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Dadkhah A, Mounesi Sohi AS, Rakhshankhah N, Mirsardoo A. A case report of eosinophilic jejunal enteritis with spared stomach presenting as abdominal pain. Radiol Case Rep 2024; 19:881-885. [PMID: 38188948 PMCID: PMC10770494 DOI: 10.1016/j.radcr.2023.10.053] [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] [Received: 10/12/2023] [Accepted: 10/20/2023] [Indexed: 01/09/2024] Open
Abstract
Eosinophilic gastroenteritis (EoGE) is a group of infrequent conditions that arise from the accumulation of eosinophils in the gastrointestinal (GI) tract without any secondary causes of eosinophilia. Most cases of EoGE cases show involvement of different parts of the GI tract. Herein, we report a case of EoGE with the sole involvement of Jejunum. A 57-year-old male patient presented to our center with a chief complaint of acute abdominal pain. The patient had experienced chronic abdominal pain and intermittent diarrhea for several years, but he presented to the emergency department with severe acute flank pain. The patient was first diagnosed with renal stone and treated accordingly. However, the computed tomography (CT) scan also showed other incidental findings related to his chronic abdominal pain from several years ago, including mesenteric infiltration which shows fluid appearance in some areas, mild wall thickening, and mucosal edema of the duodenum and jejunal loops with normal appearance of the ileum. Complete blood count (CBC) showed increased eosinophil (15.5%) and decreased lymphocytes (13.1%) percent. Pathological examination of enteroscopy samples of jejunum showed a mild increase in the number of eosinophils in lamina propria. Neither parasites nor granuloma was detected. However, no such changes were found in other parts of the GI tracts. Based on pathological examination, the patient was diagnosed with eosinophilic enteritis of the jejunum. EoGE does not typically involve a specific part of the GI and generally affects both the stomach and intestine. This study reported the first case of EoGE where only the jejunal part of the intestine was involved and other parts of the GI tract were spared.
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Affiliation(s)
- Adeleh Dadkhah
- Department of Radiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | | | - Nima Rakhshankhah
- Department of Radiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Ali Mirsardoo
- Department of Radiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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Pavel C, Diculescu MM, Stepan AE, Constantinescu G, Sandru V, Ţieranu CG, Tomescu L, Constantinescu A, Patoni C, Plotogea OM, Ilie M. Considering Histologic Remission in Ulcerative Colitis as a Long-Term Target. J Clin Med 2024; 13:289. [PMID: 38202296 PMCID: PMC10780018 DOI: 10.3390/jcm13010289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 12/17/2023] [Accepted: 12/31/2023] [Indexed: 01/12/2024] Open
Abstract
Monitoring disease activity in inflammatory bowel disease (IBD) is challenging since clinical manifestations do not represent reliable surrogates for an accurate reflection of the inflammatory burden. Endoscopic remission had been the most significant endpoint target in the last years; nevertheless, a remarkable proportion of patients continue to relapse despite a normal-appearing mucosa, highlighting that endoscopy may underestimate the true extent of the disease. A subtle hint of the importance that histology plays in the long-term course of the disease has been endorsed by the STRIDE-II consensus, which recommends considering histologic healing for ulcerative colitis (UC), even though it is not stated to be a compulsory formal target. It is a continuum-changing paradigm, and it is almost a certainty that in the near future, histologic healing may become the new formal target for ulcerative colitis. It must be emphasized that there is great heterogeneity in defining histological remission, and the main criteria or cut-off values for inflammatory markers are still in an ill-defined area. The complexity of some histologic scores is a source of confusion among clinicians and pathologists, leading to low adherence in clinical practice when it comes to a homogenous histopathological report. Therefore, a standardized and more practical approach is urgently needed.
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Affiliation(s)
- Christopher Pavel
- Department of Gastroenterology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.P.); (M.M.D.); (G.C.); (V.S.); (C.G.Ţ.); (A.C.); (C.P.); (M.I.)
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania
| | - Mircea Mihai Diculescu
- Department of Gastroenterology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.P.); (M.M.D.); (G.C.); (V.S.); (C.G.Ţ.); (A.C.); (C.P.); (M.I.)
