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Campbell DE, Mehr S, Moscatelli OG, Anderson RP, Tye-Din JA. Immune therapies in coeliac disease and food allergies: Advances, challenges, and opportunities. Semin Immunol 2025; 78:101960. [PMID: 40273881 DOI: 10.1016/j.smim.2025.101960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2024] [Revised: 04/19/2025] [Accepted: 04/19/2025] [Indexed: 04/26/2025]
Abstract
Coeliac disease and food allergy management primarily relies on the strict avoidance of dietary antigens. This approach is challenging to maintain in real-world settings and in food allergy carries the risk of life-threatening anaphylaxis. Despite their distinct pathogenesis, both disorders are driven by maladaptive responses to dietary proteins, creating opportunities for shared treatment strategies. In food allergy, desensitisation therapies such as oral, sublingual, and epicutaneous immunotherapy are well-established, complemented by biologics like omalizumab and dupilumab. However, the induction of sustained tolerance remains challenging. In contrast, therapeutic advancements for coeliac disease are still in their early stages. Current efforts focus on gluten detoxification or modification, immune blockade or modulation, tolerogenic approaches, and barrier restoration. Emerging therapies, including JAK and BTK inhibitors and microbiome-targeted interventions, support further targeted treatment options for both conditions. Biomarkers tracking gluten-specific T cells have emerged as valuable tools for immunomonitoring and symptom assessment in coeliac disease, although standardisation of patient-reported outcome measures and gluten challenge protocols is still needed. Food allergy trials are reliant on double-blind placebo-controlled food challenges to measure allergen reactivity, but these are time-consuming, carry risks, and underscore the need for surrogate biomarkers. The successful development of immune-targeted therapies will require building an immune toolset to optimally assess systemic responses to antigens in both conditions. Clinically, this could lead to better outcomes for patients who might otherwise remain undiagnosed or untreated due to the absence of significant enteropathy or allergen-specific symptoms.
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Affiliation(s)
- Dianne E Campbell
- Children's Hospital at Westmead, Sydney, New South Wales, Australia; University of Sydney, Sydney, New South Wales, Australia; National Allergy Centre of Excellence, Murdoch Children's Research Institute, Parkville, Victora, Australia
| | - Sam Mehr
- Royal Children's Hospital, Melbourne, Victoria, Australia
| | - Olivia G Moscatelli
- Immunology Division, Walter and Eliza Hall Institute, Parkville, Victoria, Australia
| | - Robert P Anderson
- Gastroenterology Service, Mackay Base Hospital, West Mackay, Queensland, Australia
| | - Jason A Tye-Din
- Immunology Division, Walter and Eliza Hall Institute, Parkville, Victoria, Australia; Department of Gastroenterology, the Royal Melbourne Hospital, Parkville, Victoria, Australia; The Murdoch Children's Research Institute, Parkville, Victoria, Australia.
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Bonner ER, Tschollar W, Anderson R, Mourabit S. Review Article: Novel Enzyme Therapy Design for Gluten Peptide Digestion Through Exopeptidase Supplementation. Aliment Pharmacol Ther 2025; 61:1123-1139. [PMID: 39955716 PMCID: PMC11908114 DOI: 10.1111/apt.70014] [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: 08/27/2024] [Revised: 09/26/2024] [Accepted: 01/29/2025] [Indexed: 02/17/2025]
Abstract
BACKGROUND Dietary peptides are increasingly linked to inflammatory gastrointestinal diseases, exemplified by coeliac disease. Coeliac disease is caused by an acquired immune response to proline- and glutamine-rich gluten peptides, which bottleneck proteolysis and provide substrates for immune recognition. Enzyme therapies aim to eliminate gluten immunogenic peptides as an adjunct to gluten-free diet. AIMS To investigate overlooked aspects of enzyme development given difficulties in translating preclinical efficacy into clinical benefit. METHODS We assessed mode-of-action, target organ and drug delivery in the context of digestive physiology and motility for gluten-digesting enzymes on the market or in development until 1 December 2024. RESULTS Most enzymes were gastric endopeptidases specific for proline or glutamine residues. Gastric enzymes may achieve poor enzyme-substrate exposure due to limited mixing and rapid emptying of water-soluble particles. Moreover, endopeptidases cleave proteins/peptides into shorter peptides but do not systematically cleave protein into absorbable fractions. Natural digestive physiology provides thorough mixing at the intestinal brush border, which produces exopeptidases necessary to fully digest proline-rich peptides. Despite reduced activity in patients with coeliac disease, exopeptidases remain underexplored as therapeutic agents. Given limited substrate scope and end-to-end digestion, exopeptidases are ineffective as single agents, requiring functional combinations. Furthermore, vulnerability to gastric acid requires stabilisation or formulation for rapid enteric release. CONCLUSIONS Enzymes should be stabilised throughout the gastrointestinal tract including the small intestine. Exopeptidases perform a critical function by systematically generating absorbable fractions, warranting future investigation as therapeutic agents. Sensitive and translational biomarkers are needed to better assess enzyme efficacy in real-meal conditions.
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Nawaiseh HK, McKyer LJ, Abdelrahim DN, Al-Domi HA, AL-Nawaiseh FK, AL-Assaf MS, AL-Nadi SAA. Assessment of Knowledge of Celiac Disease and Associated Conditions Among Dietitians in Jordan. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2025; 22:442. [PMID: 40238529 PMCID: PMC11941886 DOI: 10.3390/ijerph22030442] [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: 12/20/2024] [Revised: 02/27/2025] [Accepted: 03/06/2025] [Indexed: 04/18/2025]
Abstract
BACKGROUND Celiac disease (CD) is a type of systemic autoimmune condition triggered by gluten consumption among genetically predisposed individuals. AIM To assess the knowledge, awareness, and practices pertaining to CD and associated conditions among dietitians in Jordan. METHOD A cross-sectional web-based survey was carried out between April and October 2023. The survey was an internet-based questionnaire with closed-ended questions. RESULTS The majority of dietitians answered correctly that CD is caused due to an immunological reaction to gluten, gliadin, and protamine (91.7%); it is an autoimmune disease (71.2%); and the risk of developing an autoimmune disease is higher among CD patients (78.8). The majority of respondents (93.6%) correctly identified that a strict gluten-free diet is the treatment approach for CD patients. However, only (18.9%) of dietitians correctly identified the FDA guidelines for "Gluten Free" food labeling. Approximately 53.4% of respondents identified immunoglobulin (IgA) antibody testing as the most reliable way to diagnose patients with CD. CONCLUSIONS The dietitians have a good understanding of CD topics. The development of credentials in CD would ensure that dietitians practicing in CD are skilled.
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Affiliation(s)
- Hala K. Nawaiseh
- Department of Nutrition and Food Technology, School of Agriculture, The University of Jordan, Amman 11942, Jordan; (H.A.A.-D.); (S.A.A.A.-N.)
| | - Lisako J. McKyer
- Department of Health Promotion and Community Health Sciences, Texas A&M School of Public Health, College Station, TX 76107, USA;
| | - Dana N. Abdelrahim
- Research Institute for Medical and Health Sciences, Sharjah University, Sharjah 27272, United Arab Emirates;
| | - Hayder A. Al-Domi
- Department of Nutrition and Food Technology, School of Agriculture, The University of Jordan, Amman 11942, Jordan; (H.A.A.-D.); (S.A.A.A.-N.)
| | | | - Mohammad S. AL-Assaf
- Department of Ears, Nose and Throat, King Hussein Medical Centre (KHMC), Amman 11941, Jordan;
| | - Shatha A. Abu AL-Nadi
- Department of Nutrition and Food Technology, School of Agriculture, The University of Jordan, Amman 11942, Jordan; (H.A.A.-D.); (S.A.A.A.-N.)
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Robert ME, Ciacci C, Lebwohl B. Opportunities for Improving Biopsy and Non-Biopsy-Based Diagnosis of Celiac Disease. Gastroenterology 2024; 167:79-89. [PMID: 38302007 DOI: 10.1053/j.gastro.2024.01.031] [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: 11/19/2023] [Revised: 01/17/2024] [Accepted: 01/24/2024] [Indexed: 02/03/2024]
Abstract
The accumulating data regarding a non-biopsy diagnosis of celiac disease has led to its adoption in certain scenarios, although debate on whether and when to use non-biopsy criteria in clinical practice is ongoing. Despite the growing popularity and evidence basis for a biopsy-free approach to diagnosis in the context of highly elevated serologies, there will continue to be a role for a biopsy in some groups. This review summarizes the current evidence supporting a non-biopsy approach and arguments supporting continued reliance on biopsy, and focuses on opportunities to improve both approaches.
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Affiliation(s)
- Marie E Robert
- Department of Pathology, Medicine (Digestive Diseases) and Human and Translational Immunology, Yale University School of Medicine, New Haven, Connecticut
| | - Carolina Ciacci
- Department of Medicine, Surgery, Dentistry, Scuola Medica Salernitana, University of Salerno, Baronissi, Salerno, Italy.
| | - 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
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Pinto-Sanchez MI, Blom JJ, Gibson PR, Armstrong D. Nutrition Assessment and Management in Celiac Disease. Gastroenterology 2024; 167:116-131.e1. [PMID: 38593924 DOI: 10.1053/j.gastro.2024.02.049] [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: 11/12/2023] [Revised: 02/20/2024] [Accepted: 02/21/2024] [Indexed: 04/11/2024]
Abstract
Celiac disease (CeD) is the most common immune condition affecting the gastrointestinal tract; it is triggered by gluten and the only available treatment is a strict gluten-free diet (GFD). Therefore, for patients with CeD, adopting a GFD is not a lifestyle choice. The major problem is that a GFD is restrictive and, like all restrictive diets, it has the potential for adverse nutritional outcomes, especially if adopted for a long term. It is well known that GFD can be nutritionally inadequate and is frequently associated with vitamin and mineral deficiencies; it is also associated with excessive sugar and fat intake, particularly when gluten-free substitutes are consumed. Consequently, people with CeD are affected by higher rates of overweight and obesity and metabolic complications, such as fatty liver and cardiovascular disease. Therefore, assessment of nutritional status and diet quality at diagnosis and while on a long-term GFD is key in the management of CeD. This narrative review addresses nutritional considerations in CeD and management of common challenges associated with a GFD.
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Affiliation(s)
- M Ines Pinto-Sanchez
- Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Jedid-Jah Blom
- Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Peter R Gibson
- Central Clinical School, Department of Gastroenterology, Monash University, Clayton, Victoria, Australia
| | - David Armstrong
- Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
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Elli L, Leffler D, Cellier C, Lebwohl B, Ciacci C, Schumann M, Lundin KEA, Chetcuti Zammit S, Sidhu R, Roncoroni L, Bai JC, Lee AR, Dennis M, Robert ME, Rostami K, Khater S, Comino I, Cebolla A, Branchi F, Verdu EF, Stefanolo JP, Wolf R, Bergman-Golden S, Trott N, Scudeller L, Zingone F, Scaramella L, Sanders DS. Guidelines for best practices in monitoring established coeliac disease in adult patients. Nat Rev Gastroenterol Hepatol 2024; 21:198-215. [PMID: 38110546 DOI: 10.1038/s41575-023-00872-2] [Citation(s) in RCA: 24] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/09/2023] [Indexed: 12/20/2023]
Abstract
Coeliac disease (CeD) is an immunological disease triggered by the consumption of gluten contained in food in individuals with a genetic predisposition. Diagnosis is based on the presence of small bowel mucosal atrophy and circulating autoantibodies (anti-type 2 transglutaminase antibodies). After diagnosis, patients follow a strict, life-long gluten-free diet. Although the criteria for diagnosis of this disease are well defined, the monitoring phase has been studied less and there is a lack of specific guidelines for this phase. To develop a set of clinical guidelines for CeD monitoring, we followed the Grading of Recommendations Assessment, Development and Evaluation methodology. Statements and recommendations with the level of evidence were developed and approved by the working group, which comprised gastroenterologists, pathologists, dieticians and biostatisticians. The proposed guidelines, endorsed by the North American and European coeliac disease scientific societies, make recommendations for best practices in monitoring patients with CeD based on the available evidence. The evidence level is low for many topics, suggesting that further research in specific aspects of CeD would be valuable. In conclusion, the present guidelines support clinicians in improving CeD treatment and follow-up and highlight novel issues that should be considered in future studies.
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Affiliation(s)
- Luca Elli
- Center for Prevention and Diagnosis of Celiac Disease-Gastroenterology and Endoscopy Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
| | - Daniel Leffler
- Celiac Center, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston, MA, USA
| | - Christophe Cellier
- Department of Gastroenterology and Endoscopy, CELAC network, AP-HP Centre, Hôpital Européen Georges Pompidou, Université de Paris, Cité and Institut National du Cancer, Paris, France
| | - Benjamin Lebwohl
- Celiac Disease Center, Department of Medicine, Columbia University Irving Medical Center, Columbia University, New York, NY, USA
| | - Carolina Ciacci
- Center for Celiac Disease, Gastrointestinal Unit, AOU San Giovanni di Dio e Ruggi D'Aragona and Department of Medicine Surgery Dentistry, Scuola Medica Salernitana, University of Salerno, Salerno, Italy
| | - Michael Schumann
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Berlin, Germany
| | - Knut E A Lundin
- K.G. Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Rikshospitalet, Oslo University Hospital, Oslo, Norway
| | | | - Reena Sidhu
- Department of Infection, Immunity and Cardiovascular Diseases, Royal Hallamshire Hospital, University of Sheffield, Sheffield, UK
| | - Leda Roncoroni
- Center for Prevention and Diagnosis of Celiac Disease-Gastroenterology and Endoscopy Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
| | - Julio C Bai
- Department of Medicine, Dr. C. Bonorino Udaondo Gastroenterology Hospital, Buenos Aires, Argentina
| | - Anne R Lee
- Celiac Disease Center, Department of Medicine, Columbia University Irving Medical Center, Columbia University, New York, NY, USA
| | - Melinda Dennis
- Celiac Center, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston, MA, USA
| | - Marie E Robert
- Department of Pathology and Medicine, Yale University School of Medicine, New Haven, CT, USA
| | - Kamran Rostami
- Department of Gastroenterology, Palmerston North District Health Board (DHB), Palmerston North, New Zealand
| | - Sherine Khater
- Department of Gastroenterology and Endoscopy, CELAC network, AP-HP Centre, Hôpital Européen Georges Pompidou, Université de Paris, Cité and Institut National du Cancer, Paris, France
| | - Isabel Comino
- Department of Microbiology and Parasitology, Faculty of Pharmacy, University of Seville, Seville, Spain
| | | | - Federica Branchi
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Berlin, Germany
| | - Elena F Verdu
- Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Juan Pablo Stefanolo
- Department of Medicine, Dr. C. Bonorino Udaondo Gastroenterology Hospital, Buenos Aires, Argentina
| | - Randi Wolf
- Program in Nutrition, Department of Health Studies & Applied Educational Psychology, Teachers College, Columbia University, New York, NY, USA
| | - Sheba Bergman-Golden
- Program in Nutrition, Department of Health Studies & Applied Educational Psychology, Teachers College, Columbia University, New York, NY, USA
| | - Nick Trott
- Department of Infection, Immunity and Cardiovascular Diseases, Royal Hallamshire Hospital, University of Sheffield, Sheffield, UK
| | - Luigia Scudeller
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Fabiana Zingone
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
- Gastroenterology Unit, Azienda Ospedale-Università Padova, Padua, Italy
| | - Lucia Scaramella
- Center for Prevention and Diagnosis of Celiac Disease-Gastroenterology and Endoscopy Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - David S Sanders
- Department of Infection, Immunity and Cardiovascular Diseases, Royal Hallamshire Hospital, University of Sheffield, Sheffield, UK
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Bouery P, Attieh R, Sacca L, Sacre Y. Assessment of the social quality of life and the physical activity of adult celiac disease patients following a gluten-free diet in Lebanon. Nutr Health 2024; 30:103-113. [PMID: 35603827 DOI: 10.1177/02601060221095685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
To date, the primary and only treatment recommended for effective management of celiac disease (CD) is adherence to a strict gluten-free diet (GFD) which entails a new approach to eating that affects the social quality of life (QoL) and physical activity (PA) of patients. This cross-sectional study aimed at assessing the social QoL and PA of adult Lebanese CD patients aged between 18 and 59 years old who are following a GFD. An online CD questionnaire was administered to 136 Lebanese celiac participants on a GFD. The findings of this study show a significant association between celiac patients following a GFD and their social QoL (P-value = 0.0001). The results also showed a significant association between the same population and their PA (p-value = 0.0001). Further awareness-raising and learning activities about gluten-free products are needed to improve the adherence to a strict GFD to facilitate its availability to the Lebanese population.
