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Arias-González L, Rodríguez-Alcolado L, Laserna-Mendieta EJ, Navarro P, Lucendo AJ, Grueso-Navarro E. Fibrous Remodeling in Eosinophilic Esophagitis: Clinical Facts and Pathophysiological Uncertainties. Int J Mol Sci 2024; 25:927. [PMID: 38256003 PMCID: PMC10815180 DOI: 10.3390/ijms25020927] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Revised: 01/08/2024] [Accepted: 01/09/2024] [Indexed: 01/24/2024] Open
Abstract
Eosinophilic esophagitis (EoE) is a chronic, progressive, type 2 inflammatory disease with increasing global prevalence. An eosinophil-predominant inflammation that permeates the epithelium and deeper esophageal layers characterizes the disease. Several cytokines, mainly derived from inflammatory T-helper 2 (Th2) cells and epithelial cells, are involved in perpetuating inflammatory responses by increasing surface permeability and promoting tissue remodeling characterized by epithelial-mesenchymal transition (EMT) and collagen deposition. This leads to esophageal strictures and narrow caliber esophagi, which are proportional a patient's age and untreated disease length. Pathophysiological mechanisms leading to EoE have been described in recent years, and transforming growth factor beta (TGF)-beta have been involved in fibrotic phenomena in EoE. However, evidence on the dependence of these phenomena on TGF-beta is scarce and contradictory. This review provides state-of-the art knowledge on intimate mechanisms of esophageal fibrosis in EoE and its clinical consequences.
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Affiliation(s)
- Laura Arias-González
- Department of Gastroenterology, Hospital General de Tomelloso, Vereda de Socuéllamos s/n, 13700 Tomelloso, Spain; (L.A.-G.); (L.R.-A.); (E.J.L.-M.); (P.N.); (E.G.-N.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain
- Instituto de Investigación Sanitaria Princesa, 28006 Madrid, Spain
| | - Leticia Rodríguez-Alcolado
- Department of Gastroenterology, Hospital General de Tomelloso, Vereda de Socuéllamos s/n, 13700 Tomelloso, Spain; (L.A.-G.); (L.R.-A.); (E.J.L.-M.); (P.N.); (E.G.-N.)
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain
| | - Emilio J. Laserna-Mendieta
- Department of Gastroenterology, Hospital General de Tomelloso, Vereda de Socuéllamos s/n, 13700 Tomelloso, Spain; (L.A.-G.); (L.R.-A.); (E.J.L.-M.); (P.N.); (E.G.-N.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain
- Instituto de Investigación Sanitaria Princesa, 28006 Madrid, Spain
| | - Pilar Navarro
- Department of Gastroenterology, Hospital General de Tomelloso, Vereda de Socuéllamos s/n, 13700 Tomelloso, Spain; (L.A.-G.); (L.R.-A.); (E.J.L.-M.); (P.N.); (E.G.-N.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain
| | - Alfredo J. Lucendo
- Department of Gastroenterology, Hospital General de Tomelloso, Vereda de Socuéllamos s/n, 13700 Tomelloso, Spain; (L.A.-G.); (L.R.-A.); (E.J.L.-M.); (P.N.); (E.G.-N.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain
- Instituto de Investigación Sanitaria Princesa, 28006 Madrid, Spain
| | - Elena Grueso-Navarro
- Department of Gastroenterology, Hospital General de Tomelloso, Vereda de Socuéllamos s/n, 13700 Tomelloso, Spain; (L.A.-G.); (L.R.-A.); (E.J.L.-M.); (P.N.); (E.G.-N.)
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain
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Abe Y, Sasaki Y, Yagi M, Mizumoto N, Onozato Y, Kon T, Shoji M, Sakuta K, Sakai T, Umehara M, Ito M, Nakamura S, Tsuchida H, Ueno Y. Linked color imaging improves the diagnostic accuracy of eosinophilic esophagitis. DEN OPEN 2023; 3:e146. [PMID: 35898847 PMCID: PMC9310047 DOI: 10.1002/deo2.146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 06/03/2022] [Accepted: 06/10/2022] [Indexed: 11/25/2022]
Abstract
Objectives To assess the usefulness of linked color imaging (LCI), a recently developed image‐enhanced endoscopy technique, in the endoscopic diagnosis of eosinophilic esophagitis (EoE). Methods Thirty white light images (WLIs) and 30 WLI+LCI images collected from patients with and without EoE were randomly and blindly reviewed by 10 endoscopists, including four experts (Exs) and six non‐Exs. Edema, ring, exudate furrows, and strictures were rated on the adjusted EoE endoscopic reference score; the diagnosis of EoE was assessed. Using the kappa value, inter‐ and intra‐observer agreements were analyzed among endoscopists. Results WLI+LCI images had a higher diagnostic accuracy for EoE than WLIs (0.85 vs. 0.70, respectively), especially in non‐Exs or endoscopists with no experience with EoE patients. Inter‐observer agreement for WLI+LCI images statistically surpassed WLIs for furrows (kappa, 0.73 vs. 0.67, respectively; p = 0.0013), stricture (kappa, 0.51 vs. 0.39, respectively; p = 0.0072), and diagnosis (kappa, 0.67 vs. 0.57, respectively; p < 0.0001) of EoE. The increase in inter‐observer agreement in WLI+LCI images allowed for a reduction in the differences between the Exs and non‐Ex endoscopists. Intra‐observer agreement for WLI+LCI images surpassed WLIs for a ring (kappa, 0.62 vs. 0.43, p = 0.0052), and a similar trend was found in exudates, furrows, and diagnosis irrespective of the Exs or non‐Exs. Conclusions LCI can contribute to the improvement of the endoscopic diagnosis for EoE, with “moderate” to “substantial” consistency, by enhancing the visibility of abnormal findings, leading to reduced diagnostic disparities among endoscopists.
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Affiliation(s)
- Yasuhiko Abe
- Division of Endoscopy Yamagata University Hospital Yamagata Japan
| | - Yu Sasaki
- Department of Gastroenterology Faculty of Medicine Yamagata University Yamagata Japan
| | - Makoto Yagi
- Division of Endoscopy Yamagata University Hospital Yamagata Japan
| | - Naoko Mizumoto
- Department of Gastroenterology Faculty of Medicine Yamagata University Yamagata Japan
| | - Yusuke Onozato
- Department of Gastroenterology Faculty of Medicine Yamagata University Yamagata Japan
| | - Takashi Kon
- Department of Gastroenterology Faculty of Medicine Yamagata University Yamagata Japan
| | - Masakuni Shoji
- Department of Gastroenterology Faculty of Medicine Yamagata University Yamagata Japan
| | - Kazuhiro Sakuta
- Department of Gastroenterology Faculty of Medicine Yamagata University Yamagata Japan
| | - Takayuki Sakai
- Department of Gastroenterology Faculty of Medicine Yamagata University Yamagata Japan
| | - Matsuki Umehara
- Department of Gastroenterology Faculty of Medicine Yamagata University Yamagata Japan
| | - Minami Ito
- Department of Gastroenterology Faculty of Medicine Yamagata University Yamagata Japan
| | - Shuhei Nakamura
- Department of Gastroenterology Faculty of Medicine Yamagata University Yamagata Japan
| | - Hidemoto Tsuchida
- Department of Gastroenterology Faculty of Medicine Yamagata University Yamagata Japan
| | - Yoshiyuki Ueno
- Department of Gastroenterology Faculty of Medicine Yamagata University Yamagata Japan
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Abe Y, Sasaki Y, Yagi M, Mizumoto N, Onozato Y, Umehara M, Ueno Y. Endoscopic Diagnosis of Eosinophilic Esophagitis: Basics and Recent Advances. Diagnostics (Basel) 2022; 12:diagnostics12123202. [PMID: 36553209 PMCID: PMC9777529 DOI: 10.3390/diagnostics12123202] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Accepted: 12/14/2022] [Indexed: 12/24/2022] Open
Abstract
Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammatory disease, characterized by esophageal dysfunction and intense eosinophil infiltration localized in the esophagus. In recent decades, EoE has become a growing concern as a major cause of dysphagia and food impaction in adolescents and adults. EoE is a clinicopathological disease for which the histological demonstration of esophageal eosinophilia is essential for diagnosis. Therefore, the recognition of the characteristic endoscopic features with subsequent biopsy are critical for early definitive diagnosis and treatment, in order to prevent complications. Accumulating reports have revealed that EoE has several non-specific characteristic endoscopic findings, such as rings, furrows, white exudates, stricture/narrowing, edema, and crepe-paper esophagus. These findings were recently unified under the EoE endoscopic reference score (EREFS), which has been widely used as an objective, standard measurement for endoscopic EoE assessment. However, the diagnostic consistency of those findings among endoscopists is still inadequate, leading to underdiagnosis or misdiagnosis. Some endoscopic findings suggestive of EoE, such as multiple polypoid lesions, caterpillar sign, ankylosaurus back sign, and tug sign/pull sign, will aid the diagnosis. In addition, image-enhanced endoscopy represented by narrow band imaging, endocytoscopy, and artificial intelligence are expected to render endoscopic diagnosis more efficient and less invasive. This review focuses on suggestions for endoscopic assessment and biopsy, including recent advances in optical technology which may improve the diagnosis of EoE.
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Affiliation(s)
- Yasuhiko Abe
- Division of Endoscopy, Yamagata University Hospital, Yamagata 990-2321, Japan
- Correspondence:
| | - Yu Sasaki
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata 990-2321, Japan
| | - Makoto Yagi
- Division of Endoscopy, Yamagata University Hospital, Yamagata 990-2321, Japan
| | - Naoko Mizumoto
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata 990-2321, Japan
| | - Yusuke Onozato
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata 990-2321, Japan
| | - Matsuki Umehara
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata 990-2321, Japan
| | - Yoshiyuki Ueno
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata 990-2321, Japan
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Dhar A, Haboubi HN, Attwood SE, Auth MKH, Dunn JM, Sweis R, Morris D, Epstein J, Novelli MR, Hunter H, Cordell A, Hall S, Hayat JO, Kapur K, Moore AR, Read C, Sami SS, Turner PJ, Trudgill NJ. British Society of Gastroenterology (BSG) and British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) joint consensus guidelines on the diagnosis and management of eosinophilic oesophagitis in children and adults. Gut 2022; 71:1459-1487. [PMID: 35606089 PMCID: PMC9279848 DOI: 10.1136/gutjnl-2022-327326] [Citation(s) in RCA: 54] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 05/12/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Eosinophilic oesophagitis (EoE) is an increasingly common cause of dysphagia in both children and adults, as well as one of the most prevalent oesophageal diseases with a significant impact on physical health and quality of life. We have provided a single comprehensive guideline for both paediatric and adult gastroenterologists on current best practice for the evaluation and management of EoE. METHODS The Oesophageal Section of the British Society of Gastroenterology was commissioned by the Clinical Standards Service Committee to develop these guidelines. The Guideline Development Group included adult and paediatric gastroenterologists, surgeons, dietitians, allergists, pathologists and patient representatives. The Population, Intervention, Comparator and Outcomes process was used to generate questions for a systematic review of the evidence. Published evidence was reviewed and updated to June 2021. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was used to assess the evidence and make recommendations. Two rounds of voting were held to assess the level of agreement and the strength of recommendations, with 80% consensus required for acceptance. RESULTS Fifty-seven statements on EoE presentation, diagnosis, investigation, management and complications were produced with further statements created on areas for future research. CONCLUSIONS These comprehensive adult and paediatric guidelines of the British Society of Gastroenterology and British Society of Paediatric Gastroenterology, Hepatology and Nutrition are based on evidence and expert consensus from a multidisciplinary group of healthcare professionals, including patient advocates and patient support groups, to help clinicians with the management patients with EoE and its complications.
