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Volta U, Rostami K, Auricchio R, Lundin KEA. Diagnosis of Seronegative and Ultrashort Celiac Disease. Gastroenterology 2024; 167:104-115. [PMID: 38286391 DOI: 10.1053/j.gastro.2024.01.029] [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: 11/24/2023] [Revised: 12/19/2023] [Accepted: 01/04/2024] [Indexed: 01/31/2024]
Abstract
In its conventional form, celiac disease (CeD) is characterized by both positive serology and flat villi in the duodenum, and is well known by gastroenterologists and general practitioners. The aim of this review was to shed light on 2 neglected and not yet well-defined celiac phenotypes, that is, seronegative and ultrashort CeD. Seronegative CeD can be suspected in the presence of flat villi, positive HLA-DQ2 and/or HLA-DQ8, and the absence of CeD antibodies. After ruling out other seronegative enteropathies, the diagnosis can be confirmed by both clinical and histologic improvements after 1 year of a gluten-free diet. Ultrashort CeD is characterized by the finding of flat villi in the duodenal bulb in the absence of mucosal damage in the distal duodenum and with serologic positivity. Data on the prevalence, clinical manifestations, histologic lesions, genetic features, and outcome of seronegative and ultrashort CeD are inconclusive due to the few studies available and the small number of patients diagnosed. Some additional diagnostic tools have been developed recently, such as assessing intestinal transglutaminase 2 deposits, flow cytometry technique, microRNA detection, or proteomic analysis, and they seem to be useful in the identification of complex cases. Further cooperative studies are highly desirable to improve the knowledge of these 2 still-obscure variants of CeD.
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Affiliation(s)
- Umberto Volta
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
| | - Kamran Rostami
- Department of Gastroenterology MidCentral District Health Board, Palmerston, North New Zealand
| | - Renata Auricchio
- Department of Translational Medical Science, University Federico II, Naples, Italy
| | - Knut E A Lundin
- Department of Gastroenterology, Oslo University Hospital Rikshospitalet, Oslo, Norway; Norwegian Coeliac Disease Research Centre, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
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Bari Z, Hadipour M, Fakheri H, Kazemi A, Maleki I, Taghvaei T, Hosseini V, Valizadeh SM, Masoumi D, Shahbazkhani B, Shokri Shirvani J, Tirgar Fakheri S, Ebrahimi R. Epidemiological, Endoscopic, Clinical, and Pathological Features of Patients with Celiac Diseases in Southern Littoral of Caspian Sea. Middle East J Dig Dis 2023; 15:257-262. [PMID: 38523893 PMCID: PMC10955989 DOI: 10.34172/mejdd.2023.355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Accepted: 07/29/2023] [Indexed: 03/26/2024] Open
Abstract
Background: Celiac disease is an autoimmune disorder resulting from gluten consumption in genetically predisposed individuals. The present study investigated the epidemiological, endoscopic, and clinicopathological features of patients with celiac disease in the southern littoral of the Caspian Sea. Methods: 140 patients with celiac disease were interviewed and examined regarding demographic characteristics, clinical symptoms, and serologic, endoscopic, and pathological findings. Results: 44 (31.4%) of the patients were male and 68.6% were female. The mean age of the patients at diagnosis was 27.13±13.4 years (ranging from 2 to 60 years). The most common gastrointestinal (GI) symptoms were bloating (47.8%), abdominal pain (47.1%) and diarrhea (30.7%), respectively. Also, 17 (12.1%) patients did not complain of any GI symptoms.18 (12.8%) patients had aphthous stomatitis, 10.7% had dermatitis herpetiformis, 3.6% suffered from itching without a rash, two (1.4%) mentioned psoriasis and one (0.7%) had lichen planus. 19 (19.7%) of the female patients complained of menstrual bleeding disorders, 4% mentioned infertility, and 2% experienced primary amenorrhea. The most common comorbid condition was hypothyroidism in 16 (11.4%) patients. The most common endoscopic finding was duodenal scalloping (37.25%). In addition, 7.8% of the patients had a normal endoscopic appearance. 43 (30.7%) patients were classified as Marsh IIIC, 25.7% Marsh IIIB, 17.8% Marsh IIIA, 12.8% Marsh II and 12.8% were classified as Marsh I. Conclusion: Since celiac disease can present with non-GI manifestations and the majority of our patients had Marsh III classification, it seems that celiac disease must be considered as a routine screening test in GI clinics, and also, it should be kept in mind as a differential diagnosis in other specialty fields.
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Affiliation(s)
- Zohreh Bari
- Department of Internal Medicine, Gut and Liver Research Center, Non-communicable Disease Research Institute, Mazandaran University of Medical Sciences, Sari, Iran
| | | | - Hafez Fakheri
- Department of Internal Medicine, Gut and Liver Research Center, Non-communicable Disease Research Institute, Mazandaran University of Medical Sciences, Sari, Iran
| | - Arash Kazemi
- Department of Internal Medicine, Gut and Liver Research Center, Non-communicable Disease Research Institute, Mazandaran University of Medical Sciences, Sari, Iran
| | - Iradj Maleki
- Department of Internal Medicine, Gut and Liver Research Center, Non-communicable Disease Research Institute, Mazandaran University of Medical Sciences, Sari, Iran
| | - Tarang Taghvaei
- Department of Internal Medicine, Gut and Liver Research Center, Non-communicable Disease Research Institute, Mazandaran University of Medical Sciences, Sari, Iran
| | - Vahid Hosseini
- Department of Internal Medicine, Gut and Liver Research Center, Non-communicable Disease Research Institute, Mazandaran University of Medical Sciences, Sari, Iran
| | - Seyed Mohammad Valizadeh
- Department of Internal Medicine, Gut and Liver Research Center, Non-communicable Disease Research Institute, Mazandaran University of Medical Sciences, Sari, Iran
| | - Danial Masoumi
- Student of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Bijan Shahbazkhani
- Department of Gastroenterology, Imam Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Javad Shokri Shirvani
- Department of Internal Medicine, Rouhani Hospital, Babol University of Medical Sciences, Babol, Iran
| | - Sepehr Tirgar Fakheri
- Gut and Liver Research Center, Non-communicable Disease Research Institute, Mazandaran University of Medical Sciences, Sari, Iran
| | - Reyhaneh Ebrahimi
- Gut and Liver Research Center, Non-communicable Disease Research Institute, Mazandaran University of Medical Sciences, Sari, Iran
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Costantino A, Aversano GM, Lasagni G, Smania V, Doneda L, Vecchi M, Roncoroni L, Pastorello EA, Elli L. Diagnostic management of patients reporting symptoms after wheat ingestion. Front Nutr 2022; 9:1007007. [PMID: 36276818 PMCID: PMC9582535 DOI: 10.3389/fnut.2022.1007007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Accepted: 09/12/2022] [Indexed: 12/11/2022] Open
Abstract
Many patients report symptoms after wheat ingestion experiencing a wide spectrum of clinical manifestations. Three possible diagnoses have been recognized: celiac disease (CD), wheat allergy (WA), and non-celiac (gluten) wheat sensitivity (NCGS/NCWS). CD is a chronic immune-mediated disease of the small bowel caused by exposure to dietary gluten in genetically predisposed individuals, with a prevalence of approximately 1%. It is characterized by mucosal inflammation and atrophy following exposure to gluten and improvement after gluten withdrawal. Food allergies are immunological responses to a food antigen. WA is the expression of an immunologically mediated process that can be immunoglobulin E (IgE) or non-IgE mediated; its many symptoms include urticaria/angioedema, asthma, rhinitis, and anaphylaxis. NCGS/NCWS is characterized by gastrointestinal and/or extra-intestinal symptoms after ingestion of gluten-containing food in subjects not affected by CD or WA. The aim of this review is to help physicians and nutritionists diagnose the cause of symptoms reported after wheat ingestion, thus avoiding patient frustration, inappropriate testing, and incorrect or missed diagnoses. An algorithm for the diagnostic approach in these patients is provided, to help to diagnose CD, WA, NCGS/NCWS or to identify possible functional disorders as the wheat-sensitive irritable bowel syndrome. A personalized approach, regular follow-up, and the help of a skilled healthcare professional are mandatory for patients with symptoms following wheat ingestion is provided. A gluten-free-diet is often recommended for patients with self-reported gluten/wheat-dependent symptoms; for patients with symptoms similar to those of functional diseases while there is evidence that a low-FODMAP diet could be the first option.
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Affiliation(s)
- Andrea Costantino
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy,Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Gloria Maria Aversano
- Department of Internal Medicine, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Giovanni Lasagni
- Department of Allergology and Immunology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Veronica Smania
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Luisa Doneda
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
| | - Maurizio Vecchi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy,Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Leda Roncoroni
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
| | | | - Luca Elli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy,*Correspondence: Luca Elli,
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Lenti MV, Rossi CM, Melazzini F, Gastaldi M, Bugatti S, Rotondi M, Bianchi PI, Gentile A, Chiovato L, Montecucco C, Corazza GR, Di Sabatino A. Seronegative autoimmune diseases: A challenging diagnosis. Autoimmun Rev 2022; 21:103143. [PMID: 35840037 DOI: 10.1016/j.autrev.2022.103143] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 07/10/2022] [Indexed: 12/19/2022]
Abstract
Autoimmune diseases (AID) are increasingly prevalent conditions which comprise more than 100 distinct clinical entities that are responsible for a great disease burden worldwide. The early recognition of these diseases is key for preventing their complications and for tailoring proper management. In most cases, autoantibodies, regardless of their potential pathogenetic role, can be detected in the serum of patients with AID, helping clinicians in making a definitive diagnosis and allowing screening strategies for early -and sometimes pre-clinical- diagnosis. Despite their undoubted crucial role, in a minority of cases, patients with AID may not show any autoantibody, a condition that is referred to as seronegative AID. Suboptimal accuracy of the available laboratory tests, antibody absorption, immunosuppressive therapy, immunodeficiencies, antigen exhaustion, and immunosenescence are the main possible determinants of seronegative AID. Indeed, in seronegative AID, the diagnosis is more challenging and must rely on clinical features and on other available tests, often including histopathological evaluation and radiological diagnostic tests. In this review, we critically dissect, in a narrative fashion, the possible causes of seronegativity, as well as the diagnostic and management implications, in several AID including autoimmune gastritis, celiac disease, autoimmune liver disease, rheumatoid arthritis, autoimmune encephalitis, myasthenia gravis, Sjögren's syndrome, antiphospholipid syndrome, and autoimmune thyroid diseases.
