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Yadavalli CS, Upparahalli Venkateshaiah S, Verma AK, Kathera C, Duncan PS, Vaezi M, Paul RJ, Mishra A. Vasoactive Intestinal Peptide Receptor, CRTH2, Antagonist Treatment Improves Eosinophil and Mast Cell-Mediated Esophageal Remodeling and Motility Dysfunction in Eosinophilic Esophagitis. Cells 2024; 13:295. [PMID: 38391908 PMCID: PMC10886969 DOI: 10.3390/cells13040295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 01/30/2024] [Accepted: 02/01/2024] [Indexed: 02/24/2024] Open
Abstract
BACKGROUND AND AIMS Ultrasonography has shown that eosinophils accumulate in each segment of the esophageal mucosa in human EoE, ultimately promoting esophageal motility dysfunction; however, no mechanistic evidence explains how or why this accumulation occurs. METHODS Quantitative PCR, ELISA, flow cytometry, immunostaining, and immunofluorescence analyses were performed using antibodies specific to the related antigens and receptors. RESULTS In deep esophageal biopsies of EoE patients, eosinophils and mast cells accumulate adjacent to nerve cell-derived VIP in each esophageal segment. qRT-PCR analysis revealed five- to sixfold increases in expression levels of VIP, CRTH2, and VAPC2 receptors and proteins in human blood- and tissue-accumulated eosinophils and mast cells. We also observed a significant correlation between mRNA CRTH2 levels and eosinophil- and nerve cell-derived VIPs in human EoE (p < 0.05). We provide evidence that eosinophil and mast cell deficiency following CRTH2 antagonist treatment improves motility dysfunction in a chronic DOX-inducible CC10-IL-13 murine model of experimental EoE. CONCLUSIONS CRTH2 antagonist treatment is a novel therapeutic strategy for inflammatory cell-induced esophageal motility dysfunction in IL-13-induced chronic experimental EoE.
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Affiliation(s)
- Chandra Sekhar Yadavalli
- Department of Medicine, Section of Pulmonary Diseases, Tulane Eosinophilic Disorder Center, School of Medicine, Tulane University, New Orleans, LA 70112, USA; (C.S.Y.); (S.U.V.); (C.K.)
| | - Sathisha Upparahalli Venkateshaiah
- Department of Medicine, Section of Pulmonary Diseases, Tulane Eosinophilic Disorder Center, School of Medicine, Tulane University, New Orleans, LA 70112, USA; (C.S.Y.); (S.U.V.); (C.K.)
| | - Alok K. Verma
- Division of Gastroenterology, Cincinnati Childrens Medical Center, Cincinnati, OH 45229, USA;
| | - Chandrasekhar Kathera
- Department of Medicine, Section of Pulmonary Diseases, Tulane Eosinophilic Disorder Center, School of Medicine, Tulane University, New Orleans, LA 70112, USA; (C.S.Y.); (S.U.V.); (C.K.)
| | - Pearce S. Duncan
- Division of Gastroenterology, School of Medicine, Tulane University, New Orleans, LA 70118, USA;
| | - Michael Vaezi
- Division of Gastroenterology, Vanderbilt University Medical Center, Nashville, TN 37232, USA;
| | - Richard J. Paul
- Division of Physiology, Cincinnati University, Cincinnati, OH 45220, USA;
| | - Anil Mishra
- Department of Medicine, Section of Pulmonary Diseases, Tulane Eosinophilic Disorder Center, School of Medicine, Tulane University, New Orleans, LA 70112, USA; (C.S.Y.); (S.U.V.); (C.K.)
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Wu J, Duan C, Han C, Hou X. Identification of CXC Chemokine Receptor 2 (CXCR2) as a Novel Eosinophils-Independent Diagnostic Biomarker of Pediatric Eosinophilic Esophagitis by Integrated Bioinformatic and Machine-Learning Analysis. Immunotargets Ther 2024; 13:55-74. [PMID: 38328342 PMCID: PMC10849108 DOI: 10.2147/itt.s439289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 01/17/2024] [Indexed: 02/09/2024] Open
Abstract
Background Eosinophilic esophagitis (EoE) is a complex allergic condition frequently accompanied by various atopic comorbidities in children, which significantly affects their life qualities. Therefore, this study aimed to evaluate pivotal molecular markers that may facilitate the diagnosis of EoE in pediatric patients. Methods Three available EoE-associated gene expression datasets in children: GSE184182, GSE 197702, GSE55794, along with GSE173895 were downloaded from the GEO database. Differentially expressed genes (DEGs) identified by "limma" were intersected with key module genes identified by weighted gene co-expression network analysis (WGCNA), and the shared genes went through functional enrichment analysis. The protein-protein interaction (PPI) network and the machine learning algorithms: least absolute shrinkage and selection operator (LASSO), random forest (RF), and XGBoost were used to reveal candidate diagnostic markers for EoE. The receiver operating characteristic (ROC) curve showed the efficacy of differential diagnosis of this marker, along with online databases predicting its molecular regulatory network. Finally, we performed gene set enrichment analysis (GSEA) and assessed immune cell infiltration of EoE/control samples by using the CIBERSORT algorithm. The correlations between the key diagnostic biomarker and immune cells were also investigated. Results The intersection of 936 DEGs and 1446 key module genes in EoE generated 567 genes, which were primarily enriched in immune regulation. Following the construction of the PPI network and filtration by machine learning, CXCR2 served as a potential diagnostic biomarker of pediatric EoE with a perfect diagnostic efficacy (AUC = ~1.00) in regional tissue/peripheral whole blood samples. Multiple infiltrated immune cells were observed to participate in disrupting the homeostasis of esophageal epithelium to varying degrees. Conclusion The immune-correlated CXCR2 gene was proved to be a promising diagnostic indicator for EoE, and dysregulated regulatory T cells (Tregs)/neutrophils might play a crucial role in the pathogenesis of EoE in children.
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Affiliation(s)
- Junhao Wu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China
| | - Caihan Duan
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China
| | - Chaoqun Han
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China
| | - Xiaohua Hou
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China
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Arangia A, Marino Y, Impellizzeri D, D’Amico R, Cuzzocrea S, Di Paola R. Hydroxytyrosol and Its Potential Uses on Intestinal and Gastrointestinal Disease. Int J Mol Sci 2023; 24:ijms24043111. [PMID: 36834520 PMCID: PMC9964144 DOI: 10.3390/ijms24043111] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 01/30/2023] [Accepted: 02/01/2023] [Indexed: 02/09/2023] Open
Abstract
In recent years, the phytoconstituents of foods in the Mediterranean diet (MD) have been the subject of several studies for their beneficial effects on human health. The traditional MD is described as a diet heavy in vegetable oils, fruits, nuts, and fish. The most studied element of MD is undoubtedly olive oil due precisely to its beneficial properties that make it an object of interest. Several studies have attributed these protective effects to hydroxytyrosol (HT), the main polyphenol contained in olive oil and leaves. HT has been shown to be able to modulate the oxidative and inflammatory process in numerous chronic disorders, including intestinal and gastrointestinal pathologies. To date, there is no paper that summarizes the role of HT in these disorders. This review provides an overview of the anti-inflammatory and antioxidant proprieties of HT against intestinal and gastrointestinal diseases.
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Affiliation(s)
- Alessia Arangia
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
| | - Ylenia Marino
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
| | - Daniela Impellizzeri
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
- Correspondence: (D.I.); (R.D.); Tel.: +39-090-676-5208 (D.I. & R.D.)
| | - Ramona D’Amico
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
- Correspondence: (D.I.); (R.D.); Tel.: +39-090-676-5208 (D.I. & R.D.)
| | - Salvatore Cuzzocrea
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
| | - Rosanna Di Paola
- Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy
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Clinical presentation and endoscopic findings in adult patients with eosinophilic esophagitis. JOURNAL OF SURGERY AND MEDICINE 2022. [DOI: 10.28982/josam.7516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Background/Aim: The frequency of eosinophilic esophagitis has been rising over the last decades. It is diagnosed primarily based on symptoms and endoscopic and histopathological examination findings. Although eosinophilic esophagitis is not associated with malignancy, it remains an important condition affecting both children and adults, as it is associated with morbidity such as dysphagia, food impaction, and esophageal strictures. This study aimed to define clinical and endoscopic characteristics of adult patients diagnosed with eosinophilic esophagitis based on recently recommended histopathological criteria.
Methods: This retrospective cross-sectional descriptive study included 54 adult patients (mean age: 33.6 yr, range: 16–61 yr) who underwent upper gastrointestinal system endoscopy for dyspeptic complaints (epigastric pain, reflux, dysphagia, or food impaction) and diagnosed with eosinophilic esophagitis based on the latest histopathological criteria (≥15 eosinophils per high-power field). Patients with a history of malignancy were excluded. Patients’ clinical, endoscopic, and histopathological data were examined.
Results: In patients diagnosed with eosinophilic esophagitis, the most common presenting complaint was dysphagia (61.1%), followed by dyspepsia (24.0%), regurgitation (16.6%), chest pain (16.6%), epigastric pain (12.9%), food impaction (11.1%), and halitosis (3.7%), without any age predilection for the complaints. White papules and linear furrow were the most frequent findings on endoscopic examination (35.1% each), followed by circular rings (24.0%), paleness (22.2%), normal endoscopic finding (20.3%), and small-caliber esophagus (11.1%).
Conclusion: The diagnosis of eosinophilic esophagitis remains challenging due to considerable variations in definitions and in the relative frequencies of endoscopic findings. Therefore, we recommend combining clinical, endoscopic, and histologic criteria to establish diagnosis. The identification of standards for diagnosis in future studies is warranted.
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Genta RM. Editorial: the CTA on EGIDs-author's reply. Aliment Pharmacol Ther 2022; 56:332-333. [PMID: 35748826 DOI: 10.1111/apt.17047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Robert M Genta
- Inform Diagnostics, Irving, Texas, USA.,Baylor College of Medicine, Houston, Texas, USA
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Upparahalli Venkateshaiah S, Yadavalli CS, Kandikattu HK, Kumar S, Oruganti L, Mishra A. Molecules involved in the development of Barrett's esophagus phenotype in chronic eosinophilic esophagitis. Am J Physiol Gastrointest Liver Physiol 2022; 323:G31-G43. [PMID: 35437997 PMCID: PMC9190763 DOI: 10.1152/ajpgi.00321.2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 03/15/2022] [Accepted: 04/10/2022] [Indexed: 01/31/2023]
Abstract
This paper aims to investigate the molecules involved in development of Barrett's esophagus (BE) in human eosinophilic esophagitis (EoE). Histopathological, immunohistochemical, real-time PCR Immuno blot, and ELISA analyses are performed to identify the signature genes and proteins involved in the progression of BE in EoE. We detected characteristic features of BE like intermediate columnar-type epithelial cells, induced BE signature genes like ErbB3, CDX1, ErbB2IP in the esophageal mucosa of patients with EoE. In addition, we had observed several BE-associated proteins such as TFF3, p53 and the progression markers like EGFR, p16, MICA, MICB, and MHC molecules in esophageal biopsies of patients with chronic EoE. Interestingly, we also detected mucin-producing columnar cells and MUC-2, MUC-4, and MUC5AC genes and proteins along with induced IL-9 in patients with chronic EoE. A strong correlation of IL-9 with mucin genes is observed that implicated a possible role for IL-9 in the transformation of esophageal squamous epithelial cells to columnar epithelial cells in patients with EoE. These findings indicate that IL-9 may have an important role in BE development in patients with chronic EoE. We also discovered that IL-9 stimulates mucin-producing and barrier cell transcripts and proteins such CK8/18, GATA4, SOX9, TFF1, MUC5AC, and tight junction proteins in primary esophageal epithelial cells when exposed to IL-9. Taken together, these findings provide evidence that indeed IL-9 has a role in the initiation and progression of BE characteristics like development of mucin-producing columnar epithelial cells in patients with chronic EoE.NEW & NOTEWORTHY Intermediate columnar-type epithelial cells are observed in biopsies of patients with EoE. Induced BE signature genes (CK8/18, CDX1 GATA4, SOX9, and Occludin) were observed in patients with chronic EoE. Induction of IL-9 and its correlation with eosinophils mucin-producing genes and proteins was observed in patients with EoE. Induced IL-9 may be responsible for the development of BE in patients with chronic EoE.