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Affiliation(s)
- Anjan Dhar
- Gastroenterology, Darlington Memorial Hospital, Darlington, UK .,Teesside University, Middlesbrough, UK
| | - Hasan N Haboubi
- Cancer Biomarker Group, Swansea University, Swansea, UK,Department of Gastroenterology, University Hospital Llandough, Llandough, UK
| | | | - Marcus K H Auth
- Department of Paediatric Gastroenterology, Alder Hey Children's NHS Foundation Trust, Liverpool, UK,University of Liverpool, Liverpool, UK
| | - Jason M Dunn
- Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK,Comprehensive Cancer Centre, King's College London, London, UK
| | - Rami Sweis
- Research Department of Tissue and Energy, Division of Surgery & Interventional Science, University College London, London, UK
| | - Danielle Morris
- Department of Gastroenterology, East and North Hertfordshire NHS Trust, Stevenage, UK
| | - Jenny Epstein
- Department of Paediatric Gastroenterology, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
| | | | - Hannah Hunter
- Department of Dietetics, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Amanda Cordell
- Trustee & Chair, EOS Network, Eosinophilic Disease Charity, London, UK
| | - Sharon Hall
- Department of Paediatric Allergy, Imperial College Healthcare NHS Trust, London, UK
| | - Jamal O Hayat
- Gastroenterology, St George's Healthcare NHS Trust, London, UK
| | - Kapil Kapur
- Gastroenterology, Barnsley Hospital NHS Foundation Trust, Barnsley, UK
| | - Andrew Robert Moore
- Gastroenterology, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Carol Read
- Medical advisor/Patient advocate, EOS Network, Eosinophilic Disease Charity, London, UK
| | - Sarmed S Sami
- Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
| | - Paul J Turner
- National Heart and Lung Institute Section of Allergy and Clinical Immunology, London, UK,Paediatric Allergy, Imperial College Healthcare NHS Trust, London, UK
| | - Nigel J Trudgill
- Department of Gastroenterology, Sandwell General Hospital, West Bromwich, UK
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Mari A, Abu Baker F, Said Ahmad H, Omari A, Jawabreh Y, Abboud R, Shahin A, Shibli F, Sbeit W, Khoury T. The Yield of Endoscopy and Histology in the Evaluation of Esophageal Dysphagia: Two Referral Centers' Experiences. MEDICINA (KAUNAS, LITHUANIA) 2021; 57:1336. [PMID: 34946281 PMCID: PMC8705225 DOI: 10.3390/medicina57121336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 11/25/2021] [Accepted: 12/02/2021] [Indexed: 11/16/2022]
Abstract
Background and Objectives: The initial diagnostic test required to evaluate esophageal dysphagia is upper endoscopy (EGD) to assess the structure of the esophagus and the esophageo-gastric junction (EGJ). Taking biopsies during EGD has become a common practice in patients with dysphagia to rule out eosinophilic esophagitis (EoE). The aims of this study were to evaluate the endoscopic findings of patients who underwent EGD for esophageal dysphagia, to assess the rate of biopsy taking from the esophagus to diagnose/exclude EoE, and to report histology outcomes of these biopsies. Materials and Methods: This was a retrospective multicenter study that included individuals ≥18 years who underwent EGD due to esophageal dysphagia between the years 2015 and2020, (with no other alarm signs, such as weight loss, new iron deficiency anemia, and lymphadenopathy). We obtained data from patients' electronic files. The endoscopy and histology findings were obtained from endoscopy reports saved in our electronic files. Results: A total of 209 patients were included in the study. The average age was 57.1 ± 17.1 years. The most common endoscopic findings were normal endoscopy in 76 patients (36.4%) and erosive esophagitis in 75 patients (35.9%). Barrett's esophagus and esophageal malignancy were encountered in 11 patients (5.3%) and 2 patients (0.95%), respectively. Esophageal biopsies were taken in 50.2% of patients, and one patient had histological evidence of EoE (0.5%). On univariate analysis, there was a trend for association between proton pump inhibitors (PPIs) use and a normal EGD, but it was not statistically significant (OR 0.28, 95% CI 0.07-1.11, p = 0.07). Conclusions: Endoscopic findings were prevalent in dysphagia patients even when no other alarm symptoms exist. Neoplastic lesions and EOE were rare in our study.
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Affiliation(s)
- Amir Mari
- Gastroenterology and Endoscopy Units, The Nazareth Hospital, EMMS, Nazareth 16100, Israel;
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed 1311502, Israel; (A.S.); (W.S.); (T.K.)
| | - Fadi Abu Baker
- Department of Gastroenterology, Hillel Yaffe Medical Center, Hadera 38100, Israel;
| | - Helal Said Ahmad
- Gastroenterology and Endoscopy Units, The Nazareth Hospital, EMMS, Nazareth 16100, Israel;
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed 1311502, Israel; (A.S.); (W.S.); (T.K.)
| | - Ali Omari
- Internal Medicine Department, The Nazareth Hospital, EMMS, Nazareth 16100, Israel; (A.O.); (Y.J.)
| | - Yazed Jawabreh
- Internal Medicine Department, The Nazareth Hospital, EMMS, Nazareth 16100, Israel; (A.O.); (Y.J.)
| | - Rand Abboud
- Surgery Department, The Nazareth Hospital, EMMS, Nazareth 16100, Israel;
| | - Amir Shahin
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed 1311502, Israel; (A.S.); (W.S.); (T.K.)
- Department of Gastroenterology, Galilee Medical Center, Nahariya 22100, Israel
| | - Fahmi Shibli
- Department of Gastroenterology and Liver Disease, Emek Medical Center, Afula 1855701, Israel;
- Rappaport Faculty of Medicine, Technion—Israel Institute of Technology, Haifa 38100, Israel
| | - Wisam Sbeit
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed 1311502, Israel; (A.S.); (W.S.); (T.K.)
- Department of Gastroenterology, Galilee Medical Center, Nahariya 22100, Israel
| | - Tawfik Khoury
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed 1311502, Israel; (A.S.); (W.S.); (T.K.)
- Department of Gastroenterology, Galilee Medical Center, Nahariya 22100, Israel
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Bora V, Olive A, Chiou E, Raj P, Mehta D. Eosinophilic esophagitis with and without airway involvement in children - A comparative analysis. Int J Pediatr Otorhinolaryngol 2020; 139:110422. [PMID: 33049554 DOI: 10.1016/j.ijporl.2020.110422] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 09/30/2020] [Accepted: 09/30/2020] [Indexed: 11/19/2022]
Abstract
BACKGROUND Eosinophilic esophagitis (EoE) is an allergic disease characterized by marked eosinophilic infiltration and inflammation of the esophagus eventually leading to esophageal dysfunction. This condition at times may involve the airway leading to breathing difficulties. OBJECTIVE To compare the course of EoE in patients with or without airway involvement. METHODS A retrospective chart review was done on patients with a diagnosis of Eosinophilic Esophagitis and that were managed in our Aerodigestive clinic from 2012 to 2018. A total of 121 EoE patients were included in the study. Each patient's disease course was examined for pertinent information including - but not limited to - age at presentation, allergies, endoscopic and pathology results, treatments prescribed, and time to resolution. The data was analyzed for any differences between the airway and non-airway groups for each of these variables. RESULTS The variables that were analyzed showed no significant difference between patients suffering from EoE with (n = 19) and without (n = 102) airway involvement. However, patients with airway disease trended towards being younger in age at presentation as compared to those without airway symptoms (6.68 years vs. 9.69 years, p = 0.69). Analysis of endoscopic and pathology findings revealed no difference. Similarly, no differences were found between the prescribed treatments. Kaplan-Meier estimates of time to disease remission indicated that 50% of patients had resolution at one year, regardless of airway involvement (p = 0.31). CONCLUSIONS Our findings indicate that the disease course of patients with EoE does not vary depending on the presence of airway symptoms. Thus, patients with airway symptoms should not be diagnosed or treated any different than those without airway symptoms.
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Affiliation(s)
- Varun Bora
- Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, 77030, USA.
| | - Anthony Olive
- Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, 77030, USA; Texas Children's Hospital, 6621 Fannin Street, Houston, TX, 77030, USA.
| | - Eric Chiou
- Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, 77030, USA; Texas Children's Hospital, 6621 Fannin Street, Houston, TX, 77030, USA.
| | - Priya Raj
- Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, 77030, USA; Texas Children's Hospital, 6621 Fannin Street, Houston, TX, 77030, USA.
| | - Deepak Mehta
- Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, 77030, USA; Texas Children's Hospital, 6621 Fannin Street, Houston, TX, 77030, USA.
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Red Between the Lines: Evolution of Eosinophilic Esophagitis as a Distinct Clinicopathologic Syndrome. Dig Dis Sci 2020; 65:3434-3447. [PMID: 33052498 PMCID: PMC7669680 DOI: 10.1007/s10620-020-06642-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/25/2020] [Indexed: 12/09/2022]
Abstract
Eosinophilic esophagitis (EoE) is characterized by eosinophilic infiltration of the esophageal mucosa and symptoms of esophageal dysfunction, including dysphagia. While EoE is still considered a rare disease, in practice it seems that more and more cases are diagnosed every week, research in the field is exploding, and the pipeline for treatments contains multiple agents, some of which are quite far along the development pathway. After only scattered cases and small series were published in the late 1970s and 1980, Stephen Attwood, Thomas Smyrk, Tom DeMeester, and James Jones, published in Digestive Diseases and Sciences in 1993 a seminal report that described a clinicopathologic syndrome of esophageal eosinophilia with dysphagia. This review details the origins of this paper and compares and contrast what was observed then and what is known now about multiple aspects of EoE, including the clinical presentation, diagnosis, epidemiology, natural history, and treatments and outcomes. Moreover, it will highlight how the paper presaged a number of controversies in the field that have yet to be resolved, as well as foreshadowed the collaborative, multidisciplinary approach that has led to rapid advances.
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Mari A, Tsoukali E, Yaccob A. Eosinophilic Esophagitis in Adults: A Concise Overview of an Evolving Disease. Korean J Fam Med 2020; 41:75-83. [PMID: 32062959 PMCID: PMC7093678 DOI: 10.4082/kjfm.18.0162] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Accepted: 10/15/2018] [Indexed: 12/19/2022] Open
Abstract
Eosinophilic esophagitis (EoE) is a chronic inflammatory disease that encompasses esophageal symptoms along with eosinophilic infiltration of the esophageal epithelium. EoE is an evolving disease that has been a subject of interest to many researchers since the first studies recognized this condition as a new and distinct clinicopathological entity 25 years ago. Clinical presentation in adult patients may include dysphagia, food impaction, vomiting, and reflux symptoms. The diagnosis of EoE is based on the combination of clinical history suggestive of esophageal dysfunction, endoscopic features indicative of the disease, and histology revealing eosinophilic infiltration of the esophageal epithelium that persists after a trial of proton pump inhibitor therapy along with the exclusion of other disorders that may be associated with esophageal tissue eosinophilia. The interplay between EoE and gastroesophageal reflux disease (GERD) is complex, and differentiating these two conditions continues to be difficult and challenging in clinical practice. The mainstay treatment includes dietary modification, topical steroids, and/or endoscopic dilation. The primary care physician (PCP) plays an important role in improving patient care and quality of life by ensuring early referral and participating in management and follow-up. This article provides an overview of the current knowledge base regarding the disease including epidemiology, genetics, pathogenesis, common clinical presentations, the interplay between EoE and GERD, diagnostic approaches, and therapeutic options available to the PCP.
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Affiliation(s)
- Amir Mari
- Gastroenterology Institute, Nazareth EMMS Hospital, Nazareth, Israel.,The Azrieli Faculty of Medicine, Bar-Ilan University, Ramat Gan, Israel
| | - Emmanouela Tsoukali
- Gastroenterology and Hepatology Department, Evangelismos General Hospital of Athens, Athens, Greece
| | - Afif Yaccob
- Gastroenterology and Liver Disease Department, Rambam Healthcare Campus, Haifa, Israel
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Mari A, Abu Baker F, Mahamid M, Khoury T, Sbeit W, Pellicano R. Eosinophilic esophagitis: pitfalls and controversies in diagnosis and management. Minerva Med 2020; 111:9-17. [PMID: 31755670 DOI: 10.23736/s0026-4806.19.06322-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Formerly considered a rare disorder, eosinophilic esophagitis (EoE) has emerged as a leading cause of feeding problems in children and an increasingly recognized cause of dysphagia and food impaction in adults. Our understanding of EoE and its complex interplay with gastro-esophageal reflux disease (GERD) has evolved over the past decade and culminated in the introduction of proton pump inhibitor (PPI) responsive EoE as a distinct entity which has added to this complexity. It is now clear that this entity is on the same spectrum as the original EoE, and that PPIs should be considered as part of treatment protocol and should not be recommended as a diagnostic tool. As such, removing the PPI trial from the diagnostic algorithm has been encouraged recently. Recent guidelines and reviews thoroughly address various aspects in EoE pathogenesis and diagnostic workup as well as management endpoints, treatment options and novel therapies. However, despite the recent extensive study and the advances in our knowledge of this disease, unmet needs and pitfalls in diagnostic workup and management of these patients are still to be clarified and will be under focus in this review.