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Affiliation(s)
- Priscilla Bouery
- Department of Nutrition and Food Sciences, Faculty of Arts and Sciences, Holy Spirit University of Kaslik (USEK), Jounieh, Lebanon
| | - Randa Attieh
- Department of Nutrition and Food Sciences, Faculty of Arts and Sciences, Holy Spirit University of Kaslik (USEK), Jounieh, Lebanon
| | - Lea Sacca
- Department of Health, Humanities, and Society, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
| | - Yonna Sacre
- Department of Nutrition and Food Sciences, Faculty of Arts and Sciences, Holy Spirit University of Kaslik (USEK), Jounieh, Lebanon
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Ho AHY, Lui RN. The current and future clinical applications of capsule endoscopy. J Gastroenterol Hepatol 2024; 39:28-33. [PMID: 38238541 DOI: 10.1111/jgh.16490] [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: 01/04/2024] [Accepted: 01/04/2024] [Indexed: 01/31/2024]
Affiliation(s)
- Agnes H Y Ho
- Division of Gastroenterology and Hepatology, Department of Medicine and Therapeutics, Prince of Wales Hospital, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Rashid N Lui
- Division of Gastroenterology and Hepatology, Department of Medicine and Therapeutics, Prince of Wales Hospital, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
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Rossi RE, Busacca A, Brandaleone L, Masoni B, Massironi S, Fraquelli M, Repici A. Small Bowel Imaging in Celiac Disease: Is there a role for Small Bowel Ultrasound? Curr Gastroenterol Rep 2023; 25:430-439. [PMID: 37979097 DOI: 10.1007/s11894-023-00907-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/06/2023] [Indexed: 11/19/2023]
Abstract
PURPOSE OF REVIEW The incidence of celiac disease (CD) has increased over the last decades in part due to better disease awareness. Small bowel ultrasound (sb US) enables dynamic assessment of the bowel; although this topic has been addressed, the use of sb US in the diagnosis and in the follow-up of CD patients is limited to a few specialized tertiary referral centers. Herein, we aimed at summarizing the available literature on this topic to better define the potential clinical implications of sb US in CD, also through a comparison with other available diagnostic techniques. RECENT FINDINGS According to available data, sb US can be of help in confirming or excluding CD in patients with clinical suspicion; specifically, the finding of increased gall bladder volume, free abdominal fluid and enlargement of mesenteric lymph nodes reliably and accurately predicts the diagnosis of CD, whereas the absence of bowel dilatation and increased peristalsis may exclude the diagnosis. However, the place of intestinal US in the diagnostic algorithm of CD is likely to vary depending on the probability of the disease in a given population. There are only a few studies on the role of sb US in complicated CD, even if recent reports suggest a possible clinical role. There is a lack of data on follow-up of CD patients, particularly with the aim of detecting a poor diet adherence. According to current data sb US parameters have been shown to be of value in confirming and excluding the diagnosis of CD. Prospective studies with large sample size are warranted to determine whether to include sb US in the available guidelines for CD diagnosis and monitoring.
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Affiliation(s)
- Roberta Elisa Rossi
- Gastroenterology and Endoscopy Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Milan, Italy.
| | - Anita Busacca
- Gastroenterology and Endoscopy Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Luca Brandaleone
- Gastroenterology and Endoscopy Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Benedetta Masoni
- Gastroenterology and Endoscopy Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Sara Massironi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Ospedale San Gerardo, and Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Mirella Fraquelli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Alessandro Repici
- Gastroenterology and Endoscopy Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20090, Milan, Italy
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Singh SK, Srivastava A. Transition of Care in Celiac Disease. Indian J Pediatr 2023; 90:1142-1148. [PMID: 37273133 DOI: 10.1007/s12098-023-04611-y] [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: 11/25/2022] [Accepted: 03/17/2023] [Indexed: 06/06/2023]
Abstract
Celiac disease (CD) is a gluten related disorder which affects all age-groups and occurs in genetically susceptible population after introduction of gluten in diet. The worldwide prevalence of CD is ~1% and it is higher in certain "at-risk groups". The clinical features are variable, ranging from classical diarrhea to an asymptomatic state. Diagnosis requires serology and duodenal histology although a non-biopsy diagnosis is recommended by European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) for a select group of children. Treatment of CD is with a life-long strict gluten free diet (GFD) along with correction of nutritional deficiencies. Regular follow-up to assess compliance and efficacy of GFD is mandatory. Non-responsive CD needs evaluation by a specialist as it can be due to incorrect diagnosis, poor dietary compliance, coexisting conditions like small bowel bacterial overgrowth, pancreatic insufficiency etc. and lastly, refractory CD. Most patients diagnosed as CD in childhood receive no medical or dietary supervision after transition to adulthood and nearly a third are non-compliant to GFD. No requirement of medications, patient's perception of understanding GFD and absence of symptoms with intermittent non-compliance leads to neglect of care after transition. Poor dietary adherence leads to nutritional deficiencies, osteoporosis, fertility issues and risk of malignancy. It is mandatory that the patients know about CD, need of strict GFD, regular follow-up, disease complications, and are capable of communicating with the health-care personnel before transition. Formulating a phased transition care program with joint pediatric and adult clinics is required for a successful transition and improving the long-term outcome.
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Affiliation(s)
- Sumit K Singh
- Department of Pediatrics, Sri Aurobindo Medical College and Postgraduate Institute, Indore, Madhya Pradesh, India
| | - Anshu Srivastava
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh, 226014, India.
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Ahonen I, Laurikka P, Koskimaa S, Huhtala H, Lindfors K, Kaukinen K, Kurppa K, Kivelä L. Prevalence of vomiting and nausea and associated factors after chronic and acute gluten exposure in celiac disease. BMC Gastroenterol 2023; 23:301. [PMID: 37674120 PMCID: PMC10481613 DOI: 10.1186/s12876-023-02934-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 08/25/2023] [Indexed: 09/08/2023] Open
Abstract
BACKGROUND Vomiting and nausea seem to be relatively specific symptoms related to gluten ingestion in treated celiac disease. However, the overall prevalence and associated factors of these symptoms after chronic gluten exposure at celiac disease diagnosis and acute re-exposure during gluten challenge remain obscure. METHODS Medical data on 815 adult celiac disease patients were collected at diagnosis from the medical records and through supplementary interviews. An additional 74 patients underwent a three-day (10 g/day) gluten challenge (wheat, barley, rye or a combination of the three grains) while in remission. Prevalence of vomiting/nausea and associated factors were evaluated in both cohorts. A literature review was conducted to summarize earlier studies. RESULTS Twenty-eight (3%) patients presented with vomiting at diagnosis. They were less often screen-detected and suffered from extra-intestinal symptoms, and had more often abdominal pain (71% vs. 49%, p = 0.021), diarrhea (61% vs. 40%, p = 0.031), weight loss (36% vs. 17%, p = 0.019) and childhood symptoms (61% vs. 33%, p = 0.002) than those without vomiting (n = 787). The groups were comparable in other clinical-demographic data and in genetic, serological, and histological findings. Short-term gluten challenge provoked vomiting/nausea in 14/74 (19%) patients. They consumed gluten-free oats less often than those without these symptoms (64% vs. 92%, p = 0.017), whereas the groups did not differ in clinical-demographic features at diagnosis, presence of comorbidities, duration of gluten-free diet, or in other symptoms or grain used ingested during the challenge. According to the literature, prevalence of vomiting/nausea at celiac disease diagnosis has varied 3-46% and during gluten challenge 13-61%. CONCLUSIONS In chronic gluten exposure at celiac disease diagnosis, vomiting was associated with other gastrointestinal symptoms and onset of symptoms already in childhood, whereas regular consumption of oats may increase the tolerance against vomiting/nausea after acute re-exposure in treated celiac disease.
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Affiliation(s)
- Iida Ahonen
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Pilvi Laurikka
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
| | - Sara Koskimaa
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Tampere Center for Child, Adolescent and Maternal Health Research, Tampere University and Tampere University Hospital, Tampere, Finland
| | - Heini Huhtala
- Faculty of Social Sciences, Tampere University, Tampere, Finland
| | - Katri Lindfors
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Katri Kaukinen
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
| | - Kalle Kurppa
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Tampere Center for Child, Adolescent and Maternal Health Research, Tampere University and Tampere University Hospital, Tampere, Finland
- The University Consortium of Seinäjoki, Seinäjoki, Finland
| | - Laura Kivelä
- Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
- Tampere Center for Child, Adolescent and Maternal Health Research, Tampere University and Tampere University Hospital, Tampere, Finland.
- Children's Hospital and Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
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12
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Behl S, Khan MR, Ismail Y, Swantek C, Chen ZME, Murray JA, Absah I. The Characteristics of Isolated Bulb Celiac Disease in Children. J Pediatr Gastroenterol Nutr 2023; 77:79-85. [PMID: 37084335 DOI: 10.1097/mpg.0000000000003799] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/23/2023]
Abstract
OBJECTIVES Mucosal injury in celiac disease (CD) patients can be patchy, and up to 12% of CD patients can have mucosal changes limited to the duodenal bulb. Hence, recent guidelines recommend obtaining bulb biopsies in addition to distal duodenum. This study aimed to describe a cohort of children with isolated bulb CD and assess the benefit of separating bulb biopsies. METHODS A retrospective chart review between January 2011 and January 2022 at 2 medical centers was conducted. We included children with CD who underwent endoscopy with separated biopsies from the bulb and distal duodenum. A blinded pathologist performed Marsh-Oberhuber grading on selected cases. RESULTS We identified 224 CD patients, of which 33 (15%) had histologically confirmed isolated bulb CD. Patients with isolated bulb CD were older at diagnosis (10 vs 8 years; P = 0.03). Median anti-tissue transglutaminase immunoglobulin A (TTG IgA) level was lower in isolate bulb CD (2.8 vs 16.7 times the upper limit of normal [ULN], P < 0.001). Almost 88% (29/33) of isolated bulb CD patients had an anti-TTG IgA value of less than 10 times the ULN. Time to anti-TTG IgA normalization (mean 14 months) was similar between the 2 groups. A pathologist review of diagnostic biopsies could not distinguish between the bulb and distal duodenum biopsies in approximately one-third of the reviewed samples. CONCLUSIONS Separating bulb from distal duodenum biopsies can be considered during CD diagnosis, particularly in children with anti-TTG IgA levels less than 10 times the ULN. Larger prospective cohorts are needed to decide whether isolated bulb CD is a unique cohort or an early stage of the conventional CD.
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Affiliation(s)
- Supriya Behl
- From the Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN
| | - Muhammad Rehan Khan
- the Division of Pediatric Gastroenterology, Hepatology & Nutrition, University of Illinois College of Medicine at Peoria; Children's Hospital of Illinois, Peoria, IL
| | - Yasmine Ismail
- the Division of Pediatric Gastroenterology and Hepatology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN
| | - Courtney Swantek
- the Department of Pediatrics/Medicine, University of Illinois College of Medicine at Peoria, Peoria, IL
| | | | - Joseph A Murray
- the Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Imad Absah
- the Division of Pediatric Gastroenterology and Hepatology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN
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13
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Evaluation of a Single Determination of Gluten Immunogenic Peptides in Urine from Unaware Celiac Patients to Monitor Gluten-Free Diet Adherence. Nutrients 2023; 15:nu15051259. [PMID: 36904257 PMCID: PMC10004805 DOI: 10.3390/nu15051259] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 02/23/2023] [Accepted: 02/26/2023] [Indexed: 03/06/2023] Open
Abstract
INTRODUCTION AND AIM Usually, adherence to the gluten-free diet (GFD) in celiac patients is indirectly assessed through serological analysis, questionnaires, or invasive methods such as intestinal biopsy. The detection of gluten immunogenic peptides in urine (urinary gluten immunogenic peptides-uGIP) is a novel technique that directly evaluates the ingestion of gluten. The aim of this study was to evaluate the clinical efficacy of uGIP in the follow-up of celiac disease (CD). METHODS From April 2019 to February 2020, CD patients reporting complete adherence to the GFD were prospectively enrolled but were unaware of the reason for the tests. Urinary GIP, the celiac dietary adherence test (CDAT), symptomatic visual analog scales (VAS), and tissue transglutaminase antibodies (tTGA) titres were evaluated. Duodenal histology and capsule endoscopy (CE) were performed when indicated. RESULTS A total of 280 patients were enrolled. Thirty-two (11.4%) had a positive uGIP test (uGIP+). uGIP+ patients did not show significant differences in demographic parameters, CDAT, or VAS scores. The tTGA+ titre was not related to the positivity of uGIP (14.4% vs. 10.9% in patients with tTGA+ and tTGA-). Regarding histology, 66.7% of the GIP+ patients had atrophy compared to 32.7% of the GIP patients (p-value 0.01). However, the presence of atrophy did not correlate with tTGA. Mucosal atrophy was detected in 29 (47.5%) out of 61 patients by CE. With this method, no noticeable dependence on uGIP results (24 GIP- vs. 5 GIP+) was observed. CONCLUSIONS The single uGIP test was positive in 11% of CD cases referring a correct GFD adherence. Furthermore, uGIP results significantly correlated with the duodenal biopsy, formerly considered the gold standard for assessing CD activity.
