|
1
|
Deb A, Moond V, Thongtan T, Deliwala S, Chandan S, Mohan BP, Adler DG. Role of Duodenal Bulb Biopsy in Diagnosing Suspected Celiac Disease in Adult Patients: A Systematic Review and Meta-analysis. J Clin Gastroenterol 2024; 58:588-595. [PMID: 37646538 DOI: 10.1097/mcg.0000000000001913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 07/19/2023] [Indexed: 09/01/2023]
Abstract
BACKGROUND AND AIMS Current guidelines recommend multiple biopsies from the first (D1) and second (D2) part of duodenum to establish a diagnosis of celiac disease. In this meta-analysis we aimed to find whether D1 biopsy can increase the diagnostic yield of adult celiac disease. METHODS Literature databases were searched until January 2023 for studies reporting diagnosis of celiac disease in the adult population using D1 biopsy. Meta-analysis was done using a random-effects model. Heterogeneity was assessed by I 2 % and 95% prediction interval statistics. Measured outcomes were diagnostic yield with D1 and D2 biopsies and from 4 versus 2 biopsy samples. RESULTS A total of 16 studies were included in the final analysis. The pooled diagnostic rate of celiac disease from D1 biopsy was 77.4% [95% CI (64.7-86.5, I 2 94%)] and from D2 biopsy was 75.3% [60.8-85.7, I 2 96%]. The pooled rate of increase in diagnostic yield with D1 biopsy was 6.9% I [4.6-10.2, I 2 66%]. The pooled diagnosis rate with 2 biopsy samples were 77.3% [50-92, I 2 93%] and 86.4% I [58.4-96.7, I 2 87%] from D1 and D2 respectively, whereas that with 4 biopsy samples were 83.3% [49.8-96.2, I 2 76%] and 70.5% I [51-84.6, I 2 96%] from D1 and D2, respectively, the difference being non-significant. CONCLUSION Our study demonstrates that taking 4 biopsy samples does not incur any additional diagnostic value over taking 2 biopsy samples from each duodenum segment. Although biopsy from the D1 and D2 has similar diagnostic yield in the adult population, there was an overall increase in diagnostic yield with D1 biopsy, especially in those with a patchy disease distribution.
Collapse
Affiliation(s)
- Anasua Deb
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock
| | - Vishali Moond
- Department of Internal Medicine, Saint Peter's University Hospital/Robert Wood Johnson Medical School, New Brunswick, NJ
| | - Thanita Thongtan
- Division of Gastroenterology & Hepatology, The University of Texas Rio Grande Valley, Edinburg, TX
| | - Smit Deliwala
- Division of Digestive Diseases, Emory University School of Medicine, Atlanta, GA
| | - Saurabh Chandan
- Division of Gastroenterology & Hepatology, Creighton University School of Medicine, Omaha, NE
| | - Babu P Mohan
- Gastroenterology & Hepatology, University of Utah Health School of Medicine, Salt Lake City, UT
| | - Douglas G Adler
- Director, Center for Advanced Therapeutic Endoscopy, Centura Health, Porter Adventist Hospital, Denver, CO
| |
Collapse
|
|
2
|
Jansson-Knodell CL, Rubio-Tapia A. Gluten-related Disorders From Bench to Bedside. Clin Gastroenterol Hepatol 2024; 22:693-704.e1. [PMID: 37879521 DOI: 10.1016/j.cgh.2023.09.042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 09/26/2023] [Accepted: 09/29/2023] [Indexed: 10/27/2023]
Abstract
Celiac disease, non-celiac gluten sensitivity, and wheat allergy comprise 3 of the main conditions with wheat- and gluten-containing foods as the symptom trigger. Distinguishing between these entities can be daunting. In this review, we compare and contrast celiac disease, non-celiac gluten sensitivity, and wheat allergy to allow clinicians to determine which diagnosis fits their patient to facilitate high-quality management and longitudinal care.
Collapse
Affiliation(s)
- Claire L Jansson-Knodell
- Celiac Disease Program, Division of Gastroenterology, Hepatology, and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio
| | - Alberto Rubio-Tapia
- Celiac Disease Program, Division of Gastroenterology, Hepatology, and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio.
| |
Collapse
|
|
3
|
Ancona S, Bianchin S, Zampatti N, Nosratian V, Bigatti C, Ferro J, Trambaiolo Antonelli C, Viglizzo G, Gandullia P, Malerba F, Crocco M. Cutaneous Disorders Masking Celiac Disease: Case Report and Mini Review with Proposal for a Practical Clinical Approach. Nutrients 2023; 16:83. [PMID: 38201912 PMCID: PMC10780572 DOI: 10.3390/nu16010083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 12/16/2023] [Accepted: 12/21/2023] [Indexed: 01/12/2024] Open
Abstract
Celiac disease (CD) is an immune-mediated systemic gluten-related disorder characterized by a wide spectrum of intestinal and extra-intestinal manifestations, including damage to cutaneous and connective tissue. We report a rare case of chronic severe dermatitis involving connective tissue and cutaneous vascular vessels as the main clinical presentation of undiagnosed seronegative gluten disorder. A gluten-free diet dramatically improved the intestinal and cutaneous clinical damage in the patient. Pitfalls and the steps of differential diagnosis are described. We also review the literature regarding studies of CD and connective tissue diseases to extend the knowledge of these rare associations. We propose a practical diagnostic approach in suspected CD in autoimmune cutaneous disorders.
Collapse
Affiliation(s)
- Silvana Ancona
- Pediatric Gastroenterology and Endoscopy Unit, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy (P.G.); (F.M.)
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genova, 16132 Genoa, Italy
| | - Silvia Bianchin
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genova, 16132 Genoa, Italy
| | - Noemi Zampatti
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genova, 16132 Genoa, Italy
| | | | - Carolina Bigatti
- UO Nephrology Dialysis and Transplant, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy
| | - Jacopo Ferro
- Pathology Unit, U.O.C. Anatomia Patologica, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy; (J.F.); (C.T.A.)
| | - Chiara Trambaiolo Antonelli
- Pathology Unit, U.O.C. Anatomia Patologica, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy; (J.F.); (C.T.A.)
| | | | - Paolo Gandullia
- Pediatric Gastroenterology and Endoscopy Unit, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy (P.G.); (F.M.)
| | - Federica Malerba
- Pediatric Gastroenterology and Endoscopy Unit, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy (P.G.); (F.M.)
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genova, 16132 Genoa, Italy
| | - Marco Crocco
- Pediatric Gastroenterology and Endoscopy Unit, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy (P.G.); (F.M.)
| |
Collapse
|
|
4
|
Behl S, Khan MR, Ismail Y, Swantek C, Chen ZME, Murray JA, Absah I. The Characteristics of Isolated Bulb Celiac Disease in Children. J Pediatr Gastroenterol Nutr 2023; 77:79-85. [PMID: 37084335 DOI: 10.1097/mpg.0000000000003799] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/23/2023]
Abstract
OBJECTIVES Mucosal injury in celiac disease (CD) patients can be patchy, and up to 12% of CD patients can have mucosal changes limited to the duodenal bulb. Hence, recent guidelines recommend obtaining bulb biopsies in addition to distal duodenum. This study aimed to describe a cohort of children with isolated bulb CD and assess the benefit of separating bulb biopsies. METHODS A retrospective chart review between January 2011 and January 2022 at 2 medical centers was conducted. We included children with CD who underwent endoscopy with separated biopsies from the bulb and distal duodenum. A blinded pathologist performed Marsh-Oberhuber grading on selected cases. RESULTS We identified 224 CD patients, of which 33 (15%) had histologically confirmed isolated bulb CD. Patients with isolated bulb CD were older at diagnosis (10 vs 8 years; P = 0.03). Median anti-tissue transglutaminase immunoglobulin A (TTG IgA) level was lower in isolate bulb CD (2.8 vs 16.7 times the upper limit of normal [ULN], P < 0.001). Almost 88% (29/33) of isolated bulb CD patients had an anti-TTG IgA value of less than 10 times the ULN. Time to anti-TTG IgA normalization (mean 14 months) was similar between the 2 groups. A pathologist review of diagnostic biopsies could not distinguish between the bulb and distal duodenum biopsies in approximately one-third of the reviewed samples. CONCLUSIONS Separating bulb from distal duodenum biopsies can be considered during CD diagnosis, particularly in children with anti-TTG IgA levels less than 10 times the ULN. Larger prospective cohorts are needed to decide whether isolated bulb CD is a unique cohort or an early stage of the conventional CD.
Collapse
Affiliation(s)
- Supriya Behl
- From the Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN
| | - Muhammad Rehan Khan
- the Division of Pediatric Gastroenterology, Hepatology & Nutrition, University of Illinois College of Medicine at Peoria; Children's Hospital of Illinois, Peoria, IL
| | - Yasmine Ismail
- the Division of Pediatric Gastroenterology and Hepatology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN
| | - Courtney Swantek
- the Department of Pediatrics/Medicine, University of Illinois College of Medicine at Peoria, Peoria, IL
| | | | - Joseph A Murray
- the Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Imad Absah
- the Division of Pediatric Gastroenterology and Hepatology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN
| |
Collapse
|
|
5
|
Trovato CM, Oliva S, Pietropaoli N, Pignataro MG, Berni S, Tancredi A, Cucchiara S, Giordano C, Montuori M. A new double immunohistochemistry method to detect mucosal anti-transglutaminase IgA deposits in coeliac children. Dig Liver Dis 2022; 54:200-206. [PMID: 34844876 DOI: 10.1016/j.dld.2021.11.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 11/02/2021] [Accepted: 11/08/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Intestinal transglutaminase (TG2) IgA deposits represent early marker of coeliac disease (CeD) and can predict the evolution towards intestinal atrophy. AIMS To validate a double immunohistochemistry method for the determination of intestinal TG2 IgA deposits on formalin-fixed paraffin-embedded biopsies. METHODS Immunohistochemistry was tested on: 1) children with overt CeD [persistently positive serum IgA anti-tissue transglutaminase type 2 (TGA-IgA) with moderate or low titer, and histological findings of CeD]; 2) potential CeD (persistently positive serum TGA-IgA and normal intestinal mucosa) and 3) controls (negative serum TGA-IgA and normal intestinal mucosa). RESULTS Samples from 61 children were analyzed (32 overt CeD, 14 potential CeD, and 15 controls). Deposits appeared as focal, multifocal, or confluent extracellular foci of red and brown staining colocalization in the sub-epithelium and around mucosal vessels. Deposits were present in all 32 children with overt CeD and in 9/14 potential CeD. Deposits were never observed in the 15 controls. Patients with higher serum level of TGA-IgA and with mucosal atrophy showed mostly a multifocal/diffuse pattern of deposits distribution. The bulb appeared most severely involved. In potential CeD deposits showed mainly a focal distribution. CONCLUSION Our results indicate double immunohistochemistry as promising diagnostic tool to improve diagnosis of CeD.