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Affiliation(s)
- Amir Mari
- Gastroenterology Unit, Nazareth Hospital EMMS, Faculty of Medicine, Bar Ilan University, Safed, Israel -
| | - Fadi Abu Baker
- Gastroenterology Unit, Hillel Yaffe MC, Technion, Haifa, Israel
| | - Mahmud Mahamid
- Gastroenterology Unit, Nazareth Hospital EMMS, Faculty of Medicine, Bar Ilan University, Safed, Israel
| | - Tawfik Khoury
- Gastroenterology Unit, Nazareth Hospital EMMS, Faculty of Medicine, Bar Ilan University, Safed, Israel
- Department of Gastroenterology, Galilee MC, Faculty of Medicine, Bar Ilan University, Safed, Israel
| | - Wisam Sbeit
- Department of Gastroenterology, Galilee MC, Faculty of Medicine, Bar Ilan University, Safed, Israel
| | - Rinaldo Pellicano
- Gastroenterology Unit, Molinette-San Giovanni Antica Sede Hospitals, Turin, Italy
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10
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Gómez-Aldana A, Jaramillo-Santos M, Delgado A, Jaramillo C, Lúquez-Mindiola A. Eosinophilic esophagitis: Current concepts in diagnosis and treatment. World J Gastroenterol 2019; 25:4598-4613. [PMID: 31528089 PMCID: PMC6718043 DOI: 10.3748/wjg.v25.i32.4598] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Revised: 07/13/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Eosinophilic esophagitis is an immune-allergic pathology of multifactorial etiology (genetic and environmental) that affects both pediatric and adult patients. Its symptoms, which include heartburn, regurgitation, and esophageal stenosis (with dysphagia being more frequent in eosinophilic esophagitis in young adults and children), are similar to those of gastroesophageal reflux disease, causing delays in diagnosis and treatment. Although endoscopic findings such as furrows, esophageal mucosa trachealization, and whitish exudates may suggest its presence, this diagnosis should be confirmed histologically based on the presence of more than 15 eosinophils per high-power field and the exclusion of other causes of eosinophilia (parasitic infections, hypereosinophilic syndrome, inflammatory bowel disease, among others) for which treatment could be initiated. Currently, the 3 "D"s ("Drugs, Diet, and Dilation") are considered the fundamental components of treatment. The first 2 components, which involve the use of proton pump inhibitors, corticosteroids, immunosuppressants and empirical diets or guided food elimination based on allergy tests, are more useful in the initial phases, whereas endoscopic dilation is reserved for esophageal strictures. Herein, the most important aspects of eosinophilic esophagitis pathophysiology will be reviewed, in addition to evidence for the various treatments.
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Affiliation(s)
- Andrés Gómez-Aldana
- Departament of Internal Medicine, Section of Gastroenterology, Santa Fe Foundation of Bogotá (Fundación Santa Fe de Bogotá), Bogotá 220246, Colombia
- University of Los Andes, Bogotá 111711, Colombia
| | - Mario Jaramillo-Santos
- Department of Endoscopy, Caldas University, Manizales 275, Colombia
- Department of Endoscopy, Surgeons’ Union SAS (Joint stock company) (Union de cirujanos SAS), Manizales 170001661, Colombia
| | - Andrés Delgado
- Departament of Internal Medicine, Section of Gastroenterology, Santa Fe Foundation of Bogotá (Fundación Santa Fe de Bogotá), Bogotá 220246, Colombia
| | - Carlos Jaramillo
- Department of Endoscopy, Caldas University, Manizales 275, Colombia
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11
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Pérez-Martínez I, Rodrigo L, Lucendo AJ. Esofagitis eosinofílica: aproximación al diagnóstico y tratamiento desde la evidencia. Med Clin (Barc) 2019; 152:444-449. [DOI: 10.1016/j.medcli.2018.10.022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Revised: 10/12/2018] [Accepted: 10/16/2018] [Indexed: 01/07/2023]
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12
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Arias Á, Lucendo AJ. Molecular basis and cellular mechanisms of eosinophilic esophagitis for the clinical practice. Expert Rev Gastroenterol Hepatol 2019; 13:99-117. [PMID: 30791784 DOI: 10.1080/17474124.2019.1546120] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Eosinophilic esophagitis (EoE) is a chronic, allergen-driven inflammatory esophageal disease characterized by predominantly eosinophilic inflammation leading to esophageal dysfunction. Recent efforts to understand EoE have increased our knowledge of the disease. Areas covered: Multiple cells, molecules, and genes interplay with early life environmental factors in the pathophysiology of EoE to converge in the esophageal epithelium at the center of disease pathogenesis. Epithelial cells constitute a mayor cytokine source for TSLP and Calpain-14; an impaired epithelial barrier function allowing penetration of food and microbiota-derived antigens is involved in triggering and maintaining inflammation. Eosinophil and mast cell-derived products, including TGFβ, together with IL-1β and TNFα, promote epithelial mesenchymal transition in EoE, contributing to tissue remodeling by synthetizing and depositing extracellular matrix in subepithelial layers. This article aims to provide a state-of-the-art update on the pathophysiology of EoE applied to clinical practice, and latest research and developments with potential interest to improve the diagnosis and treatment of patients with EoE are revised. Expert commentary: Preliminary approaches have provided promising results toward incorporating minimally invasive methods for patient diagnosis and monitoring in clinical practice. Early diagnosis and optimized therapies will allow for personalized medicine in EoE.
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Affiliation(s)
- Ángel Arias
- a Research Unit , Hospital General La Mancha Centro , Alcázar de San Juan , Spain.,b Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) , Madrid , Spain
| | - Alfredo J Lucendo
- b Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) , Madrid , Spain.,c Department of Gastroenterology , Hospital General de Tomelloso , Ciudad Real , Spain
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13
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Wong S, Ruszkiewicz A, Holloway RH, Nguyen NQ. Gastro-oesophageal reflux disease and eosinophilic oesophagitis: What is the relationship? World J Gastrointest Pathophysiol 2018; 9:63-72. [PMID: 30386667 PMCID: PMC6209579 DOI: 10.4291/wjgp.v9.i3.63] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Revised: 09/17/2018] [Accepted: 10/11/2018] [Indexed: 02/06/2023] Open
Abstract
Eosinophilic oesophagitis (EoE) and gastro-oesophageal reflux disease (GORD) are the most common causes of chronic oesophagitis and dysphagia associated with oesophageal mucosal eosinophilia. Distinguishing between the two is imperative but challenging due to overlapping clinical and histological features. A diagnosis of EoE requires clinical, histological and endoscopic correlation whereas a diagnosis of GORD is mainly clinical without the need for other investigations. Both entities may exhibit oesophageal eosinophilia at a similar level making a histological distinction between them difficult. Although the term proton-pump inhibitor responsive oesophageal eosinophilia has recently been retracted from the guidelines, a relationship between EoE and GORD still exists. This relationship is complex as they may coexist, either interacting bidirectionally or are unrelated. This review aims to outline the differences and potential relationship between the two conditions, with specific focus on histology, immunology, pathogenesis and treatment.
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Affiliation(s)
- Stephanie Wong
- Discipline of Medicine, University of Adelaide, Adelaide SA 5000, Australia
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide SA 5000, Australia
| | - Andrew Ruszkiewicz
- Discipline of Medicine, University of Adelaide, Adelaide SA 5000, Australia
- Anatomical Pathology, SA Pathology, Adelaide SA 5000, Australia
| | - Richard H Holloway
- Discipline of Medicine, University of Adelaide, Adelaide SA 5000, Australia
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide SA 5000, Australia
| | - Nam Q Nguyen
- Discipline of Medicine, University of Adelaide, Adelaide SA 5000, Australia
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide SA 5000, Australia
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14
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Esofagitis eosinofílica: diagnóstico y tratamiento actual basado en la evidencia. GASTROENTEROLOGIA Y HEPATOLOGIA 2018; 41:281-291. [DOI: 10.1016/j.gastrohep.2017.12.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/20/2017] [Revised: 12/01/2017] [Accepted: 12/15/2017] [Indexed: 12/19/2022]
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15
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Aktuelle Konzepte zur eosinophilen Ösophagitis. ALLERGO JOURNAL 2017. [DOI: 10.1007/s15007-017-1457-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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16
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Abstract
Background Eosinophilic esophagitis (EoE) is a disease entity first described in the 1990s, but showing an increasing incidence that is characterized clinically by esophageal dysfunction and histologically by a striking eosinophil infiltration. Methods This article discusses new aspects of the pathogenesis, symptoms, diagnosis, and treatment of EoE. Results EoE affects both children and adults and is frequently associated with atopic disease and IgE sensitization. Barrier dysfunction and T‑helper 2 inflammation are considered to be pathogenetically important factors. Recently, a proton pump inhibitor (PPI)-sensitive EoE subtype as well as an EoE-like disorder have been described. Conclusion Research in recent years has contributed to a better understanding of the disease spectrum and pathogenesis of EoE, including genetic dispositions, thereby laying the foundation for innovative treatment approaches.
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Affiliation(s)
- Dagmar Simon
- Department of Dermatology, Bern University Hospital, Inselspital, University of Bern, 3010 Bern, Switzerland
| | | | - Alain M Schoepfer
- Department of Gastroenterology and Hepatology, Lausanne University Hospital CHUV, Lausanne, Switzerland
| | - Hans-Uwe Simon
- Institute of Pharmacology, University of Bern, 3010 Bern, Switzerland
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17
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Runge TM, Eluri S, Woosley JT, Shaheen NJ, Dellon ES. Control of inflammation decreases the need for subsequent esophageal dilation in patients with eosinophilic esophagitis. Dis Esophagus 2017; 30:1-7. [PMID: 29206905 PMCID: PMC5906132 DOI: 10.1093/dote/dox042] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2017] [Accepted: 04/04/2017] [Indexed: 12/11/2022]
Abstract
It is unknown if successful control of esophageal inflammation in eosinophilic esophagitis (EoE) decreases the need for subsequent esophageal dilation. We aimed to determine whether histologic response to topical steroid treatment decreases the likelihood and frequency of subsequent esophageal dilation. We conducted a retrospective cohort study. Patients with an incident diagnosis of EoE were included if they had an initial esophageal dilation, received topical steroids, and had a subsequent endoscopy with biopsies. The number of dilations performed in each group was determined, and histologic responders (<15 eos/hpf) were compared to nonresponders. The 55 EoE patients included (27 responders and 28 nonresponders) underwent a mean of 3.0 dilations over a median follow-up of 19 months. Responders required fewer dilations than nonresponders (1.6 vs. 4.6, P = 0.03), after adjusting for potential confounders. Despite undergoing significantly fewer dilations, responders achieved a similar increase in esophageal diameter with dilation (4.9 vs. 5.0 mm; P = 0.92). In EoE patients undergoing esophageal dilation at baseline, control of inflammation with topical steroids was associated with a 65% decrease in the number of subsequent dilations to maintain the same esophageal caliber. This suggests that inflammation control is an important goal in patients with fibrostenotic changes of EoE.