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Affiliation(s)
- Sathisha Upparahalli Venkateshaiah
- Section of Pulmonary Diseases, John W. Deming Department of Medicine, Tulane Eosinophilic Disorder Center (TEDC), Tulane University School of Medicine, New Orleans, Louisiana
| | - Chandra Sekhar Yadavalli
- Section of Pulmonary Diseases, John W. Deming Department of Medicine, Tulane Eosinophilic Disorder Center (TEDC), Tulane University School of Medicine, New Orleans, Louisiana
| | - Hemanth Kumar Kandikattu
- Section of Pulmonary Diseases, John W. Deming Department of Medicine, Tulane Eosinophilic Disorder Center (TEDC), Tulane University School of Medicine, New Orleans, Louisiana
| | - Sandeep Kumar
- Section of Pulmonary Diseases, John W. Deming Department of Medicine, Tulane Eosinophilic Disorder Center (TEDC), Tulane University School of Medicine, New Orleans, Louisiana
| | - Lokanatha Oruganti
- Section of Pulmonary Diseases, John W. Deming Department of Medicine, Tulane Eosinophilic Disorder Center (TEDC), Tulane University School of Medicine, New Orleans, Louisiana
| | - Anil Mishra
- Section of Pulmonary Diseases, John W. Deming Department of Medicine, Tulane Eosinophilic Disorder Center (TEDC), Tulane University School of Medicine, New Orleans, Louisiana
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Camilleri AE, Nag S, Russo AR, Stiles KM, Crystal RG, Pagovich OE. Gene therapy for a murine model of eosinophilic esophagitis. Allergy 2021; 76:2740-2752. [PMID: 33748982 DOI: 10.1111/all.14822] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Revised: 01/05/2021] [Accepted: 01/15/2021] [Indexed: 01/07/2023]
Abstract
BACKGROUND Eosinophils are specialized granulocytic effector cells that store and release highly active mediators used in immune defense. Eosinophils are also implicated in the pathogenesis of allergic disorders, including eosinophilic esophagitis (EoE), a chronic disorder characterized by infiltration of eosinophils into the esophagus and release of mediators that damage tissue, resulting in gastrointestinal morbidity, food impaction, and dysphagia. Treatment with elimination diets and/or topical corticosteroid therapy slow disease progression, but are complicated by adverse effects, limited compliance, and loss of response to therapy. We hypothesized that a single administration of an adeno-associated virus (AAV) coding for an anti-eosinophil monoclonal antibody that induces eosinophil clearance (anti-Siglec-F) would treat on a persistent basis a murine model of EoE. METHODS A mouse model of peanut-induced EoE that mimics the human disease was established by sensitization and challenge with peanut extract. After challenge, these mice exhibited an EoE phenotype demonstrated by elevated levels of blood eosinophils, infiltration of eosinophils in the esophagus with associated esophageal remodeling and food impaction. RESULTS The mice were treated with a single intravenous administration (1011 genome copies) of AAVrh.10mAnti-Eos, a serotype rh.10 AAV vector coding for an anti-Siglec-F monoclonal antibody. Vector administration resulted in persistent, high levels of anti-Siglec-F antibody expression. Administration of AAVrh.10mAnti-Eos to the mouse model of EoE reduced blood (P < 0.02) and esophageal eosinophil numbers (P < 0.002) protected from esophageal tissue remodeling and minimized food impaction. CONCLUSION These results suggest that a single treatment with AAVrh.10mAnti-Eos has the potential to provide persistent therapeutic benefit to patients with EoE.
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Affiliation(s)
- Anna E. Camilleri
- Department of Genetic Medicine Weill Cornell Medical College New York NY USA
| | - Saparja Nag
- Department of Genetic Medicine Weill Cornell Medical College New York NY USA
| | - Anthony R. Russo
- Department of Genetic Medicine Weill Cornell Medical College New York NY USA
| | - Katie M. Stiles
- Department of Genetic Medicine Weill Cornell Medical College New York NY USA
| | - Ronald G. Crystal
- Department of Genetic Medicine Weill Cornell Medical College New York NY USA
| | - Odelya E. Pagovich
- Department of Genetic Medicine Weill Cornell Medical College New York NY USA
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Devi S, Kar N, Sahoo D, Dey A, Das DS. Eosinophilic Ascites: A Rare Case Report With Diagnostic and Therapeutic Challenges. Cureus 2020; 12:e11362. [PMID: 33304695 PMCID: PMC7720916 DOI: 10.7759/cureus.11362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Eosinophilic ascites is a manifestation of serosal eosinophilic gastrointestinal disease. We present a 44-year-old male with low serum ascites albumin gradient with high eosinophil count and contrast-enhanced computed tomography of the abdomen showing circumferential wall thickening of the esophagus, mid to distal ileal loops, and ascending colon. The patient was managed with tablet prednisolone 20 mg twice daily for two weeks, then gradual tapering over one month. The patient responded to treatment. Awareness of the condition, timely diagnosis, and early treatment carries excellent responses.
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Affiliation(s)
- Sujata Devi
- Internal Medicine, All India Institute of Medical Sciences, Bhubaneswar, IND
| | - Nilanjan Kar
- Internal Medicine, All India Institute of Medical Sciences, Bhubaneswar, IND
| | - Debananda Sahoo
- Internal Medicine, All India Institute of Medical Sciences, Bhubaneswar, IND
| | - Anupam Dey
- General Medicine, All India Institute of Medical Sciences, Bhubaneswar, IND
| | - Dhriti Sundar Das
- General Medicine, All India Institute of Medical Sciences, Bhubaneswar, IND
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Mousavinasab F, Babaie D, Nilipour Y, Mansouri M, Imanzadeh F, Dara N, Rohani P, Khatami K, Sayyari A, Khoddami M, Kazemiaghdam M, Mesdaghi M. Increased number of regulatory T cells in esophageal tissue of patients with eosinophilic esophagitis in comparison to gastro esophageal reflux disease and control groups. Allergol Immunopathol (Madr) 2019; 47:431-436. [PMID: 31178311 DOI: 10.1016/j.aller.2019.02.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2018] [Revised: 01/21/2019] [Accepted: 02/08/2019] [Indexed: 11/25/2022]
Abstract
BACKGROUND Eosinophilic esophagitis (EoE) is a primarily polygenic allergic disorder. Although most patients have IgE sensitization, it seems that non-IgE mediated responses mainly contribute to the pathogenesis of EoE. Regulatory T cells (Tregs) may have an important role in allergies. There are limited data on the association of Tregs and EoE. In this study, we enumerated and compared T lymphocytes and Tregs in esophageal tissue of patients with EoE, gastroesophageal reflux disease (GERD) and normal controls. METHODS Ten patients with EoE, ten patients with GERD and eight normal controls were included. Immunohistochemistry staining was used to enumerate T lymphocytes and Tregs. CD3+ cells were considered as T cells and FOXP3+, CD3+ cells were considered as Tregs. T cells and Tregs were counted in 10 high power fields (HPF) (×400) for each patient and the average of 10 HPFs was recorded. RESULTS The mean±SEM of Tregs in esophageal tissue of patients with EoE (10.90±2.14cells/HPF) was significantly higher than the GERD (2.77±0.66cells/HPF) and control groups (0.37±0.08cells/HPF) (P<0.001). Additionally, the mean±SEM of T lymphocytes in esophageal tissue of patients with EoE (24.39±3.86cells/HPF) were increased in comparison to the GERD (10.07±2.65cells/HPF) and control groups (3.17±0.93cells/HPF) (P<0.001). CONCLUSION There is an increase in the number of esophageal T lymphocytes and regulatory T cells in patients with EoE compared to the GERD and control groups.
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Straumann A. Eosinophil-Associated Gastrointestinal Disorders. Clin Immunol 2019. [DOI: 10.1016/b978-0-7020-6896-6.00046-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Safety and Efficacy of Reslizumab for Children and Adolescents With Eosinophilic Esophagitis Treated for 9 Years. J Pediatr Gastroenterol Nutr 2018; 66:893-897. [PMID: 29176476 DOI: 10.1097/mpg.0000000000001840] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Eosinophilic esophagitis (EoE) is a chronic disease characterized by infiltration of eosinophils in the esophageal epithelium. There are limited treatment options for EoE. The rationale of the study was to evaluate the long-term safety and efficacy of reslizumab (RSZ) in pediatric patients who received RSZ in a randomized controlled trial (RCT) and expanded access program. METHODS Records of patients who received RSZ in our center were reviewed. Patients received RSZ 2 mg/kg (or placebo) every 4 weeks as part of the RCT, open-label extension (OLE), and compassionate use (CU). Data were analyzed as of their most recent evaluation in August 2017. Labwork, history, and examinations were conducted every 12 weeks. Biopsy results were compared from baseline (before RCT) and at the most recent evaluation. Adverse events (AE) were recorded. RESULTS Twelve patients entered the RCT at our center; 6 patients completed the OLE and 4 received RSZ through CU. Between the RCT, OLE, and CU periods, patients received 549 doses of RSZ (median 37, range 2-116). No serious AE were attributed to RSZ. Symptoms improved on treatment: dysphagia (42% vs 0%), abdominal pain (58% vs 0%), heartburn (18% vs 0%), vomiting (67% vs. 17%), reflux (58% vs. 0%). Median esophageal eosinophil count improved (35 eosinophils per high-power field vs 3, P < 0.001). Patients receiving RSZ maintain a relatively unrestricted diet. CONCLUSIONS RSZ appears to be safe in children with EoE over 9 years of treatment experience. Symptoms and eosinophil count improved considerably during treatment with RSZ despite a relatively unrestricted diet.