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14
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Nemteanu R, Danciu M, Clim A, Girleanu I, Ciortescu I, Gheorghe L, Trifan A, Plesa A. Predictors of slow responsiveness and partial mucosal recovery in adult patients with celiac disease. GASTROENTEROLOGY AND HEPATOLOGY FROM BED TO BENCH 2023; 16:194-202. [PMID: 37554747 PMCID: PMC10404835 DOI: 10.22037/ghfbb.v16i2.2734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 03/12/2023] [Indexed: 08/10/2023]
Abstract
AIM The present study aims to determine the rate of mucosal recovery and predictors of persistent mucosal damage after gluten free diet (GFD). BACKGROUND Celiac disease (CD) is a complex multi-systemic autoimmune disease triggered by exposure to dietary gluten in genetically predisposed individuals. There is still little evidence on the best method for assessing GFD adherence and mucosal recovery during treatment. METHODS The retrospective study included only adult patients (age≥18 years old), with biopsy-proven CD evaluated at a tertiary referral centre between 2016 and 2021. We performed a logistic regression analysis to identify factors associated with partial mucosal recovery (MR) after GFD. We included in the multivariate analysis parameters available at the time of CD diagnosis. RESULTS A total of 102 patients were enrolled, two thirds were females, median age of 39 years (yrs). The initial biopsy analysis showed different stages of villous atrophy (VA) in 79 (77.4%) cases, while in 23(22.5%) cases showed mild enteropathy (Marsh 1, 2). After at least 12 months of GFD, 26 (25.5%) patients had persistent VA despite good or excellent adherence to GFD. Younger patients (< 35yrs), who showed severe mucosal damage (Marsh 3c lesions) and who had increased anti-gliadin antibody (AGA) levels were at risk for failure to obtain mucosal recovery (MR). Logistic regression analysis demonstrated that complete mucosal atrophy (P=0.007) and high AGA antibody levels (cutoff 129 U/ml, P=0.001) were independent risk factors for lack of mucosal improvement after at least 12 months of GFD. Interestingly, genotype, tTG-IgA antibody levels, or duration of GFD levels did not influence the occurrence of MR. CONCLUSION Although AGA seropositivity has lost much of their diagnostic significance in recent years due to the introduction of the more sensitive and specific antibody tests, our study reported that patients aged < 35 yrs, who showed severe mucosal damage (Marsh 3c lesions) and who had increased AGA antibody levels at diagnosis were at risk for failure to obtain MR. The elevated AGA levels at diagnosis could be used as a prognostic tool for assessing MR.
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Affiliation(s)
- Roxana Nemteanu
- “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” County Hospital, Iași, Romania
| | - Mihai Danciu
- “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
- Department of Pathology, “Saint Spiridon” County Hospital, Iasi, Romania
| | - Andreea Clim
- “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
| | - Irina Girleanu
- “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” County Hospital, Iași, Romania
| | - Irina Ciortescu
- “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” County Hospital, Iași, Romania
| | - Liliana Gheorghe
- Department of Radiology, “Saint Spiridon” County Hospital, Iasi, Romania
| | - Anca Trifan
- “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” County Hospital, Iași, Romania
| | - Alina Plesa
- “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Saint Spiridon” County Hospital, Iași, Romania
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15
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Pennazio M, Rondonotti E, Despott EJ, Dray X, Keuchel M, Moreels T, Sanders DS, Spada C, Carretero C, Cortegoso Valdivia P, Elli L, Fuccio L, Gonzalez Suarez B, Koulaouzidis A, Kunovsky L, McNamara D, Neumann H, Perez-Cuadrado-Martinez E, Perez-Cuadrado-Robles E, Piccirelli S, Rosa B, Saurin JC, Sidhu R, Tacheci I, Vlachou E, Triantafyllou K. Small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2022. Endoscopy 2023; 55:58-95. [PMID: 36423618 DOI: 10.1055/a-1973-3796] [Citation(s) in RCA: 130] [Impact Index Per Article: 65.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
MR1: ESGE recommends small-bowel capsule endoscopy as the first-line examination, before consideration of other endoscopic and radiological diagnostic tests for suspected small-bowel bleeding, given the excellent safety profile of capsule endoscopy, its patient tolerability, and its potential to visualize the entire small-bowel mucosa.Strong recommendation, moderate quality evidence. MR2: ESGE recommends small-bowel capsule endoscopy in patients with overt suspected small-bowel bleeding as soon as possible after the bleeding episode, ideally within 48 hours, to maximize the diagnostic and subsequent therapeutic yield.Strong recommendation, high quality evidence. MR3: ESGE does not recommend routine second-look endoscopy prior to small-bowel capsule endoscopy in patients with suspected small-bowel bleeding or iron-deficiency anemia.Strong recommendation, low quality evidence. MR4: ESGE recommends conservative management in those patients with suspected small-bowel bleeding and high quality negative small-bowel capsule endoscopy.Strong recommendation, moderate quality evidence. MR5: ESGE recommends device-assisted enteroscopy to confirm and possibly treat lesions identified by small-bowel capsule endoscopy.Strong recommendation, high quality evidence. MR6: ESGE recommends the performance of small-bowel capsule endoscopy as a first-line examination in patients with iron-deficiency anemia when small bowel evaluation is indicated.Strong recommendation, high quality evidence. MR7: ESGE recommends small-bowel capsule endoscopy in patients with suspected Crohn's disease and negative ileocolonoscopy findings as the initial diagnostic modality for investigating the small bowel, in the absence of obstructive symptoms or known bowel stenosis.Strong recommendation, high quality evidence. MR8: ESGE recommends, in patients with unremarkable or nondiagnostic findings from dedicated small-bowel cross-sectional imaging, small-bowel capsule endoscopy as a subsequent investigation if deemed likely to influence patient management.Strong recommendation, low quality evidence. MR9: ESGE recommends, in patients with established Crohn's disease, the use of a patency capsule before small-bowel capsule endoscopy to decrease the capsule retention rate.Strong recommendation, moderate quality evidence. MR10: ESGE recommends device-assisted enteroscopy (DAE) as an alternative to surgery for foreign bodies retained in the small bowel requiring retrieval in patients without acute intestinal obstruction.Strong recommendation, moderate quality evidence. MR11: ESGE recommends DAE-endoscopic retrograde cholangiopancreatography (DAE-ERCP) as a first-line endoscopic approach to treat pancreaticobiliary diseases in patients with surgically altered anatomy (except for Billroth II patients).Strong recommendation, moderate quality evidence.
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Affiliation(s)
- Marco Pennazio
- University Division of Gastroenterology, City of Health and Science University Hospital, University of Turin, Turin, Italy
| | | | - Edward J Despott
- Royal Free Unit for Endoscopy, The Royal Free Hospital and UCL Institute for Liver and Digestive Health, London, UK
| | - Xavier Dray
- Sorbonne University, Endoscopy Unit, AP-HP, Hôpital Saint-Antoine, Paris, France
| | - Martin Keuchel
- Clinic for Internal Medicine, Agaplesion Bethesda Krankenhaus Bergedorf, Hamburg, Germany
| | - Tom Moreels
- Division of Gastroenterology and Hepatology, University Hospital Saint-Luc, Brussels, Belgium
| | - David S Sanders
- Sheffield Teaching Hospitals NHS Foundation Trust, Gastroenterology Sheffield, Sheffield, UK
| | - Cristiano Spada
- Digestive Endoscopy Unit and Gastroenterology, Fondazione Poliambulanza, Brescia, Italy
- Università Cattolica del Sacro Cuore, Rome, Italy
| | - Cristina Carretero
- Department of Gastroenterology. University of Navarre Clinic, Healthcare Research Institute of Navarre, Pamplona, Spain
| | - Pablo Cortegoso Valdivia
- Gastroenterology and Endoscopy Unit, University Hospital of Parma, University of Parma, Parma, Italy
| | - Luca Elli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Lorenzo Fuccio
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Department of Medical and Surgical Sciences, Gastroenterology Unit, University of Bologna, Bologna, Italy
| | - Begona Gonzalez Suarez
- Gastroenterology Department - ICMDiM, Hospital Clínic of Barcelona, DIBAPS, CiBERHED, Barcelona, Spain
| | - Anastasios Koulaouzidis
- Centre for Clinical Implementation of Capsule Endoscopy, Store Adenomer Tidlige Cancere Center, Svendborg, University of Southern Denmark, Denmark
| | - Lumir Kunovsky
- 2nd Department of Internal Medicine - Gastroenterology and Geriatrics, University Hospital Olomouc, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic
- Department of Surgery, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic
- Department of Gastroenterology and Digestive Endoscopy, Masaryk Memorial Cancer Institute, Brno, Czech Republic
| | - Deirdre McNamara
- TAGG Research Centre, Department of Clinical Medicine, Trinity Centre, Tallaght Hospital, Dublin, Ireland
| | - Helmut Neumann
- Department of Medicine I, University Medical Center Mainz, Mainz, Germany
| | | | | | - Stefania Piccirelli
- Digestive Endoscopy Unit and Gastroenterology, Fondazione Poliambulanza, Brescia, Italy
| | - Bruno Rosa
- Department of Gastroenterology, Hospital da Senhora da Oliveira, Guimarães, Portugal
- Life and Health Sciences Research Institute, School of Medicine, University of Minho, Braga/Guimarães, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Jean-Christophe Saurin
- Gastroenterology and Endoscopy Unit, Hospices Civils de Lyon, Hôpital E. Herriot, Lyon, France
| | - Reena Sidhu
- Academic Department of Gastroenterology and Hepatology, Sheffield Teaching Hospitals, Sheffield, United Kingdom
- Department of Infection, Immunity and Cardiovascular Diseases, University of Sheffield, United Kingdom
| | - Ilja Tacheci
- 2nd Department of Internal Medicine - Gastroenterology, University Hospital Hradec Králové, Charles University, Faculty of Medicine in Hradec Králové, Czech Republic
| | | | - Konstantinos Triantafyllou
- Hepatogastroenterology Unit, Second Department of Internal Medicine - Propaedeutic, Research Institute and Diabetes Center, Medical School, National and Kapodistrian University of Athens, Attikon University General Hospital, Athens, Greece
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16
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Cortegoso Valdivia P, Deding U, Bjørsum-Meyer T, Baatrup G, Fernández-Urién I, Dray X, Boal-Carvalho P, Ellul P, Toth E, Rondonotti E, Kaalby L, Pennazio M, Koulaouzidis A. Inter/Intra-Observer Agreement in Video-Capsule Endoscopy: Are We Getting It All Wrong? A Systematic Review and Meta-Analysis. Diagnostics (Basel) 2022; 12:2400. [PMID: 36292089 PMCID: PMC9600122 DOI: 10.3390/diagnostics12102400] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 09/28/2022] [Accepted: 09/29/2022] [Indexed: 12/09/2022] Open
Abstract
Video-capsule endoscopy (VCE) reading is a time- and energy-consuming task. Agreement on findings between readers (either different or the same) is a crucial point for increasing performance and providing valid reports. The aim of this systematic review with meta-analysis is to provide an evaluation of inter/intra-observer agreement in VCE reading. A systematic literature search in PubMed, Embase and Web of Science was performed throughout September 2022. The degree of observer agreement, expressed with different test statistics, was extracted. As different statistics are not directly comparable, our analyses were stratified by type of test statistics, dividing them in groups of "None/Poor/Minimal", "Moderate/Weak/Fair", "Good/Excellent/Strong" and "Perfect/Almost perfect" to report the proportions of each. In total, 60 studies were included in the analysis, with a total of 579 comparisons. The quality of included studies, assessed with the MINORS score, was sufficient in 52/60 studies. The most common test statistics were the Kappa statistics for categorical outcomes (424 comparisons) and the intra-class correlation coefficient (ICC) for continuous outcomes (73 comparisons). In the overall comparison of inter-observer agreement, only 23% were evaluated as "good" or "perfect"; for intra-observer agreement, this was the case in 36%. Sources of heterogeneity (high, I2 81.8-98.1%) were investigated with meta-regressions, showing a possible role of country, capsule type and year of publication in Kappa inter-observer agreement. VCE reading suffers from substantial heterogeneity and sub-optimal agreement in both inter- and intra-observer evaluation. Artificial-intelligence-based tools and the adoption of a unified terminology may progressively enhance levels of agreement in VCE reading.
