, a subset of antibody-negative subjects were tested for HLA-DQA1and DQB1. RESULTS Among the 2277 subjects, 29 subjects were defined as coeliac disease autoimmune (positive results for anti-tTG IgA and EMA-IgA) (1.27%; 95% confidence interval, 0.81%-1.73%), eight of them underwent biopsy and all showed coeliac disease histology (0.35%; 95% Cl, 0.11%-0.59%). The frequency of coeliac disease autoimmunity was lowest among the Han (0.79%), followed by the Uyghur (1.81%), the Kazakh (2.05%) and the Hui (3.03%). The frequency of the HLA-DQ2 and/or DQ8 haplotype was highest in the Uyghur (52.1%), followed by the Hui (44.4%), the Kazakh (40.0%) and the Han (39.4%). Besides, a three times higher frequency of coeliac disease autoimmunity was found among rural living subjects with significantly higher wheat consumption compared to urban living subjects (3.16% vs 0.97%, P < 0.01). CONCLUSIONS In Xinjiang, coeliac disease does occur, especially in the rural area. The HLA haplotype and environment play key roles in the development of coeliac disease.
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Affiliation(s)
- Chunyan Zhou
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi, China
- School of Food Science and Technology, Nanchang University, Nanchang, Jiangxi, China
| | - Feng Gao
- Department of Gastroenterology, People's Hospital of Xinjiang Uyghur Autonomous Region, Urumqi, China
| | - Jinyan Gao
- School of Food Science and Technology, Nanchang University, Nanchang, Jiangxi, China
| | - Juanli Yuan
- School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi, China
| | - Jiajie Lu
- Department of Gastroenterology, People's Hospital of Xinjiang Uyghur Autonomous Region, Urumqi, China
| | - Zhenzhu Sun
- Pathology Department, People's Hospital of Xinjiang Uyghur Autonomous Region, Urumqi, China
| | - Mengyu Xu
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi, China
- School of Food Science and Technology, Nanchang University, Nanchang, Jiangxi, China
| | - Jasper Engel
- Wageningen Plant Research - Biometris, Wageningen University & Research, Wageningen, The Netherlands
| | - Wenjia Hui
- Department of Gastroenterology, People's Hospital of Xinjiang Uyghur Autonomous Region, Urumqi, China
| | - Luud Gilissen
- Wageningen Plant Research - Bioscience, Wageningen University & Research, Wageningen, The Netherlands
| | - Hongbing Chen
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi, China
- Sino-German Joint Research Institute, Nanchang University, Nanchang, Jiangxi, China
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Patterns of Marijuana Use Among Patients With Celiac Disease in the United States: A Population-based Analysis of the NHANES Survey. J Clin Gastroenterol 2020; 54:242-248. [PMID: 31339867 DOI: 10.1097/mcg.0000000000001220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND Marijuana use has been assessed in patients with chronic gastrointestinal disorders and may contribute to either symptoms or palliation. Use in those with celiac disease (CD) has not been assessed. Our aim was to evaluate patterns of marijuana use in a large population-based survey among patients with CD, people who avoid gluten (PWAG), and controls. STUDY We analyzed data from the National Health and Nutrition Examination Survey from 2009 to 2014. χ tests and multivariable logistic regression were used to compare participants with CD and PWAG to controls regarding the use of marijuana. RESULTS Among respondents who reported ever using marijuana (overall 59.1%), routine (at-least monthly) marijuana use was reported by 46% of controls versus 6% of participants with diagnosed CD (P=0.005) and 66% undiagnosed CD as identified on serology (P=0.098) and 51% of PWAG (P=0.536). Subjects with diagnosed CD had lower odds of routine marijuana use compared with controls (odds ratio, 0.08; 95% confidence interval, 0.01-0.73), whereas participants with undiagnosed CD had increased odds of routine use (odds ratio, 2.26; 95% confidence interval, 0.83-6.13), which remained elevated even after adjusting for age, sex, race/ethnicity, health insurance status, alcohol, tobacco use, educational level, and poverty/income ratio. CONCLUSIONS In all groups, marijuana use was high. Although there were no differences among subjects with CD, PWAG, and controls who ever used marijuana, subjects with diagnosed CD appear to have decreased routine use of marijuana when compared with controls and PWAG. Those with undiagnosed CD have significantly higher rates of regular use. Future research should focus on the utilization of marijuana as it may contribute to further understanding of symptoms and treatments.