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Affiliation(s)
- T M Runge
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.,Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
| | - S Eluri
- Center for Esophageal Diseases and Swallowing,U niversity of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.,Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
| | - J T Woosley
- Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
| | - N J Shaheen
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.,Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
| | - E S Dellon
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.,Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease ,University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
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18
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Diagnosis and treatment of eosinophilic esophagitis in clinical practice. Clin J Gastroenterol 2017; 10:87-102. [DOI: 10.1007/s12328-017-0725-4] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2016] [Accepted: 02/15/2017] [Indexed: 12/12/2022]
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19
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Rodríguez-Sánchez J, Barrio-Andrés J, Nantes Castillejo O, Valdivieso-Cortazar E, Pérez-Martínez I, Boumidi A, Olmos-Jérez JA, Payeras-Llodra G, Alcaide-Suarez N, Ruiz-Rebollo L, Madrigal-Rubiales B, Gonzalez-Obeso E, de la Santa Belda E, López Viedma B, Molina-Infante J. The Endoscopic Reference Score shows modest accuracy to predict either clinical or histological activity in adult patients with eosinophilic oesophagitis. Aliment Pharmacol Ther 2017; 45:300-309. [PMID: 27868216 DOI: 10.1111/apt.13845] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2016] [Revised: 04/05/2016] [Accepted: 10/06/2016] [Indexed: 12/19/2022]
Abstract
BACKGROUND Conflicting results have been recently reported for the accuracy of the Endoscopic Reference Score (EREFS), an standardised endoscopic classification, to predict the histological activity of eosinophilic oesophagitis (EoE). AIM To evaluate the accuracy of the EREFS to predict either histological or clinical activity of EoE. METHODS Prospective multicentre study conducted in eight Spanish centres evaluating adult EoE patients, either naïve or after treatment. Symptoms were evaluated before upper endoscopy through the Dysphagia Symptom Score, whereas researchers scored the EREFS immediately after the endoscopic procedure, unaware of the histological outcome. RESULTS One hundred and forty-five EoE patients undergoing 240 consecutive endoscopic procedures were included. Exudates (P = 0.03), furrows (P = 0.03) and a composite score of inflammatory signs (exudates, furrows and oedema) (P < 0.001) accurately predicted histological activity. Exudates were the only endoscopic sign showing a good correlation with histological outcome after therapy. Furrows and oedema persisted in 50% and 70% of patients despite histological remission. No endoscopic feature exceeded 70% accuracy to predict histological activity. Likewise, no endoscopic finding could adequately predict dysphagia severity. Crepe paper mucosa, diffuse exudates and severe rings correlated with higher symptom scores. CONCLUSIONS Endoscopic findings assessed by the Endoscopic Reference Score did not correlate with histological or clinical disease activity in adult EoE patients. Only exudates correlated with peak eosinophil count and histological outcome, whereas furrows and oedema persisted in over half of patients despite histological remission.
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Affiliation(s)
- J Rodríguez-Sánchez
- Department of Gastroenterology, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain
| | | | | | | | | | - A Boumidi
- Hospital de Santa Bárbara, Puertollano, Spain
| | | | | | | | | | - B Madrigal-Rubiales
- Department of Pathology, Hospital Universitario Rio Hortega, Valladolid, Spain
| | | | - E de la Santa Belda
- Department of Gastroenterology, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain
| | - B López Viedma
- Department of Gastroenterology, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain
| | - J Molina-Infante
- Department of Gastroenterology, Hospital San Pedro de Alcántara, Cáceres, Spain
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20
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Venkateshaiah SU, Manohar M, Verma AK, Blecker U, Mishra A. Possible Noninvasive Biomarker of Eosinophilic Esophagitis: Clinical and Experimental Evidence. Case Rep Gastroenterol 2016; 10:685-692. [PMID: 27920662 PMCID: PMC5126594 DOI: 10.1159/000452654] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2016] [Accepted: 10/17/2016] [Indexed: 12/30/2022] Open
Abstract
Eosinophilic esophagitis (EoE) diagnosis and follow-up response to therapy is based on repeated endoscopies and histological examination for eosinophils/HPF. The procedure is invasive and risky in particular for the pediatric population. Presently, there is no highly sensitive and specific noninvasive blood test available to monitor the disease pathogenesis. Reports indicate the expression of PDL1 (CD274) on the eosinophils in allergic patients. Herein, we report that CD274-expressing and -nonexpressing eosinophils were detected in both examined pediatric and adult EoE patients. We show that CD274 expression on blood eosinophils and blood mRNA expression levels increase in the blood of EoE patients and decrease following treatment. These observations are consistent with the esophageal eosinophilia of before and after treatment in both examined patients. These two clinical and experimental analysis reports provide the possibility that the CD274 mRNA and CD274-expressing esinophil levels may be novel possible noninvasive biomarkers for EoE.
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Affiliation(s)
| | - Murli Manohar
- Department of Medicine, Tulane Eosinophilic Disorders Center (TEDC), Section of Pulmonary Diseases, New Orleans, LA, USA
| | - Alok K Verma
- Department of Medicine, Tulane Eosinophilic Disorders Center (TEDC), Section of Pulmonary Diseases, New Orleans, LA, USA
| | - Uwe Blecker
- Section of Pediatric Gastroentrology, Tulane University, School of Medicine, New Orleans, LA, USA
| | - Anil Mishra
- Department of Medicine, Tulane Eosinophilic Disorders Center (TEDC), Section of Pulmonary Diseases, New Orleans, LA, USA
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21
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Larsson H, Norder Grusell E, Tegtmeyer B, Ruth M, Bergquist H, Bove M. Grade of eosinophilia versus symptoms in patients with dysphagia and esophageal eosinophilia. Dis Esophagus 2016; 29:971-976. [PMID: 26390287 DOI: 10.1111/dote.12417] [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: 12/11/2022]
Abstract
The aim of this study was to assess whether the symptom severity and health-related quality of life (HRQL) of patients with dysphagia and esophageal eosinophilia correlate with disease activity as expressed by the number of eosinophils in the esophageal mucosa. This study included newly diagnosed (n = 58) or relapsed patients (n = 7), where 40% were diagnosed in connection with esophageal bolus impaction. The mean age was 45 years (19-88), and 74% were men. Symptoms and HRQL were recorded using the Watson Dysphagia Scale (WDS), the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Oesophageal Module 18 and the Short Form-36 Questionnaire. Histological samples gathered from the proximal and distal esophageal mucosa were stained using both hematoxylin and eosin (HE) and an immunohistochemical (IHC) technique against 'Eosinophil Major Basic Protein,' and the peak number of eosinophils per high-power field was assessed. More eosinophils were detected after IHC staining than HE staining (P < 0.001). No correlation was found between symptoms or the HRQL and the number of eosinophils. However, higher numbers of eosinophils at the proximal esophagus were found in patients with concomitant bolus impaction (IHC P < 0.05 and HE P < 0.05) and could serve as a risk marker.
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Affiliation(s)
- H Larsson
- Department of ENT, Head and Neck Surgery, NÄL Medical Centre, Trollhättan, Sweden
| | - E Norder Grusell
- Department of ENT, Head and Neck Surgery, Sahlgrenska University Hospital, University of Gothenburg, Göteborg, Sweden
| | - B Tegtmeyer
- Department of Pathology, NÄL Medical Centre, Trollhättan, Sweden
| | - M Ruth
- Department of ENT, Head and Neck Surgery, Sahlgrenska University Hospital, University of Gothenburg, Göteborg, Sweden
| | - H Bergquist
- Department of ENT, Head and Neck Surgery, Sahlgrenska University Hospital, University of Gothenburg, Göteborg, Sweden
| | - M Bove
- Department of ENT, Head and Neck Surgery, NÄL Medical Centre, Trollhättan, Sweden
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22
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Dellon ES, Gebhart JH, Higgins LL, Hathorn KE, Woosley JT, Shaheen NJ. The esophageal biopsy "pull" sign: a highly specific and treatment-responsive endoscopic finding in eosinophilic esophagitis (with video). Gastrointest Endosc 2016; 83:92-100. [PMID: 26142556 PMCID: PMC4691559 DOI: 10.1016/j.gie.2015.05.046] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2015] [Accepted: 05/23/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Esophageal biopsy specimens from patients with eosinophilic esophagitis (EoE) can feel firm, with resistance felt when pulling the forceps to obtain the tissue sample. We aimed to assess the diagnostic utility of the esophageal biopsy "pull" sign and determine its histologic associations and response to treatment. METHODS This was a prospective cohort study of adults undergoing outpatient upper endoscopy. Cases of EoE were diagnosed per consensus guidelines, and patients were subsequently treated with either topical steroids or dietary elimination. Control subjects were individuals who did not have EoE. The frequency of the esophageal biopsy "pull" sign was assessed in EoE patients and controls, and diagnostic metrics were calculated. The "pull" sign was also reassessed in patients after therapy. RESULTS A total of 83 EoE patients and 121 control subjects were included. Sixty-three EoE patients (76%) were "pull" sign positive compared with just 2 control subjects (2%; P < .001), corresponding to a sensitivity and specificity of 76% and 98%, positive and negative predictive values of 97% and 86%, and positive and negative likelihood ratios of 45.9 and 0.245, respectively. The "pull" sign was the strongest endoscopic predictor of EoE case status at baseline and was less frequent after successful treatment (20% vs 79%; P < .001). CONCLUSIONS The "pull" sign is highly specific for EoE and is rarely seen in non-EoE control subjects. In patients with EoE who respond to treatment, the "pull" sign often resolves. The "pull" sign may be a simple and easily obtained measure of esophageal remodeling.
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Affiliation(s)
- Evan S. Dellon
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC,Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine; University of North Carolina School of Medicine, Chapel Hill, NC
| | - Jessica H. Gebhart
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Leana L. Higgins
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Kelly E. Hathorn
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC
| | - John T. Woosley
- Department of Pathology and Laboratory Medicine; University of North Carolina School of Medicine, Chapel Hill, NC
| | - Nicholas J. Shaheen
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC,Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine; University of North Carolina School of Medicine, Chapel Hill, NC
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23
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Bousquet J, Anto JM, Wickman M, Keil T, Valenta R, Haahtela T, Lodrup Carlsen K, van Hage M, Akdis C, Bachert C, Akdis M, Auffray C, Annesi-Maesano I, Bindslev-Jensen C, Cambon-Thomsen A, Carlsen KH, Chatzi L, Forastiere F, Garcia-Aymerich J, Gehrig U, Guerra S, Heinrich J, Koppelman GH, Kowalski ML, Lambrecht B, Lupinek C, Maier D, Melén E, Momas I, Palkonen S, Pinart M, Postma D, Siroux V, Smit HA, Sunyer J, Wright J, Zuberbier T, Arshad SH, Nadif R, Thijs C, Andersson N, Asarnoj A, Ballardini N, Ballereau S, Bedbrook A, Benet M, Bergstrom A, Brunekreef B, Burte E, Calderon M, De Carlo G, Demoly P, Eller E, Fantini MP, Hammad H, Hohman C, Just J, Kerkhof M, Kogevinas M, Kull I, Lau S, Lemonnier N, Mommers M, Nawijn M, Neubauer A, Oddie S, Pellet J, Pin I, Porta D, Saes Y, Skrindo I, Tischer CG, Torrent M, von Hertzen L. Are allergic multimorbidities and IgE polysensitization associated with the persistence or re-occurrence of foetal type 2 signalling? The MeDALL hypothesis. Allergy 2015; 70:1062-78. [PMID: 25913421 DOI: 10.1111/all.12637] [Citation(s) in RCA: 77] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/22/2015] [Indexed: 12/22/2022]
Abstract
Allergic diseases [asthma, rhinitis and atopic dermatitis (AD)] are complex. They are associated with allergen-specific IgE and nonallergic mechanisms that may coexist in the same patient. In addition, these diseases tend to cluster and patients present concomitant or consecutive diseases (multimorbidity). IgE sensitization should be considered as a quantitative trait. Important clinical and immunological differences exist between mono- and polysensitized subjects. Multimorbidities of allergic diseases share common causal mechanisms that are only partly IgE-mediated. Persistence of allergic diseases over time is associated with multimorbidity and/or IgE polysensitization. The importance of the family history of allergy may decrease with age. This review puts forward the hypothesis that allergic multimorbidities and IgE polysensitization are associated and related to the persistence or re-occurrence of foetal type 2 signalling. Asthma, rhinitis and AD are manifestations of a common systemic immune imbalance (mesodermal origin) with specific patterns of remodelling (ectodermal or endodermal origin). This study proposes a new classification of IgE-mediated allergic diseases that allows the definition of novel phenotypes to (i) better understand genetic and epigenetic mechanisms, (ii) better stratify allergic preschool children for prognosis and (iii) propose novel strategies of treatment and prevention.