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Affiliation(s)
- Marco Vincenzo Lenti
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy; Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, Pavia, Italy
| | - Carlo Maria Rossi
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy; Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, Pavia, Italy
| | - Federica Melazzini
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy; Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, Pavia, Italy
| | - Matteo Gastaldi
- Neuroimmunology Laboratory, IRCCS Mondino Foundation, Pavia, Italy
| | - Serena Bugatti
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy; Unit of Rheumatology, IRCCS San Matteo Hospital Foundation, Pavia, Italy
| | - Mario Rotondi
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy; Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Pavia, Italy
| | - Paola Ilaria Bianchi
- Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, Pavia, Italy
| | - Antonella Gentile
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy; Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, Pavia, Italy
| | - Luca Chiovato
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy; Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Pavia, Italy
| | - Carlomaurizio Montecucco
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy; Unit of Rheumatology, IRCCS San Matteo Hospital Foundation, Pavia, Italy
| | - Gino Roberto Corazza
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy; Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, Pavia, Italy
| | - Antonio Di Sabatino
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy; Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, Pavia, Italy.
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Felber J, Bläker H, Fischbach W, Koletzko S, Laaß M, Lachmann N, Lorenz P, Lynen P, Reese I, Scherf K, Schuppan D, Schumann M, Aust D, Baas S, Beisel S, de Laffolie J, Duba E, Holtmeier W, Lange L, Loddenkemper C, Moog G, Rath T, Roeb E, Rubin D, Stein J, Török H, Zopf Y. Aktualisierte S2k-Leitlinie Zöliakie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:790-856. [PMID: 35545109 DOI: 10.1055/a-1741-5946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Jörg Felber
- Medizinische Klinik II - Gastroenterologie, Hepatologie, Endokrinologie, Hämatologie und Onkologie, RoMed Klinikum Rosenheim, Rosenheim, Deutschland
| | - Hendrik Bläker
- Institut für Pathologie, Universitätsklinikum Leipzig AöR, Leipzig, Deutschland
| | | | - Sibylle Koletzko
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU-Klinikum München, München, Deutschland.,Department of Pediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum University of Warmia and Mazury, 10-719 Olsztyn, Polen
| | - Martin Laaß
- Klinik und Poliklinik für Kinder- und Jugendmedizin, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Deutschland
| | - Nils Lachmann
- Institut für Transfusionsmedizin, Charité - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Pia Lorenz
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin, Deutschland
| | - Petra Lynen
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin, Deutschland
| | - Imke Reese
- Ernährungsberatung und -therapie Allergologie, München, Deutschland
| | - Katharina Scherf
- Institute of Applied Biosciences Department of Bioactive and Functional Food Chemistry, Karlsruhe Institute of Technology (KIT), Karlsruhe, Deutschland
| | - Detlef Schuppan
- Institut für Translationale Immunologie, Johannes Gutenberg-Universität Mainz, Mainz, Deutschland.,Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Michael Schumann
- Medizinische Klinik I für Gastroenterologie, Infektiologie und Rheumatologie, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Deutschland
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Danciu M, Negură I. Diagnosis of gluten-related disorders. GLUTEN-RELATED DISORDERS 2022:129-147. [DOI: 10.1016/b978-0-12-821846-4.00013-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Dhingra K, Maharshi S, Sapra B, Ratra S, Sharma SS, Nijhawan S. Seronegative Celiac Disease; Frequently Encountered Yet Undiagnosed Clinical Entity. Middle East J Dig Dis 2021; 13:35-42. [PMID: 34712436 PMCID: PMC8531937 DOI: 10.34172/mejdd.2021.201] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Accepted: 10/28/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND There are limited studies on the seronegative celiac disease from the Indian subcontinent. The aim of this study was to assess the prevalence, pathological, genetic, and clinical profile of patients with seronegative celiac disease. METHODS This prospective observational study was conducted in the Department of Gastroenterology, SMS Hospital, Jaipur, between October 2017 to March 2019. Consecutive patients with seronegative celiac disease with age ≥ 3 years were enrolled for the assessment of demography, clinical features, histological findings, celiac serology, genetic analysis, and response to gluten-free diet. RESULTS Out of total of 312 patients with celiac disease, 13 (4.16 %) patients (median age 25 years [range 5-46 years], 10 female) were diagnosed as having seronegative celiac disease. Presenting symptoms were chronic diarrhea in nine (69.23%), abdominal pain in six (46.15%), weight loss in five (38.46%), and short stature in two (15.38 %) patients. On histological analysis, Marsh stage 2 was seen in five (38.46%), Marsh 3c in two (15.38%), Marsh 3a in three (23.07%), and Marsh 3b in three (23.07%) patients. On HLA analysis, HLA-DQ2.5 was seen in six (46.15%) patients, HLA-DQ2.2 in five (38.46%), and HLA-DQ8 in two (15.38%) patients. CONCLUSION The prevalence of seronegative celiac disease in our study was 4.16%. The most common symptoms were chronic diarrhea and abdominal pain, and the histological grade was Marsh stage 2.
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Affiliation(s)
- Kapil Dhingra
- Senior Resident, Department of Gastroenterology, SMS Medical College and Hospitals, Jaipur, India
| | - Sudhir Maharshi
- Associate Professor, Department of Gastroenterology, SMS Medical College and Hospitals, Jaipur, India
| | - Bharat Sapra
- Senior Professor, Department of Gastroenterology, SMS Medical College and Hospitals, Jaipur, India
| | - Sandeep Ratra
- Senior Resident, Department of Gastroenterology, SMS Medical College and Hospitals, Jaipur, India
| | - Shyam Sunder Sharma
- Senior Professor, Department of Gastroenterology, SMS Medical College and Hospitals, Jaipur, India
| | - Sandeep Nijhawan
- Senior Professor, Department of Gastroenterology, SMS Medical College and Hospitals, Jaipur, India
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Sahin Y. Celiac disease in children: A review of the literature. World J Clin Pediatr 2021; 10:53-71. [PMID: 34316439 PMCID: PMC8290992 DOI: 10.5409/wjcp.v10.i4.53] [Citation(s) in RCA: 77] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 03/23/2021] [Accepted: 05/22/2021] [Indexed: 02/06/2023] Open
Abstract
Celiac disease is an immune-mediated systemic disease triggered by intake of gluten in genetically susceptible individuals. The prevalence of celiac disease in the general population is estimated to be 1% in the world. Its prevalence differs depending on geographical and ethnic variations. The prevalence of celiac disease has increased significantly in the last 30 years due to the increased knowledge and awareness of physicians and the widespread use of highly sensitive and specific diagnostic tests for celiac disease. Despite increased awareness and knowledge about celiac disease, up to 95% of celiac patients still remain undiagnosed. The presentations of celiac disease have significantly changed in the last few decades. Classical symptoms of celiac disease occur in a minority of celiac patients, while older children have either minimal or atypical symptoms. Serologic tests for celiac disease should be done in patients with unexplained chronic or intermittent diarrhea, failure to thrive, weight loss, delayed puberty, short stature, amenorrhea, iron deficiency anemia, nausea, vomiting, chronic abdominal pain, abdominal distension, chronic constipation, recurrent aphthous stomatitis, and abnormal liver enzyme elevation, and in children who belong to specific groups at risk. Early diagnosis of celiac disease is very important to prevent long-term complications. Currently, the only effective treatment is a lifelong gluten-free diet. In this review, we will discuss the epidemiology, clinical findings, diagnostic tests, and treatment of celiac disease in the light of the latest literature.
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Affiliation(s)
- Yasin Sahin
- Pediatric Gastroenterology-Hepatology and Nutrition, Medical Park Gaziantep Hospital, Gaziantep 27560, Turkey
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Lebwohl B, Rubio-Tapia A. Epidemiology, Presentation, and Diagnosis of Celiac Disease. Gastroenterology 2021; 160:63-75. [PMID: 32950520 DOI: 10.1053/j.gastro.2020.06.098] [Citation(s) in RCA: 180] [Impact Index Per Article: 45.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 04/22/2020] [Accepted: 06/06/2020] [Indexed: 12/16/2022]
Abstract
The incidence of celiac disease is increasing, partly because of improved recognition of, and testing for, the disease. The rise in incidence is also due to a real increase of this immune-based disorder, independent of disease detection. The reasons for this true rise in recent decades are unknown but may be related to environmental factors that may promote loss of tolerance to dietary gluten. Strategies to reduce the development of celiac disease have not been proven successful in randomized trials, but the quantity of early-life gluten exposure has been a major focus of prevention efforts. The criteria for the diagnosis of celiac disease are changing, but in adults, diagnosis still depends on the presence of duodenal villous atrophy while the patient is on a gluten-containing diet, along with findings from serology analysis. Although guidelines in the United States continue to mandate a biopsy at all ages, some children receive a diagnosis of celiac disease without a biopsy. If proven accurate and scalable, assays that detect gluten-HLA tetramer complexes might be used in diagnosis to be made in the context of a gluten-free diet without intestinal biopsy.