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Kim GH, Jung KW, Jung HY, Choi KD, Lee J, Park YS, Kim SW, Lee JH, Kim DH, Ahn JY, Song HJ, Lee GH, Kim JH. Diagnostic Trends and Clinical Characteristics of Eosinophilic Esophagitis: A Korean, Single-center Database Study. J Neurogastroenterol Motil 2018; 24:248-254. [PMID: 29605980 PMCID: PMC5885724 DOI: 10.5056/jnm17047] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2017] [Revised: 07/28/2017] [Accepted: 10/19/2017] [Indexed: 12/28/2022] Open
Abstract
Background/Aims The prevalence of eosinophilic esophagitis (EoE) is reportedly increasing in Western countries. However, its prevalence in Korea remains unknown. We investigated the diagnostic trends and clinical characteristics of EoE in Korea. Methods Using an endoscopic database maintained at a tertiary care center, we retrospectively reviewed the biopsy reports regarding 18 399 biopsy specimens collected from all patients who underwent esophagogastroduodenoscopy and esophageal biopsy at this facility between 2006 and 2014. The presence of more than 15 eosinophils per high-power field with symptoms related to esophageal dysfunction was considered to indicate EoE. Results A total of 37 patients (male:female ratio, 29:8; mean age, 44.0 ± 13.0 years) were diagnosed with EoE. These patients presented with dysphagia (21.6%), epigastric pain (21.6%), heartburn (24.3%), and other symptoms (32.4%). Typical endoscopic appearance of EoE was noted in 33 cases (89.1%) and included linear furrows in 24 cases (64.8%), ringed esophagus in 10 cases (27.0%), and white exudates in 11 cases (29.7%). The median eosinophilic count was 25 per high-power field (interquartile range, 20-70). Notable histopathological findings included eosinophilic microabscesses in 21 cases (56.7%). The diagnosis rate of EoE was found to have increased from 2006 and to 2014 (P-value ＜ 0.001 by the Cochran-Armitage trend test). Conclusions The number of patients with EoE appears to have increased significantly over the 9-year period investigated, while the number of endoscopic investigations increased only marginally. Greater awareness of EoE and the role of esophageal biopsies should be considered.
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Affiliation(s)
- Ga Hee Kim
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Asan Digestive Disease Research Institute, Seoul, Korea.,Department of Health Promotion Medicine, Ewha Womans University School of Medicine, Ewha Medical Research Institute, Seoul, Korea
| | - Kee Wook Jung
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Asan Digestive Disease Research Institute, Seoul, Korea
| | - Hwoon-Yong Jung
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Asan Digestive Disease Research Institute, Seoul, Korea
| | - Kee Don Choi
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Asan Digestive Disease Research Institute, Seoul, Korea
| | - JungBok Lee
- Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Young Soo Park
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - So-Woon Kim
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Jeong Hoon Lee
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Asan Digestive Disease Research Institute, Seoul, Korea
| | - Do Hoon Kim
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Asan Digestive Disease Research Institute, Seoul, Korea
| | - Ji Yong Ahn
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Asan Digestive Disease Research Institute, Seoul, Korea
| | - Ho June Song
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Asan Digestive Disease Research Institute, Seoul, Korea
| | - Gin Hyug Lee
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Asan Digestive Disease Research Institute, Seoul, Korea
| | - Jin-Ho Kim
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Asan Digestive Disease Research Institute, Seoul, Korea
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Yu C, Sterling D, Albayati I, Al-Obaidi S, Moraveji S, Bustamante MA, Torabi A, Hakim N, Naim A, Dutta A, Naik PS, McCallum RW. The Prevalence of Biopsy-Proven Eosinophilic Esophagitis in Hispanics Undergoing Endoscopy Is Infrequent Compared to Caucasians: A Cross-Sectional Study. Dig Dis Sci 2017; 62:3511-3516. [PMID: 29086329 DOI: 10.1007/s10620-017-4791-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2017] [Accepted: 06/20/2017] [Indexed: 12/17/2022]
Abstract
INTRODUCTION The prevalence of eosinophilic esophagitis (EoE), a chronic, immune-mediated, clinicopathologic, inflammatory disorder, has been well described in the pediatric and adult Caucasian population but not as well studied in the Hispanic population. The major aims of this study are to determine the prevalence and gene expression profile of EoE in these populations. METHODS This is a retrospective cohort study of patients from two institutions predominantly serving a Hispanic population. Patients included at Los Angeles County Hospital (LACH) had an esophagogastroduodenoscopy (EGD) and esophageal biopsies performed for evaluation of dysphagia and/or food impaction, while patients included from the University Hospital Medical Center of El Paso (UHMCEP) had an EGD and esophageal biopsies performed for any appropriate clinical indication. Gene expression analysis which has been shown to accurately diagnose EOE in Caucasians was performed for 9 patients at UHMCEP to determine its accuracy in Hispanics. RESULTS At LACH, 234 patients were included in the study of whom 155 (66.3%) were Hispanic and 22 (9.4%) were Caucasian. 3.2% of the Hispanic patients and 9.1% of the Caucasian patients were diagnosed with EOE with threefold difference. At UHMCEP 1700 patients were included of whom 1350 (79.4%) were Hispanic and 179 (10.5%) were Caucasian. 0.96% of the Hispanic patients and 7.26% of the Caucasian patients were diagnosed with EOE with a sevenfold difference. Gene expression accurately diagnosed EOE in a small number of both Hispanics and Caucasians who underwent analysis. CONCLUSIONS Hispanic patients at LAC and UMHCEP had a significantly lower prevalence of EOE as compared to Caucasians at these two institutions and a lower prevalence as compared to Caucasians with EOE previously reported in the literature. Gene expression analysis, which has previously been shown to accurately diagnose EOE in Caucasian patients, accurately diagnosed EOE in a small sample of this Hispanic population. Based on this similar gene expression, other factors such as environmental, ethnic, and cultural causes should be investigated to explain the markedly lower prevalence of EOE in Hispanics.
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Affiliation(s)
- Christine Yu
- Department of Gastroenterology, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Dubin Sterling
- Department of Gastroenterology, Keck Medical Center of USC, Los Angeles, CA, USA
| | - Ihsan Albayati
- Department of Gastroenterology, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Sarah Al-Obaidi
- Department of Gastroenterology, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Sharareh Moraveji
- Department of Gastroenterology, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Marco A Bustamante
- Department of Gastroenterology, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Alireza Torabi
- Department of Gastroenterology, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Nawar Hakim
- Department of Gastroenterology, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Alan Naim
- Department of Gastroenterology, Keck Medical Center of USC, Los Angeles, CA, USA
| | - Anand Dutta
- Department of Gastroenterology, Keck Medical Center of USC, Los Angeles, CA, USA
| | - Pratik S Naik
- Department of Gastroenterology, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Richard W McCallum
- Department of Gastroenterology, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA. .,Division of Gastroenterology, Center for Neurogastroenterology and GI Motility, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, 4800 Alberta Avenue, El Paso, TX, 79905, USA.
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Abstract
ABSTRACT
A 4 mo old intact male kitten was presented for chronic regurgitation and failure to thrive after weaning to dry food. Esophageal dilatation and severe diffuse proliferative lesions of the esophageal mucosa were found via radiography and esophagoscopy, respectively. Histopathologic examination revealed severe, chronic, diffuse, hyperplastic eosinophilic and mastocytic esophagitis. Eosinophilic infiltrates were prominent, with a mean of 29.8 eosinophils per high power field, supportive of eosinophilic esophagitis (EoE). Significant clinical improvement was seen with dietary modification using a hydrolyzed diet. The addition of glucocorticoids did not result in further improvement in clinical signs. Repeat histopathology showed near resolution of eosinophilic infiltration. EoE is an uncommon and rarely reported condition in dogs and cats. Diagnosis involves histopathologic confirmation and exclusion of other causes of eosinophilic infiltration within the esophagus. This case report demonstrates the importance of biopsy in identification of EoE and the efficacy of dietary modification in the treatment of this disease in a kitten.
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Affiliation(s)
- Julie Pera
- From the Hope Advanced Veterinary Center, Rockville, Maryland (J.P.); and the Animal Medical Center, New York, New York (D.P., T.D.)
| | - Douglas Palma
- From the Hope Advanced Veterinary Center, Rockville, Maryland (J.P.); and the Animal Medical Center, New York, New York (D.P., T.D.)
| | - Taryn A. Donovan
- From the Hope Advanced Veterinary Center, Rockville, Maryland (J.P.); and the Animal Medical Center, New York, New York (D.P., T.D.)
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15
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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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16
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Kavitt RT, Ates F, Slaughter JC, Higginbotham T, Shepherd BD, Sumner EL, Vaezi MF. Randomized controlled trial comparing esophageal dilation to no dilation among adults with esophageal eosinophilia and dysphagia. Dis Esophagus 2016; 29:983-991. [PMID: 26228516 DOI: 10.1111/dote.12398] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The role of esophageal dilation in patients with esophageal eosinophilia with dysphagia remains unknown. The practice of dilation is currently based on center preferences and expert opinion. The aim of this study is to determine if, and to what extent, dysphagia improves in response to initial esophageal dilation followed by standard medical therapies. We conducted a randomized, blinded, controlled trial evaluating adult patients with dysphagia and newly diagnosed esophageal eosinophilia from 2008 to 2013. Patients were randomized to dilation or no dilation at time of endoscopy and blinded to dilation status. Endoscopic features were graded as major and minor. Subsequent to randomization and endoscopy, all patients received fluticasone and dexlansoprazole for 2 months. The primary study outcome was reduction in overall dysphagia score, assessed at 30 and 60 days post-intervention. Patients with severe strictures (less than 7-mm esophageal diameter) were excluded from the study. Thirty-one patients were randomized and completed the protocol: 17 randomized to dilation and 14 to no dilation. Both groups were similar with regard to gender, age, eosinophil density, endoscopic score, and baseline dysphagia score. The population exhibited moderate to severe dysphagia and moderate esophageal stricturing at baseline. Overall, there was a significant (P < 0.001) but similar reduction in mean dysphagia score at 30 and 60 days post-randomization compared with baseline in both groups. No significant difference in dysphagia scores between treatment groups after 30 (P = 0.93) or 60 (P = 0.21) days post-intervention was observed. Esophageal dilation did not result in additional improvement in dysphagia score compared with treatment with proton pump inhibitor and fluticasone alone. In patients with symptomatic esophageal eosinophilia without severe stricture, dilation does not appear to be a necessary initial treatment strategy.
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Affiliation(s)
- R T Kavitt
- Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, Illinois, USA
| | - F Ates
- Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - J C Slaughter
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - T Higginbotham
- Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - B D Shepherd
- Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - E L Sumner
- Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - M F Vaezi
- Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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17
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Lee EH, Yang HR, Lee HS. Analysis of Gastric and Duodenal Eosinophils in Children with Abdominal Pain Related Functional Gastrointestinal Disorders According to Rome III Criteria. J Neurogastroenterol Motil 2016; 22:459-69. [PMID: 27053514 PMCID: PMC4930301 DOI: 10.5056/jnm15174] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2015] [Revised: 01/27/2016] [Accepted: 03/05/2016] [Indexed: 12/14/2022] Open
Abstract
Background/Aims Abdominal pain-related functional gastrointestinal disorder (AP-FGID) is common in children and adults. However, the mechanism of AP-FGID is not clearly known. Recently, micro-inflammation, especially eosinophilia in the gastrointestinal tract, was suggested in the pathophysiology of AP-FGID in adults. The aim of this study was to evaluate the association of gastric and duodenal eosinophilia with pediatric AP-FGID. Methods In total, 105 pediatric patients with AP-FGID were recruited and classified into 4 subgroups based on the Rome III criteria. Eosinophil counts in the gastric and duodenal tissues of children with AP-FGID were compared to those from normal pathology references or those of children with Helicobacter pylori infection. Tissue eosinophil counts were also compared among the 4 subtypes of AP-FGID. Results Eosinophil counts in the gastric antrum and body were significantly higher in children with AP-FGID than normal reference values. Duodenal eosinophil counts were higher in children with AP-FGID, but not significantly when compared with normal reference values. There were no significant differences in eosinophil counts of the stomach or duodenum among the 4 subtypes of AP-FGID. Eosinophils counts in the gastric antrum and body were significantly higher in children with H. pylori infection than in those with AP-FGID. Duodenal eosinophilia was prominent in cases of H. pylori infection, but not statistically significant when compared with AP-FGID. Conclusions Our study revealed that gastric eosinophilia is associated with AP-FGID in children, regardless of the subtype of functional abdominal pain. This suggests some contribution of gastrointestinal eosinophils in the development of pediatric AP-FGID.