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McAllister BP, Williams E, Clarke K. A Comprehensive Review of Celiac Disease/Gluten-Sensitive Enteropathies. Clin Rev Allergy Immunol 2020; 57:226-243. [PMID: 29858750 DOI: 10.1007/s12016-018-8691-2] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Celiac disease is a complex immune-mediated gluten-sensitive enteropathy with protean clinical manifestations. It is manifest in genetically predisposed individuals who ingest gluten in varying amounts. In broad terms, it is thought to affect 1% of the population in the USA. More specifically, the prevalence increases drastically from 1:133 in patients not-at-risk, to 1:56 in symptomatic patients, to 1:39 in patients with a second-degree relative with the diagnosis, and to 1:22 in patients with a first-degree relative with the diagnosis. It may be associated with several immune-mediated phenomena, autoimmune diseases, and complicated by vitamin and other trace element deficiencies, bone disease, and malignancy. Our understanding of celiac disease has evolved rapidly over the past two decades. This has led to several lines of enquiry on the condition and potential treatment options. More recently, several entities including gluten intolerance, non-celiac gluten sensitivity, and seronegative celiac disease have been described. These conditions are distinct from allergies or intolerance to wheat or wheat products. There are challenges in defining some of these entities since a large number of patients self-report these conditions. The absence of confirmatory diagnostic tests poses an added dilemma in distinguishing these entities. The differences in spectrum of symptoms and highlights of the variability between the pediatric and adult populations have been studied in some detail. The role of screening for celiac disease is examined in both the general population and "at risk" populations. Diagnostic strategies including the best available serologic testing, utility of HLA haplotypes DQ2 and DQ8 which are seen in over 90% of patients with celiac disease as compared with approximately 40% of the general population, and endoscopic evaluation are also reviewed. Comprehensive nutritional management after diagnosis is key to sustained health in patients with celiac disease. Simple algorithms for care based on a comprehensive multidisciplinary approach are proposed. Refractory and non-responsive celiac diseases in the setting of a gluten-free diet are examined as are novel non-dietary therapies. Finally, the association of other disease states including psychiatric illness, infertility, lymphoproliferative malignancy, and mortality is explored with special attention paid to autoimmune and atopic disease.
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Affiliation(s)
- Brian P McAllister
- Department of Medicine, Division of Gastroenterology and Hepatology, Penn State Health Milton S. Hershey Medical Center, Mail Code HU33, 500 University Drive, UPC Suite 2400, Hershey, PA, 17033-0850, USA
| | - Emmanuelle Williams
- Department of Medicine, Division of Gastroenterology and Hepatology, Penn State Health Milton S. Hershey Medical Center, Mail Code HU33, 500 University Drive, UPC Suite 2400, Hershey, PA, 17033-0850, USA
| | - Kofi Clarke
- Department of Medicine, Division of Gastroenterology and Hepatology, Penn State Health Milton S. Hershey Medical Center, Mail Code HU33, 500 University Drive, UPC Suite 2400, Hershey, PA, 17033-0850, USA.
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Shahbazkhani B, Fanaeian MM, Farahvash MJ, Aletaha N, Alborzi F, Elli L, Shahbazkhani A, Zebardast J, Rostami-Nejad M. Prevalence of Non-Celiac Gluten Sensitivity in Patients with Refractory Functional Dyspepsia: a Randomized Double-blind Placebo Controlled Trial. Sci Rep 2020; 10:2401. [PMID: 32051513 PMCID: PMC7016109 DOI: 10.1038/s41598-020-59532-z] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Accepted: 01/30/2020] [Indexed: 12/11/2022] Open
Abstract
Refractory functional dyspepsia (RFD) is characterized by symptoms persistence in spite of medical treatment or H. pylori eradication. No study has yet investigated the presence of gluten-dependent RFD as a clinical presentation of Non-Celiac Gluten Sensitivity (NCGS). Patients with RFD, in whom celiac disease, wheat allergy and H. pylori infection had been ruled out, followed a six weeks long gluten-free diet (GFD). Symptoms were evaluated by means of visual analogue scales; patients with ≥30% improvement in at least one of the reported symptoms after GFD underwent a double-blind placebo controlled gluten challenge. Subjects were randomly divided in two groups and symptoms were evaluated after the gluten/placebo challenge. GFD responders were further followed on for 3 months to evaluate the relationship between symptoms and gluten consumption. Out of 77 patients with RFD, 50 (65%) did not respond to GFD; 27 (35%) cases showed gastrointestinal symptoms improvement while on GFD; after blind gluten ingestion, symptoms recurred in 5 cases (6.4% of patients with RFD, 18% of GFD responders) suggesting the presence of NCGS. Furthermore, such extra-intestinal symptoms as fatigue and weakness (P = 0.000), musculo-skeletal pain (P = 0.000) and headache (P = 0.002) improved in NCGS patients on GFD. Because of the high prevalence of NCGS among patients with RFD, a diagnostic/therapeutic roadmap evaluating the effect of GFD in patients with RFD seems a reasonable (and simple) approach.