Collapse
Affiliation(s)
- Chiara Maria Trovato
- Maternal and Child Health Department, Sapienza - University of Rome, Rome, Italy; Hepatology Gastroenterology and Nutrition Unit, "Bambino Gesù" Children Hospital, 00165 Rome, Italy
| | - Salvatore Oliva
- Maternal and Child Health Department, Sapienza - University of Rome, Rome, Italy
| | | | - Maria Gemma Pignataro
- Department of Radiology, Oncology and Pathology, Sapienza, University of Rome, Rome, Italy
| | - Silvia Berni
- Department of Radiology, Oncology and Pathology, Sapienza, University of Rome, Rome, Italy
| | - Andrea Tancredi
- Department of Methods and Models for Economy, Territory and Finance, Sapienza, University of Rome, Rome, Italy
| | - Salvatore Cucchiara
- Maternal and Child Health Department, Sapienza - University of Rome, Rome, Italy
| | - Carla Giordano
- Department of Radiology, Oncology and Pathology, Sapienza, University of Rome, Rome, Italy.
| | - Monica Montuori
- Maternal and Child Health Department, Sapienza - University of Rome, Rome, Italy.
| |
Collapse
|
|
6
|
Montoya-Cerrillo D, Bernieh A, Saad AG. Critical diagnoses in paediatric gastrointestinal diseases. Pathology 2022; 54:195-206. [PMID: 35033374 DOI: 10.1016/j.pathol.2021.09.023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 09/26/2021] [Accepted: 09/30/2021] [Indexed: 12/11/2022]
Abstract
Gastrointestinal biopsies represent an increasing proportion of the paediatric pathologist's workload, an increase fundamentally due to an expansion of the understanding of the basic clinical, molecular, genetic, and histopathological features of paediatric gastrointestinal disorders. The histological interpretation of endoscopically retrieved gastrointestinal biopsies in children requires a unique set of diagnostic expertise and detailed knowledge of various gastrointestinal disorders that have a predilection for the paediatric population. This article's major role is to highlight the unique problems inherent to paediatric gastrointestinal disorders that require immediate communication with the paediatric surgeon or the gastroenterologist. For this, we tried to cover the most important diseases that a paediatric pathologist might encounter in daily practice. Some of these diseases are relatively rare, such as microvillous inclusion disease and tufting enteropathy, but some are more common such as eosinophilic disorders and inflammatory bowel disease. Awareness of the histopathological features of these diseases, particularly those that are relatively uncommon, is crucial to spare the patient a lengthy and costly evaluation. We made a particular effort to abundantly reference this article should the reader wish to expand on the content of any section.
Collapse
Affiliation(s)
| | - Anas Bernieh
- Division of Pathology, Cincinnati Children's Hospital, Cincinnati, OH, USA
| | - Ali G Saad
- Department of Pathology, University of Miami Miller School of Medicine, Miami, FL, USA.
| |
Collapse
|
|
7
|
Rostami-Nejad M, Asri N. Conclusion and insights. GLUTEN-RELATED DISORDERS 2022:265-277. [DOI: 10.1016/b978-0-12-821846-4.00015-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
8
|
Abstract
Celiac disease is a chronic, immune-mediated enteropathy driven by dietary gluten found in genetically susceptible hosts. It has a worldwide distribution, is one of the most common autoimmune disorders globally, and is the only autoimmune condition for which the trigger is known. Despite advances in characterizing mechanisms of disease, gaps in understanding of celiac disease pathogenesis remain. A "frontier" concept is considering what moves an HLA-DQ2 or DQ8-positive individual from asymptomatic gluten tolerance to celiac disease manifestation. In this arena, environmental triggers, including age at the time of initial gluten exposure, the occurrence of usual childhood viral infections, and microbiome alterations have emerged as key events in triggering the symptomatic disease. Pathologists play a major role in frontier aspects of celiac disease. This includes the discovery that duodenal mucosal histology in follow-up biopsies does not correlate with ongoing patient symptoms, antitissue transglutaminase antibody titers and diet adherence in celiac disease patients. Further, in light of recent evidence that the detection of monoclonal T-cell populations in formalin-fixed biopsies is not specific for type II refractory celiac disease, pathologists should resist performing such analyses until common causes of "apparent" refractoriness are excluded. The promise of therapies in celiac disease has led to clinical trials targeting many steps in the inflammatory cascade, which depend upon a pathologist's confirmation of the initial diagnosis and evaluation of responses to therapies. As pathologists continue to be active participants in celiac disease research, partnering with other stakeholders, we will continue to impact this important autoimmune disease.
Collapse
Affiliation(s)
- Natalie Patel
- El Camino Pathology Medical Group, Mountain View, CA
| | - Marie E Robert
- Department of Pathology and Medicine, Yale University School of Medicine, New Haven, CT
| |
Collapse
|
|
9
|
Bishop J, Ravikumara M. Coeliac disease in childhood: An overview. J Paediatr Child Health 2020; 56:1685-1693. [PMID: 33197972 DOI: 10.1111/jpc.14674] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Revised: 10/04/2019] [Accepted: 10/09/2019] [Indexed: 12/13/2022]
Abstract
Coeliac disease (CD) is an autoimmune condition, characterised by an immunological response to ingestion of gluten in genetically susceptible individuals, affecting about 1% of the population in many regions of the world. Increased knowledge regarding the pathogenesis, improved diagnostic techniques and increased awareness over the years have transformed our understanding of CD such that it is no longer a rare enteropathy, but rather a common multisystem disorder which affects individuals of all ages and results in wide-ranging clinical manifestations. Only a minority of children now present with the classical clinical picture of profound diarrhoea and malnutrition. An increasing number of children with CD present with either mild, non-specific gastrointestinal symptoms or extra-intestinal manifestations or even be asymptomatic, as in many screening-detected children. Knowledge about these diverse manifestations and a high index of suspicion is essential so that appropriate investigations can be undertaken, diagnosis established and treatment initiated. Although traditionally small bowel biopsy is considered essential for the diagnosis, recent guidelines from various professional bodies have paved the way to a biopsy-free diagnosis in a subset of symptomatic children. Life long, strict gluten-free diet still remains the only effective treatment at present, although several novel therapeutic agents are in various phases of clinical trials.
Collapse
Affiliation(s)
- Jonathan Bishop
- Department of Gastroenterology, Starship Hospital, Auckland, New Zealand
| | - Madhur Ravikumara
- Department of Gastroenterology, Perth Children's Hospital, Perth, Western Australia, Australia
| |
Collapse
|
|
10
|
Badizadegan K, Vanlandingham DM, Hampton W, Thompson KM. Value of biopsy in a cohort of children with high-titer celiac serologies: observation of dynamic policy differences between Europe and North America. BMC Health Serv Res 2020; 20:962. [PMID: 33081760 PMCID: PMC7576777 DOI: 10.1186/s12913-020-05815-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Accepted: 10/12/2020] [Indexed: 12/16/2022] Open
Abstract
Background Healthcare systems implement change at different rates because of differences in incentives, organizational processes, key influencers, and management styles. A comparable set of forces may play out at the national and international levels as demonstrated in significant differences in the diagnostic management of pediatric Celiac Disease (CD) between European and North American practitioners. Methods We use retrospective clinical cohorts of 27,868 serum tissue transglutaminase (tTG) immunoglobulin A levels and 7907 upper gastrointestinal endoscopy pathology reports to create a dataset of 793 pathology reports with matching tTG results between July 1 of 2014 and July 1 of 2018. We use this dataset to characterize histopathological findings in the duodenum, stomach and esophagus of patients as a function of serum tTG levels. In addition, we use the dataset to estimate the local and national cost of endoscopies performed in patients with serum tTG levels greater than 10 times the upper limit of normal. Results Using evidence from a US tertiary care center, we show that in the cohort of pediatric patients with high pre-test probability of CD as determined by serum tTG levels, biopsy provides no additional diagnostic value for CD, and that it counter-intuitively introduces diagnostic uncertainty in a number of patients. We estimate that using the European diagnostic algorithms could avoid between 4891 and 7738 pediatric endoscopies per year in the US for evaluation of CD. Conclusions This study considers the North American and European management guidelines for the diagnosis of pediatric CD and highlights the slow adoption in North America of evidence-based algorithms developed and applied in Europe for triage of endoscopy and biopsy. We suggest that system dynamics influences that help maintain the status quo in North America include a variety of social and economic factors in addition to medical evidence. This work contributes to the growing body of evidence that the dynamics that largely favor maintaining status quo management policies in a variety of systems extend to clinical medicine and potentially influence clinical decisions at the level of individual patients and the population. Supplementary information Supplementary information accompanies this paper at 10.1186/s12913-020-05815-0.
Collapse
Affiliation(s)
| | - David M Vanlandingham
- Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA
| | - Wesley Hampton
- Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA
| | | |
Collapse
|
|
11
|
Boschee E, Lacson A, Turner J, Yap J. Duodenal Bulb Histology in Paediatric Celiac Disease: A Case-Control Study. J Can Assoc Gastroenterol 2020; 3:210-215. [PMID: 32905200 PMCID: PMC7465544 DOI: 10.1093/jcag/gwz014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2019] [Accepted: 04/25/2019] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Controversy exists about optimal methods for duodenal biopsy in diagnosis of celiac disease (CD), in terms of both number of samples and anatomic location. The reliability of duodenal bulb biopsy has been questioned given that normal bulb architecture may mimic disease. However, multiple studies have reported patients with CD have histopathological lesions limited to proximal changes in the duodenal bulb alone. METHODS We retrospectively compared duodenal and duodenal bulb histology in a population of paediatric patients with CD and compared with a population of nonceliac controls at Stollery Children's Hospital, 2010 to 2012. RESULTS Fifty-seven paediatric patients diagnosed with CD and 16 nonceliac controls were included in the study. Fifty-three celiac patients (93.0%) had histopathology consistent with CD (modified Marsh score of 3A, 3B or 3C) in the duodenal bulb. The modified Marsh classification differed significantly between duodenum and duodenal bulb in nine celiac patients (15.8%). Of these, five (8.8%) had Marsh 3 in the bulb and Marsh 0 in the distal duodenum. Among controls, no patients had villous atrophy in either the distal duodenum or duodenal bulb, and all patients had a modified Marsh score of 0 at both sites. CONCLUSIONS The results of this study reinforce that duodenal bulb samples are critically important for diagnosing CD in paediatric patients. We suggest that duodenal bulb samples be submitted in separate containers from distal duodenal samples to facilitate accurate interpretation. In contrast to prior reports, we found villous blunting and intraepithelial lymphocytosis are actually uncommon findings in paediatric patients with nonceliac gastrointestinal disorders.
Collapse
Affiliation(s)
- Erin Boschee
- Division of Pediatric Hospital Medicine, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
| | - Atilano Lacson
- Department of Laboratory Medicine & Pathology, University of Alberta, Edmonton, Alberta, Canada
| | - Justine Turner
- Division of Pediatric Gastroenterology, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
| | - Jason Yap
- Division of Pediatric Gastroenterology, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
| |
Collapse
|
|
12
|
Duodenal bulb biopsy in the diagnostic work-up of coeliac disease. Virchows Arch 2020; 477:507-515. [PMID: 32405928 DOI: 10.1007/s00428-020-02832-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Revised: 04/21/2020] [Accepted: 04/28/2020] [Indexed: 12/20/2022]
Abstract
Coeliac disease (CD) is an autoimmune enteropathy which can present with patchy mucosal lesions. The aim of the present study is to investigate the significance of duodenal bulb biopsy in the diagnostic work-up of CD in both pediatric and adult patients, and to highlight the key points for pathologists. D1 (duodenal bulb) and D2 (distal duodenum) biopsies of 153 newly diagnosed serology-positive CD patients were evaluated for villous/crypt ratio and intraepithelial lymphocyte (IEL) counts on CD3-stained slides and were classified according to Marsh. Mucosal pathology was patchy in 15% (13% only D1 and 2% only D2) of patients, and 85% of patients had diffuse mucosal pathology involving both D1 and D2 biopsies which showed concordant histology in 60% and discordant in 25% of the cases. Though majority of the patients (75%) with only D1 involvement were pediatric cases, no significant difference was found between pediatric and adult patients when all cases were considered (17 vs 14%). Our results clearly indicate that without D1 sampling, diagnosis of CD would have been missed in a significant number of cases (13%), thereby highlighting the importance of taking duodenal biopsies from multiple sites in the diagnostic work-up of CD. We, therefore, conclude that every biopsy piece from both D1 and D2 should be carefully evaluated for the whole spectrum of mucosal changes caused by gluten ingestion and classified using a scheme based on Marsh to allow recognition of mild lesions.