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Affiliation(s)
- J. Bousquet
- University Hospital; Montpellier France
- MACVIA-LR; Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon; European Innovation Partnership on Active and Healthy Ageing Reference Site; Paris France
- INSERM; VIMA: Ageing and Chronic Diseases Epidemiological and Public Health Approaches, U1168; Paris France
- UVSQ; UMR-S 1168; Université Versailles St-Quentin-en-Yvelines; Versailles France
| | - J. M. Anto
- Centre for Research in Environmental Epidemiology (CREAL); Barcelona Spain
- Hospital del Mar Research Institute (IMIM); Barcelona Spain
- CIBER Epidemiología y Salud Pública (CIBERESP); Barcelona Spain
- Department of Experimental and Health Sciences; University of Pompeu Fabra (UPF); Barcelona Spain
| | - M. Wickman
- Sachs’ Children's Hospital; Stockholm Sweden
- Institute of Environmental Medicine; Karolinska Institutet; Stockholm Sweden
| | - T. Keil
- Institute of Social Medicine, Epidemiology and Health Economics; Charité - Universitätsmedizin Berlin; Berlin Germany
- Institute for Clinical Epidemiology and Biometry; University of Wuerzburg; Wuerzburg Germany
| | - R. Valenta
- Division of Immunopathology; Department of Pathophysiology and Allergy Research; Center for Pathophysiology, Infectiology and Immunology; Medical University of Vienna; Vienna Austria
| | - T. Haahtela
- Skin and Allergy Hospital; Helsinki University Hospital; Helsinki Finland
| | - K. Lodrup Carlsen
- Department of Paediatrics; Oslo University Hospital; Oslo Norway
- Faculty of Medicine; Institute of Clinical Medicine; University of Oslo; Oslo Norway
| | - M. van Hage
- Clinical Immunology and Allergy Unit; Department of Medicine Solna; Karolinska Institutet and University Hospital; Stockholm Sweden
| | - C. Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF); University of Zurich; Davos Switzerland
| | - C. Bachert
- ENT Department; Ghent University Hospital; Gent Belgium
| | - M. Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF); University of Zurich; Davos Switzerland
| | - C. Auffray
- European Institute for Systems Biology and Medicine; Lyon France
| | - I. Annesi-Maesano
- EPAR U707 INSERM; Paris France
- EPAR UMR-S UPMC; Paris VI; Paris France
| | - C. Bindslev-Jensen
- Department of Dermatology and Allergy Centre; Odense University Hospital; Odense Denmark
| | - A. Cambon-Thomsen
- UMR Inserm U1027; Université de Toulouse III Paul Sabatier; Toulouse France
| | - K. H. Carlsen
- Department of Paediatrics; Oslo University Hospital; Oslo Norway
- University of Oslo; Oslo Norway
| | - L. Chatzi
- Department of Social Medicine; Faculty of Medicine; University of Crete; Heraklion Crete Greece
| | - F. Forastiere
- Department of Epidemiology; Regional Health Service Lazio Region; Rome Italy
| | - J. Garcia-Aymerich
- Centre for Research in Environmental Epidemiology (CREAL); Barcelona Spain
- Hospital del Mar Research Institute (IMIM); Barcelona Spain
- CIBER Epidemiología y Salud Pública (CIBERESP); Barcelona Spain
- Department of Experimental and Health Sciences; University of Pompeu Fabra (UPF); Barcelona Spain
| | - U. Gehrig
- Julius Center of Health Sciences and Primary Care; University Medical Center Utrecht; University of Utrecht; Utrecht the Netherlands
| | - S. Guerra
- Centre for Research in Environmental Epidemiology (CREAL); Barcelona Spain
| | - J. Heinrich
- Institute of Epidemiology; German Research Centre for Environmental Health; Helmholtz Zentrum München; Neuherberg Germany
| | - G. H. Koppelman
- Department of Pediatric Pulmonology and Pediatric Allergology; GRIAC Research Institute; University Medical Center Groningen; Beatrix Children's Hospital; University of Groningen; Groningen the Netherlands
| | - M. L. Kowalski
- Department of Immunology, Rheumatology and Allergy; Medical University of Lodz; Lodz Poland
| | - B. Lambrecht
- VIB Inflammation Research Center; Ghent University; Ghent Belgium
| | - C. Lupinek
- Division of Immunopathology; Department of Pathophysiology and Allergy Research; Center for Pathophysiology, Infectiology and Immunology; Medical University of Vienna; Vienna Austria
| | | | - E. Melén
- Institute of Environmental Medicine; Karolinska Institutet; Stockholm Sweden
| | - I. Momas
- Department of Public Health and Biostatistics, EA 4064; Paris Descartes University; Paris France
- Paris Municipal Department of Social Action, Childhood, and Health; Paris France
| | - S. Palkonen
- EFA European Federation of Allergy and Airways Diseases Patients' Associations; Brussels Belgium
| | - M. Pinart
- Centre for Research in Environmental Epidemiology (CREAL); Barcelona Spain
| | - D. Postma
- Department of Respiratory Medicine; GRIAC Research Institute; University Medical Center Groningen; Beatrix Children's Hospital; University of Groningen; Groningen the Netherlands
| | | | - H. A. Smit
- Julius Center of Health Sciences and Primary Care; University Medical Center Utrecht; University of Utrecht; Utrecht the Netherlands
| | - J. Sunyer
- Centre for Research in Environmental Epidemiology (CREAL); Barcelona Spain
- Hospital del Mar Research Institute (IMIM); Barcelona Spain
- CIBER Epidemiología y Salud Pública (CIBERESP); Barcelona Spain
- Department of Experimental and Health Sciences; University of Pompeu Fabra (UPF); Barcelona Spain
| | - J. Wright
- Bradford Institute for Health Research; Bradford Royal Infirmary; Bradford UK
| | - T. Zuberbier
- Allergy-Centre-Charité at the Department of Dermatology; Charité - Universitätsmedizin Berlin; Berlin Germany
- Secretary General of the Global Allergy and Asthma European Network (GA2LEN); Berlin Germany
| | - S. H. Arshad
- David Hide Asthma and Allergy Research Centre; Isle of Wight UK
| | - R. Nadif
- INSERM; VIMA: Ageing and Chronic Diseases Epidemiological and Public Health Approaches, U1168; Paris France
- UVSQ; UMR-S 1168; Université Versailles St-Quentin-en-Yvelines; Versailles France
| | - C. Thijs
- Department of Epidemiology; CAPHRI School of Public Health and Primary Care; Maastricht University; Maastricht the Netherlands
| | - N. Andersson
- Sachs’ Children's Hospital; Stockholm Sweden
- Institute of Environmental Medicine; Karolinska Institutet; Stockholm Sweden
| | - A. Asarnoj
- Sachs’ Children's Hospital; Stockholm Sweden
- Institute of Environmental Medicine; Karolinska Institutet; Stockholm Sweden
| | - N. Ballardini
- Sachs’ Children's Hospital; Stockholm Sweden
- Institute of Environmental Medicine; Karolinska Institutet; Stockholm Sweden
| | - S. Ballereau
- European Institute for Systems Biology and Medicine; Lyon France
| | - A. Bedbrook
- MACVIA-LR; Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon; European Innovation Partnership on Active and Healthy Ageing Reference Site; Paris France
| | - M. Benet
- Centre for Research in Environmental Epidemiology (CREAL); Barcelona Spain
| | - A. Bergstrom
- Sachs’ Children's Hospital; Stockholm Sweden
- Institute of Environmental Medicine; Karolinska Institutet; Stockholm Sweden
| | - B. Brunekreef
- Julius Center of Health Sciences and Primary Care; University Medical Center Utrecht; University of Utrecht; Utrecht the Netherlands
| | - E. Burte
- INSERM; VIMA: Ageing and Chronic Diseases Epidemiological and Public Health Approaches, U1168; Paris France
- UVSQ; UMR-S 1168; Université Versailles St-Quentin-en-Yvelines; Versailles France
| | - M. Calderon
- National Heart and Lung Institute; Imperial College London; Royal Brompton Hospital NHS; London UK
| | - G. De Carlo
- EFA European Federation of Allergy and Airways Diseases Patients' Associations; Brussels Belgium
| | - P. Demoly
- Department of Respiratory Diseases; Montpellier University Hospital; Montpellier France
| | - E. Eller
- Department of Dermatology and Allergy Centre; Odense University Hospital; Odense Denmark
| | - M. P. Fantini
- Department of Medicine and Public Health; Alma Mater Studiorum - University of Bologna; Bologna Italy
| | - H. Hammad
- VIB Inflammation Research Center; Ghent University; Ghent Belgium
| | - C. Hohman
- Institute of Social Medicine, Epidemiology and Health Economics; Charité - Universitätsmedizin Berlin; Berlin Germany
| | - J. Just
- Allergology Department; Centre de l'Asthme et des Allergies; Hôpital d'Enfants Armand-Trousseau (APHP); Paris France
- Institut Pierre Louis d'Epidémiologie et de Santé Publique; Equipe EPAR; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136; Paris France
| | - M. Kerkhof
- Department of Respiratory Medicine; GRIAC Research Institute; University Medical Center Groningen; Beatrix Children's Hospital; University of Groningen; Groningen the Netherlands
| | - M. Kogevinas
- Centre for Research in Environmental Epidemiology (CREAL); Barcelona Spain
- Hospital del Mar Research Institute (IMIM); Barcelona Spain
- CIBER Epidemiología y Salud Pública (CIBERESP); Barcelona Spain
- Department of Experimental and Health Sciences; University of Pompeu Fabra (UPF); Barcelona Spain
| | - I. Kull
- Sachs’ Children's Hospital; Stockholm Sweden
- Institute of Environmental Medicine; Karolinska Institutet; Stockholm Sweden
| | - S. Lau
- Department for Pediatric Pneumology and Immunology; Charité Medical University; Berlin Germany
| | - N. Lemonnier
- European Institute for Systems Biology and Medicine; Lyon France
| | - M. Mommers
- Department of Epidemiology; CAPHRI School of Public Health and Primary Care; Maastricht University; Maastricht the Netherlands
| | - M. Nawijn
- Department of Pediatric Pulmonology and Pediatric Allergology; GRIAC Research Institute; University Medical Center Groningen; Beatrix Children's Hospital; University of Groningen; Groningen the Netherlands
| | | | - S. Oddie
- Bradford Institute for Health Research; Bradford Royal Infirmary; Bradford UK
| | - J. Pellet
- European Institute for Systems Biology and Medicine; Lyon France
| | - I. Pin
- Département de pédiatrie; CHU de Grenoble; Grenoble Cedex 9 France
| | - D. Porta
- Department of Epidemiology; Regional Health Service Lazio Region; Rome Italy
| | - Y. Saes
- VIB Inflammation Research Center; Ghent University; Ghent Belgium
| | - I. Skrindo
- Department of Paediatrics; Oslo University Hospital; Oslo Norway
- Faculty of Medicine; Institute of Clinical Medicine; University of Oslo; Oslo Norway
| | - C. G. Tischer
- Institute of Epidemiology; German Research Centre for Environmental Health; Helmholtz Zentrum München; Neuherberg Germany
| | - M. Torrent
- Centre for Research in Environmental Epidemiology (CREAL); Barcelona Spain
- Area de Salut de Menorca, ib-salut; Illes Balears Spain
| | - L. von Hertzen
- Skin and Allergy Hospital; Helsinki University Hospital; Helsinki Finland
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Abstract
OBJECTIVE We designed this systematic review and meta-analysis aiming to clarify the advantage of steroid therapy compared with non-steroid therapy for the treatment of eosinophilic esophagitis (EoE). METHODS PubMed, EMBASE, Medline, ISI Web of Science and the Cochrane Database of Systematic Reviews were searched to identify relevant randomized controlled trials (RCTs) comparing steroid and non-steroid therapy, and retrospective and prospective trials on steroid therapy for EoE. RevMan 5.2 was used for the analysis. Weighted mean difference and 95% confidence interval (CI) were estimated and pooled using meta-analysis methods. RESULTS Six RCTs including 193 participants fulfilled the inclusion criteria for meta-analysis, and another two RCTs, three prospective and five retrospective trials were included in systematic review. Meta-analysis showed that topical steroids significantly decreased the mean and peak esophageal eosinophils (EOS) count compared to non-steroid therapy (MDmean = -23.41, 95% CImean -42.08--4.73, P = 0.01 and MDpeak = -51.27, 95% CIpeak -78.62--23.92, P = 0.0002). There were 14 trials showing the efficacy of steroids on decreasing the EOS count, 10 showing the amelioration of symptoms, and five showing endoscopic improvement. Only mild adverse events were reported for topical steroids. CONCLUSIONS Steroids are effective on decreasing the EOS count in EoE patients. Its value in ameliorating symptoms and endoscopic changes remains undetermined due to the lack of comparable criteria.