- Department of Gastroenterology, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Alex-Emilian Stepan
- Department of Pathology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Gabriel Constantinescu
- Department of Gastroenterology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.P.); (M.M.D.); (G.C.); (V.S.); (C.G.Ţ.); (A.C.); (C.P.); (M.I.)
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania
| | - Vasile Sandru
- Department of Gastroenterology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.P.); (M.M.D.); (G.C.); (V.S.); (C.G.Ţ.); (A.C.); (C.P.); (M.I.)
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania
| | - Cristian George Ţieranu
- Department of Gastroenterology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.P.); (M.M.D.); (G.C.); (V.S.); (C.G.Ţ.); (A.C.); (C.P.); (M.I.)
- Department of Gastroenterology, “Elias” Emergency University Hospital, 011461 Bucharest, Romania
| | - Luiza Tomescu
- Department of Pathology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
- Oncology Institute “Prof. Dr. Alexandru Trestioreanu”, 022328 Bucharest, Romania
| | - Alexandru Constantinescu
- Department of Gastroenterology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.P.); (M.M.D.); (G.C.); (V.S.); (C.G.Ţ.); (A.C.); (C.P.); (M.I.)
- Department of Gastroenterology, Emergency University Hospital, 050098 Bucharest, Romania
| | - Cristina Patoni
- Department of Gastroenterology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.P.); (M.M.D.); (G.C.); (V.S.); (C.G.Ţ.); (A.C.); (C.P.); (M.I.)
- Department of Gastroenterology, Central Military Emergency Hospital “Dr. Carol Davila”, 010825 Bucharest, Romania
| | - Oana-Mihaela Plotogea
- Department of Gastroenterology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.P.); (M.M.D.); (G.C.); (V.S.); (C.G.Ţ.); (A.C.); (C.P.); (M.I.)
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania
| | - Madalina Ilie
- Department of Gastroenterology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.P.); (M.M.D.); (G.C.); (V.S.); (C.G.Ţ.); (A.C.); (C.P.); (M.I.)
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania
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Kinoshita Y, Sanuki T. Review of Non-Eosinophilic Esophagitis-Eosinophilic Gastrointestinal Disease (Non-EoE-EGID) and a Case Series of Twenty-Eight Affected Patients. Biomolecules 2023; 13:1417. [PMID: 37759817 PMCID: PMC10526434 DOI: 10.3390/biom13091417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2023] [Revised: 09/07/2023] [Accepted: 09/18/2023] [Indexed: 09/29/2023] Open
Abstract
Eosinophilic gastrointestinal disease (EGID) is divided into eosinophilic esophagitis (EoE) and non-eosinophilic esophagitis eosinophilic gastrointestinal disease (non-EoE-EGID) based on the involved gastrointestinal segments. Reports regarding non-EoE-EGID are limited, in part because of its rarity. The present study was performed to review non-EoE-EGID, including its pathogenesis, diagnosis, treatment, and prognosis. Additionally, details regarding 28 cases of non-EoE-EGID recently diagnosed at our Japanese tertial medical center are presented and compared with 20 EoE cases diagnosed during the same period at the same medical center. Comparisons of the two groups clarified differences regarding age- and gender-dependent prevalence between the two conditions, and also showed that systemic involvement and disease severity were greater in the non-EoE-EGID patients. Notably, diagnosis of non-EoE-EGID is difficult because of its lack of specific or characteristic symptoms and endoscopic findings. The clinical characteristics of EoE and non-EoE-EGID differ in many ways, while they also share several genetic, clinical, laboratory, and histopathological features.
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Affiliation(s)
- Yoshikazu Kinoshita
- Department of Medicine and Gastroenterology, Hyogo Prefectural Harima-Himeji General Medical Center, Himeji 670-8560, Japan
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Pérez de Arce E, Quera R, Quigley EMM. The Dilemma of Persistent Irritable Bowel Syndrome Symptoms in Patients with Quiescent Inflammatory Bowel Disease. Gastroenterol Clin North Am 2021; 50:689-711. [PMID: 34304795 DOI: 10.1016/j.gtc.2021.03.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Irritable bowel syndrome and inflammatory bowel disease differ in their natural evolution, etiopathogenesis, diagnostic criteria, and therapeutic approach. However, recent evidence has suggested some similarities in mechanisms underlying symptom development and progression. There is a relevant role for alterations in the microbiome-brain-gut axis in both diseases. The presence of irritable bowel syndrome symptoms in patients with quiescent inflammatory bowel disease is common in clinical practice. To determine the cause of irritable bowel syndrome symptoms in patients with quiescent inflammatory bowel disease is a clinical challenge. This review aims to illustrate possible causes and solutions for these patients.