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Affiliation(s)
- Pablo Cortegoso Valdivia
- Gastroenterology and Endoscopy Unit, University Hospital of Parma, University of Parma, 43126 Parma, Italy
| | - Ulrik Deding
- Department of Clinical Research, University of Southern Denmark, 5230 Odense, Denmark
- Department of Surgery, Odense University Hospital, 5000 Odense, Denmark
| | - Thomas Bjørsum-Meyer
- Department of Clinical Research, University of Southern Denmark, 5230 Odense, Denmark
- Department of Surgery, Odense University Hospital, 5000 Odense, Denmark
| | - Gunnar Baatrup
- Department of Clinical Research, University of Southern Denmark, 5230 Odense, Denmark
- Department of Surgery, Odense University Hospital, 5000 Odense, Denmark
| | | | - Xavier Dray
- Center for Digestive Endoscopy, Sorbonne University, Saint Antoine Hospital, APHP, 75012 Paris, France
| | - Pedro Boal-Carvalho
- Gastroenterology Department, Hospital da Senhora da Oliveira, Creixomil, 4835 Guimarães, Portugal
| | - Pierre Ellul
- Division of Gastroenterology, Mater Dei Hospital, 2090 Msida, Malta
| | - Ervin Toth
- Department of Gastroenterology, Skåne University Hospital, Lund University, 20502 Malmö, Sweden
| | | | - Lasse Kaalby
- Department of Clinical Research, University of Southern Denmark, 5230 Odense, Denmark
- Department of Surgery, Odense University Hospital, 5000 Odense, Denmark
| | - Marco Pennazio
- University Division of Gastroenterology, City of Health and Science University Hospital, University of Turin, 10126 Turin, Italy
| | - Anastasios Koulaouzidis
- Department of Clinical Research, University of Southern Denmark, 5230 Odense, Denmark
- Department of Medicine, OUH Svendborg Sygehus, 5700 Svendborg, Denmark
- Surgical Research Unit, OUH, 5000 Odense, Denmark
- Department of Social Medicine and Public Health, Pomeranian Medical University, 70-204 Szczecin, Poland
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17
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Elli L, Marinoni B, Sidhu R, Bojarski C, Branchi F, Tontini GE, Chetcuti Zammit S, Khater S, Eliakim R, Rondonotti E, Saurin JC, Bruno M, Buchkremer J, Cadoni S, Cavallaro F, Dray X, Ellul P, Urien IF, Keuchel M, Kopylov U, Koulaouzidis A, Leenhardt R, Baltes P, Beaumont H, Marmo C, McNamara D, Mussetto A, Nemeth A, Cuadrado Robles EP, Perrod G, Rahmi G, Riccioni ME, Robertson A, Spada C, Toth E, Triantafyllou K, Wurm Johansson G, Rimondi A. Nomenclature and Definition of Atrophic Lesions in Small Bowel Capsule Endoscopy: A Delphi Consensus Statement of the International CApsule endoscopy REsearch (I-CARE) Group. Diagnostics (Basel) 2022; 12:1704. [PMID: 35885608 PMCID: PMC9325291 DOI: 10.3390/diagnostics12071704] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Revised: 06/25/2022] [Accepted: 07/07/2022] [Indexed: 11/16/2022] Open
Abstract
(1) Background: Villous atrophy is an indication for small bowel capsule endoscopy (SBCE). However, SBCE findings are not described uniformly and atrophic features are sometimes not recognized; (2) Methods: The Delphi technique was employed to reach agreement among a panel of SBCE experts. The nomenclature and definitions of SBCE lesions suggesting the presence of atrophy were decided in a core group of 10 experts. Four images of each lesion were chosen from a large SBCE database and agreement on the correspondence between the picture and the definition was evaluated using the Delphi method in a broadened group of 36 experts. All images corresponded to histologically proven mucosal atrophy; (3) Results: Four types of atrophic lesions were identified: mosaicism, scalloping, folds reduction, and granular mucosa. The core group succeeded in reaching agreement on the nomenclature and the descriptions of these items. Consensus in matching the agreed definitions for the proposed set of images was met for mosaicism (88.9% in the first round), scalloping (97.2% in the first round), and folds reduction (94.4% in the first round), but granular mucosa failed to achieve consensus (75.0% in the third round); (4) Conclusions: Consensus among SBCE experts on atrophic lesions was met for the first time. Mosaicism, scalloping, and folds reduction are the most reliable signs, while the description of granular mucosa remains uncertain.
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Affiliation(s)
- Luca Elli
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122 Milan, Italy;
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (B.M.); (F.C.); (A.R.)
| | - Beatrice Marinoni
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (B.M.); (F.C.); (A.R.)
- Postgraduate Specialization in Gastrointestinal Diseases, Università degli Studi di Milano, 20122 Milan, Italy
| | - Reena Sidhu
- Department of Infection, Immunity and Cardiovascular Diseases, Royal Hallamshire Hospital, University of Sheffield, Sheffield S10 2TN, UK;
| | - Christian Bojarski
- Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, 10117 Berlin, Germany; (C.B.); (F.B.); (J.B.)
| | - Federica Branchi
- Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, 10117 Berlin, Germany; (C.B.); (F.B.); (J.B.)
| | - Gian Eugenio Tontini
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122 Milan, Italy;
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (B.M.); (F.C.); (A.R.)
| | - Stefania Chetcuti Zammit
- Department of Medicine, Division of Gastroenterology, Mater Dei Hospital, MSD 2090 Msida, Malta; (S.C.Z.); (P.E.)
| | - Sherine Khater
- Department of Gastroenterology, Georges-Pompidou European Hospital, 75015 Paris, France; (S.K.); (E.P.C.R.); (G.P.); (G.R.)
| | - Rami Eliakim
- Gastroenterology Department, Sheba Medical Center, Tel Aviv University, Tel Aviv 52621, Israel; (R.E.); (U.K.)
| | | | - Jean Cristhophe Saurin
- Gastroenterology Department, Hospices Civils de Lyon-Centre Hospitalier Universitaire, 69002 Lyon, France;
| | - Mauro Bruno
- University Division of Gastroenterology, City of Health and Science University Hospital, 10126 Turin, Italy;
| | - Juliane Buchkremer
- Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, 10117 Berlin, Germany; (C.B.); (F.B.); (J.B.)
| | - Sergio Cadoni
- Digestive Endoscopy Unit, CTO Hospital, 09016 Iglesias, Italy;
| | - Flaminia Cavallaro
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (B.M.); (F.C.); (A.R.)
| | - Xavier Dray
- Centre for Digestive Endoscopy, Sorbonne University, Saint Antoine Hospital, APHP, 75012 Paris, France; (X.D.); (R.L.)
| | - Pierre Ellul
- Department of Medicine, Division of Gastroenterology, Mater Dei Hospital, MSD 2090 Msida, Malta; (S.C.Z.); (P.E.)
| | | | - Martin Keuchel
- Clinic for Internal Medicine, Agaplesion Bethesda Krankenhaus Bergedorf, Academic Teaching Hospital of the University of Hamburg, 21029 Hamburg, Germany; (M.K.); (P.B.)
| | - Uri Kopylov
- Gastroenterology Department, Sheba Medical Center, Tel Aviv University, Tel Aviv 52621, Israel; (R.E.); (U.K.)
| | - Anastasios Koulaouzidis
- Department of Medicine, Odense University Hospital (OUH)-Svendborg Sygehus, 5700 Svendborg, Denmark;
- Department of Clinical Research, University of Southern Denmark (SDU), 5230 Odense, Denmark
- Surgical Research Unit, OUH, 5000 Odense, Denmark
| | - Romain Leenhardt
- Centre for Digestive Endoscopy, Sorbonne University, Saint Antoine Hospital, APHP, 75012 Paris, France; (X.D.); (R.L.)
| | - Peter Baltes
- Clinic for Internal Medicine, Agaplesion Bethesda Krankenhaus Bergedorf, Academic Teaching Hospital of the University of Hamburg, 21029 Hamburg, Germany; (M.K.); (P.B.)
| | - Hanneke Beaumont
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Location VU, 1118 Amsterdam, The Netherlands;
| | - Clelia Marmo
- Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Università Cattolica del Sacro Cuore, 00168 Roma, Italy; (C.M.); (M.E.R.); (C.S.)
| | - Deirdre McNamara
- Trinity College Dublin, Tallaght University Hospital, D24 NR0A Dublin, Ireland;
| | - Alessandro Mussetto
- Gastroenterology Unit, Santa Maria delle Croci Hospital, 48121 Ravenna, Italy;
| | - Artur Nemeth
- Skåne University Hospital Malmö, Lund University, 221 00 Lund, Sweden; (A.N.); (E.T.); (G.W.J.)
| | - Enrique Perez Cuadrado Robles
- Department of Gastroenterology, Georges-Pompidou European Hospital, 75015 Paris, France; (S.K.); (E.P.C.R.); (G.P.); (G.R.)
- Small Bowel Unit, Morales Meseguer Hospital, 30008 Murcia, Spain
| | - Guillame Perrod
- Department of Gastroenterology, Georges-Pompidou European Hospital, 75015 Paris, France; (S.K.); (E.P.C.R.); (G.P.); (G.R.)
| | - Gabriel Rahmi
- Department of Gastroenterology, Georges-Pompidou European Hospital, 75015 Paris, France; (S.K.); (E.P.C.R.); (G.P.); (G.R.)
| | - Maria Elena Riccioni
- Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Università Cattolica del Sacro Cuore, 00168 Roma, Italy; (C.M.); (M.E.R.); (C.S.)
| | - Alexander Robertson
- Department of Gastroenterology, Western General Hospital, Edinburgh EH4 2XU, UK;
| | - Cristiano Spada
- Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Università Cattolica del Sacro Cuore, 00168 Roma, Italy; (C.M.); (M.E.R.); (C.S.)
- Digestive Endoscopy and Gastroenterology Unit, Poliambulanza Foundation, 25124 Brescia, Italy
| | - Ervin Toth
- Skåne University Hospital Malmö, Lund University, 221 00 Lund, Sweden; (A.N.); (E.T.); (G.W.J.)
| | - Konstantinos Triantafyllou
- Hepatogastroenterology Unit, 2nd Department of Propaedeutic Internal Medicine, Medical School, Attikon University General Hospital, National and Kapodistrian University, 157 72 Athens, Greece;
| | - Gabriele Wurm Johansson
- Skåne University Hospital Malmö, Lund University, 221 00 Lund, Sweden; (A.N.); (E.T.); (G.W.J.)
| | - Alessandro Rimondi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (B.M.); (F.C.); (A.R.)
- Postgraduate Specialization in Gastrointestinal Diseases, Università degli Studi di Milano, 20122 Milan, Italy
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Abstract
Celiac disease is a chronic, immune-mediated enteropathy driven by dietary gluten found in genetically susceptible hosts. It has a worldwide distribution, is one of the most common autoimmune disorders globally, and is the only autoimmune condition for which the trigger is known. Despite advances in characterizing mechanisms of disease, gaps in understanding of celiac disease pathogenesis remain. A "frontier" concept is considering what moves an HLA-DQ2 or DQ8-positive individual from asymptomatic gluten tolerance to celiac disease manifestation. In this arena, environmental triggers, including age at the time of initial gluten exposure, the occurrence of usual childhood viral infections, and microbiome alterations have emerged as key events in triggering the symptomatic disease. Pathologists play a major role in frontier aspects of celiac disease. This includes the discovery that duodenal mucosal histology in follow-up biopsies does not correlate with ongoing patient symptoms, antitissue transglutaminase antibody titers and diet adherence in celiac disease patients. Further, in light of recent evidence that the detection of monoclonal T-cell populations in formalin-fixed biopsies is not specific for type II refractory celiac disease, pathologists should resist performing such analyses until common causes of "apparent" refractoriness are excluded. The promise of therapies in celiac disease has led to clinical trials targeting many steps in the inflammatory cascade, which depend upon a pathologist's confirmation of the initial diagnosis and evaluation of responses to therapies. As pathologists continue to be active participants in celiac disease research, partnering with other stakeholders, we will continue to impact this important autoimmune disease.
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Affiliation(s)
- Natalie Patel
- El Camino Pathology Medical Group, Mountain View, CA
| | - Marie E Robert
- Department of Pathology and Medicine, Yale University School of Medicine, New Haven, CT
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Yoosuf S, Therrien A, Leffler DA. Non-dietary therapies for celiac disease. COELIAC DISEASE AND GLUTEN-RELATED DISORDERS 2022:111-160. [DOI: 10.1016/b978-0-12-821571-5.00011-8] [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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20
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Das P, Makharia G, Datta Gupta S. Pathology of Malabsorption Syndrome. SURGICAL PATHOLOGY OF THE GASTROINTESTINAL SYSTEM 2022:279-338. [DOI: 10.1007/978-981-16-6395-6_9] [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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21
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Möller SP, Apputhurai P, Tye-Din JA, Knowles SR. Quality of life in coeliac disease: relationship between psychosocial processes and quality of life in a sample of 1697 adults living with coeliac disease. J Psychosom Res 2021; 151:110652. [PMID: 34739942 DOI: 10.1016/j.jpsychores.2021.110652] [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: 06/18/2021] [Revised: 10/11/2021] [Accepted: 10/11/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND Coeliac disease is a chronic gastrointestinal condition associated with an increased risk of psychiatric comorbidity, and diminished quality of life. Ongoing gastrointestinal symptomatology is frequently reported post-diagnosis, despite undertaking a gluten-free diet. PURPOSE To examine the role of psychosocial factors in mediating the relationship between gastrointestinal symptoms and quality of life, using a cross-sectional structural equation modelling mediation analysis guided by the Common-Sense Model. METHODS 1697 adults with coeliac disease (83.1% female, mean age = 55.79, SD = 14.98 years) completed an online questionnaire. Measures included gluten-free diet adherence, gastrointestinal symptoms, illness perceptions, coping, gastrointestinal-specific anxiety, pain catastrophising, psychological flexibility, psychological distress, and quality of life. RESULTS A structural equation model was developed explaining 50.6% of the variation in quality of life and demonstrating good fit (χ2 (2) = 8.54, p = .014, χ2/N = 4.27, RMSEA = 0.04, SRMR = 0.01, CFI = 0.999, TLI = 0.98, GFI = 0.999). Gastrointestinal symptoms directly affected quality of life, and indirectly, via negative illness perceptions, maladaptive coping, pain catastrophising, and psychological distress. CONCLUSION Psychosocial processes may affect adjustment in coeliac disease by mediating the relationship between gastrointestinal symptoms and quality of life. Individuals living with coeliac disease may benefit from interventions targeting maladaptive psychosocial factors.
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Affiliation(s)
- Stephan P Möller
- Department of Psychological Sciences, Faculty of Health, Arts and Design, Swinburne University of Technology, Melbourne, Australia
| | - Pragalathan Apputhurai
- Department of Statistics Data Science and Epidemiology, Swinburne University of Technology, Melbourne, Australia
| | - Jason A Tye-Din
- Immunology Division, Walter and Eliza Hall Institute, Melbourne, Australia; Department of Gastroenterology, the Royal Melbourne Hospital, Melbourne, Australia
| | - Simon R Knowles
- Department of Psychological Sciences, Faculty of Health, Arts and Design, Swinburne University of Technology, Melbourne, Australia; Department of Gastroenterology, Alfred Health, Melbourne, Australia.
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22
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Urbaszek K, Drabińska N, Szaflarska-Popławska A, Jarocka-Cyrta E. TMPRSS6 rs855791 Polymorphism Status in Children with Celiac Disease and Anemia. Nutrients 2021; 13:nu13082782. [PMID: 34444942 PMCID: PMC8398390 DOI: 10.3390/nu13082782] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 08/06/2021] [Accepted: 08/09/2021] [Indexed: 12/11/2022] Open
Abstract
Celiac disease (CD) is an autoimmune chronic inflammatory disease occurring in genetically predisposed individuals in response to the intake of gluten. Clinical presentation can be heterogeneous. Iron-deficient anemia (IDA) is one of the most common extra-intestinal manifestations of CD. Although IDA usually reverts with a gluten-free diet (GFD), some patients show persistent IDA, the mechanisms of which are poorly understood. Recent studies suggest an association between the rs855791 polymorphism in the TMPRSS6 gene and persistent IDA in adults with CD. The current study aimed to assess the potential link between rs855791 and persistent IDA in pediatric patients with CD. The study included 106 children diagnosed with CD between 2015 and 2019. Clinical and blood parameters (including blood count, serum iron) were collected at diagnosis and after ≥12 months of GFD, and the rs855791 genotype was assessed for each patient. IDA was present at diagnosis in 25 patients (23.6%); only three (3%) had persistent IDA after GFD. The prevalence of rs855791 genotypes was 9% (n = 10) for TT, 53% (n = 56) for CT, and 38% (n = 40) for CC. There was a tendency toward a higher proportion of the T allele in patients with IDA and lower hemoglobin in the TT genotype but without statistical significance. An association between rs855791 and persistent IDA was not observed. These findings suggest that persistent IDA is uncommon in pediatric patients with CD. The prevalence of rs855791 in children with CD is reported for the first time.