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Affiliation(s)
- Nian Di Tan
- Department of Gastroenterology and Hepatology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, China
| | - Ying Lian Xiao
- Department of Gastroenterology and Hepatology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, China
| | - Min Hu Chen
- Department of Gastroenterology and Hepatology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, China
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25
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Rodríguez-Sánchez J, García Rojo M, López Viedma B, de la Santa Belda E, Palomar PO, Torrijos EG, López LG, Camacho JO. Accuracy of liquid cytology in the diagnosis and monitoring of eosinophilic oesophagitis. United European Gastroenterol J 2014; 2:475-81. [PMID: 25452842 DOI: 10.1177/2050640614552315] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2014] [Accepted: 08/24/2014] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Oesophagoscopy with biopsy is considered the gold standard for diagnosing and monitoring eosinophilic oesophagitis (EoE). Therefore is important to discover less-invasive diagnostic methods. METHODS Cytology specimens were obtained in patients with active EoE (AEoE) (≥15 eos/hpf) and EoE in remission (EoER) (<15 eos/hpf). The samples were assessed by two independent pathologists and were compared with biopsy samples. EoE cytology specimens were compared with specimens obtained from patients with GERD. RESULTS Specimens of 36 patients (69.4% male, mean age 30.88 years) were included. AEoE (17, 47.2%), EoER (11, 30.5%) and GERD (22.2%). eos/hpf in cytology (AEoE 9.23 vs. EoER 1.54 vs. GERD 2, p = 0.01). Linear correlation between eos/hpf average biopsy and cytology eos/hpf: r = 0.57, p < 0.001. For diagnosis of EoE ≥3 eos/hpf in cytology obtained a sensitivity of 70%, specificity 81%, PPV 86% and NPV 60% (AUC = 0.81, p = 0.01). For detection of AEoE, ≥3 eos/hpf in LBC obtained a sensitivity of 70%, specificity 82%, PPV 81% and NPV 66% (AUC = 0.87, p = 0.001). CONCLUSIONS LBC in oesophageal aspirate seems to be effective for the diagnosis and monitoring activity in EoE. These results support the usefulness of non-invasive methods for the diagnosis and monitoring of EoE.
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Affiliation(s)
| | | | | | - Eva de la Santa Belda
- Department of Gastroenterology, Hospital General Universitario de Ciudad Real, Spain
| | | | | | - Lucia González López
- Department of Pathology, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain
| | - José Olmedo Camacho
- Department of Gastroenterology, Hospital General Universitario de Ciudad Real, Spain
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26
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Rybnicek DA, Hathorn KE, Pfaff ER, Bulsiewicz WJ, Shaheen NJ, Dellon ES. Administrative coding is specific, but not sensitive, for identifying eosinophilic esophagitis. Dis Esophagus 2014; 27:703-8. [PMID: 24215617 PMCID: PMC4018425 DOI: 10.1111/dote.12141] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The use of administrative databases to conduct population-based studies of eosinophilic esophagitis (EoE) in the United States is limited because it is unknown whether the International Classification of Diseases, Ninth Revision (ICD-9) code for EoE, 530.13, accurately identifies those who truly have the disease. The aim of this retrospective study was to validate the ICD-9 code for identifying cases of EoE in administrative data. Confirmed cases of EoE as per consensus guidelines (symptoms of esophageal dysfunction and ≥15 eosinophils per high-power field on biopsy after 8 weeks of twice daily proton pump inhibitor therapy) were identified in the University of North Carolina (UNC) EoE Clinicopathologic Database from 2008 to 2010; 2008 was the first year in which the 530.13 code was approved. Using the Carolina Data Warehouse, the administrative database for patients seen in the UNC system, all diagnostic and procedure codes were obtained for these cases. Then, with the EoE cases as the reference standard, we re-queried the Carolina Data Warehouse over the same time frame for all patients seen in the system (n=308,372) and calculated the sensitivity and specificity of the ICD-9 code 530.13 as a case definition of EoE. To attempt to refine the case definition, we added procedural codes in an iterative fashion to optimize sensitivity and specificity, and restricted our analysis to privately insured patients. We also conducted a sensitivity analysis with 2011 data to identify trends in the operating parameters of the code. We identified 226 cases of EoE at UNC to serve as the reference standard. The ICD-9 code 530.13 yielded a sensitivity of 37% (83/226; 95% confidence interval: 31-43%) and specificity of 99% (308,111/308,146; 95% confidence interval: 98-100%). These operating parameters were not substantially altered if the case definition required a procedure code for endoscopy or if cases were limited to those with commercial insurance. However, in 2011, the sensitivity of the code had increased to 61%, while the specificity remained at 99%. The ICD-9 code for EoE, 530.13, had excellent specificity for identifying cases of EoE in administrative data, although this high specificity was achieved at an academic center. Additionally, the sensitivity of the code appears to be increasing over time, and the threshold at which it will stabilize is not known. While use of this administrative code will still miss a number of cases, those identified in this manner are highly likely to have the disease.
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Affiliation(s)
- David A. Rybnicek
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC,Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Kelly E. Hathorn
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC,Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Emily R. Pfaff
- Carolina Data Warehouse, North Carolina Translational and Clinical Sciences Institute, University of North Carolina, Chapel Hill
| | - William J. Bulsiewicz
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC,Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Nicholas J. Shaheen
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC,Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Evan S. Dellon
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC,Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
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27
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Abstract
The identification of a distinct syndrome, designated eosinophilic oesophagitis (EoE), with its own clinical and histopathological characteristics, was first described in the early 1990s. Meanwhile intense research has uncovered many molecular, immunological and clinical aspects of this chronic-inflammatory disorder. This article focuses exclusively on basic and clinical insights of EoE gathered during the last few years. Regarding aetiopathogenesis it has become clear that EoE is a food-triggered disease with milk and wheat as the dominant culprit food categories. However, it is still debated whether a disturbed mucosal integrity allowing allergens to cross the mucosal barrier, or changes in wheat and milk manufacturing might induce these inflammatory responses. Furthermore, basic science and clinical studies have accordingly confirmed that a chronic eosinophilic inflammation leads to a remodelling of the oesophagus with micro- and macro-morphological alterations, ending in a strictured oesophagus with impaired function. Fortunately, long-term therapeutic trials, using either topical corticosteroids or dietary allergen avoidance, have demonstrated that this sequela can be prevented or even reversed. This finding is of clinical relevance as it supports the initiation of a consistent anti-inflammatory therapy. Nevertheless, EoE is still an enigmatic disease and the long list of unanswered questions will certainly stimulate further research.
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Affiliation(s)
- Alex Straumann
- Swiss EoE Clinic, Department of Gastroenterology and Hepatology, University Hospital Basel, Basel, Switzerland
| | - Alain Schoepfer
- Department of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois/CHUV, Lausanne, Switzerland
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28
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Attwood S, Furuta GT. Eosinophilic esophagitis: historical perspective on an evolving disease. Gastroenterol Clin North Am 2014; 43:185-99. [PMID: 24813509 PMCID: PMC4035232 DOI: 10.1016/j.gtc.2014.02.010] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Initial case series describing children and adults with symptoms related to esophageal dysfunction and dense esophageal eosinophilia lead to recognition of a "new" disease, eosinophilic esophagitis (EoE). Clinical, basic, and translational studies have provided a deeper understanding of this somewhat enigmatic disease that mechanistically is defined as an antigen-driven condition limited to the esophagus. This article summarizes many of the key historical features of EoE and provides a glimpse of potential future developments.
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Affiliation(s)
- Stephen Attwood
- North Tynesdie Hospital, Rake Lane, North Shields NE29 8NH, UK, Telephone 00 44 191 293 4079
| | - Glenn T. Furuta
- Children’s Hospital Colorado, Aurora, Colorado, 13123 East 16 Ave. B290, Aurora, CO 80045, Telephone-720-777-7457, Fax-720-777-7277
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29
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Abstract
Eosinophilic esophagitis (EoE) is an increasingly recognized immune antigen-mediated esophageal disease found in both children and adults. It is defined as a clinicopathologic disease characterized by symptoms of esophageal dysfunction accompanied by an eosinophil-predominant esophageal inflammation that occurs in the absence of other causes of esophageal eosinophilia. Classic symptoms in adults include dysphagia to solids and food bolus impaction but a variety of other symptoms are also encountered. Despite the increasing awareness of EoE among practicing physicians, a long delay from onset of symptoms to diagnosis remains a problem in this disease.
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30
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Abstract
Eosinophilic esophagitis (EoE) may affect individuals at any age with a predominance for Caucasian males. The clinical manifestation of EoE is strongly age dependent. While dysphagia and food impaction are typical lead symptoms in adults and adolescents, infants often present with unspecific symptoms such as feeding problems, abdominal pain and vomiting. Some EoE patients may also experience heartburn. Therefore, EoE should always be considered in cases of heartburn refractory to antireflux therapy. Concomitant allergic diseases such as asthma, rhinitis and eczema are prevalent. Peripheral eosinophilia and elevated total serum IgE values are found in up to 50 and 70% of cases, respectively. Endoscopic features of EoE are variable and none of them is pathognomonic. Frequent findings are mucosal edema, furrows, exudates and corrugated rings. These endoscopic abnormalities have high specificities (90-95%), but low sensitivities (15-48%). A novel grading and classification system for the endoscopic assessment of EoE has been proposed which includes fixed rings, exudates, furrows and edema as major features. This classification system demonstrated good interobserver agreement among pediatric and adult gastroenterologists, and presents a useful tool to standardize endoscopic assessments and to further investigate the relation between endoscopic manifestation, clinical activity and response to treatment in EoE. Long-term follow-up studies have shown that EoE is a chronic disease causing recurrent dysphagia in the majority of cases. The prevalence of strictures significantly increases with the duration of disease, which stresses the importance of early diagnosis and consequent treatment of EoE.
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Affiliation(s)
- Stephan Miehlke
- Center for Digestive Diseases, Internal Medicine Center Eppendorf, Hamburg, Germany
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31
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Attwood S, Sabri S. Historical aspects of eosinophilic esophagitis: from case reports to clinical trials. Dig Dis 2014; 32:34-9. [PMID: 24603378 DOI: 10.1159/000357007] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Eosinophilic esophagitis (EoE) is a clinicopathological condition characterized clinically by symptoms of esophageal dysfunction in the absence of acid reflux, with typical endoscopic findings and eosinophilia on biopsy. This article looks into the historical clinical recognition and description of EoE, in particular clinical manifestations, natural history, and epidemiology. Additionally, the evolution of endoscopic recognition and development of clinical trials are described: EoE is an isolated disease of the esophagus, although it is associated with other antigen-driven diseases such as asthma, rhinitis, and atopic dermatitis. After initial case reports which were mostly not typical of the disease state now described, the first case series were described in 1993 and 1994 in adults, and 1995 in children. Although rarely seen before 2000, the disease is now commonly recognized. Randomized clinical trials have now been performed on topical steroids, and on biological agents targeted against IL-5, IL-13, and other mediators. Therapy with dilatation may be best guided by measures of compliance and distensibility. Work is needed on biomarkers of the disease's severity and progression, and predictive indexes of complications. EoE is a relatively new disease of increasing importance. It represents an important diagnosis in patients with upper gastrointestinal symptoms and must be considered in all patients with dysphagia where the diagnosis is not certain and in all patients who have an assumed diagnosis of reflux but are not responding to standard reflux therapy.
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Affiliation(s)
- Stephen Attwood
- Department of Surgery, Durham University, Durham, and North Tyneside General Hospital, North Shields, UK
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32
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Abstract
Eosinophilic esophagitis (EoE) is currently defined as an immune-mediated chronic esophageal disorder that is diagnosed using both clinical and pathologic information. A series of consensus diagnostic guidelines for EoE have brought a measure of consistency to the field, but in practice the diagnosis of EoE can be challenging. Typical clinical symptoms of EoE, including dysphagia, heartburn, and chest pain, can overlap with gastroesophageal reflux disease, which itself is a common indication for performing endoscopic evaluation. The endoscopic findings of EoE, such as esophageal rings, strictures, linear furrows, and white exudates, are not specific. Esophageal eosinophilia, the histologic hallmark of EoE, is also not pathognomonic and can be seen in a range of conditions. Further complicating the diagnosis of EoE is the newly recognized entity of proton pump inhibitor-responsive esophageal eosinophilia, a condition that must be excluded prior to confirming a diagnosis of EoE. This paper will review the current diagnostic criteria for EoE and discuss multiple clinical, endoscopic, and histologic pitfalls in making the diagnosis of EoE.