Collapse
|
|
13
|
Abstract
PURPOSE OF REVIEW The aim of this review is to provide insight into the diagnosis and management of patients with refractory coeliac disease (RCD) and highlight recent advances in this field. RECENT FINDINGS The diagnosis of RCD can be more accurately confirmed with flow cytometry in addition to immunohistochemistry. Dietary input and excretion of gluten immunogenic peptides can help rule out gluten contamination, and therefore, substantiate a diagnosis of RCD type I. Small bowel capsule endoscopy (SBCE) is important at diagnosis and follow-up in addition to duodenal histology. Apart from ruling out complications, it can give information on extent of disease in the small bowel, and therefore, help assess response to therapy. Those patients with a poor response can have earlier intensification of therapy, which may result in an improved outcome. RCD also occurs in patients with serology negative coeliac disease but with an increased mortality compared with patients with serology-positive coeliac disease. SUMMARY Patients with RCD can present with persistent symptoms of malnutrition but can also be completely asymptomatic. Serology is not a reliable marker to detect refractory disease. Immunostaining and flow cytometry are necessary for a diagnosis of RCD. Small bowel endoscopy enables disease extent to be assessed and allows for small bowel biopsies to be taken in case of suspicious lesions. Small bowel radiology can be complementary to small bowel endoscopy.
Collapse
|
|
14
|
Molder A, Balaban DV, Jinga M, Molder CC. Current Evidence on Computer-Aided Diagnosis of Celiac Disease: Systematic Review. Front Pharmacol 2020; 11:341. [PMID: 32372947 PMCID: PMC7179080 DOI: 10.3389/fphar.2020.00341] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2019] [Accepted: 03/09/2020] [Indexed: 02/05/2023] Open
Abstract
Celiac disease (CD) is a chronic autoimmune disease that occurs in genetically predisposed individuals in whom the ingestion of gluten leads to damage of the small bowel. It is estimated to affect 1 in 100 people worldwide, but is severely underdiagnosed. Currently available guidelines require CD-specific serology and atrophic histology in duodenal biopsy samples for the diagnosis of adult CD. In pediatric CD, but in recent years in adults also, nonbioptic diagnostic strategies have become increasingly popular. In this setting, in order to increase the diagnostic rate of this pathology, endoscopy itself has been thought of as a case finding strategy by use of digital image processing techniques. Research focused on computer aided decision support used as database video capsule, endoscopy and even biopsy duodenal images. Early automated methods for diagnosis of celiac disease used feature extraction methods like spatial domain features, transform domain features, scale-invariant features and spatio-temporal features. Recent artificial intelligence (AI) techniques using deep learning (DL) methods such as convolutional neural network (CNN), support vector machines (SVM) or Bayesian inference have emerged as a breakthrough computer technology which can be used for computer aided diagnosis of celiac disease. In the current review we summarize methods used in clinical studies for classification of CD from feature extraction methods to AI techniques.
Collapse
Affiliation(s)
- Adriana Molder
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Center of Excellence in Robotics and Autonomous Systems, Military Technical Academy Ferdinand I, Bucharest, Romania
| | - Daniel Vasile Balaban
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Gastroenterology Department, Dr. Carol Davila Central Military Emergency University Hospital, Bucharest, Romania
- *Correspondence: Daniel Vasile Balaban,
| | - Mariana Jinga
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Gastroenterology Department, Dr. Carol Davila Central Military Emergency University Hospital, Bucharest, Romania
| | - Cristian-Constantin Molder
- Center of Excellence in Robotics and Autonomous Systems, Military Technical Academy Ferdinand I, Bucharest, Romania
| |
Collapse
|
|
15
|
The Challenge of Treatment in Potential Celiac Disease. Gastroenterol Res Pract 2019; 2019:8974751. [PMID: 31772571 PMCID: PMC6854910 DOI: 10.1155/2019/8974751] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Accepted: 08/19/2019] [Indexed: 02/06/2023] Open
Abstract
Potential celiac disease (PCD) is defined by the presence of positive serum antibodies, HLA-DQ2/DQ8 haplotypes, and a normal small intestinal mucosa (Marsh grade 0-1). This condition occurs in one-fifth of celiac disease (CD) patients and usually represents a clinical challenge. We reviewed genetic, histologic, and clinical features of this specific condition by performing a systematic search on MEDLINE, Embase, and Scholar database. Accordingly, we identified different genetic features in patients with PCD compared to the classical forms. Frequently, signs of inflammation (deposits of immunoglobulin A (IgA) and/or increased number of intraepithelial lymphocytes) can be clearly identify in the mucosa of PCD patients after an accurate histological assessment. Finally, the main challenge is represented by the treatment: the gluten-free diet should be considered only in the presence of gluten-dependent symptoms in both children and adults. What is known: (i) potential celiac disease (PCD) occurs in one-fifth of all celiac diseases (CD), and (ii) despite the absence of classical lesions, clear signs of inflammation are often detectable. What is new: (i) patients with PCD show different genetic features, and (ii) the presence of gluten-dependent symptoms is the main determinant to initiate the gluten-free diet, after a complete diagnostic work-up.
Collapse
|
|
16
|
Statement on Best Practices in the Use of Pathology as a Diagnostic Tool for Celiac Disease: A Guide for Clinicians and Pathologists. Am J Surg Pathol 2019; 42:e44-e58. [PMID: 29923907 DOI: 10.1097/pas.0000000000001107] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Small intestinal biopsy interpretation has been the cornerstone for the diagnosis of celiac disease for over 50 years. Despite the existence of sensitive and specific serological tests, duodenal mucosal biopsies continue to be obtained in the vast majority of patients in whom a diagnosis of celiac disease is being considered. The accurate evaluation of these biopsies requires coordination and information sharing between the gastroenterologist, laboratory, and pathologist in order to optimize tissue sampling, preparation and interpretation. This document, a collaboration between the Rodger C. Haggitt Gastrointestinal Pathology Society and the North American Association for the Study of Celiac Disease, is intended to provide clinicians and pathologists with a summary of best practices in the use of endoscopy and biopsy for patients with suspected celiac disease. The authors present a comprehensive and critical appraisal of the literature with respect to the topics of endoscopic findings, best methods for the obtaining biopsies, completing the pathology form and pathologic assessment, including evaluating intraepithelial lymphocytes and villous architecture. A discussion of conditions with overlapping pathologic findings in duodenal mucosal biopsies is presented. In order to provide additional guidance for challenging situations, the authors include an appendix containing practical suggestions. This review may be utilized in interdisciplinary discussions to optimize care for patients with possible celiac disease.
Collapse
|
|
17
|
Gibson JA, Odze RD. Tissue Sampling, Specimen Handling, and Laboratory Processing. CLINICAL GASTROINTESTINAL ENDOSCOPY 2019:51-68.e6. [DOI: 10.1016/b978-0-323-41509-5.00005-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
18
|
Prospective Evaluation of the ESPGHAN Guidelines for Diagnosis of Celiac Disease in New Zealand Children. J Pediatr Gastroenterol Nutr 2018; 67:749-754. [PMID: 29916948 DOI: 10.1097/mpg.0000000000002065] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE The 2012 European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guideline for diagnosis of celiac disease (CD) questioned the requirement for intestinal biopsy to confirm the diagnosis. The guideline recommends that in symptomatic patients with consistent human leukocyte antigen (HLA) subtypes, the diagnostic accuracy of strongly positive serology is sufficient to confirm the diagnosis. We prospectively assessed these guidelines in a "real-life" clinical setting. METHODS One hundred and four children referred for evaluation of possible CD were prospectively recruited. Following informed consent, blood was drawn for serological testing and HLA analysis at upper gastrointestinal endoscopy. Histological findings according to Marsh criteria were correlated with blood results and the accuracy of the guideline analyzed.The study also examined the role of deamidated gliadin peptide (DGP) in the diagnosis of CD. RESULTS For symptomatic patients with consistent HLA subtypes, strongly positive serology (as described in the ESPGHAN guidelines) accurately predicted biopsy-proven CD in >95% of cases. DGP was positive in fewer patients than anti-TG2 or EMA. Incorporation of DGP as a second confirmatory serological test in place of EMA was associated with maintained predictive value of guideline, but fewer patients fulfilling criteria for biopsy-free diagnosis. CONCLUSIONS The ESPGHAN guideline performs well in our population. Adoption of the guideline would reduce the number of patients requiring endoscopy without compromise in diagnostic accuracy. The involvement of pediatric gastroenterological expertise, however, remains key to diagnosis of CD.
Collapse
|
|
19
|
McCarty TR, O’Brien CR, Gremida A, Ling C, Rustagi T. Efficacy of duodenal bulb biopsy for diagnosis of celiac disease: a systematic review and meta-analysis. Endosc Int Open 2018; 6:E1369-E1378. [PMID: 30410959 PMCID: PMC6221829 DOI: 10.1055/a-0732-5060] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Accepted: 07/23/2018] [Indexed: 02/07/2023] Open
Abstract
Background and study aims Although duodenal biopsy is considered the "gold standard" for diagnosis of celiac disease, the optimal location of biopsy within the small bowel for diagnosis remains unclear. The primary aim of this study was to perform a structured systematic review and meta-analysis to evaluate the diagnostic utility of endoscopic duodenal bulb biopsy for celiac disease. Patients and methods Searches of PubMed, EMBASE, Web of Science, and Cochrane Library databases were performed from 2000 through December 2017. Review of titles/abstracts, full review of potentially relevant studies, and data abstraction was performed. Measured outcomes of adult and pediatric patients included location of biopsy, mean number of biopsies performed, and diagnosis of celiac disease as defined by the modified Marsh-Oberhuber classification. Results A total of 17 studies (n = 4050) were included. Seven studies evaluated adults and 11 studies assessed pediatric populations. Mean age of adults and pediatric patients was 46.70 ± 2.69 and 6.33 ± 1.26 years, respectively. Overall, sampling from the duodenal bulb demonstrated a 5 % (95 % CI 3 - 9; P < 0.001) increase in the diagnostic yield of celiac disease. When stratified by pediatric and adult populations, duodenal bulb biopsy demonstrated a 4 % (95 % CI: 1 to 9; P < 0.001) and 8 % (95 % CI: 6 to 10; P < 0.001) increase in the diagnostic yield of celiac disease. Non-celiac histologic diagnoses including Brunner gland hyperplasia and peptic duodenitis were reported more commonly in the duodenal bulb as compared to the distal duodenum with an increase in diagnostic yield of 4 % (95 % CI 3 - 5; P < 0.001) and 1 % (95 % CI 1 - 2; P < 0.001), respectively. Conclusions Based upon our results, biopsy and histologic examination of duodenal bulb during routine upper endoscopy increases the diagnostic yield of celiac disease.