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Affiliation(s)
- Benjamin Lebwohl
- Department of Medicine, Columbia University Irving Medical Center, New York, New York; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
| | - Alberto Rubio-Tapia
- Department of Gastroenterology, Hepatology, and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, Ohio
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10
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Routine Multiple Duodenal Biopsy during Endoscopy of Dyspeptic Patients Seems Unnecessary for Screening of Celiac Disease. Gastroenterol Res Pract 2020; 2020:6664741. [PMID: 33424963 PMCID: PMC7772036 DOI: 10.1155/2020/6664741] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 12/13/2020] [Accepted: 12/16/2020] [Indexed: 01/03/2023] Open
Abstract
Introduction Celiac disease (CD) is a chronic and common cause of dyspepsia with a rising prevalence worldwide. This study is aimed at investigating the prevalence of CD in dyspeptic patients based on serology and biopsy, determining the associated factors, and assessing the necessity of regular duodenal biopsies from normal mucosa in diagnosis of CD among dyspeptic patients. Methods This cross-sectional study was performed on 530 adult dyspeptic patients who underwent gastroduodenoscopy in Imam Reza hospital, Mashhad, during 2016-2018. Demographic characteristics, clinical data, and laboratory analyses were extracted from hospital records. CD was diagnosed based on intestinal biopsy and serum antitissue transglutaminase (anti-TTG) levels. Mucosal lesions were classified according to the modified Marsh classification. Data were analyzed in SPSS with P < 0.05 being considered significant. Results Overall, 163 males (30.8%) and 367 females (69.2%) with an average age of 46.38 ± 15.54 years were studied. High anti-TTG levels were seen in 36 (6.8%) patients, and duodenal pathologies were seen in 23 (4.5%) patients. Fifteen (2.8%) were diagnosed with CD based on both serology and biopsy. Bloating was the most common type of dyspepsia in CD patients (7, 46.7%), followed by epigastric pain (6, 40%), and postprandial fullness (2, 13.3%). Two CD patients (13.3%) reported a positive family history for CD. Logistic regression model showed that iron deficiency anemia (IDA), anti-TTG level, and Helicobacter pylori infection were predictors of histological changes of CD, whereas IDA was the only independent predictor of CD in dyspeptic patients (OR = 17.65, 95%CI = 1.53‐202.52, and P = 0.021). Conclusion CD is prevalent in dyspeptic patients, but routine biopsy from normal-appearing duodenal mucosa is not recommended for all patients. Serological studies, complete history, and careful endoscopic evaluation may provide better cost-effective clinical solutions to improve the diagnostic yield of celiac disease in dyspeptic patients.
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11
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Fasano A, Leonard MM, Mitchell DM, Eng G. Case 1-2020: An 11-Year-Old Boy with Vomiting and Weight Loss. N Engl J Med 2020; 382:180-189. [PMID: 31914246 PMCID: PMC8176458 DOI: 10.1056/nejmcpc1913469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Affiliation(s)
- Alessio Fasano
- From the Departments of Pediatrics (A.F., M.M.L., D.M.M.) and Pathology (G.E.), Massachusetts General Hospital, and the Departments of Pediatrics (A.F., M.M.L., D.M.M.) and Pathology (G.E.), Harvard Medical School - both in Boston
| | - Maureen M Leonard
- From the Departments of Pediatrics (A.F., M.M.L., D.M.M.) and Pathology (G.E.), Massachusetts General Hospital, and the Departments of Pediatrics (A.F., M.M.L., D.M.M.) and Pathology (G.E.), Harvard Medical School - both in Boston
| | - Deborah M Mitchell
- From the Departments of Pediatrics (A.F., M.M.L., D.M.M.) and Pathology (G.E.), Massachusetts General Hospital, and the Departments of Pediatrics (A.F., M.M.L., D.M.M.) and Pathology (G.E.), Harvard Medical School - both in Boston
| | - George Eng
- From the Departments of Pediatrics (A.F., M.M.L., D.M.M.) and Pathology (G.E.), Massachusetts General Hospital, and the Departments of Pediatrics (A.F., M.M.L., D.M.M.) and Pathology (G.E.), Harvard Medical School - both in Boston
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Abstract
Celiac disease (CD) is an immune-mediated gastrointestinal (GI) disorder driven by innate and adaptive immune responses to gluten. Presentation of CD has changed over time, with non-GI symptoms, such as anemia and osteoporosis, presenting more commonly. With improved screening and diagnostic methods, the reported prevalence of CD has increased globally, and there is considerable global variation in diagnostic and treatment practices. The objective of this study was to describe the current state of CD diagnosis and treatment patterns. A targeted review of literature from MEDLINE, Embase, the Cochrane Library, and screening of relevant conference abstracts was performed. The generally recommended diagnostic approach is GI endoscopy with small bowel biopsy; however, in selected patients, biopsy may be avoided and diagnosis based on positive serology and clinical symptoms. Diagnosis often is delayed; the average diagnostic delay after symptom onset is highly variable and can last up to 12 years. Barriers to accurate and timely diagnosis include atypical presentation, lack of physician awareness about current diagnostic criteria, misdiagnosis, and limited access to specialists. Currently, strict adherence to a gluten-free diet (GFD) is the only recommended treatment, which is not successful in all patients. Only one-third of patients are monitored regularly following diagnosis. Unmet needs for CD include improvements in the accuracy and timeliness of diagnosis, and the development of treatments for both refractory CD and GFD nonresponsive CD. Further research should investigate the impact of education about gluten-free eating and the availability of gluten-free foods support adherence and improve outcomes in patients with CD.
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13
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Caio G, Volta U, Sapone A, Leffler DA, De Giorgio R, Catassi C, Fasano A. Celiac disease: a comprehensive current review. BMC Med 2019; 17:142. [PMID: 31331324 PMCID: PMC6647104 DOI: 10.1186/s12916-019-1380-z] [Citation(s) in RCA: 524] [Impact Index Per Article: 87.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 06/27/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Celiac disease remains a challenging condition because of a steady increase in knowledge tackling its pathophysiology, diagnosis, management, and possible therapeutic options. MAIN BODY A major milestone in the history of celiac disease was the identification of tissue transglutaminase as the autoantigen, thereby confirming the autoimmune nature of this disorder. A genetic background (HLA-DQ2/DQ8 positivity and non-HLA genes) is a mandatory determinant of the development of the disease, which occurs with the contribution of environmental factors (e.g., viral infections and dysbiosis of gut microbiota). Its prevalence in the general population is of approximately 1%, with female predominance. The disease can occur at any age, with a variety of symptoms/manifestations. This multifaceted clinical presentation leads to several phenotypes, i.e., gastrointestinal, extraintestinal, subclinical, potential, seronegative, non-responsive, and refractory. Although small intestinal biopsy remains the diagnostic 'gold standard', highly sensitive and specific serological tests, such as tissue transglutaminase, endomysial and deamidated gliadin peptide antibodies, have become gradually more important in the diagnostic work-up of celiac disease. Currently, the only treatment for celiac disease is a life-long, strict gluten-free diet leading to improvement in quality of life, ameliorating symptoms, and preventing the occurrence of refractory celiac disease, ulcerative jejunoileitis, and small intestinal adenocarcinoma and lymphoma. CONCLUSIONS The present review is timely and provides a thorough appraisal of various aspects characterizing celiac disease. Remaining challenges include obtaining a better understanding of still-unclear phenotypes such as slow-responsive, potential (minimal lesions) and seronegative celiac disease. The identification of alternative or complementary treatments to the gluten-free diet brings hope for patients unavoidably burdened by diet restrictions.
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Affiliation(s)
- Giacomo Caio
- Department of Medical Sciences, University of Ferrara, Via Aldo Moro 8, Cona, 44124 Ferrara, Italy
- Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA 02114 USA
| | - Umberto Volta
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy
| | - Anna Sapone
- Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA 02114 USA
- Takeda Pharmaceuticals International Co, Cambridge, MA 02139 USA
| | - Daniel A. Leffler
- Takeda Pharmaceuticals International Co, Cambridge, MA 02139 USA
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA 02115 USA
| | - Roberto De Giorgio
- Department of Medical Sciences, University of Ferrara, Via Aldo Moro 8, Cona, 44124 Ferrara, Italy
| | - Carlo Catassi
- Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA 02114 USA
- Department of Pediatrics, Center for Celiac Research, Università Politecnica delle Marche, 60121 Ancona, Italy
| | - Alessio Fasano
- Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA 02114 USA
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14
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Faye AS, Lebwohl B. Celiac Disease: Diagnosis, Screening, and Prognosis. EVIDENCE‐BASED GASTROENTEROLOGY AND HEPATOLOGY 4E 2019:139-149. [DOI: 10.1002/9781119211419.ch9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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15
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Nagaishi T, Yamada D, Suzuki K, Fukuyo R, Saito E, Fukuda M, Watabe T, Tsugawa N, Takeuchi K, Yamamoto K, Arai A, Ohtsuka K, Watanabe M. Indolent T cell lymphoproliferative disorder with villous atrophy in small intestine diagnosed by single-balloon enteroscopy. Clin J Gastroenterol 2019; 12:434-440. [PMID: 30968266 PMCID: PMC6763404 DOI: 10.1007/s12328-019-00971-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Accepted: 03/24/2019] [Indexed: 02/06/2023]
Abstract
Chronic diarrhea is one of the major symptoms in gastroenterology. However, this may be caused by pathologic conditions for which the diagnosis is critical. Villous atrophy, as an endoscopic lesion, accompanied by chronic diarrhea can occasionally be observed in the patients with inflammatory diseases of the gastrointestinal (GI) tract. Herein, we present a case with persistent diarrhea accompanied by intestinal wall thickening without any other significant endoscopic features other than villous atrophy in the jejunum and the ileum, where we diagnosed as an indolent T cell lymphoproliferative disorder (T-LPD) of the GI tract, defined in the 2016–2017 revised World Health Organization classification, via single-balloon enteroscopy (SBE). Interestingly, we found the same lymphocyte infiltration from the distal third portion of the duodenum, where gastroscopy could not reach, via SBE, even though no endoscopic findings were observed such as villous atrophy. Since infiltrating cells in the intestinal tissues were CCR4+, mogamulizumab was administered with resulting durable symptomatic remission for more than 2 years. Patients with persistent diarrhea may have serious small intestinal disorder including not only chronic inflammatory diseases but also lymphoid neoplasmic conditions including T-LPD of GI tract.