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Affiliation(s)
- Edith Pérez de Arce
- Department of Medicine, Division of Gastroenterology, Hospital Clínico Universidad de Chile, Dr. Carlos Lorca Tobar 999, Independencia, Región Metropolitana, Santiago, Chile
| | - Rodrigo Quera
- Division of Gastroenterology, Inflammatory Bowel Disease Program, Clínica Universidad de los Andes, Estoril 450, Las Condes, Región Metropolitana, Santiago, Chile
| | - Eamonn M M Quigley
- Division of Gastroenterology and Hepatology, Lynda K and David M Underwood Center for Digestive Disorders, Houston Methodist Hospital, Weill Cornell Medical College, Houston, TX, USA.
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Magrone T, Magrone M, Jirillo E. Eosinophils, a Jack of All Trades in Immunity: Therapeutic Approaches for Correcting Their Functional Disorders. Endocr Metab Immune Disord Drug Targets 2021; 20:1166-1181. [PMID: 32148205 DOI: 10.2174/1871530320666200309094726] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Revised: 11/28/2019] [Accepted: 01/09/2020] [Indexed: 01/13/2023]
Abstract
BACKGROUND AND OBJECTIVE Eosinophils are primitive myeloid cells derived from bonemarrow precursors and require the intervention of interleukin (IL)-5 for their survival and persistence in blood and tissues. Under steady-state conditions, they contribute to immune regulation and homeostasis. Under pathological circumstances, eosinophils are involved in host protection against parasites and participate in allergy and inflammation. DISCUSSION Mostly, in asthma, eosinophils provoke airway damage via the release of granule contents and IL-13 with mucus hypersecretion and differentiation of goblet cells. Then, tissue remodeling follows with the secretion of transforming growth factor-β. Eosinophils are able to kill helminth larvae acting as antigen-presenting cells with the involvement of T helper (h)-2 cells and subsequent antibody response. However, they also exert pro-worm activity with the production of suppressive cytokine (IL- 10 and IL-4) and inhibition of nitric oxide. Eosinophils may play a pathogenic role in the course of chronic and autoimmune disease, e.g., inflammatory bowel disease and eosinophilic gastroenteritis, regulating Th2 responses and promoting a profibrotic effect. In atopic dermatitis, eosinophils are commonly detected and may be associated with disease severity. In cutaneous spontaneous urticaria, eosinophils participate in the formation of wheals, tissue remodeling and modifications of vascular permeability. With regard to tumor growth, it seems that IgE can exert anti-neoplastic surveillance via mast cell and eosinophil-mediated cytotoxicity, the so-called allergo-oncology. From a therapeutic point of view, monoclonal antibodies directed against IL-5 or the IL-5 receptors have been shown to be very effective in patients with severe asthma. Finally, as an alternative treatment, polyphenols for their anti-inflammatory and anti-allergic activities seem to be effective in reducing serum IgE and eosinophil count in bronchoalveolar lavage in murine asthma. CONCLUSION Eosinophils are cells endowed with multiple functions and their modulation with monoclonal antibodies and nutraceuticals may be effective in the treatment of chronic disease.