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Affiliation(s)
- Klaudia Urbaszek
- Department of Pediatrics, Gastroenterology and Nutrition, Faculty of Medicine, Collegium Medicum, University of Warmia and Mazury, Żołnierska 18A Str., 10-561 Olsztyn, Poland;
| | - Natalia Drabińska
- Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Tuwima 10 Str., 10-748 Olsztyn, Poland;
| | - Anna Szaflarska-Popławska
- Laboratory for Pediatric Endoscopy and Gastrointestinal Function Testing, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University of Torun, Jagiellonska 13-15, 85-067 Bydgoszcz, Poland;
| | - Elżbieta Jarocka-Cyrta
- Department of Pediatrics, Gastroenterology and Nutrition, Faculty of Medicine, Collegium Medicum, University of Warmia and Mazury, Żołnierska 18A Str., 10-561 Olsztyn, Poland;
- Correspondence:
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23
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Systematic review: Exploration of the impact of psychosocial factors on quality of life in adults living with coeliac disease. J Psychosom Res 2021; 147:110537. [PMID: 34139581 DOI: 10.1016/j.jpsychores.2021.110537] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 05/24/2021] [Accepted: 05/26/2021] [Indexed: 12/31/2022]
Abstract
BACKGROUND Individuals living with coeliac disease generally experience a remission of symptoms after adopting the gluten-free diet but often report substantial treatment burden and ongoing quality of life issues. Psychosocial factors have been suggested to play a significant role in post-diagnosis quality of life but have yet to be systematically reviewed. AIM To review the evidence for psychosocial factors associated with quality of life in adult coeliac disease cohorts. METHODS Studies were identified via systematic searches of eight databases (MEDLINE, Embase, Emcare, PsycINFO, Ovid Nursing, CINAHL, Informit Health Collection, Cochrane Library) in May 2019. RESULTS Fourteen studies were included involving 3372 participants (80.2% female, mean age = 46.4 years). Symptoms of depression and anxiety were the most examined psychosocial factors across all studies. Quality of life was differentially associated with psychological distress, illness perceptions, coping, and attitudes/behaviours regarding food and the gluten-free diet. CONCLUSION Several psychosocial factors are associated with quality of life in adults living with coeliac disease. Current evidence suggests these factors are interrelated and may influence quality of life directly, via reduced psychological well-being, and indirectly, via reduced adherence to the gluten-free diet. Future research is needed to examine these processes concurrently, with the aim of elucidating the psychosocial mechanisms underlying post-diagnosis well-being and identifying potential targets for psychosocial intervention.
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24
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Schiepatti A, Bacchi S, Biagi F, Panelli S, Betti E, Corazza GR, Capelli E, Ciccocioppo R. Relationship between duodenal microbiota composition, clinical features at diagnosis, and persistent symptoms in adult Coeliac disease. Dig Liver Dis 2021; 53:972-979. [PMID: 33741248 DOI: 10.1016/j.dld.2021.02.019] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 02/19/2021] [Accepted: 02/22/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Duodenal dysbiosis has been suggested to possibly influence the clinical manifestations of coeliac disease (CD), both at onset and when symptoms persist despite a gluten-free diet (GFD). AIMS To evaluate the relationship between duodenal microbiota composition and: i) clinical phenotype of untreated CD (UCD); ii) presence and type of persistent symptoms despite a satisfactory serological and histological response to a strict GFD. METHODS Duodenal microbiota was analyzed by 16S rRNA sequencing and compared with i) clinical features in 12 adult UCD patients; ii) presence/absence and type of persistent symptoms (diarrhea-predominant vs. non-diarrhea predominant) in 25 adult treated coeliac patients (TCD) on a strict GFD. RESULTS UCD with iron deficiency anemia (IDA) had a pro-inflammatory shift in their duodenal microbiota (reduction of Firmicutes, p = 0.03; increase of beta-Proteobacteria, p = 0.02) than those without IDA. TCD with persistent diarrhea showed a reduction of Actinobacteria (p = 0.03) and Rothia spp (p = 0.046) compared to TCD suffering from other type of persistent symptoms. CONCLUSION A distinctive duodenal microbiota profile is associated with IDA in UCD, and diarrhea-predominant persistent symptoms in TCD. Clinical interventions may include reconsidering patients presenting with IDA as a specific disease subtype, and dietary rebalancing if diarrhea persists despite histological response to a GFD.
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Affiliation(s)
- Annalisa Schiepatti
- Istituti Clinici Scientifici Maugeri, I.R.C.C.S., Gastroenterology Unit of Pavia Institute, University of Pavia, Pavia, Italy.
| | - Sara Bacchi
- Laboratory of Immunology and Genetic Analysis, Department of Earth and Environmental Science, University of Pavia, Pavia, Italy; Centre for Health Technologies, University of Pavia, Pavia, Italy
| | - Federico Biagi
- Istituti Clinici Scientifici Maugeri, I.R.C.C.S., Gastroenterology Unit of Pavia Institute, University of Pavia, Pavia, Italy
| | - Simona Panelli
- Department of Biomedical and Clinical Sciences "L. Sacco", Pediatric Clinical Research Center "Invernizzi", University of Milan, Milan, Italy
| | - Elena Betti
- First Department of Internal Medicine, I.R.C.C.S. San Matteo Hospital Foundation, University of Pavia, Pavia, Italy
| | - Gino Roberto Corazza
- First Department of Internal Medicine, I.R.C.C.S. San Matteo Hospital Foundation, University of Pavia, Pavia, Italy
| | - Enrica Capelli
- Laboratory of Immunology and Genetic Analysis, Department of Earth and Environmental Science, University of Pavia, Pavia, Italy; Centre for Health Technologies, University of Pavia, Pavia, Italy
| | - Rachele Ciccocioppo
- Gastroenterology Unit, Department of Medicine, A.O.U.I. Policlinico G.B. Rossi and University of Verona, Verona, Italy
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A phase 2a randomized clinical trial of intravenous vedolizumab for the treatment of steroid-refractory intestinal acute graft-versus-host disease. Bone Marrow Transplant 2021; 56:2477-2488. [PMID: 34108672 PMCID: PMC8486663 DOI: 10.1038/s41409-021-01356-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 04/23/2021] [Accepted: 05/12/2021] [Indexed: 01/10/2023]
Abstract
Steroid-refractory (SR) acute graft-versus-host disease (aGvHD) remains a significant complication after allogeneic hematopoietic cell transplantation. Systemic corticosteroids are first-line therapy for aGvHD, but apart from ruxolitinib, there are no approved treatments for SR aGvHD. Vedolizumab is approved for treatment of ulcerative colitis and Crohn’s disease, and may be effective for treatment of SR intestinal aGvHD. We conducted a phase 2a trial (NCT02993783) to evaluate the clinical efficacy, tolerability, and safety of vedolizumab 300 and 600 mg for SR intestinal aGvHD. This study was terminated before full enrollment was completed because early results failed to demonstrate positive proof-of-concept in efficacy. Before termination, 17 participants had enrolled and an early response in intestinal aGvHD was observed in 11 and eight participants at days 15 and 28, respectively. All adverse events observed were consistent with those expected in a population with SR intestinal aGvHD. Overall, vedolizumab did not meet the primary efficacy endpoint (overall response at day 28), likely owing to premature study drug discontinuation, lack of efficacy, and the competing risks inherent with a population with advanced SR intestinal aGvHD. Nevertheless, this study provides valuable insights into the considerations needed when conducting studies in patients with SR intestinal aGvHD.
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26
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Melson J, Trikudanathan G, Abu Dayyeh BK, Bhutani MS, Chandrasekhara V, Jirapinyo P, Krishnan K, Kumta NA, Pannala R, Parsi MA, Sethi A, Trindade AJ, Watson RR, Maple JT, Lichtenstein DR. Video capsule endoscopy. Gastrointest Endosc 2021; 93:784-796. [PMID: 33642034 DOI: 10.1016/j.gie.2020.12.001] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 12/01/2020] [Indexed: 02/08/2023]
Affiliation(s)
- Joshua Melson
- Division of Digestive Diseases, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA
| | - Guru Trikudanathan
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, Minnesota, USA
| | - Barham K Abu Dayyeh
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Manoop S Bhutani
- Department of Gastroenterology Hepatology and Nutrition, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Vinay Chandrasekhara
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Pichamol Jirapinyo
- Department of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Kumar Krishnan
- Division of Gastroenterology, Department of Internal Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Nikhil A Kumta
- Division of Gastroenterology, Mount Sinai Hospital, New York, New York, USA
| | - Rahul Pannala
- Department of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Mansour A Parsi
- Section for Gastroenterology and Hepatology, Tulane University Health Sciences Center, New Orleans, Louisiana, USA
| | - Amrita Sethi
- Department of Digestive and Liver Diseases, Columbia University Medical Center/New York-Presbyterian, New York, New York, USA
| | - Arvind J Trindade
- Department of Gastroenterology, Zucker School of Medicine at Hofstra/Northwell, Long Island Jewish Medical Center, New Hyde Park, New York, USA
| | - Rabindra R Watson
- Department of Gastroenterology, Interventional Endoscopy Services, California Pacific Medical Center, San Francisco, California, USA
| | - John T Maple
- Division of Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
| | - David R Lichtenstein
- Division of Gastroenterology, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts, USA
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Chetcuti Zammit S, McAlindon ME, Sanders DS, Sidhu R. Assessment of disease severity on capsule endoscopy in patients with small bowel villous atrophy. J Gastroenterol Hepatol 2021; 36:1015-1021. [PMID: 32808308 DOI: 10.1111/jgh.15217] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 05/14/2020] [Accepted: 08/09/2020] [Indexed: 01/05/2023]
Abstract
BACKGROUND AND AIM There is a lack of uniformity of reporting on features of celiac disease (CD) on small bowel capsule endoscopy (SBCE). This makes determining extent of disease and comparison of severity of disease challenging. METHODS De-identified SBCEs of 300 patients (78 CD [26%], 18 serology negative villous atrophy [6%], and 204 controls with normal duodenal histology [68%]) were included. Videos were reviewed by two experts. All patients had duodenal histology taken within 2 weeks of SBCE. The degree of agreement in CD features and extent of disease was then determined. The resulting score for each factor was used to determine overall severity of disease. RESULTS There was substantial agreement in the kappa coefficient for the detection of CD features between reviewers (0.67). Agreement for extent of affected small bowel (SB) mucosa was high (0.97). On multiple regression analysis, several features of CD correlated with extent of affected SB mucosa for both reviewers. The odds ratios derived from this analysis were then used to score features of CD, enabling scores of severity to be calculated for each patient. The median overall scores for patients increased significantly according to the independent classification of severity by the capsule reviewers: mild (20, 0-79), moderate (45, 25-123), and severe (89, 65-130) (P = 0.0001). CONCLUSION The good correlation of CD scores between expert reviewers confirms the validity of features of CD on SBCE. An objective score of CD features in the SB is useful in the follow up of patients with CD and serology negative villous atrophy.
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Affiliation(s)
| | - Mark E McAlindon
- Gastroenterology Department, Sheffield Teaching Hospitals, Sheffield, UK
| | - David S Sanders
- Gastroenterology Department, Sheffield Teaching Hospitals, Sheffield, UK
| | - Reena Sidhu
- Gastroenterology Department, Sheffield Teaching Hospitals, Sheffield, UK
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Zammit SC, Elli L, Scaramella L, Sanders DS, Tontini GE, Sidhu R. Small bowel capsule endoscopy in refractory celiac disease: a luxury or a necessity? Ann Gastroenterol 2021; 34:188-195. [PMID: 33654358 PMCID: PMC7903573 DOI: 10.20524/aog.2021.0586] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Accepted: 10/27/2020] [Indexed: 12/11/2022] Open
Abstract
Background Small bowel capsule endoscopy (SBCE) has an established role in the management of refractory celiac disease (RCD) for the detection of complications. The aim of this study was to define the role of SBCE in the management of patients with RCD. Method Patients with histologically confirmed RCD who underwent successive SBCEs were recruited retrospectively from 2 tertiary centers. Results Sixty patients with RCD were included. The percentage extent of the affected small bowel (SB) mucosa improved on repeating a second SBCE in 26 patients (49.1%) (median 27.6% vs. 18.1%, P=0.007). Patients with RCD type II had more extensive disease than those with RCD type I on first (41.4% vs. 19.2%, P=0.004) and second (29.8% vs. 12.0%, P=0.016) SBCE. Patients with RCD type I tended to show a greater improvement in percentage of abnormal SB involved on repeat SBCE compared to those with RCD type II (P=0.049). Nine patients (15%) had RCD-related complications. Five patients developed ulcerative jejunoileitis, 3 patients developed enteropathy-associated T-cell lymphoma, and 1 patient developed cutaneous T-cell lymphoma. Conclusions SBCE can be a useful tool for monitoring the effects of treatment, primarily following its initiation. Patients with RCD type II have more extensive SB disease, equating to a more aggressive disease pattern.