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Affiliation(s)
- Takashi Nagaishi
- Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
| | - Daiki Yamada
- Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
| | - Kohei Suzuki
- Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
| | | | - Eiko Saito
- Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
| | - Masayoshi Fukuda
- Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
| | - Taro Watabe
- Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
| | - Naoya Tsugawa
- Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
| | - Kengo Takeuchi
- Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
| | | | - Ayako Arai
- Department of Hematological Therapeutics, Graduate School of Medical Science, TMDU, Tokyo, Japan.,Division of Hematology and Oncology, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan
| | - Kazuo Ohtsuka
- Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
| | - Mamoru Watanabe
- Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
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16
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Silvester JA, Faucher EA, McCarty CE, Kalansky A, Hintze ZJ, Mitchell PD, Goldsmith JD, Weir DC, Leichtner AM. Red Spot Lesions in the Duodenal Bulb Are a Highly Specific Endoscopic Sign of Celiac Disease: A Prospective Study. J Pediatr Gastroenterol Nutr 2019; 68:251-255. [PMID: 30247425 PMCID: PMC6344298 DOI: 10.1097/mpg.0000000000002158] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
We have recognized red spot lesions (RSLs) in the duodenal bulb in children with celiac disease (CD) and believe they may represent an underappreciated and distinct endoscopic sign of CD. A total of 171 pediatric patients undergoing esophagogastroduodenoscopy with duodenal biopsy for symptoms consistent with CD were prospectively recruited. There were 75 patients who met criteria for CD and the remaining 96 patients served as symptomatic controls. As compared to endoscopic markers frequently mentioned in literature, RSLs had comparable sensitivity, specificity, positive predictive value, and negative predictive value of 31%, 94%, 80%, and 64%, respectively. If RSLs are noted during endoscopy in a patient with gastrointestinal symptoms that might be the result of CD, then sufficient duodenal biopsies to make the diagnosis of CD should be obtained.
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Affiliation(s)
- Jocelyn A. Silvester
- Division of Gastroenterology and Nutrition, Boston Children’s Hospital, Boston, MA
- University of Manitoba, Winnipeg MB, CA
| | | | | | - Adie Kalansky
- Department of Internal Medicine; The Jewish Hospital of Cincinnati, Cincinnati, OH
| | - Zackary J. Hintze
- Division of Gastroenterology and Nutrition, Boston Children’s Hospital, Boston, MA
| | - Paul D. Mitchell
- Institutional Centers for Clinical and Translational Research; Boston Children’s Hospital, Boston, MA
| | | | - Dascha C. Weir
- Division of Gastroenterology and Nutrition, Boston Children’s Hospital, Boston, MA
| | - Alan M. Leichtner
- Division of Gastroenterology and Nutrition, Boston Children’s Hospital, Boston, MA
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17
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Morreale GC, Montalbano LM, Cappello M, Sinagra E, Rizzo A, Carroccio A. A difficult diagnosis of coeliac disease: Repeat duodenal histology increases diagnostic yield in patients with concomitant causes of villous atrophy. Arab J Gastroenterol 2018; 18:241-244. [PMID: 29325751 DOI: 10.1016/j.ajg.2017.09.011] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2016] [Revised: 02/20/2017] [Accepted: 09/17/2017] [Indexed: 11/28/2022]
Abstract
Villous atrophy in absence of coeliac disease (CD)-specific antibodies represents a diagnostic dilemma. We report a case of a woman with anaemia, weight loss and diarrhoea with an initial diagnosis of seronegative CD and a histological documented villous atrophy who did not improve on gluten-free diet due to the concomitant presence of common variable immunodeficiency (CVID) and Giardia lamblia infection. This case report confirms that CD diagnosis in CVID patients is difficult; the combination of anti-endomysial antibodies (EmA-IgA), anti-tissue transglutaminase antibodies (tTG-IgAb) antibodies and total IgA is obligatory in basic diagnostic of CD but in CVID are negative. Furthermore, the typical histological aspects of the intestinal mucosa in CVID (absence of plasma cells and switch to the IgD immunoglobulins), cannot rule out a concomitant CD diagnosis. HLA typing in this setting has a low positive predictive value but should be considered. Histological response to a gluten-free diet on repeat biopsy and the concomitant treatment of other causes of villous atrophy leads to a definite diagnosis of CD.
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Affiliation(s)
| | | | - Maria Cappello
- Gastroenterology and Hepatology Section, DIBIMIS, University of Palermo, Italy
| | - Emanuele Sinagra
- Gastroenterology and Endoscopy Unit, Fondazione Istituto San Raffaele Giglio, Cefalù, Italy
| | - Aroldo Rizzo
- Pathology Unit, Ospedali Riuniti Villa Sofia-Cervello Palermo, Italy
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18
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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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19
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Hindryckx P, Levesque BG, Holvoet T, Durand S, Tang CM, Parker C, Khanna R, Shackelton LM, D'Haens G, Sandborn WJ, Feagan BG, Lebwohl B, Leffler DA, Jairath V. Disease activity indices in coeliac disease: systematic review and recommendations for clinical trials. Gut 2018; 67:61-69. [PMID: 27799282 DOI: 10.1136/gutjnl-2016-312762] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2016] [Revised: 10/06/2016] [Accepted: 10/10/2016] [Indexed: 12/20/2022]
Abstract
OBJECTIVE Although several pharmacological agents have emerged as potential adjunctive therapies to a gluten-free diet for coeliac disease, there is currently no widely accepted measure of disease activity used in clinical trials. We conducted a systematic review of coeliac disease activity indices to evaluate their operating properties and potential as outcome measures in registration trials. DESIGN MEDLINE, EMBASE and the Cochrane central library were searched from 1966 to 2015 for eligible studies in adult and/or paediatric patients with coeliac disease that included coeliac disease activity markers in their outcome measures. The operating characteristics of histological indices, patient-reported outcomes (PROs) and endoscopic indices were evaluated for content and construct validity, reliability, responsiveness and feasibility using guidelines proposed by the US Food and Drug Administration (FDA). RESULTS Of 19 123 citations, 286 studies were eligible, including 24 randomised-controlled trials. Three of five PROs identified met most key evaluative criteria but only the Celiac Disease Symptom Diary (CDSD) and the Celiac Disease Patient-Reported Outcome (CeD PRO) have been approved by the FDA. All histological and endoscopic scores identified lacked content validity. Quantitative morphometric histological analysis had better reliability and responsiveness compared with qualitative scales. Endoscopic indices were infrequently used, and only one index demonstrated responsiveness to effective therapy. CONCLUSIONS Current best evidence suggests that the CDSD and the CeD PRO are appropriate for use in the definition of primary end points in coeliac disease registration trials. Morphometric histology should be included as a key secondary or co-primary end point. Further work is needed to optimise end point configuration to inform efficient drug development.
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Affiliation(s)
- Pieter Hindryckx
- Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.,Department of Gastroenterology, University of Ghent, Ghent, Belgium
| | - Barrett G Levesque
- Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.,Division of Gastroenterology, University of California San Diego, La Jolla, California, USA
| | - Tom Holvoet
- Department of Gastroenterology, University of Ghent, Ghent, Belgium
| | - Serina Durand
- Division of Gastroenterology, University of California San Diego, La Jolla, California, USA
| | - Ceen-Ming Tang
- Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, Oxford, UK.,Oxford University Clinical Academic Graduate School, John Radcliffe Hospital, Oxford, UK
| | - Claire Parker
- Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada
| | - Reena Khanna
- Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.,Department of Medicine, University of Western Ontario, London, Ontario, Canada
| | - Lisa M Shackelton
- Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada
| | - Geert D'Haens
- Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.,Inflammatory Bowel Disease Centre, Academic Medical Centre, Amsterdam, The Netherlands
| | - William J Sandborn
- Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.,Division of Gastroenterology, University of California San Diego, La Jolla, California, USA
| | - Brian G Feagan
- Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.,Department of Medicine, University of Western Ontario, London, Ontario, Canada.,Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada
| | - Benjamin Lebwohl
- Celiac Disease Center, Columbia University, New York, New York, USA
| | - Daniel A Leffler
- The Celiac Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Vipul Jairath
- Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.,Department of Medicine, University of Western Ontario, London, Ontario, Canada.,Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada
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20
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Eigner W, Bashir K, Primas C, Kazemi-Shirazi L, Wrba F, Trauner M, Vogelsang H. Dynamics of occurrence of refractory coeliac disease and associated complications over 25 years. Aliment Pharmacol Ther 2017; 45:364-372. [PMID: 27885681 DOI: 10.1111/apt.13867] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2016] [Revised: 06/08/2016] [Accepted: 10/27/2016] [Indexed: 12/19/2022]
Abstract
BACKGROUND Refractory coeliac disease, enteropathy associated T-cell lymphoma and small bowel adenocarcinoma are rare but prognostically important complications in coeliac disease. AIM To analyse potential changes in occurrence of complicated coeliac disease over the last 25 years. METHODS One thousand one hundred and thirty eight patients were included and evaluated based on their time of first presentation at the Medical University of Vienna, Austria. Occurrences of refractory coeliac disease and associated malignancies were evaluated for 5-year intervals from January 1990 until December 2014 and were compared over time. RESULTS 2.6% (n = 29) were diagnosed with refractory coeliac disease (females 65.6%, mean age at diagnosis 62.8 years). The proportion of those patients was 2.6%, 3.1%, 3.3%, 2.7% and 0.5% for the 5 year intervals from 1990 onwards. Thus, the number of refractory cases has been decreasing since 2000 (P = 0.024). The number of patients presenting with lymphoma (n = 7) was 0.6%, 0.4%, 1.1%, 0.8% and 0% from 1990 to 2014. Similarly the number of patients with adenocarcinoma (n = 4) decreased to 0% until 2014. Overall mortality in patients suffering from refractory disease was 48%. Of all patients diagnosed with lymphoma 71.4% died with a 5-year survival rate of 28.6%. CONCLUSIONS Over the past 15 years the occurrence of complicated coeliac disease has been decreasing. This possibly reflects a higher awareness of coeliac disease and optimised diagnosis and treatment with avoidance of long-term immunological disease activity. Symptomatic disease and a delay in diagnosis are risk factors for refractory coeliac disease and related cancer.