Collapse
Affiliation(s)
- Thomas R. McCarty
- Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States
| | - Corey R. O’Brien
- Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States
| | - Anas Gremida
- Division of Gastroenterology and Hepatology, University of New Mexico, Albuquerque, New Mexico, United States
| | - Christina Ling
- Division of Gastroenterology and Hepatology, University of New Mexico, Albuquerque, New Mexico, United States
| | - Tarun Rustagi
- Division of Gastroenterology and Hepatology, University of New Mexico, Albuquerque, New Mexico, United States,Corresponding author Tarun Rustagi, MD Division of Gastroenterology and HepatologyUniversity of New MexicoMSC10 5550, 1 University of New MexicoAlbuquerque NM 87131+1-505-272-9751
| |
Collapse
|
|
20
|
Chetcuti Zammit S, Sanders DS, Sidhu R. A comprehensive review on the utility of capsule endoscopy in coeliac disease: From computational analysis to the bedside. Comput Biol Med 2018; 102:300-314. [PMID: 29980284 DOI: 10.1016/j.compbiomed.2018.06.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Revised: 06/23/2018] [Accepted: 06/24/2018] [Indexed: 11/29/2022]
Abstract
Small bowel capsule endoscopy (SBCE) can identify macroscopic changes of coeliac disease and assess the extent of disease in the small bowel beyond the duodenum. SBCE has a good sensitivity for the detection of coeliac disease in comparison to histology owing to several ideal features such as a high magnification. It also plays a useful role in detecting complications in patients with refractory coeliac disease. Several studies have been carried out on transforming images obtained from small bowel capsule endoscopy to enable the automated detection of features related to coeliac disease. This review discusses the current roles played by small bowel capsule endoscopy in coeliac disease. It identifies future potential roles of this technique and describes in great detail the role of computational analysis in the detection of coeliac disease and how it can be adapted to current available technology.
Collapse
Affiliation(s)
- Stefania Chetcuti Zammit
- Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Sheffield, UK.
| | - David S Sanders
- Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Sheffield, UK
| | - Reena Sidhu
- Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Sheffield, UK
| |
Collapse
|
|
21
|
Chetcuti Zammit S, Sanders DS, Sidhu R. Capsule endoscopy for patients with coeliac disease. Expert Rev Gastroenterol Hepatol 2018; 12:779-790. [PMID: 29886766 DOI: 10.1080/17474124.2018.1487289] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Coeliac disease is an autoimmune mediated condition in response to gluten. A combination of innate and adaptive immune responses results in villous shortening in the small bowel (SB) that can be morphologically picked up on capsule endoscopy. It is the only imaging modality that can provide mucosal views of the entire SB, while histology is generally limited to the proximal SB. Radiological modalities are not designed to pick up changes in villous morphology. Areas covered: In this review, we provide a comprehensive analysis on the justified use of small bowel capsule endoscopy (SBCE) in the assessment of patients with coeliac disease; compare SBCE to histology, serology, and symptomatology; and provide an overview on automated quantitative analysis for the detection of coeliac disease. We also provide insight into future work on SBCE in relation to coeliac disease. Expert commentary: SBCE has opened up new avenues for the diagnosis and monitoring of patients with coeliac disease. However, larger studies with new and established coeliac disease patients and with greater emphasis on morphological features on SBCE are required to better define the role of SBCE in the setting of coeliac disease.
Collapse
Affiliation(s)
| | - David S Sanders
- a Gastroenterology Department , Sheffield Teaching Hospitals , Sheffield , UK
| | - Reena Sidhu
- a Gastroenterology Department , Sheffield Teaching Hospitals , Sheffield , UK
| |
Collapse
|
|
22
|
Gadermayr M, Wimmer G, Kogler H, Vécsei A, Merhof D, Uhl A. Automated classification of celiac disease during upper endoscopy: Status quo and quo vadis. Comput Biol Med 2018; 102:221-226. [PMID: 29739614 DOI: 10.1016/j.compbiomed.2018.04.020] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2018] [Accepted: 04/23/2018] [Indexed: 02/08/2023]
Abstract
A large amount of digital image material is routinely captured during esophagogastroduodenoscopies but, for the most part, is not used for confirming the diagnosis process of celiac disease which is primarily based on histological examination of biopsies. Recently, considerable effort has been undertaken to make use of image material by developing semi- or fully-automated systems to improve the diagnostic workup. Recently, focus was especially laid on developing state-of-the-art deep learning architectures, exploiting the endoscopist's expert knowledge and on making systems fully automated and thereby completely observer independent. In this work, we summarize recent trends in the field of computer-aided celiac disease diagnosis based on upper endoscopy and discuss about recent progress, remaining challenges, limitations currently prohibiting a deployment in clinical practice and future efforts to tackle them.
Collapse
Affiliation(s)
- M Gadermayr
- Institute of Imaging & Computer Vision, RWTH Aachen University, 52074 Aachen, Germany.
| | - G Wimmer
- Department of Computer Sciences, University of Salzburg, 5020 Salzburg, Austria.
| | - H Kogler
- St. Anna Children's Hospital, Vienna, Austria
| | - A Vécsei
- St. Anna Children's Hospital, Vienna, Austria
| | - D Merhof
- Institute of Imaging & Computer Vision, RWTH Aachen University, 52074 Aachen, Germany
| | - A Uhl
- Department of Computer Sciences, University of Salzburg, 5020 Salzburg, Austria.
| |
Collapse
|
|
23
|
Celiac Disease Diagnosis Without Biopsy: Is a 10× ULN Antitransglutaminase Result Suitable for a Chemiluminescence Method? J Pediatr Gastroenterol Nutr 2018; 66:645-650. [PMID: 28991835 DOI: 10.1097/mpg.0000000000001773] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES 2012 European Society of Pediatric Gastroenterology, Hepatology and Nutrition guidelines allow to establish a celiac disease diagnosis without duodenal biopsy in symptomatic pediatric patients with antitissue transglutaminase (anti-tTG) titers >10 times the upper limit of normal. For some years now, new chemiluminescence immunoassays have been made available: it is important to establish the clinical performance of anti-tTG and to determine the cut-off best suited to predict Marsh ≥2 to avoid gastrointestinal endoscopy not only in children, but also in the adult population. METHODS A total of 2565 patients performed duodenal biopsy from July 2012 to September 2016; we selected all the patients who had undergone QUANTA Flash anti-tTG immunoglobulin A (IgA) within -3 months of duodenal biopsy and before the start of gluten-free diet. A total of 827 patients fulfilled the criteria for selection. RESULTS Using a cut-off of 20 chemiluminescent unit (CU; area under the curve: 0.995), sensitivity, specificity, positive, and negative predictive value were 98.2%, 98.4%, 97.9%, and 98.6%, respectively. For the correlation with Marsh ≥2, in the pediatric population, positive predictive values (PPV) were 92.1%, 99%, and 100% at 200 CU (10×), 560 CU (28×), and 1000 CU (50×), respectively. In the adult population PPV was 94.2%, 98.2%, and 100% at 200 CU (10×), 350 CU (15×), and 400 CU (20×). CONCLUSIONS Sensitivity, specificity, positive, and negative predictive value of QUANTA Flash h-tTG IgA were excellent. The cut-off providing an optimized PPV for histological lesions compatible for celiac disease (Marsh ≥2) for the QUANTA Flash h-tTG IgA is 350 CU (15×) in adult and 560 CU (28×) in children.
Collapse
|
|
24
|
Boschetto D, Mirzaei H, Leong RWL, Tarroni G, Grisan E. Semiautomatic detection of villi in confocal endoscopy for the evaluation of celiac disease. ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. ANNUAL INTERNATIONAL CONFERENCE 2018; 2015:8143-6. [PMID: 26738184 DOI: 10.1109/embc.2015.7320284] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Celiac Disease (CD) is an immune-mediated enteropathy, diagnosed in the clinical practice by intestinal biopsy and the concomitant presence of a positive celiac serology. Confocal Laser Endomicroscopy (CLE) allows skilled and trained experts to potentially perform in vivo virtual histology of small-bowel mucosa. In particular, it allows the qualitative evaluation of mucosa alteration such as a decrease in goblet cells density, presence of villous atrophy or crypt hypertrophy. We present a semi-automatic method for villi detection from confocal endoscopy images, whose appearance change in case of villous atrophy. Starting from a set of manual seeds, a first rough segmentation of the villi is obtained by means of mathematical morphology operations. A merge and split procedure is then performed, to ensure that each seed originates a different region in the final segmentation. A border refinement process is finally performed, evolving the shape of each region according to local gradient intensities. Mean and median Dice coefficients for 290 villi originating from 66 images when compared to manually obtained ground truth are 80.71% and 87.96% respectively.
Collapse
|
|
25
|
Charlesworth RPG, Andronicos NM, Scott DR, McFarlane JR, Agnew LL. Can the sensitivity of the histopathological diagnosis of coeliac disease be increased and can treatment progression be monitored using mathematical modelling of histological sections? - A pilot study. Adv Med Sci 2017; 62:136-142. [PMID: 28260668 DOI: 10.1016/j.advms.2016.06.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2016] [Revised: 04/30/2016] [Accepted: 06/01/2016] [Indexed: 12/17/2022]
Abstract
PURPOSE The aim of this pilot study was to attempt to define a set of equations from histological observations of tissue affected with coeliac disease (CD) to predict Marsh score. MATERIAL/METHODS Tissue from 15 patients with untreated CD, 6 patients with treated CD and 9 healthy control patients were stained using the standard H&E, Giemsa's staining for tissue sections and Alcian Blue protocols. A number of histological measures were then taken from each section and the data was used to ultimately design a set of linear predictive algorithms to calculate Marsh score. RESULTS Using MANOVA and discriminant analysis, two linear functions were defined which could accurately predict the Marsh score of patients 62.5% (full Marsh score) to 79.2% (simplified Marsh score) of the time. CONCLUSIONS This pilot study has shown that a set of objective histological measures can be used to define algorithms to predict Marsh score in CD patients and also monitor treatment compliance and progression.
Collapse
Affiliation(s)
| | | | - David R Scott
- Tamworth Rural Referral Hospital and Tamara Private Hospital, Tamworth, NSW, Australia
| | - James R McFarlane
- School of Science and Technology, University of New England, Armidale, NSW, Australia
| | - Linda L Agnew
- Brain Behaviour Research Group, University of New England, Armidale, NSW, Australia.
| |
Collapse
|
|
26
|
Valle J, Morgado JMT, Ruiz-Martín J, Guardiola A, Lopes-Nogueras M, García-Vela A, Martín-Sacristán B, Sánchez-Muñoz L. Flow cytometry of duodenal intraepithelial lymphocytes improves diagnosis of celiac disease in difficult cases. United European Gastroenterol J 2016; 5:819-826. [PMID: 29026596 DOI: 10.1177/2050640616682181] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2016] [Accepted: 10/25/2016] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Diagnosis of celiac disease is difficult when the combined results of serology and histology are inconclusive. Studies using flow cytometry of intraepithelial lymphocytes (IELs) have found that celiac patients have increased numbers of γδ IELs, along with a decrease in CD3-CD103 + IELs. OBJECTIVE The objective of this article is to assess the role of flow cytometric analysis of IELs in the diagnosis of celiac disease in difficult cases. METHODS A total of 312 patients with suspicion of celiac disease were included in the study. Duodenal biopsy samples were used for histological assessment and for flow cytometric analysis of IELs. RESULTS In 46 out of 312 cases (14.7%) the combination of serology and histology did not allow the confirmation or exclusion of celiac disease. HLA typing had been performed in 42 of these difficult cases. Taking into account HLA typing and the response to a gluten-free diet, celiac disease was excluded in 30 of these cases and confirmed in the remaining 12. Flow cytometric analysis of IELs allowed a correct diagnosis in 39 out of 42 difficult cases (92.8%) and had a sensitivity of 91.7% (95% CI: 61.5% to 99.8%) and a specificity of 93.3% (95% CI: 77.9% to 99.2%) for the diagnosis of celiac disease in this setting. CONCLUSION Flow cytometric analysis of IELs is useful for the diagnosis of celiac disease in difficult cases.