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Affiliation(s)
- Evan S. Dellon
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC
- Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
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33
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Pathogenesis of allergen-induced eosinophilic esophagitis is independent of interleukin (IL)-13. Immunol Cell Biol 2013; 91:408-15. [PMID: 23689305 PMCID: PMC3947911 DOI: 10.1038/icb.2013.21] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2013] [Revised: 04/12/2013] [Accepted: 04/13/2013] [Indexed: 12/22/2022]
Abstract
Several studies have shown that IL-13 is induced in the esophageal biopsies of EoE patients and promotes esophageal eosinophilia in mice following an IL-13 challenge. However, the role of IL-13 has not been clearly investigated in allergen-induced EoE. Accordingly, we tested the hypothesis that IL-13 is required in allergen-induced EoE. Mice deficient in IL-13, STAT (signal transducer and activator of transcription)6 and both IL-4/IL-13 genes with their respective controls were challenged with aspergillus extract and IL-5 gene-deficient with their control were challenged with recombinant IL-13, intranasally The lung and esophageal eosinophils, mast cells and collagen accumulation were examined. Herein, we report that intranasal delivery of IL-13 promotes IL-5 dependent esophageal eosinophilia. However, allergen-induced EoE is not impaired in the IL-13 gene-deficient mice. In addition, wild type and IL-13 gene-deficient mice demonstrated a comparable level of mast cells and collagen accumulation in the esophagus following allergen-induced experimental EoE. Similarly, we found that esophageal eosinophilia in IL-4/IL-13 double gene-deficient and STAT6 gene-deficient mice were also not reduced following allergen-induced experimental EoE. In contrast, lung eosinophilia was significantly reduced in mice deficient in IL-13, both IL-4/IL-13 and STAT6 genes following allergen challenge. In conclusion, our data establish that allergen-induced EoE pathogenesis is independent of IL-13; whereas, IL-13 is required for allergen-induced lung eosinophilia.
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34
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ACG clinical guideline: Evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE). Am J Gastroenterol 2013; 108:679-92; quiz 693. [PMID: 23567357 DOI: 10.1038/ajg.2013.71] [Citation(s) in RCA: 839] [Impact Index Per Article: 69.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Esophageal eosinophilia and eosinophilic esophagitis (EoE) are increasingly recognized and prevalent conditions, which now represent common clinical problems encountered by gastroenterologists, pathologists, and allergists. The study of EoE has become a dynamic field with an evolving understanding of the pathogenesis, diagnosis, and treatment. Although there are limited data supporting management decisions, clinical parameters are needed to guide the care of patients with eosinophilic-esophageal disorders. In this evidence-based review, recommendations developed by adult and pediatric gastroenterologists are provided for the evaluation and management of these patients. New terminology is emphasized, particularly the concepts of esophageal eosinophilia and proton-pump inhibitor-responsive esophageal eosinophilia (PPI-REE) as entities distinct from EoE.
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35
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Lucendo AJ, Sánchez-Cazalilla M. Adult versus pediatric eosinophilic esophagitis: important differences and similarities for the clinician to understand. Expert Rev Clin Immunol 2013; 8:733-45. [PMID: 23167685 DOI: 10.1586/eci.12.68] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Eosinophilic esophagitis (EoE) is recognized as a common, allergy-associated cause of chronic esophageal symptoms affecting both children and adults. Research has begun to shed light on its epidemiology with consistent results from various geographical areas. Differences in clinical presentation, endoscopic aspects and response to treatment have all been reported for patients of different ages, and the question as to whether adult and pediatric EoE are manifestations of a single entity or in fact two distinct disorders has been posed. The most relevant differences between pediatric and adult EoE come from evolutionary changes in the consequences of the disease, including fibrous remodeling, and the ability to express symptoms. However, most studies support a common pathogenesis and similar histopathological features for adult and pediatric patients, being the same diagnostic criteria applied to them. This article comprehensively reviews the most recently published information and addresses important questions about the natural history of EoE.
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Affiliation(s)
- Alfredo J Lucendo
- Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Ciudad Real, Spain.
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36
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Abstract
Eosinophilic esophagitis (EoE) is a chronic immune-mediated condition whereby infiltration of eosinophils into the esophageal mucosa leads to symptoms of esophageal dysfunction. EoE is encountered in a substantial proportion of patients undergoing diagnostic upper endoscopy. This review discusses the clinical, endoscopic, and histologic features of EoE and presents the most recent guidelines for its diagnosis. Selected diagnostic dilemmas are described, including distinguishing EoE from gastroesophageal reflux disease and addressing the newly recognized clinical entity of proton-pump inhibitor-responsive esophageal eosinophilia. Also highlighted is evidence to support both pharmacologic and nonpharmacologic treatments, including topical corticosteroids, dietary elimination therapy, and endoscopic dilation.
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Affiliation(s)
- Evan S. Dellon
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
,Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
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Rodríguez-Sánchez J, López Viedma B, Verdejo Gil C, Martín Dávila F, Hernández Albujar A, Lorente Poyatos R, de La Santa Belda E, Martín Escobedo LR, Olmedo Camacho J. [Predictive factors of eosinophilic esophagitis in esophageal food bolus impaction]. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2013; 78:5-11. [PMID: 23374542 DOI: 10.1016/j.rgmx.2012.10.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/09/2012] [Revised: 09/10/2012] [Accepted: 10/09/2012] [Indexed: 01/07/2023]
Abstract
BACKGROUND Food bolus esophageal impaction is often the first symptom in patients diagnosed with eosinophilic esophagitis, representing a change in the epidemiology and management of this urgency. AIM To detect eosinophilic esophagitis predictive factors in patients with esophageal impaction due to food bolus. METHODS Patients seen for foreign body impaction were retrospectively analyzed. Epidemiologic characteristics, endoscopic findings, and impaction history were studied. The statistical analysis was carried out using the Student's t test and the chi square test and a logistic regression model. RESULTS Of the 131 patients, 65% were men and the mean age was 56 years. The endoscopic suspicion of eosinophilic esophagitis was the most frequent finding in patients with food bolus impaction (n=89); those patients that did not have histologic confirmation were excluded (n=7). The remaining patients (n=82) were divided into two groups: confirmed eosinophilic esophagitis (Group A) (n=18) and other endoscopic findings (Group B) (n=64). Group A presented with a lower mean age (36.47 vs. 64.45, P=.001) and a more frequent past history of impaction (38% vs. 6%, OR=15.70, 95% CI (3.60-62.50), P=.001) than Group B. Age and impaction history acted as predictors for eosinophilic esophagitis with 82% sensitivity, 80% specificity, and 84% diagnostic accuracy (P<.001). CONCLUSIONS Age and a history of impaction predict the presence of eosinophilic esophagitis in patients with food bolus impaction.
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Affiliation(s)
- J Rodríguez-Sánchez
- Unidad de Endoscopia Digestiva, Sección de Aparato Digestivo, Hospital General Universitario de Ciudad Real, Ciudad Real, España.
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Ali MA, Lam-Himlin D, Voltaggio L. Eosinophilic esophagitis: a clinical, endoscopic, and histopathologic review. Gastrointest Endosc 2012; 76:1224-37. [PMID: 23025974 DOI: 10.1016/j.gie.2012.08.023] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2012] [Accepted: 08/21/2012] [Indexed: 02/08/2023]
Affiliation(s)
- Mohammed Aamir Ali
- Department of Gastroenterology, George Washington University Hospital, Washington, DC 20037, USA
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Bussmann C. [Eosinophilic esophagitis. Role of the pathologist in the diagnosis]. DER PATHOLOGE 2012; 33 Suppl 2:228-30. [PMID: 23011023 DOI: 10.1007/s00292-012-1676-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Eosinophilic esophagitis (EoE) is a chronic, immune-mediated esophageal disease with clinical symptoms and eosinophil-predominant inflammation. The diagnosis of EoE is therefore complex. It is not reflux or infectious or drug-induced. Histological cases with a high number of eosinophils are not a diagnostic problem. However, limits are of necessity in borderline cases. These must be based on the high power field (HPF) size and the percentage of squamous epithelium covering an HPF, which may greatly vary. Also, it must be considered that EoE is patchy in nature. In order to establish a reliable diagnosis a minimal number of biopsies is essential. Alongside the number of eosinophils further histological features associated with EoE, such as abcesses of eosinophils or basal layer enlargement, may be of diagnostic help in borderline cases.
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Affiliation(s)
- C Bussmann
- Institut für Pathologie, Kantonsspital Luzern, CH-6000 Luzern, Schweiz.
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Kim HP, Vance RB, Shaheen NJ, Dellon ES. The prevalence and diagnostic utility of endoscopic features of eosinophilic esophagitis: a meta-analysis. Clin Gastroenterol Hepatol 2012; 10:988-96.e5. [PMID: 22610003 PMCID: PMC3424367 DOI: 10.1016/j.cgh.2012.04.019] [Citation(s) in RCA: 240] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2012] [Revised: 04/12/2012] [Accepted: 04/26/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Endoscopic findings such as esophageal rings, strictures, narrow-caliber esophagus, linear furrows, white plaques, and pallor or decreased vasculature might indicate the presence of eosinophilic esophagitis (EoE). We aimed to determine the prevalence and diagnostic utility of endoscopic features of EoE. METHODS We conducted a systematic review and meta-analysis. PubMed, EMBASE, and gastrointestinal meeting abstracts were searched to identify studies that included more than 10 patients with EoE and reported endoscopic findings. Pooled prevalence, sensitivity, specificity, and predictive values were calculated using random- and mixed-effects models. RESULTS The search yielded 100 articles and abstracts on 4678 patients with EoE and 2742 without (controls). In subjects with EoE, the overall pooled prevalence was as follows: esophageal rings, 44%; strictures, 21%; narrow-caliber esophagus, 9%; linear furrows, 48%; white plaques, 27%; and pallor/decreased vasculature, 41%. Substantial heterogeneity existed among studies. Results from endoscopy examinations were normal in 17% of patients, but this number decreased to 7% when the analysis was limited to prospective studies (P < .05). Overall levels of sensitivity were modest, ranging from 15% to 48%, whereas levels of specificity were greater, ranging from 90% to 95%. Positive predictive values ranged from 51% to 73% and negative predictive values ranged from 74% to 84%. CONCLUSIONS There is heterogeneity among studies in the reported prevalence of endoscopic findings in patients with EoE, but in prospective studies at least 1 abnormality was detected by endoscopy in 93% of patients. The operating characteristics of endoscopic findings alone are inadequate for diagnosis of EoE. Esophageal biopsy specimens should be obtained from all patients with clinical features of EoE, regardless of the endoscopic appearance of the esophagus.
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Affiliation(s)
- Hannah P. Kim
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
| | - R. Brooks Vance
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Nicholas J. Shaheen
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
- Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Evan S. Dellon
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
- Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
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Ferreira CT, Goldani HA. Contribution of endoscopy in the management of eosinophilic esophagitis. World J Gastrointest Endosc 2012; 4:347-55. [PMID: 22912908 PMCID: PMC3423515 DOI: 10.4253/wjge.v4.i8.347] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2011] [Revised: 02/27/2012] [Accepted: 08/08/2012] [Indexed: 02/05/2023] Open
Abstract
Eosinophilic esophagitis (EoE) is a clinicopathological entity characterized by a set of symptoms similar to gastroesophageal reflux disease and eosinophilic infiltration of the esophageal epithelium. EoE is an emerging worldwide disease as documented in many countries. Recent reports indicate that EoE is increasingly diagnosed in both pediatric and adult patients although the epidemiology of this new disease entity remains unclear. It is unclear whether EoE is a new disease or a new classification of an old esophageal disorder. Esophagogastroduodenoscopy (EGD) and biopsies with histological examination of esophageal mucosa are required to establish the diagnosis of EoE, verify response to therapy, assess disease remission, document and dilate strictures and evaluate symptom recurrence of EoE. Repeated endoscopies with biopsies are necessary for monitoring of disease progression and treatment efficacy. EGD has a fundamental role in the diagnosis and management of EoE, forming an essential part of the investigation and follow-up of this condition. EoE is now considered a systemic disorder and not only a local condition with an important immunological background. One of the aims of research in EoE is to study non-invasive markers, such as immune indicators found in plasma, that correlate with local presence of EoE in esophageal tissues. Studies over the next few years will provide new information about diagnosis, pathogenesis, endoscopic/histologic criteria, non-invasive markers, novel and more efficacious treatments, as well as establishing natural history. Randomized clinical trials are urgently called for to inform non-invasive diagnostic tests, hallmarks of natural history and more efficacious treatment approaches for patients with EoE. The collaboration between pediatric and adult clinical and experimental studies will be paramount in the understanding and management of this disease.