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Affiliation(s)
- Bijan Shahbazkhani
- Division of Gastroenterology and Liver Diseases, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad M Fanaeian
- Division of Gastroenterology and Liver Diseases, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
| | - Mohammad J Farahvash
- Division of Gastroenterology and Liver Diseases, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Najmeh Aletaha
- Division of Gastroenterology and Liver Diseases, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Foroogh Alborzi
- Division of Gastroenterology and Liver Diseases, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Luca Elli
- Center for Prevention and Diagnosis of Celiac Disease, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Amirhossein Shahbazkhani
- Division of Gastroenterology and Liver Diseases, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Jayran Zebardast
- Cognitive Science Special Linguistics, Institute of Cognitive Sciences, Tehran, Iran
| | - Mohammad Rostami-Nejad
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Celiac disease risk stratification based on HLA-DQ heterodimer (HLA-DQA1 ~ DQB1) typing in a large cohort of adults with suspected celiac disease. Hum Immunol 2020; 81:59-64. [PMID: 32005535 DOI: 10.1016/j.humimm.2020.01.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Revised: 12/18/2019] [Accepted: 01/19/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUNDS Patients with celiac disease (CeD) carry the major histocompatibility complex class II, HLA-DQ2 or DQ8 haplotype; the absence of these haplotypes excludes a diagnosis of CeD. While the most common and highest risk HLA haplotypes in CeD have been established, the risk profiles of the less common and equivocal HLA haplotypes need further refinement. The aim of this study was to use a large national patient cohort to further stratify the risk gradient of HLA-DQ haplotypes. METHODS The study cohort included 24,339 adult patients with suspected CeD and immunoglobulin (Ig)A sufficiency (total IgA ≥ 70 mg/dL) whose samples were assessed at Mayo Clinic Laboratories for HLA-DQ genotyping, total IgA, and tissue transglutaminase (tTG)-IgA. Data from a subset of the patients who had duodenal biopsies were analyzed to determine the risk gradient of CeD. Logistic regression models were used to evaluate the risk gradient and to calculate odds ratios (ORs) for being positive to CeD serology according to different HLA-DQ2 and DQ8 heterodimers. RESULTS Of the 24,339 patients, 55% (n = 13,456) expressed HLA-DQ2 or DQ8 heterodimers. Compared with patients who had non-permissive HLA-DQ heterodimers, patients who had HLA-DQ2 homozygosity (HLA-DQ2.5/DQ2.5, HLA-DQ2.5/DQ2.2, or HLA-DQ2.2/DQ2.2) showed increased odds for tTG-IgA positivity (OR = 96.9; 95% CI, 58.3-147.9). Interestingly, the odds for patients who were compound heterozygous for HLA-DQ2.5 and HLA-DQ8 were similar to those for HLA-DQ2.5 heterozygotes. However, a single HLA-DQ2.2 haplotype (without HLA-DQ8, DQ2.2 heterozygous) was not associated with tTG-IgA positivity. These findings were confirmed in a subset of patients (n = 738) who had duodenal biopsies performed in addition to CeD serologic testing. DISCUSSION This large national reference laboratory cohort study demonstrated that HLA-DQ2.2 heterozygous is not associated with positive tTG-IgA serology, suggesting the reclassification of this haplotype as non-permissive for CeD.