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Affiliation(s)
- W Eigner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University Hospital of Vienna, Vienna, Austria
| | - K Bashir
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University Hospital of Vienna, Vienna, Austria
| | - C Primas
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University Hospital of Vienna, Vienna, Austria
| | - L Kazemi-Shirazi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University Hospital of Vienna, Vienna, Austria
| | - F Wrba
- Department of Pathology, Medical University of Vienna, Vienna, Austria
| | - M Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University Hospital of Vienna, Vienna, Austria
| | - H Vogelsang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University Hospital of Vienna, Vienna, Austria
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21
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Ciaccio EJ, Bhagat G, Lewis SK, Green PH. Extraction and processing of videocapsule data to detect and measure the presence of villous atrophy in celiac disease patients. Comput Biol Med 2016; 78:97-106. [PMID: 27673492 DOI: 10.1016/j.compbiomed.2016.09.009] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2016] [Revised: 09/05/2016] [Accepted: 09/14/2016] [Indexed: 12/15/2022]
Abstract
BACKGROUND Videocapsule endoscopy is a relative new method to analyze the gastrointestinal tract for the presence of pathologic features. It is of relevance to detect villous atrophy in the small bowel, which is a defining symptom of celiac disease. METHOD In this tutorial, methods to extract and process videocapsule endoscopy data are elucidated. The algorithms, computer code, and paradigms to analyze image series are described in detail. The topics covered include extraction of data, analysis of texture, eigenanalysis, spectral analysis, three-dimensional projection, and estimation of motility. The basic paradigms to implement these processes are provided. RESULTS Examples of successful quantitative analysis implementations for selected untreated celiac disease patients with villous atrophy versus control patients with normal villi were illustrated. Based on the implementations, it was evident that celiac patients tended to have a rougher small intestinal texture as compared with control patients. From three-dimensional projection, celiac patients exhibited larger surface protrusions emanating from the small intestinal mucosa, which may represent clumps of atrophied villi. The periodicity of small intestinal contractions tends to be slower when villous atrophy is present, and the estimated degree of motility is reduced as compared with control image series. Basis image construction suggested that fissuring and mottling of the mucosal surface is predominant in untreated celiac patients, and mostly absent in controls. CONCLUSIONS Implementation of computerized methods, as described in this tutorial, will likely be useful for the automated detection and measurement of villous atrophy, and to map its extent along the small intestine of celiac patients.
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Affiliation(s)
- Edward J Ciaccio
- Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, United States.
| | - Govind Bhagat
- Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, United States; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, United States
| | - Suzanne K Lewis
- Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, United States
| | - Peter H Green
- Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, United States
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22
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Volta U, Caio G, Boschetti E, Giancola F, Rhoden KJ, Ruggeri E, Paterini P, De Giorgio R. Seronegative celiac disease: Shedding light on an obscure clinical entity. Dig Liver Dis 2016; 48:1018-22. [PMID: 27352981 DOI: 10.1016/j.dld.2016.05.024] [Citation(s) in RCA: 67] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2016] [Revised: 05/25/2016] [Accepted: 05/30/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND Although serological tests are useful for identifying celiac disease, it is well established that a minority of celiacs are seronegative. AIM To define the prevalence and features of seronegative compared to seropositive celiac disease, and to establish whether celiac disease is a common cause of seronegative villous atrophy. METHODS Starting from 810 celiac disease diagnoses, seronegative patients were retrospectively characterized for clinical, histological and laboratory findings. RESULTS Of the 810 patients, fourteen fulfilled the diagnostic criteria for seronegative celiac disease based on antibody negativity, villous atrophy, HLA-DQ2/-DQ8 positivity and clinical/histological improvement after gluten free diet. Compared to seropositive, seronegative celiac disease showed a significantly higher median age at diagnosis and a higher prevalence of classical phenotype (i.e., malabsorption), autoimmune disorders and severe villous atrophy. The most frequent diagnosis in the 31 cases with seronegative flat mucosa was celiac disease (45%), whereas other diagnoses were Giardiasis (20%), common variable immunodeficiency (16%) and autoimmune enteropathy (10%). CONCLUSIONS Although rare seronegative celiac disease can be regarded as the most frequent cause of seronegative villous atrophy being characterized by a high median age at diagnosis; a close association with malabsorption and flat mucosa; and a high prevalence of autoimmune disorders.
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Affiliation(s)
- Umberto Volta
- Department of Medical and Surgical Sciences, University of Bologna, St. Orsola-Malpighi Hospital, Italy
| | - Giacomo Caio
- Department of Medical and Surgical Sciences, University of Bologna, St. Orsola-Malpighi Hospital, Italy
| | - Elisa Boschetti
- Department of Medical and Surgical Sciences, University of Bologna, St. Orsola-Malpighi Hospital, Italy
| | - Fiorella Giancola
- Department of Medical and Surgical Sciences, University of Bologna, St. Orsola-Malpighi Hospital, Italy
| | - Kerry J Rhoden
- Department of Medical and Surgical Sciences, University of Bologna, St. Orsola-Malpighi Hospital, Italy
| | - Eugenio Ruggeri
- Department of Medical and Surgical Sciences, University of Bologna, St. Orsola-Malpighi Hospital, Italy
| | - Paola Paterini
- Department of Medical and Surgical Sciences, University of Bologna, St. Orsola-Malpighi Hospital, Italy
| | - Roberto De Giorgio
- Department of Medical and Surgical Sciences, University of Bologna, St. Orsola-Malpighi Hospital, Italy.
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23
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Masoodi M, Mokhtare M, Agah S, Sina M, Soltani-Kermanshahi M. Frequency of Celiac Disease in Patients With Increased Intestinal Gas (Flatulence). Glob J Health Sci 2015; 8:147-53. [PMID: 26755470 PMCID: PMC4954875 DOI: 10.5539/gjhs.v8n6p147] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Revised: 09/22/2015] [Accepted: 09/09/2015] [Indexed: 11/12/2022] Open
Abstract
Excessive flatulence which impairs social performance in patients is one of the common reasons for referrals to gastroenterology clinics. Celiac Disease is a rare but important cause of increased intestinal gas (bloating) and if not diagnosed, patients face complications such as malabsorption, anemia, osteoporosis and even intestinal lymphoma. This study aimed to determine the frequency of Celiac Disease in patients with excessive flatulence.One hundred and fifty patients with a chief complaint of experiencing flatulence more than 15 times a day and lasting for three months were referred to the gastroenterology clinic of Rasoul-e-Akram Teaching Hospital. Serological tests for Celiac Disease, Anti TTG Ab (IgA-IgG) were requested and the patients with positive tests underwent upper GI endoscopy. Biopsies of the second part of the duodenum were then sent to the laboratory.From one hundred and thirty patients who completed the study, 92 (70.7%) were female. Mean age of the patients was 32 ± 13 years. Anti TTG Ab was found in 5 patients (3.85%). Only 2 patients (1.5%) had a documented positive pathology for Celiac Disease.According to the results of this study and other studies, we conclude that Celiac Disease is an uncommon etiology for excessive flatulence but it is of importance to investigate it in excessive flatulence patients.
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Affiliation(s)
- Mohsen Masoodi
- Colorectal Research Center, Rasoul-e-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran.
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Barakauskas VE, Lam GY, Estey MP. Digesting all the options: Laboratory testing for celiac disease. Crit Rev Clin Lab Sci 2014; 51:358-78. [PMID: 25244521 DOI: 10.3109/10408363.2014.958813] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Tortora R, Capone P, Imperatore N, De Stefano G, Gerbino N, Leo M, Caporaso N, Rispo A. Predictive value of "Marsh 1" type histology in subjects with suspected cealic disease. Scand J Gastroenterol 2014; 49:801-6. [PMID: 24958090 DOI: 10.3109/00365521.2014.919019] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION The diagnosis of celiac disease (CD) is based on histology in combination with anti-tissue transglutaminase (a-tTG) and anti-endomysial antibodies (EMAs). The increase of intraepithelial lymphocytes defines the Marsh 1 histology that appears not to be specific for CD. AIM To explore the positive predictive value (PPV) and clinical relevance of Marsh 1 histology in suspected CD. METHODS We carried out an observational prospective study including all consecutive subjects with a Marsh 1 histology. All patients were tested for a-tTG and EMAs. Diagnosis of potential CD was defined in the presence of Marsh 1 with positive a-tTG and EMAs. Patients were investigated for symptoms, CD familial aggregation, other diseases, and current medication. RESULTS Sixty-three patients with Marsh 1 were included. Diagnosis of potential CD was made in 23 subjects (36%), so that Marsh 1 histology showed a PPV of 36%. With regard to familial aggregation, patients with potential CD showed a higher frequency of familiarity for CD (60.8% vs. 15.0%; p < 0.01). No significant difference was detected between CD and non-CD in terms of intestinal and extra-intestinal symptoms. We also documented the presence of conditions other than CD in the remaining population: 7 patients (17.5%) with immuno-mediated diseases while 5 patients (12.5%) showed Helicobacter pylori (HP) infection. About medication, 3 patients (7.5%) were on non-steroidal anti-inflammatory drugs, while another 4 (10%) patients were being treated with other drugs. CONCLUSION The Marsh 1 type histology is not specific for CD and it can also be associated with immuno-mediated disorders, HP infection, and drugs.