Collapse
Affiliation(s)
- Julio Valle
- Department of Gastroenterology, Complejo Hospitalario de Toledo, Spain
| | - José Mario T Morgado
- Instituto de Estudios de Mastocitosis de Castilla La Mancha, Complejo Hospitalario de Toledo, Spain
| | | | - Antonio Guardiola
- Department of Gastroenterology, Complejo Hospitalario de Toledo, Spain
| | | | | | | | - Laura Sánchez-Muñoz
- Instituto de Estudios de Mastocitosis de Castilla La Mancha, Complejo Hospitalario de Toledo, Spain
| |
Collapse
|
|
27
|
Stoven SA, Choung RS, Rubio-Tapia A, Absah I, Lam-Himlin DM, Harris LA, Ngamruengphong S, Vazquez Roque MI, Wu TT, Murray JA. Analysis of Biopsies From Duodenal Bulbs of All Endoscopy Patients Increases Detection of Abnormalities but has a Minimal Effect on Diagnosis of Celiac Disease. Clin Gastroenterol Hepatol 2016; 14:1582-1588. [PMID: 26965842 DOI: 10.1016/j.cgh.2016.02.026] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2015] [Revised: 02/11/2016] [Accepted: 02/18/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS In patients with positive results from serologic tests for celiac disease, analysis of tissues samples from the duodenal bulb, in addition to those from other parts of the small bowel, might increase the diagnostic yield. However, biopsies are not routinely collected from the duodenal bulb because of concerns that villous atrophy detected there could be caused by other disorders (Brunner glands or peptic duodenitis, gastric metaplasia, shorter villi, or lymphoid follicles). We investigated whether analysis of biopsies from duodenal bulbs of all patients undergoing endoscopy (a population with a low probability for celiac disease) increases diagnoses of celiac disease. METHODS We performed a retrospective analysis of data from 679 patients (63% female; mean age, 50 years) from whom duodenal bulb and small bowel biopsies were collected during endoscopy at 3 Mayo Clinic sites, from January 1, 2011 through December 31, 2011. Records were reviewed for age, sex, pathology findings, serology test results (HLA DQ2 or DQ), indications for biopsy analyses, and adherence to a gluten-free diet. Patients with celiac disease were identified on the basis of increased intraepithelial lymphocytosis, with or without villous atrophy and crypt hyperplasia, and results from serology tests. Findings from duodenal bulbs were compared with diagnoses using the Fisher exact test. RESULTS Of all patients undergoing endoscopy, 16 patients (2%) were found to have celiac disease. Analysis of the duodenal bulb biopsies identified 1 patient (0.1%) with celiac disease limited to this region. Of 399 patients whose celiac serology was not known before endoscopic examination, only 2 patients had histologic changes consistent with celiac disease but not limited to duodenal bulb. Abnormal duodenal histology was detected in 265 patients (39%), most commonly in the bulb (n = 241; P < .0001). Of abnormal bulb histologies, chronic peptic duodenitis was most common (observed in 114 patients, 47%). In patients with a normal distal duodenum (n = 576), the duodenal bulb had abnormal histology in 162 (28%). CONCLUSIONS In a low pretest probability cohort, separate sampling of the duodenal bulb had minimal effect on celiac disease detection. Abnormal histologic findings are more commonly detected in the duodenal bulb; although they do not seem to impair identification of celiac disease, their clinical implications are unclear.
Collapse
Affiliation(s)
- Samantha A Stoven
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Rok Seon Choung
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Alberto Rubio-Tapia
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Imad Absah
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Dora M Lam-Himlin
- Division of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, Arizona
| | - Lucinda A Harris
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona
| | | | | | - Tsung-Teh Wu
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
| | - Joseph A Murray
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota; Department of Immunology, Mayo Clinic, Rochester, Minnesota.
| |
Collapse
|
|
28
|
Association of Tissue Transglutaminase Antibody Titer with Duodenal Histological Changes in Children with Celiac Disease. Gastroenterol Res Pract 2016; 2016:6718590. [PMID: 27867394 PMCID: PMC5102726 DOI: 10.1155/2016/6718590] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2016] [Revised: 07/04/2016] [Accepted: 07/26/2016] [Indexed: 12/20/2022] Open
Abstract
Celiac disease is usually diagnosed by demonstrating gluten enteropathy in small bowel biopsy. Celiac specific antibodies are used as an initial screening test. The goal of this study is to test the relationship of the anti-tTG titer and severity of histological changes in Jordanian children with celiac disease. Method. The medical records of 81 children who had elevated anti-tTG titer and had duodenal biopsies available were retrospectively reviewed. Result. Assessing the association of anti-tTG titer with duodenal histopathological changes, 94% of those with high anti-tTG titer (≥180 U/mL) had histological evidence of celiac disease. There was statistically significant positive association between high anti-tTG titer and Marsh grading as 82% of patients with Marsh III had high anti-tTG titer (Chi2 18.5; P value 0.00; Odds Ratio 8.5). The fraction of patients with Marsh III who were correctly identified as positive by anti-tTG titer ≥ 180 U/mL was high (sensitivity = 81.6). Moreover, the fraction of patients with anti-tTG titer ≥ 180 U/mL who had Marsh III was also high (positive predictive value = 78.4). Conclusion. Anti-tTG titer ≥ 180 U/mL had significant positive association with Marsh III histopathological changes of celiac disease.
Collapse
|
|
29
|
Kurien M, Mooney PD, Cross SS, Sanders DS. Bulb Biopsy in Adult Celiac Disease: Pros Outweigh the Cons? Am J Gastroenterol 2016; 111:1205-6. [PMID: 27481425 DOI: 10.1038/ajg.2016.173] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Matthew Kurien
- Departments of Infection and Immunity and Cardiovascular Science, Academic Unit of Gastroenterology, Medical School, University of Sheffield, Sheffield, UK
| | - Peter D Mooney
- Departments of Infection and Immunity and Cardiovascular Science, Academic Unit of Gastroenterology, Medical School, University of Sheffield, Sheffield, UK
| | - Simon S Cross
- Department of Neuroscience, Faculty of Medicine, Dentistry and Health, Academic Unit of Pathology, University of Sheffield, Sheffield, UK
| | - David S Sanders
- Departments of Infection and Immunity and Cardiovascular Science, Academic Unit of Gastroenterology, Medical School, University of Sheffield, Sheffield, UK
| |
Collapse
|
|
30
|
Kurppa K, Taavela J, Saavalainen P, Kaukinen K, Lindfors K. Novel diagnostic techniques for celiac disease. Expert Rev Gastroenterol Hepatol 2016; 10:795-805. [PMID: 26838683 DOI: 10.1586/17474124.2016.1148599] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The diagnosis of celiac disease has long been based on the demonstration of gluten-induced small-bowel mucosal damage. However, due to the constantly increasing disease prevalence and limitations in the histology-based criteria there is a pressure towards more serology-based diagnostics. The serological tools are being improved and new non-invasive methods are being developed, but the constantly refined endoscopic and histologic techniques may still prove helpful. Moreover, growing understanding of the disease pathogenesis has led researchers to suggest completely novel approaches to celiac disease diagnostics regardless of disease activity. In this review, we will elucidate the most recent development and possible future innovations in the diagnostic techniques for celiac disease.
Collapse
Affiliation(s)
- Kalle Kurppa
- a Tampere Centre for Child Health Research , University of Tampere and Tampere University Hospital , Tampere , Finland
| | - Juha Taavela
- a Tampere Centre for Child Health Research , University of Tampere and Tampere University Hospital , Tampere , Finland
| | - Päivi Saavalainen
- b Molecular Genetics of Immunological Diseases Group , University of Helsinki , Helsinki , Finland
| | - Katri Kaukinen
- c Department of Internal Medicine , Tampere University Hospital , Tampere , Finland.,d School of Medicine , University of Tampere , Tampere , Finland
| | - Katri Lindfors
- a Tampere Centre for Child Health Research , University of Tampere and Tampere University Hospital , Tampere , Finland
| |
Collapse
|
|
31
|
Mooney PD, Kurien M, Evans KE, Rosario E, Cross SS, Vergani P, Hadjivassiliou M, Murray JA, Sanders DS. Clinical and Immunologic Features of Ultra-Short Celiac Disease. Gastroenterology 2016; 150:1125-1134. [PMID: 26836585 DOI: 10.1053/j.gastro.2016.01.029] [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: 03/26/2015] [Revised: 01/12/2016] [Accepted: 01/25/2016] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS The clinical effects of gluten-sensitive enteropathy with villous atrophy limited to the duodenal bulb (D1) have not been delineated in adults with celiac disease. We investigated the sensitivity of D1 biopsy analysis in the detection of celiac disease, the number and sites of biopsies required to detect ultra-short celiac disease (USCD, villous atrophy limited to D1), and the clinical phenotype of USCD. METHODS We performed a prospective study of 1378 patients (mean age, 50.3 y; 62% female) who underwent endoscopy at a tertiary medical center in the United Kingdom from 2008 through 2014; routine duodenal biopsy specimens were collected from D1 and the second part of the duodenum (D2). Quadrantic D1 biopsy specimens were collected from 171 consecutive patients with a high suspicion of celiac disease (mean age, 46.5 y; 64% female). Clinical data from patients diagnosed with USCD, based on biopsy analysis, were compared with those from patients with conventional celiac disease (CCD) (villous atrophy beyond D1) and individuals without celiac disease (controls). The number of intraepithelial lymphocytes (IELs) and immune phenotypes were compared between D1 vs D2 in patients with celiac disease. RESULTS Of the 1378 patients assessed, 268 (19.4%) were diagnosed with celiac disease; 9.7% of these patients had villous atrophy confined to D1 (USCD; P < .0001). Collection of a single additional biopsy specimen from any D1 site increased the sensitivity of celiac disease detection by 9.3%-10.8% (P < .0001). Patients with USCD were younger (P = .03), had lower titers of tissue transglutaminase antibody (P = .001), and less frequently presented with diarrhea (P = .001) than patients with CCD. Higher proportions of patients with CCD had ferritin deficiency (P = .007) or folate deficiency (P = .003) than patients with USCD or controls. Patients with celiac disease had a median of 50 IELs/100 enterocytes in D1 and a median of 48 IELs/100 enterocytes (P = .7) in D2. The phenotype of IELs from patients with D1 celiac disease was indistinguishable from those of patients with D2 celiac disease. CONCLUSIONS Collection of a single additional biopsy specimen from any site in the D1 intestine increases the sensitivity of detection for celiac disease. Patients with USCD may have early stage or limited celiac disease, with a mild clinical phenotype and infrequent nutritional deficiencies.