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Affiliation(s)
- Eun Hye Lee
- Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea
| | - Hye Ran Yang
- Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea.,Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
| | - Hye Seung Lee
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea
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18
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Mudnakudu Nagaraju KK, Babina M, Weise C, Kühl A, Schulzke J, Worm M. Bortezomib treatment diminishes hazelnut-induced intestinal anaphylaxis in mice. Eur J Immunol 2016; 46:1727-36. [PMID: 27111856 DOI: 10.1002/eji.201545918] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2015] [Revised: 04/01/2016] [Accepted: 04/19/2016] [Indexed: 12/31/2022]
Abstract
Food allergy is a common health problem and can cause anaphylaxis. Avoidance of the offending food allergen is still the mainstay therapeutic approach. In this study, we investigated the role of plasma cell reduction by proteasome inhibition in a murine model of food allergy and examined the impact of this treatment on the systemic and local immune response. For this purpose, intestinal anaphylaxis was induced in BALB/c mice with the food allergen hazelnut, in conjunction with different adjuvants (alum and Staphylococcal enterotoxin B SEB) and different administration routes (oral and intraperitoneal). In both models, allergy symptoms were observed, but the clinical severity was more pronounced in the hazelnut-alum model than in the hazelnut-SEB model. Accordingly, allergen-specific immunoglobulin E (IgE) against hazelnut was detectable, and mast cell protease-1 in serum was increased after allergen provocation. Treatment with the proteasome inhibitor bortezomib reduced plasma cells and resulted in an abolishment of hazelnut allergen-specific IgE, which was associated with amelioration of clinical symptoms as well as a significant decrease in both CD19(+) and follicular B lymphocytes. Our data demonstrate the importance of allergen-specific IgE in food allergy and point to B cells as potential therapeutic targets for its treatment.
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Affiliation(s)
| | - Magda Babina
- Department of Dermatology und Allergology, Allergie-Centrum-Charité, Charité - Universitätsmedizin, Berlin, Germany
| | - Christin Weise
- Department of Dermatology und Allergology, Allergie-Centrum-Charité, Charité - Universitätsmedizin, Berlin, Germany
| | - Anja Kühl
- Department of Medicine-I for Gastroenterology, Infectious Disease and Rheumatology, Research Center ImmunoSciences, Charité - Universitätsmedizin, Berlin, Germany
| | - Joerg Schulzke
- Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité - Universitätsmedizin, Berlin, Germany
| | - Margitta Worm
- Department of Dermatology und Allergology, Allergie-Centrum-Charité, Charité - Universitätsmedizin, Berlin, Germany
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19
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Dutt P, Shukla JS, Ventateshaiah SU, Mariswamy SJ, Mattner J, Shukla A, Mishra A. Allergen-induced interleukin-18 promotes experimental eosinophilic oesophagitis in mice. Immunol Cell Biol 2015; 93:849-57. [PMID: 25801352 PMCID: PMC4581894 DOI: 10.1038/icb.2015.30] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2014] [Revised: 01/28/2015] [Accepted: 01/29/2015] [Indexed: 02/07/2023]
Abstract
Elevated levels of interleukin (IL)-18 have been reported in a number of allergic diseases. We recently reported that IL-18 in the blood and IL-18Rα mRNA in the oesophagus are induced during human eosinophilic oesophagitis (EoE). Additionally, we earlier showed that invariant natural killer T (iNKT) cells are critical to EoE pathogenesis; however, the mechanism of iNKT cell activation in EoE is not well understood. Therefore, the current study focused on the hypothesis that allergen-induced IL-18 may have an important role in iNKT cell-mediated EoE pathogenesis. We first validated the human EoE findings of IL-18 in experimental EoE by examining blood levels of IL-18 and oesophageal IL-18Rα mRNA levels in aeroallergen- and food allergen-induced experimental mouse models of EoE. We demonstrate that blood IL-18 protein and oesophageal IL-18Rα mRNA are induced in the mouse model of EoE and that IL-18Rα is expressed by iNKT cells in the oesophagus. Intranasal delivery of rIL-18 induced both mast cells and eosinophilic inflammation in the oesophagus in a time- and dose-dependent manner. To establish the significance of IL-18 in EoE pathogenesis, we examined DOX-inducible rtTA-CC10-IL-18 bitransgenic mice that induce IL-18 protein expression in the oesophagus. Our analysis indicated that induction of IL-18 in these mice resulted in the development of many of the characteristics of EoE, including oesophageal intraepithelial eosinophilia, increased mast cells, oesophageal remodelling and fibrosis. The current study provides evidence that IL-18 may induce iNKT cell activation to release the eosinophil-activating cytokine IL-5, as IL-5-deficient mice and iNKT cell-deficient (CD1d null) mice do not induce EoE in response to intranasal IL-18 challenge. Taken together, these findings provide evidence that allergen-induced IL-18 has a significant role in promoting IL-5- and iNKT-dependent EoE pathogenesis.
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Affiliation(s)
- Parmesh Dutt
- Section of Department of Medicine, Pulmonary Diseases, Tulane Eosinophilic Disorder Center, Tulane University School of Medicine, New Orleans, LA, USA
| | - Jai Shankar Shukla
- Section of Department of Medicine, Pulmonary Diseases, Tulane Eosinophilic Disorder Center, Tulane University School of Medicine, New Orleans, LA, USA
| | - Sathisha Upparahalli Ventateshaiah
- Section of Department of Medicine, Pulmonary Diseases, Tulane Eosinophilic Disorder Center, Tulane University School of Medicine, New Orleans, LA, USA
| | - Siddesha Jalahalli Mariswamy
- Section of Department of Medicine, Pulmonary Diseases, Tulane Eosinophilic Disorder Center, Tulane University School of Medicine, New Orleans, LA, USA
| | - Jochen Mattner
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Anshi Shukla
- Section of Department of Medicine, Pulmonary Diseases, Tulane Eosinophilic Disorder Center, Tulane University School of Medicine, New Orleans, LA, USA
| | - Anil Mishra
- Section of Department of Medicine, Pulmonary Diseases, Tulane Eosinophilic Disorder Center, Tulane University School of Medicine, New Orleans, LA, USA
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20
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de Souza HS, Tortori CA, Lintomen L, Figueiredo RT, Bernardazzi C, Leng L, Bucala R, Madi K, Buongusto F, Elia CCS, Castelo-Branco MTL, Bozza MT. Macrophage migration inhibitory factor promotes eosinophil accumulation and tissue remodeling in eosinophilic esophagitis. Mucosal Immunol 2015; 8:1154-65. [PMID: 25712805 PMCID: PMC4540676 DOI: 10.1038/mi.2015.6] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2014] [Accepted: 01/02/2015] [Indexed: 02/04/2023]
Abstract
Macrophage migration inhibitory factor (MIF) is involved in eosinophil biology and in type 2 inflammation, contributing to allergic and helminthic diseases. We hypothesized that MIF participates in the pathogenesis of eosinophilic esophagitis (EoE), an allergic condition characterized by esophageal eosinophilic inflammation. MIF is highly expressed in esophageal mucosa of patients with EoE, compared with gastro-esophageal reflux disease and control patients, where it co-localizes predominantly with eosinophils. In vitro, recombinant MIF promotes human eosinophil chemotaxis, while MIF antagonist and CXCR4 antagonist, AMD3100, revert this effect. In a model of EoE induced by ovalbumin, Mif-deficient mice have reduced inflammation and collagen deposition compared with wild-type (WT) mice. Importantly, treatment of WT mice with anti-MIF or with AMD3100 during the challenge phase prevents accumulation of eosinophils and tissue remodeling. Conversely, recombinant MIF promoted tissue eosinophil inflammation in allergic mice. Together, these results implicate MIF in the pathogenesis of esophageal inflammation and suggest that targeting MIF might represent a novel therapy for EoE.
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Affiliation(s)
- H. S. de Souza
- Serviço de Gastroenterologia & Laboratório Multidisciplinar de Pesquisa, Department of Internal Medicine, Hospital Universitário, Universidade Federal do Rio de Janeiro, 21941-913,D'Or Institute for Research and Education (IDOR), 22281-100
| | - C. A. Tortori
- Serviço de Gastroenterologia & Laboratório Multidisciplinar de Pesquisa, Department of Internal Medicine, Hospital Universitário, Universidade Federal do Rio de Janeiro, 21941-913
| | - L. Lintomen
- Laboratório de Inflamação e Imunidade, Departamento de Imunologia, Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil
| | - R. T. Figueiredo
- Instituto de Ciências Biomédicas, Pólo de Xerém, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - C. Bernardazzi
- Serviço de Gastroenterologia & Laboratório Multidisciplinar de Pesquisa, Department of Internal Medicine, Hospital Universitário, Universidade Federal do Rio de Janeiro, 21941-913
| | - L. Leng
- Department of Medicine/Rheumatology, Yale University School of Medicine, The Anlyan Center, S525, 300 Cedar Street, New Haven, CT 06520-8031, USA
| | - R. Bucala
- Department of Medicine/Rheumatology, Yale University School of Medicine, The Anlyan Center, S525, 300 Cedar Street, New Haven, CT 06520-8031, USA
| | - K. Madi
- Serviço de Gastroenterologia & Laboratório Multidisciplinar de Pesquisa, Department of Internal Medicine, Hospital Universitário, Universidade Federal do Rio de Janeiro, 21941-913
| | - F. Buongusto
- Serviço de Gastroenterologia & Laboratório Multidisciplinar de Pesquisa, Department of Internal Medicine, Hospital Universitário, Universidade Federal do Rio de Janeiro, 21941-913
| | - C. C. S. Elia
- Serviço de Gastroenterologia & Laboratório Multidisciplinar de Pesquisa, Department of Internal Medicine, Hospital Universitário, Universidade Federal do Rio de Janeiro, 21941-913,D'Or Institute for Research and Education (IDOR), 22281-100
| | - M. T. L. Castelo-Branco
- Laboratório de Imunologia Celular, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, 21941-599, Rio de Janeiro, Brazil
| | - M. T. Bozza
- Laboratório de Inflamação e Imunidade, Departamento de Imunologia, Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil
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21
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Shukla A, Mishra A, Venkateshaiah SU, Manohar M, Mahadevappa CP, Mishra A. Elements Involved In Promoting Eosinophilic Gastrointestinal Disorders. ACTA ACUST UNITED AC 2015; 6. [PMID: 27840774 PMCID: PMC5102338 DOI: 10.4172/2157-7412.1000265] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Eosinophilic gastrointestinal disorders (EGID) are food allergen-induced allergic gastrointestinal disorders, characterized by accumulation of highly induced eosinophils in different segments of gastrointestinal tract along with eosinophil microabssess and extracellular eosinophilic granules in the epithelial layer. EGID are both IgE- and cell-mediated group of diseases that include eosinophilic esophagitis (EoE), eosinophilic gastritis (EG), eosinophilic gastroenteritis (EGE) and eosinophilic colitis (EC). Despite the increased incidences and considerable progress made in understanding EGID pathogenesis. The mechanism is still not well understood. It has been shown that IL-4, IL-5, IL-13, IL-15, IL-18, eotaxin-1, eotaxin-2 and eotaxin-3 play a critical role in EGID pathogenesis. Currently, the only criterion for diagnosing EoE, EGE and EC are repetitive endoscopic and histopathological evaluation of biopsies along with other clinical characteristics/manifestations. Antigen elimination and corticosteroid therapies are the most effective therapies currently in practice for the treatment of EGID. The cytokines (anti-IL-5 and anti-IL-13) therapy trials were not very successful in case of EoE. Most recently, a clinical trial using anti-IL-13 reported only 60% reduced esophageal eosinophilia without achieving primary endpoint. This clinical finding is not surprising and is in accordance with our earlier report indicating that IL-13 is not critical in the initiation of EoE. Notably, EGID still has no reliable noninvasive diagnostic biomarkers. Hence, there is a great necessity to identify novel noninvasive diagnostic biomarkers that can easily diagnose EGID and provide an effective therapy. Now, the attention is required to target cell types like iNKT cells that produce eosinophil active cytokines and is found induced in the pathogenesis of both experimental and human EoE. iNKT cell neutralization is shown to protect allergen-induced EoE in experimental model. In this review, we have discussed the key elements that are critical in the disease initiation, progression, pathogenesis and important for future diagnostic and therapeutic interventions for EGID.