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Affiliation(s)
- Thea Magrone
- Department of Basic Medical Sciences, Neuroscience and Sensory Organs, School of Medicine, University of Bari "Aldo Moro", Bari, Italy
| | - Manrico Magrone
- Department of Basic Medical Sciences, Neuroscience and Sensory Organs, School of Medicine, University of Bari "Aldo Moro", Bari, Italy
| | - Emilio Jirillo
- Department of Basic Medical Sciences, Neuroscience and Sensory Organs, School of Medicine, University of Bari "Aldo Moro", Bari, Italy
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Pérez de Arce E, Quera R, Beltrán CJ, Madrid AM, Nos P. Irritable Bowel Syndrome in Inflammatory Bowel Disease. Synergy in alterations of the gut-brain axis? GASTROENTEROLOGIA Y HEPATOLOGIA 2021; 45:66-76. [PMID: 34023477 DOI: 10.1016/j.gastrohep.2021.02.022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Revised: 02/02/2021] [Accepted: 02/15/2021] [Indexed: 10/21/2022]
Abstract
The presence of digestive symptoms associated with irritable bowel syndrome (IBS) in patients with inflammatory bowel disease (IBD) in remission is a topic of growing interest. Although there is heterogeneity in clinical studies regarding the use of IBD remission criteria and the diagnosis of IBS, the available data indicate that the IBD-IBS overlap would affect up to one third of patients in remission, and they agree on the finding of a negative impact on the mental health and quality of life of the individuals who suffer from it. The pathophysiological bases that would explain this potential overlap are not completely elucidated; however, an alteration in the gut-brain axis associated with an increase in intestinal permeability, neuroimmune activation and dysbiosis would be common to both conditions. The hypothesis of a new clinical entity or syndrome of "Irritable Inflammatory Bowel Disease" or "Post-inflammatory IBS" is the subject of intense investigation. The clinical approach is based on certifying the remission of IBD activity and ruling out other non-inflammatory causes of potentially treatable persistent functional digestive symptoms. In the case of symptoms associated with IBS and in the absence of sufficient evidence, comprehensive and personalized management of the clinical picture (dietary, pharmacological and psychotherapeutic measures) should be carried out, similar to a genuine IBS.
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Affiliation(s)
- Edith Pérez de Arce
- Departamento de Medicina Interna, Servicio de Gastroenterología, Hospital Clínico Universidad de Chile, Santiago, Chile.
| | - Rodrigo Quera
- Programa Enfermedad Inflamatoria Intestinal, Departamento de Gastroenterología, Clínica Universidad de los Andes, Santiago, Chile
| | - Caroll J Beltrán
- Laboratorio de Inmuno-gastroenterología, Servicio de Gastroenterología, Hospital Clínico Universidad de Chile, Santiago, Chile
| | - Ana María Madrid
- Departamento de Medicina Interna, Servicio de Gastroenterología, Hospital Clínico Universidad de Chile, Santiago, Chile
| | - Pilar Nos
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Medicina Digestiva, Hospital Universitari i Politècnic La Fe, Valencia, España
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Li J, Ren S, Li M, Bi J, Yang G, Li E. Paeoniflorin protects against dextran sulfate sodium (DSS)-induced colitis in mice through inhibition of inflammation and eosinophil infiltration. Int Immunopharmacol 2021; 97:107667. [PMID: 33887576 DOI: 10.1016/j.intimp.2021.107667] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Revised: 04/06/2021] [Accepted: 04/07/2021] [Indexed: 12/12/2022]
Abstract
Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) that causes inflammation and ulcers in the digestive tract. The treatment commonly includes anti-inflammatory agents like 5-aminosalicylic acid or corticosteroids or biologics for people with UC who are no longer responding to corticosteroids. The radices of Paeonia lactiflora Pall. or similar plants of the Paeonia genus have been used in Chinese medicine to treat certain diseases that resemble the symptoms of UC. Paeoniflorin, a terpenoid glycoside, is a major active component for the anti-inflammatory and antitumor activity. In this study, we evaluated the therapeutic effect of paeoniflorin (PF) against dextran sulfate sodium (DSS)-induced colitis in mice and found that PF exhibited protective activity against colitis. PF treatment suppressed NF-κB pathway activation, resulting down regulation of pro-inflammatory factor expression. In addition, we detected reduction in eosinophil-related chemokine gene expression and eosinophil infiltration. The treatment also reversed Treg cell population suppression. Although PF treatment did not block COX2 induction, the compound weakly inhibited COX2 activity in an enzymatic assay. Taken together, PF exerts its therapeutic activity against UC through inhibition of inflammation and eosinophil infiltration.
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Affiliation(s)
- Jingjing Li
- Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, China; State Key Laboratory of Pharmaceutical Biotechnology, Medical School, Nanjing University, China; Jiangsu Topcel Biological Technology Co, Ltd, Nanjing, China
| | - Suiyuan Ren
- Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, China
| | - Meng Li
- Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, China
| | - Jingai Bi
- Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, China
| | - Guang Yang
- Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China
| | - Erguang Li
- Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, China; State Key Laboratory of Pharmaceutical Biotechnology, Medical School, Nanjing University, China; Shenzhen Research Institute of Nanjing University, Shenzhen, China.