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Affiliation(s)
- Stefania Chetcuti Zammit
- Gastroenterology Department, Sheffield Teaching Hospitals, United Kingdom (Stefania Chetcuti Zammit, David S. Sanders, Reena Sidhu)
| | - Luca Elli
- Centre for Prevention and Diagnosis of Coeliac Disease, Gastroenterology and Endoscopy Unit, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Italy (Luca Elli, Lucia Scaramella, Gian Eugenio Tontini)
| | - Lucia Scaramella
- Centre for Prevention and Diagnosis of Coeliac Disease, Gastroenterology and Endoscopy Unit, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Italy (Luca Elli, Lucia Scaramella, Gian Eugenio Tontini)
| | - David S Sanders
- Gastroenterology Department, Sheffield Teaching Hospitals, United Kingdom (Stefania Chetcuti Zammit, David S. Sanders, Reena Sidhu)
| | - Gian Eugenio Tontini
- Centre for Prevention and Diagnosis of Coeliac Disease, Gastroenterology and Endoscopy Unit, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Italy (Luca Elli, Lucia Scaramella, Gian Eugenio Tontini)
| | - Reena Sidhu
- Gastroenterology Department, Sheffield Teaching Hospitals, United Kingdom (Stefania Chetcuti Zammit, David S. Sanders, Reena Sidhu)
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Delvecchio M, Bizzoco F, Lapolla R, Gentile A, Carrozza C, Barone M, Simonetti S, Giordano P, Dargenio VN, Cristofori F, Francavilla R. Iodine Absorption in Celiac Children: A Longitudinal Pilot Study. Nutrients 2021; 13:808. [PMID: 33804451 PMCID: PMC7998751 DOI: 10.3390/nu13030808] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 02/22/2021] [Accepted: 02/25/2021] [Indexed: 02/07/2023] Open
Abstract
Background: non-autoimmune thyroid disorder is a common finding in celiac patients, more frequent than in the general population. An impairment of iodine absorption has been hypothesized, but it has never been investigated so far. We aimed to evaluate the iodine absorption in children and adolescents with newly diagnosed celiac disease. Methods: 36 consecutive celiac patients (age 7.4 years, range 2.4-14.5 years) before starting a gluten-free diet (GFD) were enrolled. We assayed the urinary iodine concentration (UIC) in a 24-h urine sample, at baseline (T0) after 3 (T1) and 12 months (T2) of GFD. Results: UIC at T0 was 64 μg/L (IQR 45-93.25 μg/L) with an iodine deficiency rate of 77.8%. UIC was not different according to histological damage, clinical presentation (typical vs atypical); we found no correlation with the thyroid function tests and auxological parameters. UIC was not statistically different at T1 (76 μg/L) and T2 (89 μg/L) vs T0. UIC at T2 was similar between patients with positive and negative anti-transglutaminase antibodies at T2. No patients presented overt hypothyroidism during the study. Conclusions: We found that iodine absorption in celiac children is impaired compared to the general population; it increases slightly, but not significantly, during the GFD. We should regularly reinforce the need for a proper iodine intake in celiac disease patients to reduce iodine deficiency risk.
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Affiliation(s)
- Maurizio Delvecchio
- Metabolic Disorder and Diabetology Unit, “Giovanni XXIII” Children Hospital, 70126 Bari, Italy;
| | - Francesca Bizzoco
- Department of Pediatrics, “Giovanni XXIII” Children Hospital, “Aldo Moro” University of Bari, 70126 Bari, Italy; (F.B.); (P.G.); (V.N.D.); (F.C.); (R.F.)
| | - Rosa Lapolla
- Pediatrics Unit, “San Carlo” Hospital, 85100 Potenza, Italy;
| | - Antonia Gentile
- Pediatrics Unit, “Antonio Perrino” Hospital, 72100 Brindisi, Italy;
| | - Cinzia Carrozza
- UOC Chimica, Biochimica e Biologia Molecolare Clinica, Fondazione Policlinico Universitario “A. Gemelli”, IRCCS, Università Cattolica del Sacro Cuore, 00168 Roma, Italy;
| | - Michele Barone
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, “Aldo Moro” University of Bari, 70125 Bari, Italy
| | - Simonetta Simonetti
- Neonatal Screening Center and Clinical Pathology Unit, “Giovanni XXIII” Children Hospital, 70126 Bari, Italy;
| | - Paola Giordano
- Department of Pediatrics, “Giovanni XXIII” Children Hospital, “Aldo Moro” University of Bari, 70126 Bari, Italy; (F.B.); (P.G.); (V.N.D.); (F.C.); (R.F.)
| | - Vanessa Nadia Dargenio
- Department of Pediatrics, “Giovanni XXIII” Children Hospital, “Aldo Moro” University of Bari, 70126 Bari, Italy; (F.B.); (P.G.); (V.N.D.); (F.C.); (R.F.)
| | - Fernanda Cristofori
- Department of Pediatrics, “Giovanni XXIII” Children Hospital, “Aldo Moro” University of Bari, 70126 Bari, Italy; (F.B.); (P.G.); (V.N.D.); (F.C.); (R.F.)
| | - Ruggiero Francavilla
- Department of Pediatrics, “Giovanni XXIII” Children Hospital, “Aldo Moro” University of Bari, 70126 Bari, Italy; (F.B.); (P.G.); (V.N.D.); (F.C.); (R.F.)
- Interdisciplinary Department of Medicine-Pediatrics Section, “Aldo Moro” University of Bari, 70121 Bari, Italy
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Multidimensional Disadvantages of a Gluten-Free Diet in Celiac Disease: A Narrative Review. Nutrients 2021; 13:nu13020643. [PMID: 33669442 PMCID: PMC7920475 DOI: 10.3390/nu13020643] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 02/05/2021] [Accepted: 02/09/2021] [Indexed: 12/17/2022] Open
Abstract
A gluten-free diet is the mainstay method of treatment and the prevention of celiac disease complications. However, an inadequately balanced gluten-free diet can increase the risk of obesity, negatively affect glucose and lipid metabolism, and increase the risk of the metabolic syndrome. Therefore, an adequate nutritional counselling is necessary for patients diagnosed with celiac disease in order to prevent and treat the components of the metabolic syndrome.
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Leonard MM, Silvester JA, Leffler D, Fasano A, Kelly CP, Lewis SK, Goldsmith JD, Greenblatt E, Kwok WW, McAuliffe WJ, Galinsky K, Siegelman J, Chow IT, Wagner JA, Sapone A, Smithson G. Evaluating Responses to Gluten Challenge: A Randomized, Double-Blind, 2-Dose Gluten Challenge Trial. Gastroenterology 2021; 160:720-733.e8. [PMID: 33130104 PMCID: PMC7878429 DOI: 10.1053/j.gastro.2020.10.040] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 10/15/2020] [Accepted: 10/25/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND & AIMS Gluten challenge is used to diagnose celiac disease (CeD) and for clinical research. Sustained gluten exposure reliably induces histologic changes but is burdensome. We investigated the relative abilities of multiple biomarkers to assess disease activity induced by 2 gluten doses, and aimed to identify biomarkers to supplement or replace histology. METHODS In this randomized, double-blind, 2-dose gluten-challenge trial conducted in 2 US centers (Boston, MA), 14 adults with biopsy-proven CeD were randomized to 3 g or 10 g gluten/d for 14 days. The study was powered to detect changes in villous height to crypt depth, and stopped at planned interim analysis on reaching this end point. Additional end points included gluten-specific cluster of differentiation (CD)4 T-cell analysis with HLA-DQ2-gluten tetramers and enzyme-linked immune absorbent spot, gut-homing CD8 T cells, interleukin-2, symptoms, video capsule endoscopy, intraepithelial leukocytes, and tissue multiplex immunofluorescence. RESULTS All assessments showed changes with gluten challenge. However, time to maximal change, change magnitude, and gluten dose-response relationship varied. Villous height to crypt depth, video capsule endoscopy enteropathy score, enzyme-linked immune absorbent spot, gut-homing CD8 T cells, intraepithelial leukocyte counts, and HLA-DQ2-restricted gluten-specific CD4 T cells showed significant changes from baseline at 10 g gluten only; symptoms were significant at 3 g. Symptoms and plasma interleukin-2 levels increased significantly or near significantly at both doses. Interleukin-2 appeared to be the earliest, most sensitive marker of acute gluten exposure. CONCLUSIONS Modern biomarkers are sensitive and responsive to gluten exposure, potentially allowing less invasive, lower-dose, shorter-duration gluten ingestion. This work provides a preliminary framework for rational design of gluten challenge for CeD research. ClinicalTrials.gov number, NCT03409796.
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Affiliation(s)
- Maureen M Leonard
- Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, Massachusetts; Celiac Disease Research Program, Harvard Medical School, Boston, Massachusetts
| | - Jocelyn A Silvester
- Celiac Disease Research Program, Harvard Medical School, Boston, Massachusetts; Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, Massachusetts; Celiac Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Daniel Leffler
- Celiac Disease Research Program, Harvard Medical School, Boston, Massachusetts; Takeda Pharmaceuticals Inc Co, Cambridge, Massachusetts
| | - Alessio Fasano
- Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, Massachusetts; Celiac Disease Research Program, Harvard Medical School, Boston, Massachusetts
| | - Ciarán P Kelly
- Celiac Disease Research Program, Harvard Medical School, Boston, Massachusetts; Celiac Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Suzanne K Lewis
- Department of Medicine, Columbia University Medical Center, New York, New York
| | - Jeffrey D Goldsmith
- Celiac Disease Research Program, Harvard Medical School, Boston, Massachusetts; Department of Pathology, Boston Children's Hospital, Boston, Massachusetts
| | | | - William W Kwok
- Benaroya Research Institute at Virginia Mason, Seattle, Washington
| | | | | | | | - I-Ting Chow
- Benaroya Research Institute at Virginia Mason, Seattle, Washington
| | - John A Wagner
- Takeda Pharmaceuticals Inc Co, Cambridge, Massachusetts
| | - Anna Sapone
- Takeda Pharmaceuticals Inc Co, Cambridge, Massachusetts
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Tan IL, Withoff S, Kolkman JJ, Wijmenga C, Weersma RK, Visschedijk MC. Non-classical clinical presentation at diagnosis by male celiac disease patients of older age. Eur J Intern Med 2021; 83:28-33. [PMID: 33218785 DOI: 10.1016/j.ejim.2020.09.020] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 09/21/2020] [Accepted: 09/21/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND . In a biopsy-proven adult celiac disease (CeD) cohort from the Netherlands, male patients were diagnosed with CeD at significantly older ages than female patients. OBJECTIVES To identify which factors contribute to diagnosis later in life and whether diagnostic delay influences improvement of symptoms after starting a gluten-free diet (GFD). METHODS . We performed a questionnaire study in 211 CeD patients (67:144, male:female) with median age at diagnosis of 41.8 years (interquartile range: 25-58) and at least Marsh 2 histology. RESULTS . Classical symptoms (diarrhea, fatigue, abdominal pain and/or weight loss) were more frequent in women than men, but sex was not significantly associated with age at diagnosis. In a multivariate analysis, a non-classical presentation (without any classical symptoms) and a negative family history of CeD were significant predictors of older age at diagnosis (coefficients of 8 and 12 years, respectively). A delay of >3 years between first symptom and diagnosis was associated with slower improvement of symptoms after start of GFD, but not with sex, presentation of classical symptoms or age at diagnosis. CONCLUSION . Non-classical CeD presentation is more prevalent in men and is associated with a diagnosis of CeD later in life. Recognizing CeD sooner after onset of symptoms is important because a long diagnostic delay is associated with a slower improvement of symptoms after starting a GFD.
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Affiliation(s)
- Ineke L Tan
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands; Department of Genetics, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands
| | - Sebo Withoff
- Department of Genetics, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands
| | - Jeroen J Kolkman
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands; Department of Gastroenterology and Hepatology, Medisch Spectrum Twente, 7500 KA Enschede, the Netherlands
| | - Cisca Wijmenga
- Department of Genetics, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands
| | - Rinse K Weersma
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands; Department of Genetics, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands
| | - Marijn C Visschedijk
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands; Department of Genetics, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands.
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Sukkar G, Alshareef AM, Aljahani M, Alharthi HA, Fakieha A. The Prevalence of Growth Variations Among Pediatric Celiac Disease Patients at the Time of Diagnosis. Cureus 2020; 12:e11706. [PMID: 33391939 PMCID: PMC7769797 DOI: 10.7759/cureus.11706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Background and aim Celiac disease is an immune-mediated disorder caused by sensitivity to dietary gluten. Celiac patients typically present with malabsorption and low growth parameters; however, studies have shown that the presentation of celiac disease can have a higher percentage of patients with normal or high growth parameters and no signs of malabsorption. The study aims to estimate the prevalence of the growth variation found in children with biopsy-confirmed celiac disease at the time of diagnosis. Methods We included 31 biopsy-confirmed pediatric celiac patients diagnosed from 2007 to 2018 in King Abdulaziz Medical City, Jeddah, Saudi Arabia. Patients’ height, weight, and BMI at the time of diagnosis were converted to z-scores and growth percentiles according to the Centers for Disease Control and Prevention growth charts. In addition, patients’ comorbid conditions were also recorded. Results At the time of diagnosis, 45.16% of our patients presented as underweight, 41.94% of patients had normal weight, 6.5% were overweight and obese, respectively. The mean BMI was 15.44 (±3.65). Our population had a statistically significant lower BMI, height, and weight mean z-scores at the time of diagnosis. Conclusion A significant number of children diagnosed with celiac disease in our center had low weight, height, and BMI at the time of diagnosis. However, we emphasize that having normal growth parameters does not rule out the diagnosis of celiac disease.
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Chetcuti Zammit S, Bull LA, Sanders DS, Galvin J, Dervilis N, Sidhu R, Worden K. Towards the Probabilistic Analysis of Small Bowel Capsule Endoscopy Features to Predict Severity of Duodenal Histology in Patients with Villous Atrophy. J Med Syst 2020; 44:195. [PMID: 33005996 PMCID: PMC7529615 DOI: 10.1007/s10916-020-01657-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Accepted: 09/16/2020] [Indexed: 12/17/2022]
Abstract
Small bowel capsule endoscopy (SBCE) can be complementary to histological assessment of celiac disease (CD) and serology negative villous atrophy (SNVA). Determining the severity of disease on SBCE using statistical machine learning methods can be useful in the follow up of patients. SBCE can play an additional role in differentiating between CD and SNVA. De-identified SBCEs of patients with CD and SNVA were included. Probabilistic analysis of features on SBCE were used to predict severity of duodenal histology and to distinguish between CD and SNVA. Patients with higher Marsh scores were more likely to have a positive SBCE and a continuous distribution of macroscopic features of disease than those with lower Marsh scores. The same pattern was also true for patients with CD when compared to patients with SNVA. The validation accuracy when predicting the severity of Marsh scores and when distinguishing between CD and SNVA was 69.1% in both cases. When the proportions of each SBCE class group within the dataset were included in the classification model, to distinguish between the two pathologies, the validation accuracy increased to 75.3%. The findings of this work suggest that by using features of CD and SNVA on SBCE, predictions can be made of the type of pathology and the severity of disease.
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Affiliation(s)
- Stefania Chetcuti Zammit
- Academic Unit, Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, UK.