Collapse
Affiliation(s)
- Peter D Mooney
- Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, United Kingdom; University of Sheffield, Sheffield, United Kingdom.
| | - Matthew Kurien
- Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, United Kingdom; University of Sheffield, Sheffield, United Kingdom
| | - Kate E Evans
- Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, United Kingdom; University of Sheffield, Sheffield, United Kingdom
| | | | - Simon S Cross
- University of Sheffield, Sheffield, United Kingdom; Department of Histopathology, Royal Hallamshire Hospital, Sheffield, United Kingdom
| | - Patricia Vergani
- Department of Histopathology, Royal Hallamshire Hospital, Sheffield, United Kingdom
| | - Marios Hadjivassiliou
- University of Sheffield, Sheffield, United Kingdom; Department of Neurology, Royal Hallamshire Hospital, Sheffield, United Kingdom
| | | | - David S Sanders
- Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, United Kingdom; University of Sheffield, Sheffield, United Kingdom
| |
Collapse
|
|
32
|
Kaur Bilkhoo H, Ducruet T, Marchand V, Deslandres C, Djemli A, Dal Soglio D, Patey N. Revisiting Pathological Criteria for Earlier Diagnosis of Coeliac Disease. J Pediatr Gastroenterol Nutr 2016; 62:734-8. [PMID: 26529345 DOI: 10.1097/mpg.0000000000001026] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
OBJECTIVES The diagnosis of coeliac disease (CD) remains sometimes difficult because the histological criteria are not fully met. The aim of this study was to refine histological diagnostic criteria of CD. METHODS One hundred seventy-five duodenal bulb D1 (n = 79) and duodenal D2 (n = 96) biopsies of 96 patients with CD (58 girls, mean age 7 years), 135 normal D2 biopsies (69 girls, mean age 12 years), and 64 D2 biopsies of other digestive disorders (DDs) (39 girls, mean age 13 years) obtained from children during a period of 4 years were reviewed. RESULTS Interobserver agreement was greater for the classification of Corazza-Villanacci than for Marsh-Oberhuber (κ = 0.812 vs κ = 0.409, respectively). Between 40 and 70 intraepithelial lymphocytes (IELs) per 100 epithelial cells (ECs), 32% of patients were CD, whereas 50% had other DD. Above 70 IELs per 100 EC, 53% were CD, and only 6% had other DD. In CD, IELs were significantly located above EC nuclei compared with other DD, (12 IELs/100 EC vs 2 IELs/100 EC, respectively). In 21% of CD cases, D2 were normal and the diagnosis could only be made on D1. Finally, 6% of CD cases showed isolated increase of IELs in D1 without architectural modification. CONCLUSIONS D1 allowed diagnosis of CD in 21% of cases and IEL >70 per 100 EC correlated strongly with CD. Between 40 and 70 IELs per 100 EC, CD is very likely but other DD must be considered. Finally, the preferential localisation of IELs above EC nuclei favours CD, and increased IEL in D1 may be the sole abnormality.
Collapse
Affiliation(s)
- Harpreet Kaur Bilkhoo
- *Département de Pathologie †Unité de Recherche clinique appliquée ‡Département de Gastroentérologie Hépatologie et Nutrition §Département de Biochimie, CHU Sainte-Justine, Montréal, QC, Canada
| | | | | | | | | | | | | |
Collapse
|
|
33
|
Iacucci M, Poon T, Gui XS, Ghosh S. High definition i-SCAN endoscopy with water immersion technique accurately reflects histological severity of celiac disease. Endosc Int Open 2016; 4:E540-6. [PMID: 27227112 PMCID: PMC4874797 DOI: 10.1055/s-0042-105955] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2015] [Accepted: 03/07/2016] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND AND AIMS Severe villous atrophy can be revealed with conventional white light endoscopy (WLE), however, milder grades or patchy villous atrophy are more difficult to detect. Novel endoscopic techniques such as high definition i-SCAN endoscopy with the water immersion technique (i-SCAN-HDWI) may provide the ability to visualize duodenal villi more accurately. We aimed to determine the performance of i-SCAN-HDWI in evaluating the severity of histological damage in the duodenum of patients with celiac disease. PATIENTS AND METHODS A retrospective cohort study was performed in a single tertiary academic endoscopic center. We studied 58 patients (46 women; median age 36.5 years, range 18 - 72 years) with positive anti-TTG IgA antibody. The villous pattern of the second part of the duodenum was assessed by WLE and i-SCAN-HDWI. The endoscopic grades in both techniques were correlated using Marsh histologic grades by Spearman correlation coefficient. The diagnostic accuracy of i-SCAN-HDWI for detection of patchy or complete atrophy of the villi was evaluated. RESULTS A significant correlation was demonstrated between endoscopic grade using i-SCAN-HDWI and Marsh histologic grade (r = 0.732; P < 0.00001). The correlation between WLE grade and Marsh histologic grade was inferior to i-SCAN-HDWI (r = 0.31; P = 0.01). The sensitivity of i-SCAN-HDWI was 96 % (95 %CI: 85 - 99 %) and the specificity was 63 % (95 %CI: 26 - 90 %) in diagnosing abnormal biopsy consistent with celiac disease. CONCLUSION i-SCAN-HDWI endoscopy can reflect the histological severity of celiac disease more accurately than conventional WLE alone. This novel endoscopic imaging can improve the diagnostic yield of duodenal biopsies in celiac patients, especially for those with a patchy distribution of villous damage.
Collapse
Affiliation(s)
- Marietta Iacucci
- Gastroenterology, University of Calgary, Calgary, AB, Canada,Corresponding author Marietta Iacucci, MD PhD Division of GastroenterologyTRW 6D253280 Hospital Drive NWCalgaryAlbertaCanada T2N 4Z6+1-403-592-5090
| | - Tiffany Poon
- Gastroenterology, University of Calgary, Calgary, AB, Canada
| | - X. Sean Gui
- Pathology, University of Calgary, Calgary, AB, Canada
| | - Subrata Ghosh
- Gastroenterology, University of Calgary, Calgary, AB, Canada
| |
Collapse
|
|
34
|
Garnier-Lengliné H, Cerf-Bensussan N, Ruemmele FM. Celiac disease in children. Clin Res Hepatol Gastroenterol 2015; 39:544-51. [PMID: 26186878 DOI: 10.1016/j.clinre.2015.05.024] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2015] [Revised: 05/20/2015] [Accepted: 05/27/2015] [Indexed: 02/04/2023]
Abstract
Celiac disease is an autoimmune enteropathy, triggered by ingestion of gluten in genetically predisposed individuals. Since the use of anti-transglutaminase and anti-endomysium antibodies in the early 1990s, two main groups of clinical presentation can be identified: patients with a symptomatic form of the disease, and patients with a pauci (a)-symptomatic form detected during the work-up of another autoimmune disease or due to a family history of celiac disease. The prevalence of both forms of the disease is currently estimated between 1/100 and 1/400. Classical form of the disease is characterized by occurrence of diarrhoea, failure to thrive, and abdominal bloating in young infants in the months following gluten introduction. Serological tests show high level of anti-transglutaminase and anti-endomysium antibodies. Until recently, the diagnosis required duodenal biopsies that show villous atrophy. HLA genotype can help for diagnosis: the absence of the HLA-DQ2 or DQ8 alleles has a high negative predictive value. European guidelines recently proposed to reconsider the need for systematic endoscopy in typical symptomatic forms with high level of anti-transglutaminase and positive anti-endomysium. These recommendations are being assessed now. Currently, the gluten-free diet remains the only effective treatment for celiac disease. Children with celiac disease have to exclude from their diet all products containing wheat, barley and rye. Gluten-free diet causes clinical remission within a few weeks, but normalization of the small bowel mucosa and negativity of anti-transglutaminase antibodies are obtained in several months or even years. Gluten-free diet is useful to obtain clinical assessment, but also to prevent long-term complications of celiac disease, mainly osteoporosis, other autoimmune diseases, decreased fertility and cancers.
Collapse
Affiliation(s)
- Hélène Garnier-Lengliné
- Université Paris-Descartes, Sorbonne Paris-Cité, Paris, France; AP-HP, hôpital Necker-Enfants-Malades, service de gastroentérologie, hépatologie et nutrition pédiatriques, 149, rue de Sèvres, 75743 Paris cedex 15, France; Unité Inserm UMR_S1163, Institut Imagine, Paris, France.
| | - Nadine Cerf-Bensussan
- Université Paris-Descartes, Sorbonne Paris-Cité, Paris, France; Unité Inserm UMR_S1163, Institut Imagine, Paris, France
| | - Frank M Ruemmele
- Université Paris-Descartes, Sorbonne Paris-Cité, Paris, France; AP-HP, hôpital Necker-Enfants-Malades, service de gastroentérologie, hépatologie et nutrition pédiatriques, 149, rue de Sèvres, 75743 Paris cedex 15, France; Unité Inserm UMR_S1163, Institut Imagine, Paris, France
| |
Collapse
|
|
35
|
Central America in Transition: From Maize to Wheat Challenges and Opportunities. Nutrients 2015; 7:7163-71. [PMID: 26343711 PMCID: PMC4586525 DOI: 10.3390/nu7095330] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2015] [Revised: 07/27/2015] [Accepted: 08/11/2015] [Indexed: 12/11/2022] Open
Abstract
The Central American countries: Guatemala, El Salvador, Honduras, Nicaragua, Costa Rica, and Panama are in transition from a dietary culture based mainly on maize to a wheat-containing diet. Several other changes are occurring, such as a decrease of parasitic and infectious diseases. The environmental changes permit a prediction of an increase of celiac disease and other autoimmune diseases such as type I diabetes and thyroid disease in these genetically heterogeneous countries. At present, celiac disease and gluten-related disorders are considered to be of no relevance at the level of public health in these nations. This review documents the presence of celiac disease in Central America. It draws attention to some of the challenges in planning systematic studies in the region since up until recently celiac disease was unknown. The aim of this review is to disseminate knowledge obtained with preliminary data, to stimulate clinical and basic scientists to study these diseases in Central America and to alert authorities responsible for the planning of education and health, to find possibilities to avoid a rise in these disorders before the epidemics start, as has occurred in the Mediterranean countries.
Collapse
|
|
36
|
Oxentenko AS, Murray JA. Celiac Disease: Ten Things That Every Gastroenterologist Should Know. Clin Gastroenterol Hepatol 2015; 13:1396-404; quiz e127-9. [PMID: 25051511 DOI: 10.1016/j.cgh.2014.07.024] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2013] [Revised: 07/09/2014] [Accepted: 07/09/2014] [Indexed: 02/07/2023]
Abstract
There are 10 things that all gastroenterologists should know about celiac disease (CD). (1) The immunoglobulin A tissue transglutaminase is the single best serologic test to use for the detection of CD. (2) CD can be recognized endoscopically, and water immersion enhances villi detection, although a normal endoscopic appearance does not preclude the diagnosis. (3) It is recommended that 4 biopsies be taken from the second part of the duodenum and 2 bulb biopsies be taken at the 9 o'clock and 12 o'clock positions to maximize the sensitivity for histologic confirmation of CD. (4) Consider serologic testing of first-degree relatives, patients with type 1 diabetes mellitus, Down's, Turner's, and Williams' syndromes, as well as those with premature osteoporosis, iron deficiency, abnormal liver biochemistries, and other manifestations of CD. (5) Patients already on a prolonged gluten-free diet (GFD) should be tested for the presence of HLA DQ2 or DQ8, thereby avoiding the need for further evaluation of CD in non-allelic carriers. (6) The basic treatment of CD is a strict, lifelong GFD, enabled by an expert dietitian. (7) Newly diagnosed adults with CD should be assessed for micronutrient deficiencies (iron, B12, folate, zinc, copper), fat soluble vitamin deficiencies (vitamin D), and bone densitometry. (8) All patients diagnosed with CD should have clinical follow-up to ensure response and adherence to a GFD. (9) In those with persistent or relapsing symptoms, the robustness of the original diagnosis should be reviewed, gluten exposure sought, and a systematic evaluation for alternative and associated diseases performed. (10) Evaluate those with refractory disease for malignant transformation.