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Affiliation(s)
- Anshi Shukla
- Department of Medicine, Section of Pulmonary Diseases, Tulane Eosinophilic Disorder Center, 1430 Tulane Avenue, New Orleans, LA 70112
| | - Akanksha Mishra
- Department of Medicine, Section of Pulmonary Diseases, Tulane Eosinophilic Disorder Center, 1430 Tulane Avenue, New Orleans, LA 70112
| | | | - Murli Manohar
- Department of Medicine, Section of Pulmonary Diseases, Tulane Eosinophilic Disorder Center, 1430 Tulane Avenue, New Orleans, LA 70112
| | | | - Anil Mishra
- Department of Medicine, Section of Pulmonary Diseases, Tulane Eosinophilic Disorder Center, 1430 Tulane Avenue, New Orleans, LA 70112
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22
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Abstract
Eosinophil-associated disorders can affect practically all tissues and organs in the body, either individually or in combination. This article provides an overview of end-organ manifestations of eosinophilia and discusses selected organ systems, including the upper and lower respiratory, cardiovascular, gastrointestinal, nervous, dermatologic, and renal systems. Mechanisms by which eosinophilia leads to end-organ damage are also considered.
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Affiliation(s)
- Praveen Akuthota
- Division of Pulmonary, Critical Care, and Sleep Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA; Division of Allergy and Inflammation, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
| | - Peter F Weller
- Division of Allergy and Inflammation, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA; Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
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23
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Wang X, Li X, Ge W, Huang J, Li G, Cong Y, Li F, Liu Z, Liu Z, Li Y, Yuan H. Quantitative evaluation of duodenal eosinophils and mast cells in adult patients with functional dyspepsia. Ann Diagn Pathol 2015; 19:50-6. [PMID: 25735567 DOI: 10.1016/j.anndiagpath.2015.02.001] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2014] [Revised: 02/14/2015] [Accepted: 02/15/2015] [Indexed: 02/07/2023]
Abstract
The role of duodenal eosinophils and mast cells (MCs) in the pathogenesis of functional dyspepsia (FD) remains poorly understood. This study aimed to examine the counts and degranulation of duodenal eosinophils and MCs in FD patients to explore the association between FD and both cell types. We recruited 141 FD patients and 39 healthy controls for this study. Biopsy specimens were collected from the duodenal bulb (D1) and the descending part (D2) of the duodenum of all participants. Eosinophil counts and degranulation, and MC counts and degranulation at both sites were quantitatively evaluated by hematoxylin and eosin staining, major basic protein immunostaining, and toluidine blue staining, respectively. Receiver operating characteristic analysis was applied to evaluate the diagnostic accuracy of these parameters in identifying FD cases. We found that the eosinophil counts at D2 were considerably increased in FD patients compared with healthy controls, and that the proportion of cases with eosinophil degranulation at D2 was significantly higher in the FD group. In addition, FD patients showed significantly increased MC counts and degranulation both at D1 and D2, and receiver operating characteristic analysis further demonstrated that these parameters, in particular the degranulation of MCs, appear to be highly sensitive and specific for the identification of FD patients. Our findings suggest that the increased eosinophil counts and degranulation at D2, and the increased MC counts and degranulation at D1 and D2 may be the histologic markers of FD. MC degranulation at D1 and D2 appears to be highly sensitive and specific for FD identification.
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Affiliation(s)
- Xiaohong Wang
- Department of Gastroenterology, Taian City Central Hospital, Taian, Shandong Province, PR China
| | - Xiaopei Li
- Department of Gastroenterology, Taian City Central Hospital, Taian, Shandong Province, PR China
| | - Wenqing Ge
- Department of Emergency, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Jian Huang
- Department of Emergency, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Gaiqin Li
- Department of Gastroenterology, Taian City Central Hospital, Taian, Shandong Province, PR China
| | - Yanqun Cong
- Department of Gastroenterology, Zhejiang Hospital, Hangzhou, Zhejiang Province, PR China
| | - Fukang Li
- Department of Gastroenterology, Taian City Central Hospital, Taian, Shandong Province, PR China
| | - Zhen Liu
- Department of Gastroenterology, Taian City Central Hospital, Taian, Shandong Province, PR China
| | - Zhiyan Liu
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, Shandong Province, PR China
| | - Yanqing Li
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong Province, PR China.
| | - Haipeng Yuan
- Department of Gastroenterology, Taian City Central Hospital, Taian, Shandong Province, PR China; Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong Province, PR China.
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Niranjan R, Rajavelu P, Ventateshaiah SU, Shukla JS, Zaidi A, Mariswamy SJ, Mattner J, Fortgang I, Kowalczyk M, Balart L, Shukla A, Mishra A. Involvement of interleukin-18 in the pathogenesis of human eosinophilic esophagitis. Clin Immunol 2015; 157:103-13. [PMID: 25638412 DOI: 10.1016/j.clim.2015.01.007] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Revised: 01/08/2015] [Accepted: 01/14/2015] [Indexed: 02/06/2023]
Abstract
IL-18 is induced in food allergy and EoE is food allergen-induced disease. Therefore, we tested the hypothesis whether IL-18 is involved in food allergen-induced EoE pathogenesis. Accordingly, we examined normal SPT+ and SPT- EoE patient blood and biopsy samples for IL-18, IL-18Rα, ICAM and VCAM expression. Herein, we show increased IL-18 level is highly significant in food allergen SPT+ compared to SPT- EoE patients. We also report that IL-18Rα+ cells and mRNA levels are induced in the esophageal biopsies of EoE patients and blood IL-18 levels correlate with esophageal eosinophilia (P<0.01). Additionally, we report that the levels of esophageal eosinophil and mast cells correlate with ICAM expression in human EoE. Mechanistically, we show that IL-18 in vitro stimulates iNKT cells and endothelial cells and induce eosinophil active cytokines IL-5 and IL-13. We provide the evidence that IL-18 is critical cytokine involved in activation of iNKT cells and ICAM in promoting human EoE.
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Affiliation(s)
- Rituraj Niranjan
- Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Priya Rajavelu
- Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA
| | | | - Jai Shankar Shukla
- Section of Pulmonary Diseases, Tulane University School of Medicine, New Orleans, LA 70112, USA
| | - Asifa Zaidi
- Section of Pulmonary Diseases, Tulane University School of Medicine, New Orleans, LA 70112, USA
| | | | - Jochen Mattner
- Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander Universität Erlangen-Nürnberg, D-91054 Erlangen, Germany
| | - Ilana Fortgang
- Section of Pediatric and Adult Gastroenterology, Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA
| | - Monika Kowalczyk
- Section of Pediatric and Adult Gastroenterology, Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA
| | - Luis Balart
- Section of Pediatric and Adult Gastroenterology, Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA
| | - Anshi Shukla
- Section of Pulmonary Diseases, Tulane University School of Medicine, New Orleans, LA 70112, USA
| | - Anil Mishra
- Section of Pulmonary Diseases, Tulane University School of Medicine, New Orleans, LA 70112, USA.
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25
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Comparison of 2 delivery vehicles for viscous budesonide to treat eosinophilic esophagitis in children. J Pediatr Gastroenterol Nutr 2014; 59:317-20. [PMID: 24821535 DOI: 10.1097/mpg.0000000000000436] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Oral viscous budesonide (OVB) using Splenda as a delivery vehicle has become an attractive therapeutic option for children with eosinophilic esophagitis (EoE). Many families are wary of giving the artificial sweetener in high doses to their children. The aim of the present study was to determine whether OVB mixed with Neocate Nutra, a hypoallergenic nutritional supplement, is at least as efficacious as OVB mixed with Splenda at healing EoE. METHODS Our institutional review board approved a retrospective chart review of patients with well-documented EoE treated with OVB at the Boston Children's Hospital Eosinophilic Gastrointestinal Disorder program between June 2008 and June 2013. Primary outcome measured was histologic response defined as change in peak eosinophil count to <15 eosinophils per high-power field (eos/HPF) after at least 10 weeks of OVB therapy. RESULTS A total of 46 children were treated with OVB mixed with Splenda, and 14 were treated with OVB mixed with Neocate Nutra. The 2 groups were not significantly different in their demographic (race, age, sex) or clinical (initial eosinophil count, proton pump inhibitor use, or concomitant dietary elimination) characteristics. On follow-up endoscopy, 30 of 46 patients on Splenda and 13 of 14 patients on Neocate Nutra achieved histologic response. Mean pretreatment and posttreatment peak eosinophil counts for the children taking Neocate Nutra were 62 eos/HPF ([high-power field] range 20-120 eos/HPF) and 9 eos/HPF (range 0-100 eos/HPF), respectively. Mean pretreatment and posttreatment peak eosinophil counts for the Splenda group were 59.5 eos/HPF (range 20-180 eos/HPF) and 25.5 eos/HPF (range 0-200 eos/HPF), respectively. The odds ratio (OR) of success with Neocate Nutra as compared with Splenda was 6.93 (95% CI 0.83-57.91, P = 0.0728), demonstrating the noninferiority of Neocate Nutra. CONCLUSIONS We demonstrate that OVB mixed with Neocate Nutra is at least as effective as OVB mixed with Splenda at treating children with EoE. Neocate Nutra is an innovative, effective, and palatable mixing agent to create a viscous budesonide slurry for families who prefer not to use the standard recipe with Splenda.
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26
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Kavitt RT, Penson DF, Vaezi MF. Eosinophilic esophagitis: dilate or medicate? A cost analysis model of the choice of initial therapy. Dis Esophagus 2014; 27:418-23. [PMID: 22947137 PMCID: PMC3823713 DOI: 10.1111/j.1442-2050.2012.01409.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Eosinophilic esophagitis (EoE) is an increasingly recognized clinical entity. The optimal initial treatment strategy in adults with EoE remains controversial. The aim of this study was to employ a decision analysis model to determine the less costly option between the two most commonly employed treatment strategies in EoE. We constructed a model for an index case of a patient with biopsy-proven EoE who continues to be symptomatic despite proton-pump inhibitor therapy. The following treatment strategies were included: (i) swallowed fluticasone inhaler (followed by esophagogastroduodenoscopy [EGD] with dilation if ineffective); and (ii) EGD with dilation (followed by swallowed fluticasone inhaler if ineffective). The time horizon was 1 year. The model focused on cost analysis of initial treatment strategies. The perspective of the healthcare payer was used. Sensitivity analyses were performed to assess the robustness of the model. For every patient whose symptoms improved or resolved with the strategy of fluticasone first followed by EGD, if necessary, it cost an average of $1078. Similarly, it cost an average of $1171 per patient if EGD with dilation was employed first. Sensitivity analyses indicated that initial treatment with fluticasone was the less costly strategy to improve dysphagia symptoms as long as the effectiveness of fluticasone remains at or above 0.62. Swallowed fluticasone inhaler (followed by EGD with dilation if necessary) is the more economical initial strategy when compared with EGD with dilation first.