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Choung RS, Khaleghi S, Cartee AK, Marietta EV, Larson JJ, King KS, Savolainen O, Ross AB, Rajkumar SV, Camilleri MJ, Rubio-Tapia A, Murray JA. Community-Based Study of Celiac Disease Autoimmunity Progression in Adults. Gastroenterology 2020; 158:151-159.e3. [PMID: 31560892 PMCID: PMC7065356 DOI: 10.1053/j.gastro.2019.09.006] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Revised: 09/06/2019] [Accepted: 09/16/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS Celiac disease can develop at any age, but outcomes of adults with positive results from serologic tests for tissue transglutaminase antibodies (tTGA) without endoscopic determination of celiac disease (called celiac autoimmunity) have not been thoroughly evaluated. We investigated the proportion of adults with celiac autoimmunity at a community medical center and their progression to celiac disease. METHODS We analyzed waste blood samples from a community clinic from 15,551 adults for tTGA and, if titer results were above 2 U/mL, for endomysial antibody. The blood samples had been collected at 2 time points (median interval, 8.8 years) from 2006 through 2017. We collected data from the clinic on diagnoses of celiac disease based on duodenal biopsy analysis. RESULTS Of the serum samples collected at the first time point, 15,398 had negative results for tTGA, and 153 had positive results for tTGA (>4 U/mL). Based on medical records, 6 individuals received a diagnosis of celiac disease, for a cumulative incidence of celiac disease diagnosis of 0.06% (95% confidence interval, 0.01-0.11). Forty-nine (0.32%) individuals with a negative result from the first serologic test for tTGA had a positive result from the second test. Among the 153 adults who were tTGA positive at the first time point, 31 (20%) had a subsequent diagnosis of celiac disease, 81 (53%) remained positive for tTGA without a clinical diagnosis of celiac disease, and 41 (27%) had negative test results for tTGA at the second time point. Higher initial tTGA titers, female sex, and a history of hypothyroidism and autoimmune disease were associated with increased risks of subsequent diagnosis of celiac disease. Interestingly, adults whose first blood sample had a positive test result but second blood sample had a negative result for tTGA were older, had lower-than-average initial tTGA titer results, and had a higher mean body mass index than adults whose blood samples were positive for tTGA at both time points and adults later diagnosed with celiac disease. CONCLUSIONS In an analysis of serum samples collected from a community clinic an average of 8.8 years apart, we found that fewer than 1% of adults with negative results from an initial test for tTGA have a positive result on a second test. Of adults with positive results from the test for tTGA, only 20% are later diagnosed with celiac disease; the remaining individuals maintain persistent increases in tTGA without diagnoses of celiac disease or have negative results from second tests.
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Affiliation(s)
- Rok Seon Choung
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Shahryar Khaleghi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Amanda K Cartee
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Eric V Marietta
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Joseph J Larson
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Katherine S King
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Otto Savolainen
- Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden
| | - Alastair B Ross
- Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden; Proteins and Metabolites Team, AgResearch, Lincoln, New Zealand
| | - S Vincent Rajkumar
- Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Michael J Camilleri
- Department of Dermatology and Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
| | - Alberto Rubio-Tapia
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Joseph A Murray
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
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Motoyama M, Yamada H, Motonishi M, Matsunaga H. Elevated anti-gliadin IgG antibodies are related to treatment resistance in schizophrenia. Compr Psychiatry 2019; 93:1-6. [PMID: 31276901 DOI: 10.1016/j.comppsych.2019.05.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Revised: 05/28/2019] [Accepted: 05/31/2019] [Indexed: 01/08/2023] Open
Affiliation(s)
- Mikuni Motoyama
- Department of Neuropsychiatry, Hyogo College of Medicine, 1-1, Mukogawa, Nishinomiya, Hyogo 663-8501, Japan.
| | - Hisashi Yamada
- Department of Neuropsychiatry, Hyogo College of Medicine, 1-1, Mukogawa, Nishinomiya, Hyogo 663-8501, Japan.
| | | | - Hisato Matsunaga
- Department of Neuropsychiatry, Hyogo College of Medicine, 1-1, Mukogawa, Nishinomiya, Hyogo 663-8501, Japan.