Collapse
Affiliation(s)
- Amy S Oxentenko
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Joseph A Murray
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
| |
Collapse
|
|
37
|
Celiac disease can be predicted by high levels of anti-tissue transglutaminase antibodies in population-based screening. J Pediatr Gastroenterol Nutr 2015; 60:787-91. [PMID: 25564816 DOI: 10.1097/mpg.0000000000000688] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES The aim of the present study was to evaluate any potential correlation between anti-tissue transglutaminase antibodies of type immunoglobulin A (tTG-IgA) and the degree of gluten-induced enteropathy in children participating in a screening study for celiac disease (CD) and to assess to what extent the revised European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) guidelines cover this group of patients. METHODS The present study is a substudy of a cross-sectional CD screening study, Exploring the Iceberg of Celiacs in Sweden, a 2-phased study performed during 2005 to 2006 and 2009 to 2010. The 13,279 participating children had a blood test obtained, and those with positive tTG-IgA were recommended a small intestinal biopsy. The tTG-IgA levels at the time of biopsy were compared with those at the assessment of the biopsy. RESULTS There were 267 children included, of whom 230 were diagnosed as having CD. Of all of the children, 67 children had low tTG-IgA levels (<5 U/mL), of whom 55% had Marsh 3 lesions. All of the children with tTG-IgA levels exceeding 10 times the upper limit of normal values of 5 U/mL, that is, 50 U/mL, were diagnosed as having CD. Lowering the cutoff to 3 U/mL, all but 1 child with 30 U/mL got CD diagnosis. CONCLUSIONS By adopting the revised ESPGHAN criteria, biopsies could have been omitted in one-fourth of all of the patients. Our results indicate that the criteria may be useful even in screened children. Further studies are needed to confirm whether the 2012 ESPGHAN guidelines should be revised to also apply to the populations being screened.
Collapse
|
|
38
|
Abstract
BACKGROUND Because of its technical characteristics (i.e. 8-fold magnification, capability to inspect the entire small bowel) and minimal invasiveness, videocapsule endoscopy (VCE) has been proposed as a useful tool for managing patients with celiac disease (CD). KEY MESSAGES Although VCE has been found to be highly sensitive and specific in identifying CD endoscopic markers, it is still inadequate to replace esophagogastroduodenoscopy (EGD) with biopsies in the diagnosis of CD. Nevertheless, it represents a reliable alternative in patients unable or unwilling to undergo EGD. Up to now, available studies have failed to identify any correlation between the length of small bowel involvement and the severity of symptoms. The available evidence on the use of VCE in diagnosing CD in equivocal cases (patients with positive serology and negative or nonspecific histology or those with negative serology and histologically proven villous atrophy) is limited, and its role is still under discussion. In CD patients not improving on gluten-free diet, a complete workup is necessary. In patients with nonresponsive (NRCD) or refractory CD (RCD), VCE has been shown to be able not only to detect significant findings, driving further management, but also to rule out major complications. Nevertheless, in this setting, the inability of VCE to take tissue samples and the risk of capsule retention can represent major limitations. CONCLUSIONS At the present time, for diagnostic purposes, VCE can be proposed only in patients unable or unwilling to undergo EGD, whereas it could be useful in some equivocal cases. Conversely, there is no room for VCE either to estimate the length of the small bowel affected by villous atrophy or to follow up patients improving on gluten-free diet. In patients with NRCD or RCD, VCE can play a role, but it should be combined with other diagnostic techniques.
Collapse
|
|
39
|
Distal duodenum versus duodenal bulb: intraepithelial lymphocytes have something to say in celiac disease diagnosis. Dig Dis Sci 2015; 60:1004-9. [PMID: 25366147 DOI: 10.1007/s10620-014-3414-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2013] [Accepted: 10/24/2014] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIM After clinical screening and the serological test, many patients still require a duodenal biopsy for celiac disease diagnosis. Mild histological lesions, unspecific findings and patchiness are frequent outcomes of this mandatory diagnostic tool, thus complicating clinical decisions. METHODS We analyzed the lymphoid components [number of total intraepithelial lymphocytes (IELs), TcR-γδ and CD3(-)IELs] of the duodenal epithelium by flow cytometry in samples obtained from bulb and distal duodenum during upper gastrointestinal endoscopies performed for diagnostic purposes. RESULTS IEL counts and IEL subset distribution (IEL lymphogram) remain invariant along duodenal mucosa revealing a specific profile (immunophenotype) that characterizes either a healthy mucosa or a celiac mucosa. The celiac immunophenotype persists regardless of the biopsy's anatomical location or the corresponding histological findings. CONCLUSIONS We propose the IEL lymphogram by flow cytometry as an immunological parameter to discern celiac condition from healthy mucosa. This obviates not only misinterpretation of minor histological changes, but also patchiness and the concerns about the location and number of biopsies.
Collapse
|
|
40
|
Hegenbart S, Uhl A, Vécsei A. Survey on computer aided decision support for diagnosis of celiac disease. Comput Biol Med 2015; 65:348-58. [PMID: 25770906 PMCID: PMC4593300 DOI: 10.1016/j.compbiomed.2015.02.007] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2014] [Revised: 02/10/2015] [Accepted: 02/11/2015] [Indexed: 12/13/2022]
Abstract
Celiac disease (CD) is a complex autoimmune disorder in genetically predisposed individuals of all age groups triggered by the ingestion of food containing gluten. A reliable diagnosis is of high interest in view of embarking on a strict gluten-free diet, which is the CD treatment modality of first choice. The gold standard for diagnosis of CD is currently based on a histological confirmation of serology, using biopsies performed during upper endoscopy. Computer aided decision support is an emerging option in medicine and endoscopy in particular. Such systems could potentially save costs and manpower while simultaneously increasing the safety of the procedure. Research focused on computer-assisted systems in the context of automated diagnosis of CD has started in 2008. Since then, over 40 publications on the topic have appeared. In this context, data from classical flexible endoscopy as well as wireless capsule endoscopy (WCE) and confocal laser endomicrosopy (CLE) has been used. In this survey paper, we try to give a comprehensive overview of the research focused on computer-assisted diagnosis of CD.
The state-of-the-art research in automated diagnosis of celiac disease is presented. A systematic review of methods and techniques used in this field is given. Specific issues and challenges in the field are identified and discussed.
Collapse
Affiliation(s)
- Sebastian Hegenbart
- Department of Computer Sciences, University of Salzburg, Jakob-Haringer Strasse, 5020 Salzburg, Austria.
| | - Andreas Uhl
- Department of Computer Sciences, University of Salzburg, Jakob-Haringer Strasse, 5020 Salzburg, Austria.
| | - Andreas Vécsei
- St. Anna Children׳s Hospital, Medical University Vienna, 1090 Vienna, Austria.
| |
Collapse
|
|
41
|
Mansfield-Smith S, Savalagi V, Rao N, Thomson M, Cohen MC. Duodenal bulb histological analysis should be standard of care when evaluating celiac disease in children. Pediatr Dev Pathol 2014; 17:339-43. [PMID: 25076388 DOI: 10.2350/14-03-1451-oa.1] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
We confirmed the added value provided by sampling D1 in the diagnosis of CD in comparison to the diagnosis yield when only the more distal duodenum (D2, D3, and/or D4) was sampled. The severity of CD, as assessed by the Marsh-Oberhuber classification, did not increase distally; on the contrary, in 39/60 (65%) of the cohort, the features of CD were either more severe or only present in D1.
Collapse
Affiliation(s)
- Sonja Mansfield-Smith
- 1 Department of Histopathology, Sheffield Children's Hospital, Sheffield, United Kingdom
| | | | | | | | | |
Collapse
|
|
42
|
Caruso R, Marafini I, Del Vecchio Blanco G, Fina D, Paoluzi OA, Colantoni A, Sedda S, Pallone F, Monteleone G. Sampling of proximal and distal duodenal biopsies in the diagnosis and monitoring of celiac disease. Dig Liver Dis 2014; 46:323-9. [PMID: 24394601 DOI: 10.1016/j.dld.2013.12.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2013] [Revised: 10/30/2013] [Accepted: 12/03/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND Since celiac disease-associated mucosal lesions are patchy, the diagnosis of the disease requires histological evaluation of multiple duodenal biopsies. AIM To examine whether adequate biopsy sampling in either the bulb or distal duodenum is sufficient to diagnose celiac disease. METHODS Twenty-five patients with positive celiac disease-specific serology and 17 patients with negative serology, who were on a gluten-containing diet, and 13 celiac disease patients on a gluten-free diet were consecutively and prospectively enrolled. Mucosal damage, anti-transglutaminase-2 IgA deposits, interferon-γ, interleukin-17A and interleukin-15 transcripts were evaluated in bulb and distal duodenal biopsies. RESULTS All patients with positive celiac disease-specific serology exhibited villous atrophy in both duodenal sites. In this group, mucosal anti-transglutaminase-2 IgA deposits were found in 24/25 (96%) bulb samples and 22/25 (88%) distal duodenal samples. No villous atrophy was documented in patients with negative serology. Interferon-γ and interleukin-17A were over-expressed in both duodenal sites of patients with villous atrophy, unlike patients with normal duodenal morphology (p<0.001). Among treated celiac disease patients, 2 (15.4%) had villous atrophy exclusively in the bulb and 6 (46.2%) had minimal histological abnormalities at both sites. CONCLUSION Sampling in the bulb and distal duodenum could be sufficient to diagnose/exclude celiac disease.
Collapse
Affiliation(s)
- Roberta Caruso
- Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy
| | - Irene Marafini
- Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy
| | | | - Daniele Fina
- Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy
| | | | - Alfredo Colantoni
- Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy
| | - Silvia Sedda
- Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy
| | - Francesco Pallone
- Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy
| | - Giovanni Monteleone
- Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy.
| |
Collapse
|
|
43
|
The optimal number of biopsy fragments to establish a morphologic diagnosis of eosinophilic esophagitis. Am J Gastroenterol 2014; 109:515-20. [PMID: 24445569 DOI: 10.1038/ajg.2013.463] [Citation(s) in RCA: 79] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2013] [Accepted: 11/29/2013] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Eosinophilic esophagitis (EoE) is characterized clinically by dysphagia, chest pain, and food impaction, and morphologically by increased numbers of intraepithelial eosinophils and marked basal hyperplasia of the squamous mucosa. The consensus criteria for a diagnosis of EoE include the presence of ≥15 eosinophils/HPF in biopsies from both proximal and distal esophagus in the absence of other causes of esophageal eosinophilia, and the lack of clinical response to proton pump inhibitor therapy. Because of the variability in the distribution of intraepithelial eosinophils among biopsy fragments and the lack of standardized biopsy practices, we sought to determine the optimal number of esophageal biopsies from the mid and distal esophagus needed to reach the minimum morphologic criteria of ≥15 eosinophils/HPF. METHODS From 5 January 2009 to 26 September 2011, 771 patients were diagnosed with EoE at our institution. From that patient population, 102 sequential cases were chosen for further study, all of whom had biopsies taken from the mid and distal esophagus. Cases with only gastric mucosa present and biopsies taken from patients with a previous diagnosis of EoE were excluded. The original H&E-stained slides were reviewed, and the number of biopsy fragments containing squamous mucosa was recorded. By using a × 40 objective and × 10 oculars (field diameter=0.52 mm, field area=0.21 mm(2)), the number of eosinophils per high power field (EOS/HPF) in up to three HPFs was counted in each biopsy fragment. RESULTS The EOS/HPF were counted in 1,342 biopsy fragments. The number of biopsy fragments obtained from the mid esophagus ranged from 1 to 20 (mean 7; median 7) and those obtained from the distal esophagus ranged from 1 to 18 (mean 6; median 5). There was no significant difference between the mean number of EOS/HPF from the mid (26) and lower (25) esophagus or between the mean peak number of EOS/HPF from the mid (69.1) and lower (60.4) esophagus. The probability of one, four, five, and six biopsy fragments containing >15 EOS/HPF was 0.63, 0.98, 0.99, and >0.99, respectively. CONCLUSIONS From these data, at least four biopsy fragments should be submitted from the mid and/or proximal esophagus to optimize the chances of a positive diagnosis of EoE in populations not known to have undergone previous proton pump inhibitor therapy. However, the yield is not increased beyond six biopsy fragments. In order to morphologically exclude a diagnosis of reflux esophagitis as the cause of intraepithelial eosinophilia, distal esophageal biopsies, if obtained, must be accompanied by more proximal biopsies (i.e., mid esophagus or higher).