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Tozlu M, Cash B, Younes M, Ertan A. Dilemma in post-IBD patients with IBS-D symptoms: A 2020 overview. Expert Rev Gastroenterol Hepatol 2021; 15:5-8. [PMID: 32990090 DOI: 10.1080/17474124.2021.1829469] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Inflammatory bowel disease (IBD) patients in apparent clinical remission who present with irritable bowel syndrome (IBS)-like symptoms pose a diagnostic and therapeutic dilemma that is called post-IBD IBS. When associated with a diarrheal IBS presentation, this clinical syndrome is known as post-IBD IBS-D. AREAS COVERED We review and describe the literature regarding the clinical overlap of IBD and IBS. We discuss prevalent theories regarding the pathophysiology of post-IBD IBS-D and whether this presentation represents coincident inherent IBS-D, IBS-D triggered by IBD, or an even more subtle level of IBD activity that is unrecognized by available laboratory modalities. We also discuss observations that post-IBD IBS-D patients harbor significantly increased colon mucosal eosinophils and appear to respond to a GI-hypoallergenic diet and budesonide therapy. EXPERT OPINION The symptoms overlap between IBD and IBS complicates diagnosis and subsequent management of patients with post-IBD IBS-D. In addition to current theories regarding the pathophysiology of this condition such as alterations in mucosal inflammation, the microbiota, mucosal permeability, and gut-brain interactions. This new avenue of eosinophilic colopathy and therapy directed toward food-derived immune response in patients with post-IBD IBS-D deserves additional investigation.
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Affiliation(s)
- Mukaddes Tozlu
- Gastroenterology, Hepatology and Nutrition Section, Ertan Digestive Disease Center, University of Texas McGovern Medical School , Houston, TX, USA
| | - Brooks Cash
- Gastroenterology, Hepatology and Nutrition Section, Ertan Digestive Disease Center, University of Texas McGovern Medical School , Houston, TX, USA
| | - Mamoun Younes
- Gastroenterology, Hepatology and Nutrition Section, Ertan Digestive Disease Center, University of Texas McGovern Medical School , Houston, TX, USA
| | - Atilla Ertan
- Gastroenterology, Hepatology and Nutrition Section, Ertan Digestive Disease Center, University of Texas McGovern Medical School , Houston, TX, USA
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Arias Á, Lucendo AJ. Epidemiology and risk factors for eosinophilic esophagitis: lessons for clinicians. Expert Rev Gastroenterol Hepatol 2020; 14:1069-1082. [PMID: 32749898 DOI: 10.1080/17474124.2020.1806054] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
INTRODUCTION The rapid expansion in the epidemiology of eosinophilic esophagitis (EoE) is being documented, along with cumulative research assessing environmental exposures associated with EoE and susceptibility due to genetic variants. AREAS COVERED Incidence rates for EoE of 5-10 new cases per 100,000 inhabitants annually have shown an increase in recent reports of up to 20 in some countries; the highest prevalence being reported for Europe and North America, where EoE now affects more than 1 out of 1,000 people. EoE has been shown to be associated with several disorders, Th2-mediated atopies being the most common. Patients with EoE exhibit increased frequency of asthma, allergic rhinitis and eczema, and EoE has been considered as a late component of the atopic march. Risk variants in TSLP, CAPN14 and LRCC32 genes, among others, have all been related to EoE, and interact with prenatal and early life exposure potentially modifying abundance and composition of gut microbiome. Dysregulated interactions between bacteria and mucosal immunity emerge as leading causes of EoE. EXPERT OPINION The expanding epidemiology of EoE, the resources needed and subsequent increasing healthcare costs require additional effort to optimize cost-effective management and unveil mechanisms that enhance the development of future preventive strategies.