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Affiliation(s)
- R. T. Kavitt
- Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - D. F. Penson
- Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - M. F. Vaezi
- Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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27
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Schoepfer AM, Hirano I, Katzka DA. Eosinophilic esophagitis: overview of clinical management. Gastroenterol Clin North Am 2014; 43:329-44. [PMID: 24813519 DOI: 10.1016/j.gtc.2014.02.014] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
A validated disease-specific symptom-assessment tool for eosinophilic esophagitis (EoE) has yet to be approved by regulatory authorities for use in clinical trials. Relevant end points for daily practice include EoE-related symptoms and esophageal eosinophilic inflammation. Endoscopic features should also be taken into account when establishing a therapy plan. A reasonable clinical goal is to achieve a reduction in EoE-related symptoms and esophageal eosinophilic inflammation. Evidence is increasing to support an anti-inflammatory maintenance therapy, as this can reduce esophageal remodeling. In EoE patients in clinical remission, annual disease monitoring with symptom, endoscopic, and histologic assessments of sustained treatment response is recommended.
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Affiliation(s)
- Alain M Schoepfer
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois/CHUV, Rue de Bugnon 44, 07/2409, 1011 Lausanne, Switzerland
| | - Ikuo Hirano
- Division of Gastroenterology, Esophageal Center, Northwestern University Feinberg School of Medicine, 676 North Saint Clair, Suite 1400, Chicago, IL 60611, USA.
| | - David A Katzka
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Avenue, Southwest, Rochester, MN 55905, USA
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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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De la Cruz-Patiño E, Ruíz Juárez I, Meixueiro Daza A, Grube Pagola P, Roesch-Dietlen F, Remes-Troche JM. Eosinophilic esophagitis prevalence in an adult population undergoing upper endoscopy in southeastern Mexico. Dis Esophagus 2014; 28:524-9. [PMID: 24835543 DOI: 10.1111/dote.12238] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Eosinophilic esophagitis (EoE) prevalence fluctuates according to the population studied and varies from 0.4% in an open population to 6.5% in subjects with esophageal symptoms. Even though this entity has been described in North American and European populations, it is still considered an 'unusual' condition in Latin America. The study aimed to determine EoE prevalence in patients undergoing elective endoscopy in a tertiary referral center in southeastern Mexico. Consecutive patients were evaluated that had been referred to the Medical and Biological Research Institute, Veracruz, Mexico, for upper endoscopy due to gastrointestinal symptoms. Demographic variables and symptoms were analyzed in all the cases. Eight mucosal biopsies of the esophagus (four proximal and four distal) were obtained and were reviewed by a blinded pathologist. Histological diagnosis was established when the mean eosinophil count at a large magnification was ≥15. A total of 235 subjects (137 women, 51.16 years) were evaluated, and EoE prevalence was 1.7% (4/235 95% confidence interval 0.2-3.6%). In all four cases, pH test were normal. Among patients with histological diagnosis of EoE, a greater number of patients with a past history of asthma (50% vs. 19.3%, P = 0.04) and a tendency for a greater frequency of dysphagia (50% vs. 25%, P = 0.10). There were no differences in the endoscopic findings (rings, grooves, plaques, or stricture) when compared with the patients presenting with erosive esophagitis. EoE prevalence among patients undergoing upper endoscopy from southeastern Mexico was 1.7%, which can be regarded as intermediate to low.
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Affiliation(s)
- E De la Cruz-Patiño
- Laboratory of Digestive Physiology and Gastrointestinal Motility, Medical and Biological Research Institute, University of Veracruz, Veracruz, Mexico
| | - I Ruíz Juárez
- Ruíz Juárez Anatomopathologic Laboratory, University of Veracruz, Veracruz, Mexico
| | - A Meixueiro Daza
- Laboratory of Digestive Physiology and Gastrointestinal Motility, Medical and Biological Research Institute, University of Veracruz, Veracruz, Mexico
| | - P Grube Pagola
- Ruíz Juárez Anatomopathologic Laboratory, University of Veracruz, Veracruz, Mexico
| | - F Roesch-Dietlen
- Laboratory of Digestive Physiology and Gastrointestinal Motility, Medical and Biological Research Institute, University of Veracruz, Veracruz, Mexico
| | - J M Remes-Troche
- Laboratory of Digestive Physiology and Gastrointestinal Motility, Medical and Biological Research Institute, University of Veracruz, Veracruz, Mexico
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30
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Khan AA, Rahmani AH, Aldebasi YH, Aly SM. Biochemical and pathological studies on peroxidases -an updated review. Glob J Health Sci 2014; 6:87-98. [PMID: 25168993 PMCID: PMC4825458 DOI: 10.5539/gjhs.v6n5p87] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2014] [Accepted: 04/17/2014] [Indexed: 12/31/2022] Open
Abstract
Peroxidases represent a family of isoenzymes actively involved in oxidizing reactive oxygen species, innate immunity, hormone biosynthesis and pathogenesis of several diseases. Different types of peroxidases have organ, tissues, cellular and sub-cellular level of specificities in their function. Different diseases lead to varied expressions of peroxidases based on several mechanisms proposed. Several researches are going on to understand its deficiency, over-expression and malfunction in relation with different diseases. Some common diseases of mankind like cancer, cardiovascular diseases and diabetes directly or indirectly involve the role of peroxidases. So the status of peroxidase levels may also function as a marker of different diseases. Although many types of diseases in human beings have a strong correlation with tissue specific peroxidases, the clear role of these oxido-reductases is not yet fully understood. Here we are focusing on the role of peroxidases in relations with different diseases occurring due to oxidative stress.
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Affiliation(s)
- Amjad A Khan
- Dept. of Basic Health Sciences, College of Applied Medical Science, Qassim University, Saudi Arabia.
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31
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Abstract
AbstractEosinophils play a crucial role in the inflammatory response in conjunction with both innate and adaptive immunity. Eosinophils have long been recognized as inflammatory leukocytes that are particularly important in patients with parasitic infestations. However, recent studies in veterinary medicine demonstrate a number of canine eosinophilic gastrointestinal (GI) disorders unrelated to a parasitic infestation. Although the underlying pathophysiology behind eosinophilic infiltration of the canine GI tract remains uncertain, medical intervention aiming to decrease the activation of eosinophils seems effective in reducing symptoms and preventing organ damage. This review focuses on the biology of eosinophils and their products. It describes, the composition of eosinophil granules, mechanisms of eosinophil activation, and eosinophil-related disease processes leading to organ damage. Even though the main clinical signs of canine eosinophilic gastroenteritis, vomiting and diarrhea, are similar to those of other types of gastroenteritis, the clinical response and prognosis are worse for this condition. The clinical signs and diagnostic approach for eosinophilic GI disorders are described and compared between canine and human patients for each region of GI tract, from the esophagus to the colon. Moreover, the current treatments for this syndrome in canine and human patients are summarized and paralleled. The comparative study of canine and human patients with eosinophilic gastroenteritis will advance the understanding of this syndrome in both species and may lead to the development of novel treatment strategies.
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Zaidi AK, Mussarat A, Mishra A. Diagnostic and therapeutic strategies for eosinophilic esophagitis. ACTA ACUST UNITED AC 2014; 11:351-367. [PMID: 25400904 DOI: 10.2217/cpr.14.31] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Eosinophilic esophagitis (EoE) is a recently recognized allergic disorder, characterized by eosophageal dysfunction, accumulation of ≥15 eosinophils/high-powered field, eosinophil microabssess, basal cell hyperplasia, extracellular eosinophilic granules in the esophageal epithelial mucosal biopsy and a lack of response to a 8-week proton pump inhibitor treatment. Despite the increased incidences and considerable progress made in understanding EoE pathogenesis, there are limited diagnostic and therapeutic options available for EoE. Currently, the only criterion for diagnosing EoE is repetitive esophageal endoscopic biopsies and histopathological evaluation. Antigen elimination or corticosteroid therapies are effective therapies for EoE but are expensive and have limitations, if continued in the long term. Hence, there is a great necessity for novel noninvasive diagnostic biomarkers that can easily diagnose EoE and assess effectiveness of therapy. Herein, we have provided an update on key molecules involved in the disease initiation, and progression and proposed novel noninvasive diagnostic molecules and strategies for EoE therapy.
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Affiliation(s)
- Asifa K Zaidi
- Department of Medicine, Section of Pulmonary Diseases Tulane Eosinophilic Disorder Center, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USA
| | - Ahad Mussarat
- Department of Medicine, Section of Pulmonary Diseases Tulane Eosinophilic Disorder Center, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USA
| | - Anil Mishra
- Department of Medicine, Section of Pulmonary Diseases Tulane Eosinophilic Disorder Center, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USA
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34
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Abstract
Eosinophilic esophagitis (EoE) is an allergy-associated disease defined clinically by esophagus-related symptoms in combination with a dense esophageal eosinophilia, both of which are unresponsive to prolonged acid suppression with proton pump inhibitors. Over the last two decades EoE has increasingly been recognized in various geographical areas (mostly industrialized countries) with high socioeconomic development. The prevalence rate is increasing and reaches up to 50 patients per 100,000 inhabitants in some indicator regions. Whether this increased prevalence is due to a real increase in incidence, a result of increased awareness by health care providers or because of the nonfatal nature of EoE adding more and more cases to the patient pool is still a matter of controversy. Several studies have consistently demonstrated a male predominance in EoE, with a male-to-female risk ratio of 3:1. The average age at diagnosis ranges between 30 and 50 years and suggests that EoE is a disease of the middle-aged man. It can affect patients of every race, but the disease is more common among Caucasians. In both children and adults, EoE has been clearly associated with allergies to food and aeroallergens, and most EoE patients present with a personal allergic background (e.g. asthma, rhinoconjunctivitis or oral allergy syndrome). In conclusion, knowledge of epidemiologic parameters of EoE is crucial for identifying risk factors as well as pathogenic mechanisms, planning preventive measures and determining optimal treatment strategies.