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Affiliation(s)
- Raffaella Tortora
- Department of Clinical Medicine and Surgery - University of Naples "Federico II", Gastroenterology , Naples , Italy
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Kasirer Y, Turner D, Lerman L, Schechter A, Waxman J, Dayan B, Bergwerk A, Rachman Y, Freier Z, Silbermintz A. Scalloping is a reliable endoscopic marker for celiac disease. Dig Endosc 2014; 26:232-5. [PMID: 23746050 DOI: 10.1111/den.12130] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2013] [Accepted: 04/23/2013] [Indexed: 02/08/2023]
Abstract
BACKGROUND Scalloping of duodenal folds noted on esophagogastroduodenoscopy (EGD) has been associated with various illnesses including celiac disease (CD). The aim of the present study was to examine the frequency of scalloping in pediatric patients undergoing EGD and to assess its significance in the diagnosis of CD. We also evaluated the association of scalloping with the histopathology and celiac serology in the subgroup of celiac patients. PATIENTS AND METHODS All children (0-18 years) who underwent EGD at Shaare Zedek Medical Center for any reason during a 2.5-year period were retrospectively included, yielding a consecutive cohort without selection bias. Relevant data were obtained from the patient files. RESULTS During the study period, 623 children underwent EGD of whom 149 (24%) were eventually diagnosed with CD. In 74/623children (12%), scalloping was seen and had a sensitivity of 48% (95% CI 0.40-0.57), specificity of 99% (0.98-0.99) and positive predictive value of 97% (0.9-0.99) to diagnose CD. The prevalence of scalloping increased with advancing stage of the Marsh classification from 33% (7/21) in Marsh 1 to 63% (34/54) in Marsh 3c (P < 0.001). Scalloping was associated with a significantly higher median tissue transglutaminase level (153 [IQR 98-168] versus 49 [IQR 11-143]; P = 0.011). CONCLUSION The results suggest that the diagnosis of CD is almost certain if isolated scalloping is observed during EGD done to rule out CD. Thus, attention to this finding may serve as an additional tool in the diagnosis of CD.
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Affiliation(s)
- Yair Kasirer
- The Pediatric Gastroenterology and Nutrition Unit, Shaare Zedek Medical Center, Jerusalem, Israel
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Rahman I, Patel P, Rondonotti E, Koulaouzidis A, Pennazio M, Kalla R, Sidhu R, Mooney P, Sanders D, Despott EJ, Fraser C, Kurniawan N, Baltes P, Keuchel M, Davison C, Beejay N, Parker C, Panter S. Small Bowel Capsule Endoscopy. HANDBOOK OF CAPSULE ENDOSCOPY 2014:47-118. [DOI: 10.1007/978-94-017-9229-5_3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Ianiro G, Gasbarrini A, Cammarota G. Endoscopic tools for the diagnosis and evaluation of celiac disease. World J Gastroenterol 2013; 19:8562-8570. [PMID: 24379573 PMCID: PMC3870501 DOI: 10.3748/wjg.v19.i46.8562] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2013] [Accepted: 04/28/2013] [Indexed: 02/06/2023] Open
Abstract
Celiac disease (CD) is an autoimmune disease of the small bowel induced by ingestion of wheat, rye and barley. Current guidelines indicate histological analysis on at least four duodenal biopsies as the only way to diagnose CD. These indications are based on the conception of the inability of standard endoscopy to make diagnosis of CD and/or to drive biopsy sampling. Over the last years, technology development of endoscopic devices has greatly ameliorated the accuracy of macroscopic evaluation of duodenal villous pattern, increasing the diagnostic power of endoscopy of CD. The aim of this paper is to review the new endoscopic tools and procedures proved to be useful in the diagnosis of CD, such as chromoendoscopy, Fujinon Intelligent Chromo Endoscopy, Narrow Band Imaging, Optical Coherence Tomography, Water-Immersion Technique, confocal laser endomicroscopy, high-resolution magnification endoscopy, capsule endoscopy and I-Scan technology.
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Hammer STG, Greenson JK. The clinical significance of duodenal lymphocytosis with normal villus architecture. Arch Pathol Lab Med 2013; 137:1216-9. [PMID: 23991733 DOI: 10.5858/arpa.2013-0261-ra] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
CONTEXT The finding of increased intraepithelial lymphocytes with normal villous architecture (Marsh I lesion) is seen in up to 3% of duodenal biopsies. The differential diagnosis includes a wide range of possibilities, including celiac disease, bacterial overgrowth, nonsteroidal antiinflammatory drug damage, reaction to Helicobacter pylori infection, tropical sprue, and chronic inflammatory bowel disease. OBJECTIVES To highlight the histologic features of the Marsh I lesion, review the diseases and conditions associated with that finding, and to provide pathologists with a rationale and a template for how to identify and report such cases. DATA SOURCES A review of the literature regarding the histologic features and clinical associations of Marsh I lesions. CONCLUSIONS Marsh I lesions are a nonspecific finding associated with a number of disease conditions. Historically, between 9% and 40% of cases have been shown to represent celiac disease. Current data do not suggest histologic features to differentiate between diseases associated with this histologic change.
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Affiliation(s)
- Suntrea T G Hammer
- Department of Pathology, University of Michigan Health System, Ann Arbor, 48109, USA.
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Narrow band imaging with magnification endoscopy for celiac disease: results from a prospective, single-center study. DIAGNOSTIC AND THERAPEUTIC ENDOSCOPY 2013; 2013:580526. [PMID: 23983448 PMCID: PMC3748412 DOI: 10.1155/2013/580526] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/24/2013] [Accepted: 07/06/2013] [Indexed: 12/18/2022]
Abstract
In celiac disease (CD), the intestinal lesions can be patchy and partial villous atrophy may elude detection at standard endoscopy (SE). Narrow Band Imaging (NBI) system in combination with a magnifying endoscope (ME) is a simple tool able to obtain targeted biopsy specimens. The aim of the study was to assess the correlation between NBI-ME and histology in CD diagnosis and to compare diagnostic accuracy between NBI-ME and SE in detecting villous abnormalities in CD. Forty-four consecutive patients with suspected CD undergoing upper gastrointestinal endoscopy have been prospectively evaluated. Utilizing both SE and NBI-ME, observed surface patterns were compared with histological results obtained from biopsy specimens using the k-Cohen agreement coefficient. NBI-ME identified partial villous atrophy in 12 patients in whom SE was normal, with sensitivity, specificity, and accuracy of 100%, 92.6%, and 95%, respectively. The overall agreement between NBI-ME and histology was significantly higher when compared with SE and histology (kappa score: 0.90 versus 0.46; P = 0.001) in diagnosing CD. NBI-ME could help identify partial mucosal atrophy in the routine endoscopic practice, potentially reducing the need for blind biopsies. NBI-ME was superior to SE and can reliably predict in vivo the villous changes of CD.
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Tursi A. Endoscopic diagnosis of celiac disease: what is the role of capsule endoscopy? Gastrointest Endosc 2013; 78:381. [PMID: 23867376 DOI: 10.1016/j.gie.2013.02.020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2013] [Accepted: 02/13/2013] [Indexed: 02/08/2023]
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Kurien M, Leeds JS, Hopper AD, Wild G, Egner W, Tesfaye S, Hadjivassiliou M, Sanders DS. Serological testing for coeliac disease in Type 1 diabetes mellitus: is immunoglobulin A level measurement necessary? Diabet Med 2013; 30:840-5. [PMID: 23461783 DOI: 10.1111/dme.12163] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2012] [Revised: 12/21/2012] [Accepted: 02/15/2013] [Indexed: 12/20/2022]
Abstract
AIMS Immunoglobulin A (IgA) measurement is advocated when case finding for coeliac disease in patients with Type 1 diabetes mellitus. Currently, there is a paucity of contemporary studies assessing IgA deficiency in Type 1 diabetes. This study evaluates the prevalence of IgA deficiency in individuals with Type 1 diabetes, compared with patients with coeliac disease and control subjects. In addition, we evaluate whether routine IgA measurement is justifiable when case finding for coeliac disease in patients with Type 1 diabetes. METHODS All patients were assessed using IgA endomysial antibodies, IgA anti-tissue transglutaminase antibodies and total IgA levels. Altogether, 2434 individuals were tested: 1000 patients with Type 1 diabetes, 234 patients with coeliac disease and 1200 population control subjects. Definitive IgA deficiency was defined as total IgA levels < 0.07 g/l. RESULTS The prevalence of IgA deficiency was significantly more common in patients with Type 1 diabetes (0.9%, n = 9/1000; P = 0.036) and coeliac disease (1.29%, n = 3/234; P = 0.041) when compared with population control subjects (prevalence of 0.17%, 2/1200). No statistical difference between Type 1 diabetes and coeliac disease for IgA deficiency was identified (P = 0.87). Of patients in the group with Type 1 diabetes, 3.3% (33/1000) had coeliac disease, and of those only one patient had IgA deficiency leading to an antibody-negative presentation. Both IgA-deficient individuals within the population control subjects had normal duodenal biopsies and no relevant symptoms. CONCLUSIONS IgA deficiency is more common in Type 1 diabetes compared with population control subjects. Despite this, very few individuals with Type 1 diabetes and IgA deficiency appear to have villous atrophy on biopsy. These outcomes question the practice of routine IgA measurement when case finding for coeliac disease in patients with Type 1 diabetes.