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Caio G, Volta U, Sapone A, Leffler DA, De Giorgio R, Catassi C, Fasano A. Celiac disease: a comprehensive current review. BMC Med 2019; 17:142. [PMID: 31331324 PMCID: PMC6647104 DOI: 10.1186/s12916-019-1380-z] [Citation(s) in RCA: 545] [Impact Index Per Article: 90.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 06/27/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Celiac disease remains a challenging condition because of a steady increase in knowledge tackling its pathophysiology, diagnosis, management, and possible therapeutic options. MAIN BODY A major milestone in the history of celiac disease was the identification of tissue transglutaminase as the autoantigen, thereby confirming the autoimmune nature of this disorder. A genetic background (HLA-DQ2/DQ8 positivity and non-HLA genes) is a mandatory determinant of the development of the disease, which occurs with the contribution of environmental factors (e.g., viral infections and dysbiosis of gut microbiota). Its prevalence in the general population is of approximately 1%, with female predominance. The disease can occur at any age, with a variety of symptoms/manifestations. This multifaceted clinical presentation leads to several phenotypes, i.e., gastrointestinal, extraintestinal, subclinical, potential, seronegative, non-responsive, and refractory. Although small intestinal biopsy remains the diagnostic 'gold standard', highly sensitive and specific serological tests, such as tissue transglutaminase, endomysial and deamidated gliadin peptide antibodies, have become gradually more important in the diagnostic work-up of celiac disease. Currently, the only treatment for celiac disease is a life-long, strict gluten-free diet leading to improvement in quality of life, ameliorating symptoms, and preventing the occurrence of refractory celiac disease, ulcerative jejunoileitis, and small intestinal adenocarcinoma and lymphoma. CONCLUSIONS The present review is timely and provides a thorough appraisal of various aspects characterizing celiac disease. Remaining challenges include obtaining a better understanding of still-unclear phenotypes such as slow-responsive, potential (minimal lesions) and seronegative celiac disease. The identification of alternative or complementary treatments to the gluten-free diet brings hope for patients unavoidably burdened by diet restrictions.
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Affiliation(s)
- Giacomo Caio
- Department of Medical Sciences, University of Ferrara, Via Aldo Moro 8, Cona, 44124 Ferrara, Italy
- Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA 02114 USA
| | - Umberto Volta
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy
| | - Anna Sapone
- Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA 02114 USA
- Takeda Pharmaceuticals International Co, Cambridge, MA 02139 USA
| | - Daniel A. Leffler
- Takeda Pharmaceuticals International Co, Cambridge, MA 02139 USA
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA 02115 USA
| | - Roberto De Giorgio
- Department of Medical Sciences, University of Ferrara, Via Aldo Moro 8, Cona, 44124 Ferrara, Italy
| | - Carlo Catassi
- Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA 02114 USA
- Department of Pediatrics, Center for Celiac Research, Università Politecnica delle Marche, 60121 Ancona, Italy
| | - Alessio Fasano
- Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA 02114 USA
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Bledsoe AC, King KS, Larson JJ, Snyder M, Absah I, Choung RS, Murray JA. Micronutrient Deficiencies Are Common in Contemporary Celiac Disease Despite Lack of Overt Malabsorption Symptoms. Mayo Clin Proc 2019; 94:1253-1260. [PMID: 31248695 DOI: 10.1016/j.mayocp.2018.11.036] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Revised: 10/21/2018] [Accepted: 11/19/2018] [Indexed: 12/19/2022]
Abstract
OBJECTIVE To evaluate micronutrient deficiencies in a contemporary cohort of adult patients with newly diagnosed celiac disease (CD). PATIENTS AND METHODS This is a retrospective study of prospective adults newly diagnosed with CD from January 1, 2000, through October 31, 2014, at Mayo Clinic. Micronutrient data were collected for tissue transglutaminase IgA, zinc, 25-hydroxy vitamin D, ferritin, albumin, copper, vitamin B12, and serum folate. Data were analyzed for absolute number of deficiencies and associations with age, sex, body mass index, presenting symptoms, and tissue transglutaminase IgA; each deficiency was assessed using logistic regression. Deficiencies were compared with age- and sex-matched controls from the National Health and Nutrition Examination Survey. RESULTS In total, 309 patients with CD (196 women and 113 men; mean age, 46.1±15.1 years; mean body mass index, 25.9 kg/m2) were included. Weight loss was seen in only 25.2% (78/309) of patients. Zinc was deficient in 59.4% (126/212) of patients with CD compared with 33.2% (205/618) of controls (P<.001). Albumin was low in 19.7% (24/122) compared with 1.1% of controls (P<.001). Copper was low in 6.4% (13/204) compared with 2.1% (13/618) of controls (P=.003). Vitamin B12 was low in 5.3% (13/244) compared with 1.8% (11/618) of controls (P=.004). Folate was low in 3.6% (6/159) compared with 0.3% (2/618) of controls (P=.002). 25-Hydroxy vitamin D was low in 19.0% (44/213) compared with 18% (111/618) of controls (P=.72). Ferritin was low in 30.8% (66/214) of patients; no NHANES controls were available for comparison for ferritin. CONCLUSION Micronutrient deficiencies remain common in adults with CD despite increased nonclassic presentation. This study provides support for micronutrient assessment at the time of CD diagnosis.