- Gastroenterology Department, Royal Hallamshire Hospital, Glossop Road, Sheffield, S102JF, UK.
| | - Lawrence A Bull
- Dynamics Research Group, Department of Mechanical Engineering, University of Sheffield, Sheffield, UK
| | - David S Sanders
- Academic Unit, Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, UK
| | - Jessica Galvin
- Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Nikolaos Dervilis
- Dynamics Research Group, Department of Mechanical Engineering, University of Sheffield, Sheffield, UK
| | - Reena Sidhu
- Academic Unit, Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, UK
| | - Keith Worden
- Dynamics Research Group, Department of Mechanical Engineering, University of Sheffield, Sheffield, UK
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What is the role of small bowel capsule endoscopy in established coeliac disease? Clin Res Hepatol Gastroenterol 2020; 44:753-761. [PMID: 31928969 DOI: 10.1016/j.clinre.2019.11.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2019] [Revised: 11/22/2019] [Accepted: 11/25/2019] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Patients with established coeliac disease (CD) can present with signs and symptoms requiring small bowel capsule endoscopy (SBCE) to assess for persistent disease beyond the duodenum and to rule out complications. There is paucity of data on extent of disease on SBCE in relation to histology, clinical and serological parameters. The aim of this study was to assess the relationship between symptoms, CD serology and Marsh classification of disease and extent of disease on SBCE in patients with established CD. METHODS Hundred patients with established CD and 200 controls underwent a SBCE. SBCEs were reviewed by expert reviewers. Extent of disease on SBCE, CD findings and small bowel transit were recorded. RESULTS Considering duodenal histology (D2; Marsh 3a or above) as the gold standard for diagnosing CD activity, the sensitivity of SBCE to delineate active disease was 87.2%. The specificity was 89.0%. Age at SBCE (P=0.006), albumin (P=0.004) and haemoglobin (P=0.0001), Marsh score of histology from the duodenal bulb (D1) (P=0.0001) and the second part of the duodenum (P=0.0001), refractory CD (P=0.007) on histology correlated with extent of affected small bowel (SB) mucosa on univariate analysis. On multiple regression analysis, albumin (P=0.036) and Marsh score of histology (D1) (P=0.019), vitamin B12 (P=0.001) and folate levels (P=0.008) were statistically significant. Extent of affected SB mucosa (11.0% vs 1.35%) was greater in patients with complications including those with refractory CD (P=0.008). CONCLUSIONS This is the first study showing correlation between extent of disease and severity of duodenal histology, markers of malabsorption such as folate levels and vitamin B12 and complications of CD.
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Severity of Villous Atrophy at Diagnosis in Childhood Does Not Predict Long-term Outcomes in Celiac Disease. J Pediatr Gastroenterol Nutr 2020; 71:71-77. [PMID: 32097370 DOI: 10.1097/mpg.0000000000002675] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVES Current pediatric guidelines allow noninvasive diagnosis of celiac disease in selected children. We investigated in a large cohort study whether the severity of villous atrophy at diagnosis is associated with clinical characteristics or long-term health outcomes, thus having a prognostic significance. METHODS Comprehensive medical data on 906 children with celiac disease were analyzed. Long-term health outcomes of 503 adult patients diagnosed in childhood were moreover assessed with a specific study questionnaire and validated Gastrointestinal Symptom Rating Scale (GSRS) and Psychological General Well-Being (PGWB) questionnaires. Patients were classified into 3 groups according to the severity of villous atrophy at diagnosis, and all variables were compared. RESULTS Altogether 34% of the patients had partial, 40% subtotal, and 26% total villous atrophy. Children with milder lesions were diagnosed more recently (median year 2007 vs 2006 vs 2001, respectively, P < 0.001), more often by screening (30% vs 25% vs 17%, P < 0.001) and they suffered less often from anemia (16% vs 21% vs 32%, P < 0.001) and growth disturbances (22% vs 36% vs 54%, P < 0.001) and had lower transglutaminase-2 antibody levels (median 64 U/L vs 120 U/L vs 120 U/L, P < 0.001). There was no difference in other disease features.Altogether 212 adults diagnosed in childhood completed the questionnaires. Severity of villous atrophy at childhood diagnosis did not predict presence of complications or comorbidities, persistent symptoms, and self-perceived health, quality of life or adherence to a gluten-free diet in adulthood. CONCLUSION Presence of advanced villous atrophy at diagnosis is associated with more severe clinical characteristics but not with poorer long-term health and treatment outcomes.
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Use of small-bowel capsule endoscopy in cases of equivocal celiac disease. Gastrointest Endosc 2020; 91:1312-1321.e2. [PMID: 31923404 DOI: 10.1016/j.gie.2019.12.044] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Accepted: 12/22/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Seronegative villous atrophy (SNVA), raised intraepithelial lymphocytes (IELs), and crypt hyperplasia on duodenal histology can be secondary to celiac disease (CD) or other causes such as medications or infections. Our aims were to assess the role of small-bowel capsule endoscopy (SBCE) in these patients and to ascertain whether findings on SBCE at diagnosis can predict disease outcome. METHODS Patients (n = 177) with SNVA, IELs, ± crypt hyperplasia on duodenal histology were studied. These patients all had an equivocal diagnosis of CD. RESULTS Overall, 56 patients (31.6%) had a positive SBCE. Thirty-three patients (58.9%) had disease affecting the proximal third of the small bowel (SB). The diagnostic yield of SBCE was 40.0% (22 patients), 51.4% (18 patients), 27.0% (10 patients), and 14.0% (7 patients) in patients with an unknown cause for SNVA (SNVA-UO), patients with SNVA who responded to a gluten-free diet (SNVA-CD), patients with a known cause for SNVA, and patients with railed IELs ± crypt hyperplasia, respectively. In SNVA-UO, SBCE at diagnosis was more likely to be positive in patients with persistent SNVA (10, 90.9%) and persistent SNVA with lymphoproliferative features (4, 80.4%) than patients with spontaneous resolution of SNVA (8, 20.5%) (P = .0001). All patients in the SNVA-CD group who eventually developed adverse events had a positive SBCE (P = .022). They also had more extensive SB disease than those without adverse events (50% vs 1% P = .002). More extensive SB disease on SBCE correlated with a higher SNVA-related mortality in patients with SNVA-UO and SNVA-CD (P = .019). Severity of histology did not correlate with mortality (P = .793). CONCLUSIONS A positive SBCE at diagnosis predicts a worse outcome. More importantly, more extensive disease in these patients is associated with poor survival. Targeting patients with extensive disease at diagnosis with more aggressive therapy can help to improve prognosis.
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Yılmaz S, Tuna Kırsaçlıoğlu C, Şaylı TR. Celiac disease and hematological abnormalities in children with recurrent aphthous stomatitis. Pediatr Int 2020; 62:705-710. [PMID: 31957941 DOI: 10.1111/ped.14155] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Revised: 12/12/2019] [Accepted: 01/15/2020] [Indexed: 12/25/2022]
Abstract
BACKGROUND Recurrent aphthous stomatitis (RAS) is one of the most common diseases of the oral mucosa and may be related to vitamin deficiencies or systemic diseases such as celiac disease (CD). The aim of this study was to investigate the frequency of hematinic deficiency and CD in children with RAS. METHODS The medical records of patients diagnosed with RAS were reviewed for the presence of hematinic deficiencies (hemoglobin, mean corpuscular volume, ferritin, vitamin B12 , folic acid), and CD. The study group included 108 children with RAS and 57 healthy children who were evaluated for hematological abnormalities in routine evaluation. RESULTS The frequency of a family history of RAS was significantly higher in the RAS group compared to the control group (34.2% vs 7%, respectively; P < 0.001). A hematological abnormality was detected in 32.4% of the RAS group and 10.5% of the control group (P = 0.02). The prevalence of iron deficiency anemia was significantly higher in the RAS group (P = 0.037). Three (2.7%) patients with RAS were diagnosed with CD, which is a significantly higher frequency than that observed in healthy children in Turkey (P < 0.01; OR 6.03, 95% CI [2.37, 4.56]). These children had mild malnutrition, iron deficiency, and iron deficiency anemia. CONCLUSIONS Children with RAS should be evaluated for nutritional status and hematological indices, and in the case of hematological abnormalities and malnutrition screening for CD should be considered.
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Affiliation(s)
- Songül Yılmaz
- Department of Pediatrics, Turkish Republic Health Ministry, Ankara Child Health Diseases, Hematology and Oncology Training and Research Hospital, Ankara, Turkey
| | - Ceyda Tuna Kırsaçlıoğlu
- Department of Pediatric Gastroenterology, Turkish Republic Health Ministry, Ankara Child Health Diseases, Hematology and Oncology Training and Research Hospital, Ankara, Turkey
| | - Tülin Revide Şaylı
- Department of Pediatrics, Turkish Republic Health Ministry, Ankara Child Health Diseases, Hematology and Oncology Training and Research Hospital, Ankara, Turkey
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Duodenal bulb biopsy in the diagnostic work-up of coeliac disease. Virchows Arch 2020; 477:507-515. [PMID: 32405928 DOI: 10.1007/s00428-020-02832-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Revised: 04/21/2020] [Accepted: 04/28/2020] [Indexed: 12/20/2022]
Abstract
Coeliac disease (CD) is an autoimmune enteropathy which can present with patchy mucosal lesions. The aim of the present study is to investigate the significance of duodenal bulb biopsy in the diagnostic work-up of CD in both pediatric and adult patients, and to highlight the key points for pathologists. D1 (duodenal bulb) and D2 (distal duodenum) biopsies of 153 newly diagnosed serology-positive CD patients were evaluated for villous/crypt ratio and intraepithelial lymphocyte (IEL) counts on CD3-stained slides and were classified according to Marsh. Mucosal pathology was patchy in 15% (13% only D1 and 2% only D2) of patients, and 85% of patients had diffuse mucosal pathology involving both D1 and D2 biopsies which showed concordant histology in 60% and discordant in 25% of the cases. Though majority of the patients (75%) with only D1 involvement were pediatric cases, no significant difference was found between pediatric and adult patients when all cases were considered (17 vs 14%). Our results clearly indicate that without D1 sampling, diagnosis of CD would have been missed in a significant number of cases (13%), thereby highlighting the importance of taking duodenal biopsies from multiple sites in the diagnostic work-up of CD. We, therefore, conclude that every biopsy piece from both D1 and D2 should be carefully evaluated for the whole spectrum of mucosal changes caused by gluten ingestion and classified using a scheme based on Marsh to allow recognition of mild lesions.
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Abstract
PURPOSE OF REVIEW The aim of this review is to provide insight into the diagnosis and management of patients with refractory coeliac disease (RCD) and highlight recent advances in this field. RECENT FINDINGS The diagnosis of RCD can be more accurately confirmed with flow cytometry in addition to immunohistochemistry. Dietary input and excretion of gluten immunogenic peptides can help rule out gluten contamination, and therefore, substantiate a diagnosis of RCD type I. Small bowel capsule endoscopy (SBCE) is important at diagnosis and follow-up in addition to duodenal histology. Apart from ruling out complications, it can give information on extent of disease in the small bowel, and therefore, help assess response to therapy. Those patients with a poor response can have earlier intensification of therapy, which may result in an improved outcome. RCD also occurs in patients with serology negative coeliac disease but with an increased mortality compared with patients with serology-positive coeliac disease. SUMMARY Patients with RCD can present with persistent symptoms of malnutrition but can also be completely asymptomatic. Serology is not a reliable marker to detect refractory disease. Immunostaining and flow cytometry are necessary for a diagnosis of RCD. Small bowel endoscopy enables disease extent to be assessed and allows for small bowel biopsies to be taken in case of suspicious lesions. Small bowel radiology can be complementary to small bowel endoscopy.
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Kreutz JM, Adriaanse MPM, van der Ploeg EMC, Vreugdenhil ACE. Narrative Review: Nutrient Deficiencies in Adults and Children with Treated and Untreated Celiac Disease. Nutrients 2020; 12:nu12020500. [PMID: 32075276 PMCID: PMC7071237 DOI: 10.3390/nu12020500] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Revised: 02/05/2020] [Accepted: 02/13/2020] [Indexed: 12/16/2022] Open
Abstract
Nutrient deficiencies are well recognized as secondary consequences of celiac disease (CD) and closely related to the clinical presentation of affected patients. Despite their clinical significance, consensus is lacking on the pattern and frequency of nutrient deficiencies in CD, the usefulness of their assessment at the time of diagnosis and during follow-up. This review aims to provide an overview of nutrient deficiencies among pediatric and adult CD patients at diagnosis and on a gluten-free diet (GFD), and their potential causes in CD. Secondly, we review their impact on CD management strategies including the potential of nutrient supplementation. A search of Medline, Pubmed and Embase until January 2019 was performed. Despite a high variability between the reported deficiencies, we noted that nutrient deficiencies occur frequently in children and adults with CD at diagnosis and during treatment with a GFD. Both inadequate dietary intake and/or diminished uptake due to intestinal dysfunction contribute to nutrient deficiencies. Most deficiencies can be restored with (long-term) treatment with a GFD and/or supplementation. However, some of them persist while others may become even more prominent during GFD. Our results indicate a lack of comprehensive evidence on the clinical efficacy of nutrient supplementation in CD management highlighting the need for further studies.
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Affiliation(s)
- Johanna M. Kreutz
- Department of Paediatrics and NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands; (J.M.K.); (M.P.M.A.)
| | - Marlou P. M. Adriaanse
- Department of Paediatrics and NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands; (J.M.K.); (M.P.M.A.)
| | | | - Anita C. E. Vreugdenhil
- Department of Paediatrics and NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands; (J.M.K.); (M.P.M.A.)
- Correspondence: ; Tel.: +31-433875284
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Chetcuti Zammit S, Sanders DS, Sidhu R. Coeliac disease: older patients have the most extensive small bowel involvement on capsule endoscopy. Eur J Gastroenterol Hepatol 2019; 31:1496-1501. [PMID: 31464789 DOI: 10.1097/meg.0000000000001503] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVE The relation between symptomatology, serology and findings on small bowel capsule endoscopy (SBCE) in patients with coeliac disease (CD) remains unclear. Clarifying such associations will help to determine whether symptoms and serology can predict severity and extent of disease on SBCE. METHODS Patients with newly diagnosed CD were recruited. Information on SBCE was recorded. Signs and symptoms at presentation, serological markers and histological classification of the disease in the duodenum were noted. RESULTS Sixty patients with newly diagnosed CD (mean age: 44.9 years, SD: ±17.4, 17-76) were included in this study. Older patients (P = 0.025) and patients presenting with iron deficiency anaemia had more extensive small bowel (SB) involvement (25.7% vs. 13.5%; P = 0.026). Those with weight loss were more likely to have SB involvement beyond the duodenum (37.5% vs. 5.8%; P = 0.027). Patients presenting with iron deficiency anaemia (53.5 vs. 42.4 years; P = 0.038) and weight loss (60.5 vs. 42.4 years; P = 0.009) were significantly older at diagnosis. Serum albumin was lower in those patients diagnosed later on in life (Pearson correlation -0.0361; P = 0.007). There was no significant association between anti-tissue transglutaminase antibody (P = 0.396) and extent of affected SB mucosa. Patients with more severe Marsh scores on histology from the duodenal bulb had more extensive SB involvement (P = 0.017). CONCLUSIONS This is the largest study on the use of SBCE in newly diagnosed CD. Older patients are likely to have more extensive disease on SBCE at diagnosis. Symptoms and serology had no impact on the findings on SBCE apart from weight loss and iron deficiency anaemia.