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Affiliation(s)
- Petr Hruz
- Department of Gastroenterology, University Hospital Basel, Basel, Switzerland
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35
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Rayapudi M, Rajavelu P, Zhu X, Kaul A, Niranjan R, Dynda S, Mishra A, Mattner J, Zaidi A, Dutt P, Mishra A. Invariant natural killer T-cell neutralization is a possible novel therapy for human eosinophilic esophagitis. Clin Transl Immunology 2014; 3:e9. [PMID: 25505954 PMCID: PMC4232063 DOI: 10.1038/cti.2013.13] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2013] [Revised: 10/30/2013] [Accepted: 10/30/2013] [Indexed: 12/11/2022] Open
Abstract
Eosinophilic esophagitis (EoE) is a recently recognized inflammatory disorder that needs a potential therapeutic strategy. We earlier showed that iNKT cell-deficient mice are protected from allergen-induced EoE. Therefore, we now tested the hypothesis that iNKT cells are induced in the human EoE and is a novel possible target for the treatment of human EoE. Accordingly, we examine number of iNKT cells and eosinophils and expression of iNKT-associated cell surface receptors and chemokines by performing immunofluorescence, qPCR and ELISA in the esophageal biopsies and blood samples of normal subjects (comparison control) and EoE patients. Herein, we show that iNKT cell number, their receptor subcomponents Vα24 and Vβ11 expression, and associated chemokine CXCL16 levels (or expression) are induced significantly in EoE patients compared with normal individuals. In addition, we show that CXCL16 levels (or expression) correlate with the mRNA levels of Vα24 receptor but not well with esophageal eosinophilia in human EoE. Of note, we show that in vivo activation of iNKT cells is sufficient to induce EoE in mice. Furthermore, we show that anti-mCD1d- and anti-hVα24Jα18-neutralizing antibody treatment protects allergen-induced experimental EoE. Taken together, we have shown first time that iNKT cells have a critical pathogenic role in human and experimental EoE. iNKT cell neutralization by humanized anti-CD1d and anti-Vα24Jα18 antibodies might be a novel and potential therapy for human EoE.
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Affiliation(s)
- Madhavi Rayapudi
- Department of Pathology, University of Cincinnati , Cincinnati, OH, USA
| | - Priya Rajavelu
- Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center , Cincinnati, OH , USA
| | - Xiang Zhu
- Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center , Cincinnati, OH, USA
| | - Ajay Kaul
- Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center , Cincinnati, OH, USA
| | - Rituraj Niranjan
- Division of Gastroenterology and Liver Disease, Case Western Reserve University , Cleveland, OH, USA
| | - Scott Dynda
- Division of Gastroenterology and Liver Disease, Case Western Reserve University , Cleveland, OH, USA
| | - Akanksha Mishra
- Biomedical Engineering, Case Western Reserve University , Cleveland, OH, USA
| | - Jochen Mattner
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center ; Cincinnati, OH, USA ; Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander Universität Erlangen-Nürnberg, D-91054 , Erlangen, Germany
| | - Asifa Zaidi
- Pulmonary Diseases, Tulane Eosinophilic Disorder Center, Tulane University School of Medicine , New Orleans, LA, USA
| | - Parmesh Dutt
- Pulmonary Diseases, Tulane Eosinophilic Disorder Center, Tulane University School of Medicine , New Orleans, LA, USA
| | - Anil Mishra
- Pulmonary Diseases, Tulane Eosinophilic Disorder Center, Tulane University School of Medicine , New Orleans, LA, USA
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36
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Kavitt RT, Hirano I. Endoscopic assessment of eosinophilic esophagitis. TECHNIQUES IN GASTROINTESTINAL ENDOSCOPY 2014. [DOI: 10.1016/j.tgie.2013.10.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
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Bussmann C, Straumann A. [Eosinophilic esophagitis: the diagnostic contribution of pathology]. DER PATHOLOGE 2013; 34:110-7. [PMID: 23483314 DOI: 10.1007/s00292-012-1721-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Eosinophilic esophagitis is a chronic, clinically and histologically defined, inflammatory condition of the esophagus. The histological hallmark of eosinophilic esophagitis is a relevant, often patchy infiltration of the esophageal mucosa with eosinophils. In a consensus report a threshold value of approximately 120 eosinophils per mm(2) was arbitrarily fixed as a diagnostic criterion. Noteworthy for the quantification of the eosinophilic infiltration are several technical facts, for instance size and covering extent of the biopsy specimen of the high-power field (hpf) and quality of embedding of biopsy specimens have to be considered. In order to establish the histological diagnosis several additional abnormalities must be included in the assessment and gastrointestinal reflux disease is the main differential diagnosis of eosinophilic esophagitis. Finally it is emphasized that for an affirmative diagnosis of eosinophilic esophagitis, in addition to the histological findings the clinical facts must be included.
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Affiliation(s)
- C Bussmann
- Pathologie, Viollier AG, Basel, Schweiz.
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Yamada Y, Nishi A, Kato M, Toki F, Yamamoto H, Suzuki N, Hirato J, Hayashi Y. Esophagitis with eosinophil infiltration associated with congenital esophageal atresia and stenosis. Int Arch Allergy Immunol 2013; 161 Suppl 2:159-63. [PMID: 23711868 DOI: 10.1159/000350400] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND The esophagus is physiologically devoid of eosinophils, so their presence would suggest some underlying pathology. The prevalence of eosinophilic esophagitis (EoE) has steadily increased in Western countries. Previous studies have described EoE in association with congenital esophageal atresia (CEA), which is the most common congenital anomaly of the esophagus. However, the association remains unclear. METHODS We performed a retrospective histological analysis examining for eosinophil infiltration in the esophagus of patients with CEA following surgical repair or congenital esophageal stenosis (CES) who underwent esophageal biopsy or surgical resection in our hospital between 2005 and 2012. RESULTS There were 6 patients with CEA following surgical repair or CES who had eosinophil-dominant infiltration in the esophagus. All had associated allergic disorders, including food allergies in 4. Moreover, all except for one fulfilled the histological criteria of EoE. Impairment of eosinophil infiltration and symptomatic improvement were observed in those treated with a proton pump inhibitor (PPI), either alone or in combination with steroids after esophageal dilatation. CONCLUSIONS These findings suggest that CEA repair or CES in conjunction with allergic conditions and coexisting gastroesophageal reflux disease (GERD) may induce greater esophageal eosinophilic inflammation. In addition, esophageal dilatation followed by PPI treatment, alone or with steroids, may be a therapeutic strategy that can provide symptomatic relief by reducing eosinophilic inflammation in esophageal strictures or GERD associated with CEA or CES.
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Affiliation(s)
- Yoshiyuki Yamada
- Division of Allergy and Immunology, Gunma Children's Medical Center, Shibukawa, Japan.
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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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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: 831] [Impact Index Per Article: 69.3] [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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41
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Hruz PL, Straumann A. Eosinophil-associated gastrointestinal disorders. Clin Immunol 2013. [DOI: 10.1016/b978-0-7234-3691-1.00059-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Abstract
Eosinophilic oesophagitis (EoE) was first described in the early 1990s. Although initially reported to be a rare entity, EoE has rapidly become a regularly diagnosed disease with a prevalence of approximately 1 in 2,000 individuals in the USA and Europe. The disease is characterized by a combination of oesophageal dysfunction and predominant eosinophilic infiltration of the oesophageal tissue. At diagnosis, other diseases that can be associated with oesophageal eosinophilic infiltration must be ruled out. Children with EoE present with a wide variety of symptoms, whereas adults mostly present with dysphagia for solid food and chest pain. Histologic features of EoE resemble those of T-helper type 2 inflammation. Endoscopy should be carried out to establish the diagnosis, but endoscopic abnormalities are not pathognomonic for EoE and the examination might not show histologic abnormality. Treatment modalities for EoE include drugs (corticosteroids, PPIs, antiallergic and biologic agents), hypoallergenic diets and oesophageal dilatation for strictures that are unresponsive to medical therapy. Unresolved eosinophilic inflammation leads to the formation of oesophageal strictures, which probably increase the risk of food bolus impactions. To date, long-term strategies for the therapeutic management of this chronic inflammatory disease remain poorly defined.
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Arora AA, Weiler CR, Katzka DA. Eosinophilic esophagitis: allergic contribution, testing, and management. Curr Gastroenterol Rep 2012; 14:206-15. [PMID: 22422505 DOI: 10.1007/s11894-012-0254-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Both basic science and clinical data indicate a strong role for allergy as a cause of eosinophilic esophagitis. As a result, one of the desired goals of therapy is identification and elimination of food antigens that trigger the allergic inflammatory pathway. Traditional methods for identification of causative food antigens include induction of symptoms with exposure to the antigen, demonstration of serum IgE antibodies against antigens and induction of immediate (IgE) or delayed (Th2) reactions against dermal instillation of antigens. Although some data support the use of these tests in patients with eosinophilic esophagitis, they are limited in this disease. This limitation results from an inability to provoke recognizable symptoms and a lack of concordance between allergies identified in the skin and the blood with the antigens that trigger esophageal disease. As a result, allergy therapy in eosinophilic esophagitis consists of global elimination of food antigens with an elemental diet or exclusion of the most common antigens. As compliance is difficult with these strategies, the mainstay of allergy therapy in eosinophilic esophagitis has become the use of medications that blunt the allergic pathway such as steroids with a future aimed toward more specific inhibitors of this pathway in eosinophilic esophagitis specifically.
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Affiliation(s)
- Amindra A Arora
- Department of Gastroenterology and Hepatology, Mayo Foundation, Rochester, MN 55905, USA.
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Jawairia M, Shahzad G, Mustacchia P. Eosinophilic gastrointestinal diseases: review and update. ISRN GASTROENTEROLOGY 2012; 2012:463689. [PMID: 22792476 PMCID: PMC3389712 DOI: 10.5402/2012/463689] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/11/2012] [Accepted: 05/13/2012] [Indexed: 12/16/2022]
Abstract
Eosinophilic gastrointestinal disorders (EGIDs) are a progressively more frequent diverse group of intestinal diseases. The intention of this paper is to present the newest developments in the care of patients with EGIDs and to sum up a rising literature defining the clinical features and mechanistic elements of eosinophils and their intricate associations with the gastrointestinal tract. Clinicians ought to stay sensitive to EGIDs as a diagnostic likelihood for patients with general gastrointestinal symptoms. Further research is warranted to establish various methods leading to dysfunction coupled with eosinophilic gastrointestinal inflammation.
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Affiliation(s)
- Mahreema Jawairia
- Department of Medicine, Nassau University Medical Center, 2201 Hempstead Turnpike, East Meadow, NY 11554, USA
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45
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Joo MK, Park JJ, Kim SH, Kim KH, Jung W, Yun JW, Lee BJ, Kim JH, Yeon JE, Kim JS, Byun KS, Lee SW, Bak YT. Prevalence and endoscopic features of eosinophilic esophagitis in patients with esophageal or upper gastrointestinal symptoms. J Dig Dis 2012; 13:296-303. [PMID: 22624552 DOI: 10.1111/j.1751-2980.2012.00589.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE This study was aimed to evaluate the prevalence of eosinophilic esophagitis (EoE) among patients with esophageal or upper gastrointestinal (UGI) symptoms. METHODS Patients with esophageal or UGI symptoms including dysphagia food impaction, acid regurgitation, heartburn, chest pain, epigastric pain, nausea and/or vomiting were prospectively collected. The enrolled patients responded to a symptomatic questionnaire and underwent an esophagogastroduodenoscopy and esophageal biopsies. Supportive endoscopic findings of EoE (ring-like appearance, liner furrows, whitish papules, shearing or friability) were recorded. EoE was diagnosed if patients had chronic UGI or esophageal symptoms, the esophageal biopsy showed ≥15 eosinophils/high-power field and were unresponsive to 2-3 weeks of proton pump inhibitors. RESULTS A total of 122 patients were enrolled and supportive endoscopic findings were found in 31 (25.4%) patients [whitish papules: 19 (15.6%), ring-like appearance: 8 (6.6%), linear furrows: 5 (4.1%)]. One patient had a simultaneous ring-like appearance and linear furrows. EoE was diagnosed in 8 (6.6%) patients and supportive endoscopic findings and past history of gastroesophageal reflux disease, allergic rhinitis and atopic dermatitis were more common in EoE positive than EoE negative patients. The diagnostic yield of endoscopic findings was 40.0% (2/5) in linear furrows, 25.0% (2/8) in ring-like appearance and 15.8% (3/19) in whitish papules. CONCLUSION Prevalence of EoE among patients with esophageal or UGI symptoms was 6.6%. Linear furrows and ring-like appearance had a relatively high diagnostic value.