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Affiliation(s)
- Adam C Bledsoe
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Katherine S King
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN
| | - Joseph J Larson
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN
| | - Melissa Snyder
- Division of Clinical Biochemistry, Mayo Clinic, Rochester, MN
| | - Imad Absah
- Division of Pediatric Gastroenterology, Mayo Clinic, Rochester, MN
| | - Rok Seon Choung
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Joseph A Murray
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN; Department of Pediatrics, University of Southern Denmark, Odense
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Malamut G, Cording S, Cerf-Bensussan N. Recent advances in celiac disease and refractory celiac disease. F1000Res 2019; 8:F1000 Faculty Rev-969. [PMID: 31297187 PMCID: PMC6600866 DOI: 10.12688/f1000research.18701.1] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/14/2019] [Indexed: 12/21/2022] Open
Abstract
Celiac disease (CeD), defined as gluten-induced enteropathy, is a frequent and largely underdiagnosed disease. Diagnosis relies on the detection of highly specific serum IgA anti-transglutaminase auto-antibodies and on the demonstration of duodenal villous atrophy. Treatment necessitates a strict gluten-free diet, which resolves symptoms and enables histological recovery. However, regular follow-up is necessary to assess mucosal healing, which emerges as an important prognostic factor. Recent work on CeD pathogenesis has highlighted how the cross-talk between gluten-specific CD4 + T cells and interleukin-15 can activate cytotoxic intraepithelial lymphocytes and trigger epithelial lesions. Moreover, acquisition by a subset of intraepithelial lymphocytes of somatic gain-of-function mutations in the JAK-STAT pathway was shown to be a decisive step in the progression toward lymphomas complicating CeD, thus opening new therapeutic perspectives for these rare but life-threatening complications.
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Affiliation(s)
- Georgia Malamut
- Gastroenterology, Hôpital Cochin APHP, Paris, France
- Université Paris Descartes, Paris, France
- Inserm, UMR1163 and Institut Imagine, Laboratory Intestinal Immunity, Paris, France
| | - Sascha Cording
- Université Paris Descartes, Paris, France
- Inserm, UMR1163 and Institut Imagine, Laboratory Intestinal Immunity, Paris, France
| | - Nadine Cerf-Bensussan
- Université Paris Descartes, Paris, France
- Inserm, UMR1163 and Institut Imagine, Laboratory Intestinal Immunity, Paris, France
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Association between grains, gluten and the risk of colorectal cancer in the Cancer Prevention Study-II Nutrition Cohort. Eur J Nutr 2019; 59:1739-1749. [DOI: 10.1007/s00394-019-02032-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Accepted: 06/15/2019] [Indexed: 12/22/2022]
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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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Affiliation(s)
- Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solnavägen 1, Solna 171 77, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, City Hospital, Clinical Sciences Building 2, Nottingham, UK; Department of Medicine, Celiac Disease Center, Columbia University College of Physicians and Surgeons, New York, NY, USA.