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Abstract
Celiac disease is a gluten-triggered immune-mediated disorder, characterized by inflammation of the enteric mucosa following lymphocytic infiltration and eventually resulting in villous blunting. There have been many developments in refining diagnostic laboratory tests for celiac disease in the last decade. Biopsy-sparing diagnostic guidelines have been proposed and validated in a few recent prospective studies. However, despite these developments, histologic evaluation of duodenal mucosa remains one of the most essential diagnostic tools as it helps in the diagnosis of celiac disease in individuals who do not fulfill the biopsy-sparing diagnostic criteria and in those not responding to a gluten-free diet. Histologic evaluation also allows for the assessment of mucosal recovery after treatment and in the identification of concurrent intestinal diseases. Therefore, pathologists should be familiar with the histologic spectrum of celiac disease and need to be aware of other disorders with similar symptoms and histopathology that may mimic celiac disease. This review aims to provide pathologists with updates on celiac laboratory testing, biopsy-sparing diagnostic criteria, histopathology, complications, and differential diagnoses of celiac disease.
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Abstract
Celiac disease predominantly involves the proximal small bowel, but villus atrophy can be patchy, spare the duodenum, and be present more distally. Video capsule endoscopy is more sensitive than standard endoscopy to detect villus atrophy, and can define extent of disease, though it cannot obtain biopsies. Duodenal biopsy is the gold standard for diagnosis. Video capsule endoscopy assists in special circumstances when biopsy is not possible, and in equivocal diagnosis. Video capsule endoscopy and enteroscopy are recommended for evaluating complicated celiac disease, especially refractory celiac disease type II. Future developments include computer-assisted capsule programs and advanced capsule and enteroscope design.
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Affiliation(s)
- Suzanne K Lewis
- Division of Digestive Diseases, Celiac Disease Center at Columbia University, Columbia University, 180 Fort Washington Avenue, New York, NY 10032, USA.
| | - Carol E Semrad
- The University of Chicago, 5841 South Maryland Avenue, MC 4080 S401, Chicago, IL 60637, USA
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Letter: Celiac Disease Presenting After a Single Anastomosis Duodeno-Ileal Bypass and Sleeve Gastrectomy. Obes Surg 2019; 29:1018-1021. [PMID: 30637519 DOI: 10.1007/s11695-018-03678-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Clinical guidelines on the diagnosis and treatment of celiac disease in Mexico. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2018. [DOI: 10.1016/j.rgmxen.2018.09.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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47
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Remes-Troche JM, Uscanga-Domínguez LF, Aceves-Tavares RG, Calderón de la Barca AM, Carmona-Sánchez RI, Cerda-Contreras E, Coss-Adame E, Icaza-Chávez ME, Lopéz-Colombo A, Milke-García MP, Morales-Arámbula M, Peláez-Luna M, Ramos Martínez P, Sánchez-Sosa S, Treviño-Mejía MC, Vázquez-Frías R, Worona-Dibner LB, Zamora-Nava LE, Rubio-Tapia A. Clinical guidelines on the diagnosis and treatment of celiac disease in Mexico. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2018; 83:434-450. [PMID: 30197183 DOI: 10.1016/j.rgmx.2018.05.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Revised: 05/12/2018] [Accepted: 05/24/2018] [Indexed: 12/17/2022]
Abstract
Celiac disease, celiac sprue, or gluten-sensitive enteropathy, is a generalized autoimmune disease characterized by chronic inflammation and atrophy of the small bowel mucosa. It is caused by dietary exposure to gluten and affects genetically predisposed individuals. In Mexico, at least 800,000 are estimated to possibly have the disease, prompting the Asociación Mexicana de Gastroenterología to summon a multidisciplinary group of experts to develop the "Clinical guidelines on the diagnosis and treatment of celiac disease in Mexico" and establish recommendations for the medical community, its patients, and the general population. The participating medical professionals were divided into three working groups and were given the selected bibliographic material by the coordinators (ART, LUD, JMRT), who proposed the statements that were discussed and voted upon in three sessions: two voting rounds were carried out electronically and one at a face-to-face meeting. Thirty-nine statements were accepted, and once approved, were developed and revised by the coordinators, and their final version was approved by all the participants. It was emphasized in the document that epidemiology and risk factors associated with celiac disease (first-degree relatives, autoimmune diseases, high-risk populations) in Mexico are similar to those described in other parts of the world. Standards for diagnosing the disease and its appropriate treatment in the Mexican patient were established. The guidelines also highlighted the fact that a strict gluten-free diet is essential only in persons with confirmed celiac disease, and that the role of gluten is still a subject of debate in relation to nonceliac, gluten-sensitive patients.
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Affiliation(s)
- J M Remes-Troche
- Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Médico Biológicas, Universidad Veracruzana, Veracruz, México.
| | - L F Uscanga-Domínguez
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - R G Aceves-Tavares
- Servicio de Gastroenterología, Hospital General del Estado Dr. Ernesto Ramos, Bours, Hermosillo, Sonora, México
| | | | | | - E Cerda-Contreras
- ITESM. Medicina Interna y Gastroenterología Fundación Clínica Médica Sur, Ciudad de México, México
| | - E Coss-Adame
- Departamento de Gastroenterología y Laboratorio de Motilidad Gastrointestinal, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán , Ciudad de México, México
| | - M E Icaza-Chávez
- Hospital Star Médica de Mérida, Gastroenterología de la UNIMAYAB, , Mérida, Yucatán, México
| | - A Lopéz-Colombo
- Dirección de Educación e Investigación en Salud, UMAE Hospital de Especialidades del Centro Médico Nacional Manuel Ávila Camacho, Instituto Mexicano del Seguro Social, Puebla, México
| | - M P Milke-García
- Dirección de Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán , Ciudad de México, México
| | - M Morales-Arámbula
- Servicio de Gastroenterología y Endoscopía Gastrointestinal, Hospital Country 2000, Guadalajara, Jalisco, México
| | - M Peláez-Luna
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | | | - S Sánchez-Sosa
- Jefe de Patología, Hospital Ángeles de Puebla, Universidad de Las Américas Puebla (UDLAP), Puebla, México
| | - M C Treviño-Mejía
- Universidad Iberoamericana, Universidad Xochicalco, Tijuana, Baja California, México
| | - R Vázquez-Frías
- Universidad Iberoamericana, Universidad Xochicalco, Tijuana, Baja California, México
| | - L B Worona-Dibner
- Departamento de Gastroenterología y Nutrición, Hospital Infantil de México Federico Gómez, Ciudad de México, México
| | - L E Zamora-Nava
- Departamento de Endoscopia Gastrointestinal, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - A Rubio-Tapia
- División de Gastroenterología y Hepatología, Mayo Clinic, Rochester, Minnesota, Estados Unidos de América
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Ludvigsson JF, Ciacci C, Green PH, Kaukinen K, Korponay-Szabo IR, Kurppa K, Murray JA, Lundin KEA, Maki MJ, Popp A, Reilly NR, Rodriguez-Herrera A, Sanders DS, Schuppan D, Sleet S, Taavela J, Voorhees K, Walker MM, Leffler DA. Outcome measures in coeliac disease trials: the Tampere recommendations. Gut 2018; 67:1410-1424. [PMID: 29440464 PMCID: PMC6204961 DOI: 10.1136/gutjnl-2017-314853] [Citation(s) in RCA: 81] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Revised: 12/19/2017] [Accepted: 01/08/2018] [Indexed: 12/12/2022]
Abstract
OBJECTIVE A gluten-free diet is the only treatment option of coeliac disease, but recently an increasing number of trials have begun to explore alternative treatment strategies. We aimed to review the literature on coeliac disease therapeutic trials and issue recommendations for outcome measures. DESIGN Based on a literature review of 10 062 references, we (17 researchers and 2 patient representatives from 10 countries) reviewed the use and suitability of both clinical and non-clinical outcome measures. We then made expert-based recommendations for use of these outcomes in coeliac disease trials and identified areas where research is needed. RESULTS We comment on the use of histology, serology, clinical outcome assessment (including patient-reported outcomes), quality of life and immunological tools including gluten immunogenic peptides for trials in coeliac disease. CONCLUSION Careful evaluation and reporting of outcome measures will increase transparency and comparability of coeliac disease therapeutic trials, and will benefit patients, healthcare and the pharmaceutical industry.
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Affiliation(s)
- Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Department of Pediatrics, Örebro University Hospital, Örebro, Sweden
| | - Carolina Ciacci
- Coeliac Center at Department of Medicine and Surgery, Scuola Medica Salernitana, University of Salerno, Salerno, Italy
| | - Peter Hr Green
- Celiac Disease Center at Columbia University, New York, USA
| | - Katri Kaukinen
- Celiac Disease Research Center, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
- Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
| | - Ilma R Korponay-Szabo
- Coeliac Disease Centre, Heim Pál Children's Hospital, Budapest, Hungary
- Department of Paediatrics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Kalle Kurppa
- Celiac Disease Research Center, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
- Department of Paediatrics, Tampere University Hospital, Tampere, Finland
| | | | - Knut Erik Aslaksen Lundin
- Institute of Clinical Medicine and K.G. Jebsen Coeliac Disease Research Centre, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Oslo University Hospital, Oslo, Norway
| | - Markku J Maki
- Science Center, Tampere University Hospital, Tampere, Finland
- Tampere Centre for Child Health Research, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
| | - Alina Popp
- Institute for Mother and Child Health Bucharest, University of Medicine and Pharmacy 'Carol Davila', Bucharest, Romania
- Tampere Centre for Child Health Research, University of Tampere, Tampere University Hospital, Tampere, Finland
| | - Norelle R Reilly
- Division of Pediatric Gastroenterology, Columbia University Medical Center, New York, USA
- Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, USA
| | | | - David S Sanders
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, University of Sheffield, Sheffield, UK
| | - Detlef Schuppan
- Celiac Center, University Medical Center, Johannes-Gutenberg University, Mainz, Germany
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | | | - Juha Taavela
- Tampere Centre for Child Health Research, University of Tampere, Tampere University Hospital, Tampere, Finland
| | | | - Marjorie M Walker
- Faculty of Health and Medicine, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia
| | - Daniel A Leffler
- Celiac Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
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Perez-Cuadrado-Robles E, Lujan-Sanchis M, Elli L, Juanmartinena-Fernandez JF, Garcıa-Lledo J, Ruano-Dıaz L, Egea-Valenzuela J, Jimenez-Garcıa VA, Arguelles-Arias F, Juan-Acosta MS, Carretero-Ribon C, Alonso-Lazaro N, Rosa B, Sanchez-Ceballos F, Lopez-Higueras A, Fernandez-Urien-Sainz I, Branchi F, Valle-Muñoz J, Borque-Barrera P, Gonzalez-Vazquez S, Pons-Beltran V, Xavier S, Gonzalez-Suarez B, Herrerıas-Gutierrez JM, Perez-Cuadrado-Martınez E, Sempere-Garcıa-Arguelles J. Role of capsule endoscopy in alarm features and non-responsive celiac disease: A European multicenter study. Dig Endosc 2018; 30:461-466. [PMID: 29253321 DOI: 10.1111/den.13002] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2017] [Accepted: 12/12/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIM The role of capsule endoscopy (CE) in established celiac disease (CD) remains unclear. Our objective was to analyze the usefulness of CE in the suspicion of complicated CD. METHODS This was a retrospective multicenter study. One hundred and eighty-nine celiac patients (mean age: 46.6 ± 16.6, 30.2% males) who underwent CE for alarm symptoms (n = 86, 45.5%) or non-responsive CD (n = 103, 54.5%) were included. Diagnostic yield (DY), therapeutic impact and safety were analyzed. RESULTS Capsule endoscopy was completed in 95.2% of patients (small bowel transit time: 270.5 ± 100.2 min). Global DY was 67.2%, detecting atrophic mucosa (n = 92, 48.7%), ulcerative jejunoileitis (n = 21, 11.1%), intestinal lymphoma (n = 7, 3.7%) and other enteropathies (n = 7, 3.7%, six Crohn's disease cases and one neuroendocrine tumor). The DY of CE was significantly higher in patients presenting with non-responsive disease compared to patients with alarm symptoms (73.8% vs 59.3%, P = 0.035). The new findings of the CE modified management in 59.3% of the cases. There were no major complications. CONCLUSION Capsule endoscopy may be a moderately helpful and safe diagnostic tool in the suspicion of complicated CD, modifying the clinical course of these patients.
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Affiliation(s)
| | | | - Luca Elli
- Center for Prevention and Diagnosis of Celiac Disease, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Milan, Italy
| | | | - Javier Garcıa-Lledo
- Digestive Diseases Unit, General University Hospital Gregorio Marañon, Madrid, Spain
| | | | - Juan Egea-Valenzuela
- Department of Gastroenterology, University Hospital Virgen de la Arrixaca, Murcia, Spain
| | | | | | | | | | - Noelia Alonso-Lazaro
- Endoscopy Digestive Unit, Digestive Diseases Unit, University Hospital La Fe, Valencia, Spain
| | - Bruno Rosa
- Digestive Diseases Unit, Senhora da Oliveira Hospital, Guimaraes, Portugal
| | | | | | | | - Federica Branchi
- Center for Prevention and Diagnosis of Celiac Disease, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Milan, Italy
| | | | - Pilar Borque-Barrera
- Digestive Diseases Unit, University Hospital Nuestra Señora de Candelaria, Tenerife, Spain
| | | | - Vicente Pons-Beltran
- Endoscopy Digestive Unit, Digestive Diseases Unit, University Hospital La Fe, Valencia, Spain
| | - Sofıa Xavier
- Digestive Diseases Unit, Senhora da Oliveira Hospital, Guimaraes, Portugal
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50
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Abstract
Coeliac disease occurs in about 1% of people in most populations. Diagnosis rates are increasing, and this seems to be due to a true rise in incidence rather than increased awareness and detection. Coeliac disease develops in genetically susceptible individuals who, in response to unknown environmental factors, develop an immune response that is subsequently triggered by the ingestion of gluten. The disease has many clinical manifestations, ranging from severe malabsorption to minimally symptomatic or non-symptomatic presentations. Diagnosis requires the presence of duodenal villous atrophy, and most patients have circulating antibodies against tissue transglutaminase; in children, European guidelines allow a diagnosis without a duodenal biopsy provided that strict symptomatic and serological criteria are met. Although a gluten-free diet is an effective treatment in most individuals, a substantial minority develop persistent or recurrent symptoms. Difficulties adhering to a gluten-free diet have led to the development of non-dietary therapies, several of which are undergoing trials in human beings.
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Affiliation(s)
- Benjamin Lebwohl
- Celiac Disease Center, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University Medical Center, New York, NY, USA
| | - David S Sanders
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital & University of Sheffield, UK
| | - Peter H R Green
- Celiac Disease Center, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA.
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