Collapse
|
|
44
|
Abstract
The indication for a small intestinal biopsy is usually the work-up of malabsorption, a clinicopathologic picture caused by a number of infectious and noninfectious inflammatory conditions. The biopsy is generally taken through an endoscope, by either forceps or suction, from the duodenum or proximal jejunum. Depending upon the underlying condition, morphological abnormalities are seen in malabsorption range from normal mucosa with increased intraepithelial lymphocytes (gluten-sensitive enteropathy, viral gastroenteritis, food allergies, etc.), villous shortening with crypt hyperplasia (celiac disease (CD), treated CD, tropical sprue, and bacterial overgrowth), to completely flat mucosa (CD, refractory sprue, enteropathy-induced T-cell lymphoma, and autoimmune enteropathy). Infectious agents that affect gastrointestinal tract can be grouped as food-borne and water-borne bacteria, opportunistic infections (bacterial, fungal, and viral), viral infections (extremely rarely biopsied), and parasitic and helminthic infections. The majority of these infections are, however, self-limited. Although biopsy is more invasive, the use of this procedure allows detection of other causes, including Whipple's disease, other protozoan forms of diarrhea (e.g., cryptosporidiosis, isosporiasis, or cyclosporiasis), Crohn's disease, or lymphoma that may also present as diarrhea and malabsorption.
Collapse
|
|
45
|
Valitutti F, Di Nardo G, Barbato M, Aloi M, Celletti I, Trovato CM, Pierdomenico M, Marcheggiano A, Cucchiara S. Mapping histologic patchiness of celiac disease by push enteroscopy. Gastrointest Endosc 2014; 79:95-100. [PMID: 23886355 DOI: 10.1016/j.gie.2013.06.012] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2012] [Accepted: 06/17/2013] [Indexed: 02/08/2023]
Abstract
BACKGROUND Despite great improvements in serologic testing, duodenal biopsies are still required to diagnose the majority of celiac disease (CD) cases. Nevertheless, the histologic pattern of CD is often patchy, leading to the risk of missing the diagnosis. OBJECTIVE To evaluate the patchiness of the CD histologic lesions along the small bowel (SB), push enteroscopy has been performed instead of conventional upper GI endoscopy. DESIGN Prospective, single-center study. SETTING Tertiary-care referral center. PATIENTS A total of 41 pediatric patients with suspected CD. INTERVENTION Prospective evaluation of bulb, duodenal, and jejunal biopsy specimens in the diagnosis of CD. MAIN OUTCOME MEASUREMENTS Pattern of lesion distribution along the SB (from bulb up to 60 cm beyond the ligament of Treitz) and yield as well accuracy of pediatric CD diagnosis by using push enteroscopy. RESULTS There was a homogeneous pattern of histologic damage in 17 patients (41.5%), whereas 24 patients (58.5%) had a lesion pattern of patchiness. The second and fourth duodenal regions were involved in 38 children (92.7%) and 37 children (90.2%), respectively; the bulb was involved in 37 patients (90.2%); both distal and proximal jejunal samples showed histologic lesions in 38 children (92.7%). In 1 patient, without lesions in the bulb and duodenum, CD was diagnosed according to proximal and distal jejunal biopsies only (3B and C, respectively). A significant correlation was found between the degree of villous atrophy and the serum anti-transglutaminase titer. LIMITATIONS Small sample size; academic tertiary-care setting. CONCLUSION CD histologic lesions often have a discontinuous distribution along the SB, occasionally with an exclusive jejunal involvement. A high degree of villous atrophy correlates with a high anti-transglutaminase titer. When the new ESPGHAN "biopsy-sparing" criteria are not applicable, in case of potential CD, push enteroscopy might be a valuable second-step tool to re-evaluate and identify false "potential" CD hiding exclusive jejunal lesions.
Collapse
Affiliation(s)
- Francesco Valitutti
- Pediatric Gastroenterology and Liver Unit, Department of Pediatrics, Sapienza University of Rome, Rome, Italy
| | - Giovanni Di Nardo
- Pediatric Gastroenterology and Liver Unit, Department of Pediatrics, Sapienza University of Rome, Rome, Italy
| | - Maria Barbato
- Pediatric Gastroenterology and Liver Unit, Department of Pediatrics, Sapienza University of Rome, Rome, Italy
| | - Marina Aloi
- Pediatric Gastroenterology and Liver Unit, Department of Pediatrics, Sapienza University of Rome, Rome, Italy
| | - Ilaria Celletti
- Pediatric Gastroenterology and Liver Unit, Department of Pediatrics, Sapienza University of Rome, Rome, Italy
| | - Chiara Maria Trovato
- Pediatric Gastroenterology and Liver Unit, Department of Pediatrics, Sapienza University of Rome, Rome, Italy
| | - Maria Pierdomenico
- ENEA, Italian National Agency for new Technologies, Energy and Sustainable Economic Development, Rome, Italy
| | | | - Salvatore Cucchiara
- Pediatric Gastroenterology and Liver Unit, Department of Pediatrics, Sapienza University of Rome, Rome, Italy
| |
Collapse
|
|
46
|
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.
Collapse
|
|
47
|
Abstract
OBJECTIVE The aim of the present study was to evaluate a panel of different antibody assays, including second-generation antigliadin kits, in a local paediatric population thought to be at risk for coeliac disease (CD). METHODS Seventy-nine children, who tested positive for immunoglobulin A (IgA) antibodies to tissue transglutaminase (TG), underwent duodenal biopsy. At endoscopy, serum was collected from all of the patients, and 9 different coeliac antibody assays were performed, both as isolated assays and in combination. These included immunoglobulin A (IgA) anti-tissue transglutaminase (TGA), and IgA plus IgG anti-deamidated gliadin peptide (DGPAG). A diagnosis of CD was made if the biopsies showed Marsh grade 3 lesions. RESULTS Twenty-four of 79 children had CD confirmed histologically. Only 39 of 79 were positive for Inova TGA, and 35 of 79 were positive for Inova DGPAG. Twenty-four of 39 who were TGA positive and 24 of 35 who were DGPAG positive had confirmed CD on biopsy. There was good correlation between TGA and DGPAG-positive predictive values. None of the modified gliadin tests produced false-negative results, and neither did the TGA. CONCLUSIONS The Inova DGPAG and TGA assays have similar use in predicting CD in a selected paediatric population; however, in children who are positive for TGA when screened for CD, more than half have negative TGA serology when repeat testing is done at the time of biopsy. Those with persistent TGA positivity have only a 61.5% probability of having histologic CD, compared with 68.6% of those children positive for DGPAG.
Collapse
|
|
48
|
Rubio-Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol 2013; 108:656-76; quiz 677. [PMID: 23609613 PMCID: PMC3706994 DOI: 10.1038/ajg.2013.79] [Citation(s) in RCA: 1139] [Impact Index Per Article: 94.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
This guideline presents recommendations for the diagnosis and management of patients with celiac disease. Celiac disease is an immune-based reaction to dietary gluten (storage protein for wheat, barley, and rye) that primarily affects the small intestine in those with a genetic predisposition and resolves with exclusion of gluten from the diet. There has been a substantial increase in the prevalence of celiac disease over the last 50 years and an increase in the rate of diagnosis in the last 10 years. Celiac disease can present with many symptoms, including typical gastrointestinal symptoms (e.g., diarrhea, steatorrhea, weight loss, bloating, flatulence, abdominal pain) and also non-gastrointestinal abnormalities (e.g., abnormal liver function tests, iron deficiency anemia, bone disease, skin disorders, and many other protean manifestations). Indeed, many individuals with celiac disease may have no symptoms at all. Celiac disease is usually detected by serologic testing of celiac-specific antibodies. The diagnosis is confirmed by duodenal mucosal biopsies. Both serology and biopsy should be performed on a gluten-containing diet. The treatment for celiac disease is primarily a gluten-free diet (GFD), which requires significant patient education, motivation, and follow-up. Non-responsive celiac disease occurs frequently, particularly in those diagnosed in adulthood. Persistent or recurring symptoms should lead to a review of the patient's original diagnosis to exclude alternative diagnoses, a review of the GFD to ensure there is no obvious gluten contamination, and serologic testing to confirm adherence with the GFD. In addition, evaluation for disorders associated with celiac disease that could cause persistent symptoms, such as microscopic colitis, pancreatic exocrine dysfunction, and complications of celiac disease, such as enteropathy-associated lymphoma or refractory celiac disease, should be entertained. Newer therapeutic modalities are being studied in clinical trials, but are not yet approved for use in practice. Given the incomplete response of many patients to a GFD-free diet as well as the difficulty of adherence to the GFD over the long term, development of new effective therapies for symptom control and reversal of inflammation and organ damage are needed. The prevalence of celiac disease is increasing worldwide and many patients with celiac disease remain undiagnosed, highlighting the need for improved strategies in the future for the optimal detection of patients.
Collapse
Affiliation(s)
- Alberto Rubio-Tapia
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Ivor D Hill
- Department of Pediatrics, Wake Forest University School of Medicine, Winston-Salem, North Carolina
| | - Ciarán P Kelly
- Celiac Center, Division of Gastroenterology, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, Massachusetts
| | - Audrey H Calderwood
- Gastroenterology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
| | - Joseph A Murray
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| |
Collapse
|
|
49
|
|
|
50
|
Sharma A, Mews C, Jevon G, Ravikumara M. Duodenal bulb biopsy in children for the diagnosis of coeliac disease: experience from Perth, Australia. J Paediatr Child Health 2013; 49:210-4. [PMID: 23432775 DOI: 10.1111/jpc.12123] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/05/2012] [Indexed: 02/05/2023]
Abstract
AIM The study aims to assess the usefulness of duodenal bulb biopsy in the diagnosis of coeliac disease (CD) in a paediatric population. METHODS Since February 2009, in our institution, we have routinely included duodenal bulb biopsy in addition to distal duodenal biopsies in children undergoing diagnostic upper gastrointestinal endoscopy. All children diagnosed with CD between February 2009 and May 2011 were identified, and those children who had biopsy finding of CD limited to duodenal bulb were reviewed with regard to clinical, serological and histopathological parameters. Duodenal bulb biopsy reports of those children who did not have CD were also reviewed as control group. RESULTS A total of 101 children were diagnosed with CD during the study period. The mean age was 8.21 years (±3.63), 33 males and 68 females. There were 8 out of 101 (7.92%) who had histological changes consistent with CD exclusively in the duodenal bulb, with normal histology in the distal duodenum. None of duodenal bulb biopsy was abnormal in the control group. CONCLUSIONS In some children, diagnostic CD changes may be limited to the duodenal bulb only and hence we recommend that duodenal bulb biopsies be included routinely in children suspected with CD to improve the diagnostic yield.
Collapse
Affiliation(s)
- Ajay Sharma
- Department of Gastroenterology, Princess Margaret Hospital for Children, Perth, Western Australia, Australia
| | | | | | | |
Collapse
|