| | - Joseph A Murray
- Division of Gastroenterology and Hepatology, Department of Immunology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA; University of Southern Denmark, Odense, Denmark
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Tabibian JH, Perrault JF, Murray JA, Papadakis KA, Enders FT, Gostout CJ. Narrow band imaging evaluation of duodenal villi in patients with and without celiac disease: A prospective study. World J Gastrointest Endosc 2019; 11:145-154. [PMID: 30788033 PMCID: PMC6379743 DOI: 10.4253/wjge.v11.i2.145] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Revised: 01/09/2019] [Accepted: 01/26/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Duodenal biopsies are commonly obtained during esophagogastroduodenoscopy (EGD) but are very often histopathologically normal. Therefore, a more strategic method for evaluating the duodenal mucosa and avoiding unnecessary biopsies is needed. AIM To examine the clinical utility of narrow band imaging (NBI) for evaluating duodenal villous morphology. METHODS We performed a prospective cohort study of adult patients at Mayo Clinic Rochester from 2013-2014 who were referred for EGD with duodenal biopsies. A staff endoscopist scored, in real-time, the NBI-based appearance of duodenal villi into one of three categories (normal, partial villous atrophy, or complete villous atrophy), captured ≥ 2 representative duodenal NBI images, and obtained mucosal biopsies therein. Images were then scored by an advanced endoscopist and gastroenterology fellow, and biopsies (gold standard) by a pathologist, in a masked fashion using the same three-category classification. Performing endoscopist, advanced endoscopist, and fellow NBI scores were compared to histopathology to calculate performance characteristics [sensitivity, specificity, positive and negative, negative predictive value (NPV), and accuracy]. Inter-rater agreement was assessed with Cohen's kappa. RESULTS 112 patients were included. The most common referring indications were dyspepsia (47%), nausea (23%), and suspected celiac disease (14%). Duodenal histopathology scores were: 84% normal, 11% partial atrophy, and 5% complete atrophy. Performing endoscopist NBI scores were 79% normal, 14% partial atrophy, and 6% complete atrophy compared to 91%, 5%, and 4% and 70%, 24%, and 6% for advanced endoscopist and fellow, respectively. NBI performed favorably for all raters, with a notably high (92%-100%) NPV. NBI score agreement was best between performing endoscopist and fellow (κ = 0.65). CONCLUSION NBI facilitates accurate, non-invasive evaluation of duodenal villi. Its high NPV renders it especially useful for foregoing biopsies of histopathologically normal duodenal mucosa.
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Affiliation(s)
- James H Tabibian
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
- Division of Gastroenterology, Olive View-UCLA Medical Center, Sylmar, CA 91342, United States
| | - Jean F Perrault
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
| | - Joseph A Murray
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
| | | | - Felicity T Enders
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN 55905, United States
| | - Christopher J Gostout
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
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Walker MD, Zylberberg HM, Green PHR, Katz MS. Endocrine complications of celiac disease: a case report and review of the literature. Endocr Res 2019; 44:27-45. [PMID: 30198791 DOI: 10.1080/07435800.2018.1509868] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
PURPOSE The purpose of this article is to review recent literature regarding endocrine disorders related to celiac disease (CD). METHODS We describe a case report and review existing literature on the endocrine manifestations of CD. RESULTS CD is an autoimmune disorder characterized by intestinal inflammation in response to gluten. CD can cause a wide range of extra-intestinal complications, including endocrine manifestations. Metabolic bone disease including osteoporosis and osteopenia, vitamin D deficiency, secondary hyperparathyroidism and less frequently osteomalacia can be seen. In CD, fracture risk is increased by 30-40%, while risk for hip fracture is approximately doubled. The risk for other endocrine disorders, particularly autoimmune endocrinopathies, is also increased in those with CD compared to the general population. Epidemiologic data indicate the risk for hypothyroidism is 3-4 times higher among those with CD, while risk of type 1 diabetes is greater than double. Risk for primary adrenal insufficiency is a striking 11-fold higher in those with versus without CD, though the absolute risk is low. Fertility is reduced in women with CD before diagnosis by 37% while male fertility in the absence of hypogonadism does not appear to be affected. Other endocrine conditions including hyperthyroidism, ovarian failure, androgen insensitivity, impaired growth and growth hormone deficiency and autoimmune polyendocrine syndromes have also been associated with CD. CONCLUSIONS CD is associated with a wide range of endocrine manifestations.
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Affiliation(s)
- Marcella D Walker
- a Department of Medicine , Columbia University , New York , NY , USA
| | | | - Peter H R Green
- a Department of Medicine , Columbia University , New York , NY , USA
| | - Michael S Katz
- c Department of Medicine , University of Texas Health Science Center at San Antonio , San Antonio , TX , USA
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