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Affiliation(s)
- M Kurien
- Gastroenterology and Liver Unit, Royal Hallamshire Hospital, Sheffield, UK.
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Kurien M, Evans KE, Aziz I, Sidhu R, Drew K, Rogers TL, McAlindon ME, Sanders DS. Capsule endoscopy in adult celiac disease: a potential role in equivocal cases of celiac disease? Gastrointest Endosc 2013. [PMID: 23200728 DOI: 10.1016/j.gie.2012.09.031] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND There have been limited studies evaluating capsule endoscopy (CE) in equivocal celiac disease (CD). OBJECTIVE To determine the role CE may have in equivocal CD cases, compared with patients with biopsy-proven and serology-proven CD who have persisting symptoms. DESIGN Prospective cohort study. SETTING University hospital. PATIENTS A total of 62 patients with equivocal CD and 69 patients with nonresponsive CD. INTERVENTION CE. MAIN OUTCOME MEASUREMENTS Diagnostic yield of CE in equivocal cases and accuracy of mucosal abnormality detection in patients with nonresponsive CD. RESULTS Equivocal cases (n = 62) were divided into two subgroups: group A (antibody-negative villous atrophy, n = 32) and group B (Marsh 1-2 changes, n = 30). In group A, CE secured a diagnosis of CD or Crohn's disease in 28% (9/32), significantly higher than the diagnostic yield in group B (7%; P = .044). In patients with CD with persisting symptoms, significant CE findings were identified in 12% (8/69), including 2 cases of enteropathy-associated lymphoma, 4 type 1 refractory disease cases, 1 polypoidal mass histologically confirmed to be a fibroepithelial polyp, and 1 case of ulcerative jejunitis. This outcome was significantly lower than the diagnostic yield of CE in antibody-negative villous atrophy (P = .048). LIMITATIONS Single center. CONCLUSION There have been no previous reports systematically evaluating equivocal CD by using CE. The diagnostic yield of CE in patients with antibody-negative villous atrophy is better than that of CE in patients with CD with persisting symptoms. We advocate the use of CE in equivocal cases, particularly in patients with antibody-negative villous atrophy.
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Affiliation(s)
- Matthew Kurien
- Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, South Yorkshire, United Kingdom
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Lebwohl B, Rubio-Tapia A, Assiri A, Newland C, Guandalini S. Diagnosis of celiac disease. Gastrointest Endosc Clin N Am 2012; 22:661-77. [PMID: 23083985 PMCID: PMC4005880 DOI: 10.1016/j.giec.2012.07.004] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
This article reviews issues related to identifying the appropriate patient to test for celiac disease, the performance characteristics of serologic testing, the role of gene testing for human leukocyte antigen DQ2 and DQ8 haplotypes, and issues related to the performance of small intestinal biopsy. The article concludes with a review of special diagnostic considerations in pediatric patients.
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Affiliation(s)
- Benjamin Lebwohl
- Department of Medicine, Mailman School of Public Health, Celiac Disease Center, Columbia University, New York, NY 10032, USA.
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35
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Harris LA, Park JY, Voltaggio L, Lam-Himlin D. Celiac disease: clinical, endoscopic, and histopathologic review. Gastrointest Endosc 2012; 76:625-40. [PMID: 22898420 DOI: 10.1016/j.gie.2012.04.473] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2012] [Accepted: 04/30/2012] [Indexed: 02/08/2023]
Affiliation(s)
- Lucinda A Harris
- Department of Gastroenterology, Mayo Clinic in Arizona, Scottsdale, Arizona 85259, USA
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Kav T, Sivri B. Is enteroscopy necessary for diagnosis of celiac disease? World J Gastroenterol 2012; 18:4095-101. [PMID: 22919241 PMCID: PMC3422789 DOI: 10.3748/wjg.v18.i31.4095] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2011] [Revised: 03/26/2012] [Accepted: 04/09/2012] [Indexed: 02/06/2023] Open
Abstract
Celiac disease (CD) is an autoimmune inflammatory disease of the small intestine as a result of reaction to wheat protein, gluten. Exclusion of dietary gluten is the mainstay of the treatment that necessitates a precise diagnosis of the disease. Serological screening may aid in identifying patients with suspected CD, which should be confirmed by intestinal biopsy. It has been shown that duodenal biopsies are good for detection of the disease in most patients. However, there is a group of patients with positive serology and inconclusive pathology. As a result of the widespread use of serology, many patients with equivocal findings grow quickly. Unfortunately current endoscopic methods can only diagnose villous atrophy, which can be present in the later grades of disease (i.e., Marsh III). To diagnose CD correctly, going deeper in the intestine may be necessary. Enteroscopy can reveal changes in CD in the intestinal mucosa in 10%-17% of cases that have negative histology at initial workup. Invasiveness of the method limits its use. Capsule endoscopy may be a good substitute for enteroscopy. However, both techniques should be reserved for patients with suspected diagnosis of complications. This paper reviews the current literature in terms of the value of enteroscopy for diagnosis of CD.
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Carroccio A, Catalano T, Fiorino M, Bongiovì A, Napoli G, Di Prima L, Ambrosiano G, Pace M, Scaturro A, Di Fede G. Collagenous colitis presenting with bloody diarrhea and rectal erosions in a patient with celiac disease: a case report. ITALIAN JOURNAL OF MEDICINE 2010. [DOI: 10.1016/j.itjm.2010.03.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
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Dickey W. Diagnostic immunology in celiac disease. Expert Rev Clin Immunol 2010; 5:471-9. [PMID: 20477043 DOI: 10.1586/eci.09.26] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Serum autoantibodies to transglutaminase and endomysium are found in the majority of patients with celiac disease, an autoimmune multisystem disorder affecting approximately 1% of Western and Middle-Eastern populations. Detection of these antibodies plays a crucial role in the diagnosis of celiac disease. The aim of this review is to summarize recent publications in this field, with particular focus on the applications and limitations of celiac autoantibody testing in routine clinical practice.
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Affiliation(s)
- William Dickey
- Department of Gastroenterology, Altnagelvin Hospital, Londonderry, Northern Ireland, BT47 6SB, UK.
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Abstract
Coeliac disease is a chronic inflammatory disorder of the small bowel induced in genetically susceptible people by the irritant gluten and possibly other environmental cofactors. The disorder is characterised by a diverse clinical heterogeneity that ranges from asymptomatic to severely symptomatic, and it manifests with frank malabsorption, an increased morbidity attributable to the frequent association with autoimmune disorders and increased mortality resulting from the emergence of T-cell clonal proliferations that predispose the patient to enteropathy-type T-cell lymphoma. Our understanding of the molecular basis for this disorder has improved and enabled the identification of targets for new therapies, although a strict gluten-free diet remains the mainstay of safe and effective treatment. In this Seminar we critically reassess the clinical and diagnostic aspects of this disease and new perspectives in its pathogenesis and treatment.
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Affiliation(s)
- Antonio Di Sabatino
- First Department of Medicine, Centro per lo Studio e la Cura della Malattia Celiaca, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
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40
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Emerging technologies in upper gastrointestinal endoscopy and celiac disease. ACTA ACUST UNITED AC 2008; 6:47-56. [PMID: 19002131 DOI: 10.1038/ncpgasthep1298] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2008] [Accepted: 10/06/2008] [Indexed: 12/12/2022]
Abstract
Despite advances in our knowledge of celiac disease, the most current and authoritative recommendations conclude that diagnosis requires at least four biopsy specimens to be taken from the duodenal area. These recommendations are based on the perception that classic endoscopic markers are not adequate to target biopsy sampling to sites of villous damage in the duodenum. In the past few years, newly developed procedures and technologies have improved endoscopic recognition of the duodenum. These advances make possible the real-time recognition of the duodenal villous pattern during an upper endoscopy procedure, and thereby have the potential to optimize diagnostic accuracy. It is, therefore, reasonable to hypothesize that upper endoscopy might have a more incisive role in the diagnosis of celiac disease than merely providing a means of obtaining biopsy specimens for histological analysis. This Review highlights the new technologies in the field of upper endoscopy that could be helpful for the diagnosis of celiac disease, including the water-immersion technique, chromoendoscopy, high-resolution magnification endoscopy, optimal band imaging, optical coherence tomography and confocal endomicroscopy.
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Armelao F, Portolan F, Togni R. Mosaic-patterned and scalloped duodenal mucosa in Whipple's disease. Clin Gastroenterol Hepatol 2008; 6:A32. [PMID: 18691947 DOI: 10.1016/j.cgh.2008.04.017] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2008] [Revised: 04/17/2008] [Accepted: 04/18/2008] [Indexed: 02/07/2023]
Affiliation(s)
- Franco Armelao
- Department of Gastroenterology, Azienda Provinciale per i Servizi Sanitari, Ospedale S. Chiara, Largo Medaglie d'Oro, Trento, Italy
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Abstract
Celiac disease is a disease of the small intestine caused by an immune response to ingested gluten. This response results in characteristic damage to the villi, resulting in malabsorption. It is far more prevalent and its presentation can be far more subtle than once recognized. The prevalence of celiac disease in children in the general U.S. population is estimated to be 1 in 100. Toddlers and young children classically present with failure to thrive, diarrhea, and abdominal distension sometime after the introduction of gluten in the diet, but more often they present with subtle gastrointestinal symptoms such as constipation. Some children may be asymptomatic. Symptomatic patients and high-risk individuals should have serologic testing and testing of their total immunoglobulin A. Seropositive patients should undergo upper endoscopy and small-bowel biopsy of the distal duodenum. Treatment is lifelong adherence to a gluten-free diet. Families must meet with a dietician and should be strongly encouraged to participate in celiac support groups. The gastroenterology nurse is in an unparalleled position to assist parents of children newly diagnosed with celiac disease to identify the necessary lifestyle changes to make their child's life gluten free.