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Affiliation(s)
- Moon Kyung Joo
- Department of Internal Medicine, Guro Hospital, Korea University College of Medicine, Seoul, Korea
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Monnerat MMC, Lemme EMDO. Eosinophilic esophagitis: manometric and pHmetric findings. ARQUIVOS DE GASTROENTEROLOGIA 2012; 49:113-7. [DOI: 10.1590/s0004-28032012000200004] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/18/2011] [Accepted: 02/28/2012] [Indexed: 01/07/2023]
Abstract
CONTEXT: Eosinophilic esophagitis is an entity characterized by an esophageal inflammatory infiltrate of eosinophils, manifested by dysphagia, intermittent food impactions and symptoms similar to gastroesophageal reflux disease (GERD), that predominantly affects young adults. There may be association of eosinophilic esophagitis with GERD, and motor abnormalities have been described. OBJECTIVE: The main objectives of this study are to describe the findings at esophageal manometry and pH monitoring in patients with eosinophilic esophagitis. METHODS: Cross-sectional study of 20 patients with a diagnosis of eosinophilic esophagitis, submitted to esophageal manometry and 24h pH monitoring. Were analysed the manometric changes and the presence of abnormal reflux on pH monitoring. RESULTS: Twenty patients (15 men, 5 women) had a mean age of 29 years. Motility disorders were found in 25% (5/20) patients with ineffective esophageal motility being the most common finding. pH monitoring revealed abnormal reflux on 25%, without any relationship with manometric findings. CONCLUSIONS: Manometric abnormalities were observed in 25% of patients and abnormal reflux on pH monitoring also in 25%. This study showed no relationship between abnormal reflux and the presence of manometric changes.
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Mavi P, Rajavelu P, Rayapudi M, Paul RJ, Mishra A. Esophageal functional impairments in experimental eosinophilic esophagitis. Am J Physiol Gastrointest Liver Physiol 2012; 302:G1347-55. [PMID: 22361731 PMCID: PMC3378164 DOI: 10.1152/ajpgi.00013.2012] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Eosinophilic esophagitis (EoE) is an emerging chronic esophageal disease. Despite the increasing diagnosis of EoE globally, the causes of EoE and other esophageal eosinophilic disorders are not clearly understood. EoE pathology includes accumulation of inflammatory cells (e.g., eosinophils, mast cells), characteristic endoscopic features (e.g., furrows, the formation of fine concentric mucosal rings, exudates), and functional impairments (e.g., esophageal stricture, dysmotility). We hypothesized that the esophageal structural pathology and functional impairments of EoE develop as a consequence of the effector functions of the accumulated inflammatory cells. We analyzed eosinophils (anti-major basic protein immunostaining), esophageal stricture (X-ray barium swallowing), and esophageal motility (isometric force) in two established transgenic murine models of EoE (CD2-IL-5 and rtTA-CC10-IL-13) and a novel eosinophil-deficient model (ΔdblGATA/CD2-IL-5). Herein, we show the following: 1) CD2-IL-5 and doxycycline (DOX)-induced rtTA-CC10-IL-13 mice have chronic eosinophilic and mast cell esophageal inflammation; 2) eosinophilic esophageal inflammation promotes esophageal stricture in both transgenic murine models; 3) the eosinophil-deficient ΔdblGATA/CD-2-IL-5 mice were protected from the induction of stricture, whereas the eosinophil-competent CD2-IL-5 mice develop esophageal stricture; 4) esophageal stricture is not reversible in DOX-induced rtTA-CC10-IL-13 mice (8 wk DOX followed by 8 wk no-DOX); and 5) IL-5 transgene-induced (CD2-IL-5) EoE evidences esophageal dysmotility (relaxation and contraction) that is independent of the eosinophilic esophageal inflammation: CD2-IL-5 and ΔdblGATA/CD2-IL-5 mice have comparable esophageal dysmotility. Collectively, our present study directly implicates chronic eosinophilic inflammation in the development of the esophageal structural impairments of experimental EoE.
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Affiliation(s)
- Parm Mavi
- 1Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics and
| | - Priya Rajavelu
- 1Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics and
| | - Madhavi Rayapudi
- 1Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics and
| | - Richard J. Paul
- 2Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, University of Cincinnati, Cincinnati, Ohio
| | - Anil Mishra
- 1Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics and
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Straumann A, Aceves SS, Blanchard C, Collins MH, Furuta GT, Hirano I, Schoepfer AM, Simon D, Simon HU. Pediatric and adult eosinophilic esophagitis: similarities and differences. Allergy 2012; 67:477-90. [PMID: 22313241 DOI: 10.1111/j.1398-9995.2012.02787.x] [Citation(s) in RCA: 183] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/27/2011] [Indexed: 12/19/2022]
Abstract
Early in the 1990s, several case series described adults suffering from dysphagia and children with refractory reflux symptoms, both accompanied by an eosinophil-predominant infiltration, thereby conclusively distinguishing it from gastroesophageal reflux disease. Eosinophilic esophagitis (EoE) was recognized as its own entity in the adult and in the pediatric literature. In the last decade, evidence has accumulated that EoE represents a T-helper (Th)2-type inflammatory disease. Remodeling of the esophagus is a hallmark of EoE, leading to esophageal dysfunction and bolus impaction. Familial occurrence and disease association with single-nucleotide polymorphisms underscore the influence of genetics in this disease. Eosinophilic esophagitis may affect individuals at any age, although the clinical presentation is highly age dependent. There is a significant allergic bias in the EoE population, with the majority of patients having concurrent allergic rhinitis, asthma, eczema, and/or a history of atopy. One noteworthy difference is that in children, EoE seems to be primarily a food antigen-driven disease, whereas in adults, mainly aeroallergen sensitization has been observed. Treatment modalities for EoE include the 3Ds: drugs, diet, and dilation. The crucial question of whether adult and pediatric EoE are different phenotypes of one single entity or whether we are confronted with two different diseases is still open. Here, we review similarities and differences between EoE in adults and children.
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Affiliation(s)
- A. Straumann
- Department of Gastroenterology; University Hospital Basel; Basel; Switzerland
| | - S. S. Aceves
- Division of Allergy and Immunology; Rady Children's Hospital; University of California, San Diego; San Diego; CA; USA
| | | | - M. H. Collins
- Division of Pathology and Laboratory Medicine; Cincinnati Children's Hospital Medical Center; Cincinnati; OH; USA
| | | | - I. Hirano
- Northwestern University School of Medicine; Chicago; IL; USA
| | - A. M. Schoepfer
- Department of Gastroenterology and Hepatology; University Hospital Lausanne; Lausanne; Switzerland
| | - D. Simon
- Department of Dermatology; University Hospital Bern; Bern; Switzerland
| | - H.-U. Simon
- Institute of Pharmacology; University of Bern; Bern; Switzerland
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Lucendo AJ, De Rezende LC, Jiménez-Contreras S, Yagüe-Compadre JL, González-Cervera J, Mota-Huertas T, Guagnozzi D, Angueira T, González-Castillo S, Arias A. Montelukast was inefficient in maintaining steroid-induced remission in adult eosinophilic esophagitis. Dig Dis Sci 2011; 56:3551-8. [PMID: 21674173 DOI: 10.1007/s10620-011-1775-y] [Citation(s) in RCA: 103] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2011] [Accepted: 06/01/2011] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS Leukotriene D4 is produced by and functions as a chemotactic factor for eosinophils. Eosinophilic esophagitis (EoE) is characterized by esophageal eosinophilic infiltration, determining structural changes and dismotility symptoms. Montelukast, a selective leukotriene D4 receptor antagonist, has gained increasing consideration as a therapeutic agent for EoE. However, limited available information has shown that montelukast is not effective in reducing eosinophilic infiltration. Our paper aims at evaluating whether montelukast could be consider as a steroid-sparing therapy by assessing its efficacy in maintaining both clinical and histopathological remission achieved after topical corticosteroids in adult EoE patients. METHODS Eleven consecutively diagnosed adult EoE patients were prospectively studied. Esophageal biopsies were obtained before and after a 6-month treatment with fluticasone propionate 400 μg/twice a day. Immediately after that, montelukast 10 mg/day was instituted. A new endoscopy was foreseen after a new 3-month period, or as soon as the patients presented esophageal symptoms. Symptoms were assessed by using a questionnaire before and after fluticasone propionate treatment and after montelukast therapy. RESULTS Eosinophils density into the esophageal epithelium and lamina propria was significantly reduced after a 6-month treatment with topical steroids (P = 0.003) and increased to levels similar to baseline level into the first 3 months after treatment with montelukast. Baseline symptom scores significantly decreased after treatment with topical steroids (P = 0.003) and increased again after montelukast therapy, but baseline levels improved. CONCLUSIONS Montelukast was not efficient in maintaining the histopathological or clinical response achieved by topical steroids in adult EoE patients.
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Affiliation(s)
- Alfredo J Lucendo
- Department of Gastroenterology, Hospital General de Tomelloso, Vereda de Socuéllamos, s/n, 13700, Tomelloso, Ciudad Real, Spain.
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The development of a sensitive and specific ELISA for mouse eosinophil peroxidase: assessment of eosinophil degranulation ex vivo and in models of human disease. J Immunol Methods 2011; 375:138-47. [PMID: 22019643 DOI: 10.1016/j.jim.2011.10.002] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2011] [Revised: 10/03/2011] [Accepted: 10/05/2011] [Indexed: 12/11/2022]
Abstract
Mouse models of eosinophilic disorders are often part of preclinical studies investigating the underlying biological mechanisms of disease pathology. The presence of extracellular eosinophil granule proteins in affected tissues is a well established and specific marker of eosinophil activation in both patients and mouse models of human disease. Unfortunately, assessments of granule proteins in the mouse have been limited by the availability of specific antibodies and a reliance on assays of released enzymatic activities that are often neither sensitive nor eosinophil specific. The ability to detect immunologically and quantify the presence of a mouse eosinophil granule protein in biological fluids and/or tissue extracts was achieved by the generation of monoclonal antibodies specific for eosinophil peroxidase (EPX). This strategy identified unique pairs of antibodies with high avidity to the target protein and led to the development of a unique sandwich ELISA for the detection of EPX. Full factorial design was used to develop this ELISA, generating an assay that is eosinophil-specific and nearly 10 times more sensitive than traditional OPD-based detection methods of peroxidase activity. The added sensitivity afforded by this novel assay was used to detect and quantify eosinophil degranulation in several settings, including bronchoalveolar fluid from OVA sensitized/challenged mice (an animal model of asthma), serum samples derived from peripheral blood recovered from the tail vasculature, and from purified mouse eosinophils stimulated ex vivo with platelet activating factor (PAF) and PAF + ionomycin. This ability to assess mouse eosinophil degranulation represents a specific, sensitive, and reproducible assay that fulfills a critical need in studies of eosinophil-associated pathologies in mice.
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