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Affiliation(s)
- Cristina Targa Ferreira
- Cristina Targa Ferreira, Helena AS Goldani, Department of Pediatrics and Gastroenterology Unit, Hospital de Clinicas de Porto Alegre, Faculdade de Medicina da Universidade Federal do Rio Grande do Sul, 90430-140 Porto Alegre, RS, Brazil
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Aceves S, Hirano I, Furuta GT, Collins MH. Eosinophilic gastrointestinal diseases--clinically diverse and histopathologically confounding. Semin Immunopathol 2012; 34:715-31. [PMID: 22842863 DOI: 10.1007/s00281-012-0324-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2012] [Accepted: 06/20/2012] [Indexed: 12/19/2022]
Abstract
Eosinophilic gastrointestinal diseases are a group of chronic diseases characterized by a range of symptoms caused by eosinophilic inflammation of various parts of the gastrointestinal tract. Other causes for eosinophilia need to be ruled out prior to making the diagnosis of EGIDs. The most common form of EGID is eosinophilic esophagitis (EoE), an antigen-driven disease that afflicts children and adults and has been identified across the world. Histological features include dense eosinophilia of the esophageal mucosa, eosinophil degranulation, eosinophil microabscess formation, and other features of epithelial inflammation including basal zone hyperplasia and rete pege elongation. Treatments include dietary exclusions and topical corticosteroids.
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Affiliation(s)
- Seema Aceves
- Division of Allergy, Immunology, Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA
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Shi YN, Sun SJ, Xiong LS, Cao QH, Cui Y, Chen MH. Prevalence, clinical manifestations and endoscopic features of eosinophilic esophagitis: a pathological review in China. J Dig Dis 2012; 13:304-9. [PMID: 22624553 DOI: 10.1111/j.1751-2980.2012.00593.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE We aimed to determine the prevalence of eosinophilic esophagitis (EoE) and define its clinical and endoscopic characteristics in Chinese patients. METHODS Esophageal specimens obtained from January 2006 to December 2010 in the First Affiliated Hospital of Sun Yat-sen University were reviewed, and the data on clinical characteristics and endoscopic findings of patients were obtained. Patients with eosinophils ≥15 per high power field (HPF) were identified as having EoE. RESULTS A total of 12 patients met the criteria for EoE, establishing a prevalence of 0.34%. These patients presented with dysphagia (4/12, 33.3%), gastroesophageal reflux disease (GERD)-like symptoms (3/12, 25.0%), abdominal pain (3/12, 25.0%) and others (2/12, 16.7%). The most common endoscopic finding was plaques (5/12, 41.7%), and other findings were irregular Z-line (2/12, 16.7%), erosive esophagitis (2/12, 16.7%), white exudates (1/12, 8.3%), linear furrows (1/12, 8.3%), Schatzki ring (1/12, 8.3%), ulcers (1/12, 8.3%) and erythema (1/12, 8.3%). CONCLUSIONS The prevalence of EoE was 0.34% in our patients. Clinicians should pay attention to patients manifested with dysphagia and GERD-like symptomes with endosopic findings of white exudates, plaques, Schatzki ring and linear furrows.
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Affiliation(s)
- Yi Nan Shi
- Department of Internal Medicine, Guro Hospital, Korea University College of Medicine, Seoul, Korea
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Abstract
Eosinophilic esophagitis is a chronic disease limited to the esophagus and has a persistent or spontaneously fluctuating course. So far it does not seem to limit life expectancy, but it often substantially impairs the quality of life. To date, there has been no association with malignant conditions, but there is concern that the chronic, uncontrolled inflammation will evoke irreversible structural alterations of the esophagus, leading to tissue fibrosis, stricture formation, and impaired function. This esophageal remodeling may result in several disease-inherent and procedure-related complications.
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Cohen MC, Rao P, Thomson M, Al-Adnani M. Eosinophils in the oesophageal mucosa: clinical, pathological and epidemiological relevance in children: a cohort study. BMJ Open 2012; 2:e000493. [PMID: 22240650 PMCID: PMC3278487 DOI: 10.1136/bmjopen-2011-000493] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
Objectives Eosinophilic oesophagitis (EO) shows eosinophilic infiltration of the mucosa and can present with symptoms indistinguishable from gastrooesophageal reflux disease (GORD). The authors describe the clinical, endoscopic and histopathological features of all cases of histological EO presenting during 2007-2008 with a 2-year follow-up. The incidence of paediatric EO and the features of a subgroup with features of both GORD and EO ('overlap' syndrome (OS)) are described. Design Biopsies with an average of 15 eosinophils/high-power field (HPF) were reviewed in the cohort. OS was suggested when there was coexistence of clinical and histological features of EO and GORD (abnormal pH study), which improved with proton pump inhibitors. Setting Tertiary care. Participants All cases with ≥15 eosinophils/HPF entered the study. Primary outcome measures Patients with EO had an average of 15 eosinophils/HPF. Secondary outcome measures Other histological features of EO included microabscesses, dilated intercellular spaces, basal cell hyperplasia, papillary elongation, etc. Results 24 cases of EO were identified, 13 men and 11 women. The incidence of paediatric oesophageal eosinophilia in the region was 9/100 000 children. 11 of the 24 patients (46%) presented with some form of allergy, six with poor feeding/food aversion, five with dysphagia and four with vomiting. After follow-up, 56.5% were confirmed to have EO, 30.5% responded to treatment for GORD and were categorised as OS, 9% developed eosinophilic gastroenteritis and 4% did not have further upper gastrointestinal symptoms. Conclusions Accurate diagnosis of EO, especially the differentiation from GORD, requires appropriate clinicopathological correlation. A significant proportion of patients with eosinophilia in the mucosa also have GORD (OS). These patients improve after treating the underlying GORD. The study was registered as a Service Evaluation with the Trust (number SE74).
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Affiliation(s)
- Marta C Cohen
- Department of Histopathology, Sheffield Children's Hospital NHS Foundation Trust, Sheffield, UK
| | - Prithviraj Rao
- Department of Paediatrics, Sheffield Children's Hospital NHS Foundation Trust, Sheffield, UK
| | - Mike Thomson
- Department of Paediatrics, Sheffield Children's Hospital NHS Foundation Trust, Sheffield, UK
| | - Mudher Al-Adnani
- Department of Histopathology, Sheffield Children's Hospital NHS Foundation Trust, Sheffield, UK
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Abstract
Eosinophilic oesophagitis (EE) is a clinico-pathological entity recognized with increased frequency in children and adults. It is an atopic disease involving ingested and inhaled allergens. A pathological eosinophilic infiltrate is diagnosed by finding ≥ 15 eosinophils per high-powered field on oesophageal mucosal biopsies. This infiltrate may result in a narrowed oesophageal lumen. It does not involve the stomach or duodenum. Children commonly present with abdominal pain, vomiting and dysphagia. Presentation in adults is with dysphagia, heartburn, chest pain or impaction of a food bolus in the oesophagus. There is often a history of allergy (asthma, hay fever, eczema). A male predominance (70% in adults) is unexplained. Distinctive endoscopic features are linear furrows, mucosal rings and white papules, and the narrowed lumen may be appreciated. Although EE and gastro-oesophageal reflux disease are separate entities, there is a significant overlap of the conditions. Treatment options include nonpharmacological approaches including an elimination or elemental diet, and/ or medications, chiefly with corticosteroids. The topical administration of fluticasone propionate has been demonstrated to improve symptoms and mobilize the pathological infiltrate of eosinophils. There has been a variable effect with the leukotriene receptor antagonist montelukast and promising early results with mepolizumab, a monoclonal antibody against interleukin-5. The long-term efficacy of topical corticosteroids has not been well studied and most patients experience recurrent symptoms when treatment is completed. Currently, repeated short courses of topical corticosteroids are utilized. Acid suppression by a proton pump inhibitor may be considered in view of the overlap between EE and gastro-oesophageal reflux disease.
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Straumann A, Conus S, Degen L, Felder S, Kummer M, Engel H, Bussmann C, Beglinger C, Schoepfer A, Simon HU. Budesonide is effective in adolescent and adult patients with active eosinophilic esophagitis. Gastroenterology 2010; 139:1526-37, 1537.e1. [PMID: 20682320 DOI: 10.1053/j.gastro.2010.07.048] [Citation(s) in RCA: 402] [Impact Index Per Article: 26.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2010] [Revised: 07/08/2010] [Accepted: 07/19/2010] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus characterized by dense tissue eosinophilia; it is refractory to proton pump inhibitor therapy. EoE affects all age groups but most frequently individuals between 20 and 50 years of age. Topical corticosteroids are effective in pediatric patients with EoE, but no controlled studies of corticosteroids have been reported in adult patients. METHODS We performed a randomized, double-blind, placebo-controlled trial to evaluate the effect of oral budesonide (1 mg twice daily for 15 days) in adolescent and adult patients with active EoE. Pretreatment and posttreatment disease activity was assessed clinically, endoscopically, and histologically. The primary end point was reduced mean numbers of eosinophils in the esophageal epithelium (number per high-power field [hpf] = esophageal eosinophil load). Esophageal biopsy and blood samples were analyzed using immunofluorescence and immunoassays, respectively, for biomarkers of inflammation and treatment response. RESULTS A 15-day course of therapy significantly decreased the number of eosinophils in the esophageal epithelium in patients given budesonide (from 68.2 to 5.5 eosinophils/hpf; P < .0001) but not in the placebo group (from 62.3 to 56.5 eosinophils/hpf; P = .48). Dysphagia scores significantly improved among patients given budesonide compared with those given placebo (5.61 vs 2.22; P < .0001). White exudates and red furrows were reversed in patients given budesonide, based on endoscopy examination. Budesonide, but not placebo, also reduced apoptosis of epithelial cells and molecular remodeling events in the esophagus; no serious adverse events were observed. CONCLUSIONS A 15-day course of treatment with budesonide is well tolerated and highly effective in inducing a histologic and clinical remission in adolescent and adult patients with active EoE.
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Affiliation(s)
- Alex Straumann
- Department of Gastroenterology, University Hospital Basel, Basel, Switzerland
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Inter- and intraobserver reliability and validation of a new method for determination of eosinophil counts in patients with esophageal eosinophilia. Dig Dis Sci 2010; 55:1940-9. [PMID: 19830560 PMCID: PMC2895956 DOI: 10.1007/s10620-009-1005-z] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2009] [Accepted: 09/21/2009] [Indexed: 12/09/2022]
Abstract
BACKGROUND Diagnosis of eosinophilic esophagitis (EoE) requires quantification of esophageal eosinophilia. AIMS The aims of this study were to assess inter- and intraobserver reliability for measuring esophageal eosinophil counts and to validate a novel method of determining tissue eosinophil density using digitized histopathology slides. METHODS Patients were selected from the University of North Carolina EoE clinicopathologic database. Glass slides were de-identified and scanned to create digitized slides. Using a set protocol, 40 slides were read by each of three pathologists for interobserver measures, and were also reread by one pathologist as traditional glass slides. Different sets of 20 unique slides were read twice by each pathologist for intraobserver measures. Correlation and agreement were calculated with Pearson's rho and the kappa statistic. RESULTS There was excellent correction between digitized images and glass slides (r = 0.91-0.95, P < 0.001). For maximum eosinophil densities, interobserver correlations were 0.91, 0.76, and 0.79. For mean densities, interobserver correlations were 0.90, 0.89, and 0.85. Intraobserver correlations for maximum densities were 0.99, 0.94, and 0.96, and for mean densities were 0.97, 0.87, and 0.89 (P < 0.001 for all correlations). Agreement was in the "substantial" to "near-perfect" range for pathologists using several diagnostic cut-points for EoE. CONCLUSIONS Both inter- and intraobserver correlations were excellent for determining eosinophil densities and counts. A method of using digitized slides was valid when compared with traditional glass slides. This protocol could be adopted for research and clinical purposes to further standardize the diagnostic process for EoE.
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50
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Wilcox R, Hart J. Esophageal Eosinophilia. Surg Pathol Clin 2010; 3:277-95. [PMID: 26839132 DOI: 10.1016/j.path.2010.05.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
The presence of esophageal eosinophilia encompasses a broad differential diagnosis, and at times a specific histologic diagnosis is not possible. This content provides a systematic approach to esophageal squamous eosinophilia with emphasis on specific, distinguishing features within this expansive differential.
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Affiliation(s)
- Rebecca Wilcox
- Department of Pathology, University of Chicago Medical Center, 5841 South Maryland Avenue, Chicago, IL 60637, USA
| | - John Hart
- Department of Pathology, University of Chicago Medical Center, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
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