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Savas N, Akbulut S, Saritas U, Koseoglu T. Correlation of clinical and histopathological with endoscopic findings of celiac disease in the Turkish population. Dig Dis Sci 2007; 52:1299-303. [PMID: 17356915 DOI: 10.1007/s10620-006-9540-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2006] [Accepted: 07/20/2006] [Indexed: 12/12/2022]
Abstract
Endoscopic findings have been described for the diagnosis of celiac disease but the relationship among the clinical presentation, endoscopic markers, and the degree of histopathological findings is not clear. Thirty patients who were thought to have celiac disease were included in this study. Biopsies taken from the duodenum were examined histopathologically. The relationship among the endoscopic, clinical, and histopathological findings were investigated. Partial villous atrophy was seen in 14 patients (46.6%), and subtotal and total villous atrophy were seen in 6 (20%) patients each. Eighty six percent of patients with a mosaic appearance, 76% of patients with the finding of loss of folds, and 90% of patients with scalloping on endoscopy had either partial villous atrophy, subtotal villous atrophy, or total villous atrophy on biopsy. We conclude that endoscopic findings in celiac disease can reveal valuable information both for diagnosis and for demonstration of the severity of the disease state.
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Affiliation(s)
- Nurten Savas
- Department of Gastroenterology, Baskent University Faculty of Medicine, Fevzi Cakmak Cad. 10, Sok No. 45, Bahcelievler, Ankara, 06490, Turkey.
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Ozaslan E, Akkorlu S, Eskioğlu E, Kayhan B. Prevalence of silent celiac disease in patients with dyspepsia. Dig Dis Sci 2007; 52:692-7. [PMID: 17235704 DOI: 10.1007/s10620-006-9453-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2006] [Accepted: 05/12/2006] [Indexed: 12/31/2022]
Abstract
Celiac disease (CD) has become more common than in the past, although it frequently remains undetected for long periods of time. One reason for this is failure by health care professionals to recognize the variable clinical manifestations of CD and to perform the appropriate tests to make the diagnosis. Although dyspepsia may be part of a clinical spectrum in CD patients, there are scarce data about its prevalence in silent CD. We aimed to determine the prevalence of CD in otherwise healthy dyspeptic patients by means of serologic screening followed by endoscopic biopsies if appropriate. Anti-endomysium antibody assay was positive in 3 of 196 patients. All 3 were female, ages ranged from 19-52 years (mean +/- SD age, 36 +/- 16 years). Duodenal biopsies were compatible with CD in all, whereas abnormal endoscopic findings were noted in 2. Therefore, a 1.5% prevalence of CD was observed in this study group. The odds ratio for CD was 2.57 (95% confidence interval) in comparison with the general population. CD should be kept in mind as a cause of dyspepsia during clinical activities. The association between these 2 conditions is, at most, weak, but a gluten-free diet may still bring symptomatic relief for dyspeptic symptoms in CD. During endoscopic examination for dyspepsia, if indicated, endoscopists should carefully inspect the duodenum for CD findings. Although routine serologic screening can not be recommended, it may be appropriate for the patients with refractory dyspepsia, especially females.
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Affiliation(s)
- Ersan Ozaslan
- Department of Gastroenterology, Numune Education and Training Hospital, Ileri Mah. Mektep Sok. No: 7/10, Kurtuluş, 06660 Ankara, Turkey.
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Hopper AD, Sidhu R, Hurlstone DP, McAlindon ME, Sanders DS. Capsule endoscopy: an alternative to duodenal biopsy for the recognition of villous atrophy in coeliac disease? Dig Liver Dis 2007; 39:140-5. [PMID: 16965945 DOI: 10.1016/j.dld.2006.07.017] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2006] [Revised: 07/22/2006] [Accepted: 07/27/2006] [Indexed: 12/11/2022]
Abstract
BACKGROUND Villous atrophy present on a duodenal biopsy remains the 'gold standard' diagnostic test for coeliac disease. However, endoscopic biopsy may cause morbidity and discomfort. Our aim was to evaluate wireless capsule endoscopy as an alternative test for the recognition of villous atrophy. METHOD Twenty-one patients with a positive endomysial antibody referred for endoscopy and duodenal biopsy were also offered a wireless capsule endoscopy to evaluate their small bowel. Concurrently, other patients (n=23) referred for a wireless capsule endoscopy acted as controls. Wireless capsule endoscopy reports were assessed for the presence of villous atrophy by one blinded investigator. RESULTS Twenty endomysial antibody positive patients subsequently had villous atrophy on duodenal biopsy. The controls all had normal duodenal biopsies (with a negative endomysial antibody) and no evidence of villous atrophy noted on their wireless capsule endoscopy. Of the 20 endomysial antibody positive patients with confirmed villous atrophy on biopsy, 17 had villous atrophy also detected by wireless capsule endoscopy. The sensitivity, specificity, positive and negative predictive values for wireless capsule endoscopy recognising villous atrophy were 85%, 100%, 100%, 88.9%, respectively. CONCLUSION Wireless capsule endoscopy may be an option to recognise villous atrophy in patients with a positive endomysial antibody who are unwilling, or unable to have a gastroscopy. However, a negative test should be followed by a biopsy if coeliac disease is to be excluded.
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Affiliation(s)
- A D Hopper
- Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK.
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Ramakrishna BS, Venkataraman S, Mukhopadhya A. Tropical malabsorption. Postgrad Med J 2006; 82:779-87. [PMID: 17148698 PMCID: PMC2653921 DOI: 10.1136/pgmj.2006.048579] [Citation(s) in RCA: 64] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2006] [Accepted: 06/19/2006] [Indexed: 01/25/2023]
Abstract
Malabsorption is an important clinical problem both in visitors to the tropics and in native residents of tropical countries. Infections of the small intestine are the most important cause of tropical malabsorption. Protozoal infections cause malabsorption in immunocompetent hosts, but do so more commonly in the setting of immune deficiency. Helminth infections occasionally cause malabsorption or protein-losing enteropathy. Intestinal tuberculosis, chronic pancreatitis and small-bowel bacterial overgrowth are important causes of tropical malabsorption. In recent years, inflammatory bowel disease and coeliac disease have become major causes of malabsorption in the tropics. Sporadic tropical sprue is still an important cause of malabsorption in adults and in children in South Asia. Investigations to exclude specific infective, immunological or inflammatory causes are important before considering tropical sprue as a diagnosis. This article briefly reviews the management of tropical sprue and presents an algorithm for its investigation and management.
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Affiliation(s)
- B S Ramakrishna
- Department of Gastrointestinal Sciences, Christian Medical College, Vellore, Tamil Nadu, India.
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Dickey W. Endoscopic markers for celiac disease. ACTA ACUST UNITED AC 2006; 3:546-51. [PMID: 17008924 DOI: 10.1038/ncpgasthep0601] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2006] [Accepted: 07/14/2006] [Indexed: 12/18/2022]
Abstract
Celiac disease is common and can present with nonspecific upper gastrointestinal symptoms. Patients may therefore undergo esophagogastroduodenoscopy as their initial investigation. Markers of villous atrophy, which can be seen in the duodenum during endoscopy, are well described. They have limited sensitivity for patients with mild enteropathy and duodenal biopsies should be performed if there is strong suspicion of celiac disease irrespective of endoscopic appearance. Endoscopic markers do, however, allow the selection of patients with nonspecific symptoms for duodenal biopsy, and these markers should, therefore, be looked for routinely during esophagogastroduodenoscopy.
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Affiliation(s)
- William Dickey
- Department of Gastroenterology, Altnagelvin Hospital, Londonderry BT47 6SB, Northern Ireland, UK.
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Green PHR, Rubin M. Capsule endoscopy in celiac disease: diagnosis and management. Gastrointest Endosc Clin N Am 2006; 16:307-16. [PMID: 16644459 DOI: 10.1016/j.giec.2006.03.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Celiac disease occurs in about 1% of the population. Although diarrhea is the classical presentation, the diagnosis of celiac disease is frequently not considered as part of the differential diagnosis of a variety of different symptoms. It is,therefore, imperative that physicians who perform capsule endoscopy, and those who review the images, are aware of the variety of mucosa appearances inpatients who have celiac disease. In addition, studies are needed to determine the role of capsule endoscopy in the diagnosis and management of celiac disease.
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Affiliation(s)
- Peter H R Green
- Department of Medicine, Columbia University College of Physicians and Surgeons, 161 Fort Washington Avenue, New York, NY 10032, USA.
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Wischmann M, Buchwald AB. [20-year old woman with diarrhea of unknown etiology]. Internist (Berl) 2006; 47:287-8, 290-2. [PMID: 16416301 DOI: 10.1007/s00108-005-1546-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
We report on a 20-year old woman who suffered from watery diarrhea. The results of the histology and the serology as well as clinical symptoms lead us to the diagnosis of sprue. Under specific gluten-free diet the diarrhea frequency was reduced. After a few weeks the patient returned to hospital again because of watery diarrhea. Histological examination of duodenal biopsy specimen showed a protracted infectious duodenitis and a secondary villous flattening of the small bowel. This diagnosis was a life-threatening illness that needed antibiotic treatment. These patients receive parenteral nutrition as long as the villous have not been recovered from the flattening. Additionally octreotid can be given to reduce the frequency of the diarrhea.
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Affiliation(s)
- M Wischmann
- I. Medizinische Klinik, Städtisches Krankenhaus Kiel GmbH, Akademisches Lehrkrankenhaus des Universitätsklinikums Schleswig-Holsteins.
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