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Affiliation(s)
- Ángel Arias
- Research Unit, Hospital General Mancha Centro , Alcázar De San Juan, Spain.,Centro De Investigación Biomédica En Red De Enfermedades Hepáticas Y Digestivas (Ciberehd) , Madrid, Spain.,Instituto De Investigación Sanitaria La Princesa , Madrid, Spain
| | - Alfredo J Lucendo
- Centro De Investigación Biomédica En Red De Enfermedades Hepáticas Y Digestivas (Ciberehd) , Madrid, Spain.,Instituto De Investigación Sanitaria La Princesa , Madrid, Spain.,Department of Gastroenterology, Hospital General De Tomelloso , Ciudad Real, Spain
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Iacob SA, Olariu MC, Iacob DG. Eosinophilic Colitis and Clostridioides difficile Sepsis With Rapid Remission After Antimicrobial Treatment; A Rare Coincidence and Its Pathogenic Implications. Front Med (Lausanne) 2020; 7:328. [PMID: 32903297 PMCID: PMC7396602 DOI: 10.3389/fmed.2020.00328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Accepted: 06/03/2020] [Indexed: 11/24/2022] Open
Abstract
Eosinophilic colitis is a rare inflammatory disorder of the digestive tract with chronic evolution and unknown pathophysiological mechanisms. The article describes the case of a 64-year old woman with a history of asthma and hypereosinophilia, who presented to a surgical department for persistent abdominal pain in the past 4 months, weight loss and malabsorption. She was diagnosed with eosinophilic colitis based on the colonoscopic result indicating extensive eosinophilic infiltration of the colonic mucosa correlated with the laboratory data and abdominal CT scan results. Following the colonoscopy, the patient developed fever, hypotension and diarrhea and was transferred to an Infectious Diseases Department with a presumptive diagnosis of abdominal sepsis. Treatment with ertapenem was immediately started. Metronidazole was also added due to a PCR positive stool test for Clostridioides difficile toxins encoding-genes. The patient displayed a rapid remission of the fever and of the intestinal complaints following antibiotic therapy and was discharged after 14 days. During a 3 months follow-up, the patient remained asymptomatic with normal values of laboratory parameters except for a persistent hypereosinophilia. The case outlines two distinguishing features: a histopathologic diagnosis of eosinophilic colitis, a rare diagnosis of a patient with chronic abdominal pain and an unexpected and rapid remission of the eosinophilic colitis following the antibiotic treatment and the restoration of the intestinal eubiosis.
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Affiliation(s)
- Simona Alexandra Iacob
- Infectious Diseases Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.,Infectious Diseases Department, The National Institute of Infectious Diseases "Matei Bals", Bucharest, Romania
| | - Mihaela Cristina Olariu
- Infectious Diseases Department, The National Institute of Infectious Diseases "Matei Bals", Bucharest, Romania.,Gastroenterology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Diana Gabriela Iacob
- Infectious Diseases Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
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Alhmoud T, Gremida A, Colom Steele D, Fallahi I, Tuqan W, Nandy N, Ismail M, Aburajab Altamimi B, Xiong MJ, Kerwin A, Martin D. Outcomes of inflammatory bowel disease in patients with eosinophil-predominant colonic inflammation. BMJ Open Gastroenterol 2020; 7:e000373. [PMID: 32128230 PMCID: PMC7039632 DOI: 10.1136/bmjgast-2020-000373] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Revised: 01/22/2020] [Accepted: 01/27/2020] [Indexed: 12/28/2022] Open
Abstract
Background Inflammatory bowel disease (IBD) is characterised by acute intestinal mucosal inflammation with chronic inflammatory features. Various degrees of mucosal eosinophilia are present along with the typical acute (neutrophil-predominant) inflammation. The effect of intestinal eosinophils on IBD outcomes remains unclear. Methods This is a retrospective study. Archived intestinal mucosal biopsy specimens of treatment-naïve IBD patients were examined by two pathologists. The number of eosinophils per high-power field was counted, and the mucosal inflammation was classified according to the eosinophilic inflammatory patterns. Clinical outcomes during the follow-up period were recorded. Results 142 treatment-naïve IBD patients were included. Mean age was 39 years. 83% of patients had ulcerative colitis, and median follow-up was 3 years. 41% of patients had disease flare(s) and 24% required hospitalisation. Eosinophil count was not associated with risk of disease flare or hospitalisation. Patients with neutrophil-predominant inflammation (>70% neutrophils) had greater risk of disease flare(s): 27(55%) versus 24(36%) and 7(28%) in patients with mixed and eosinophil-predominant inflammation, respectively (p=0.04). Overall, patients with neutrophil-predominant inflammation were more likely to have a disease flare; HR: 2.49, 95% CI (1.0 to 5.6). Hospitalisation rate was higher in patients with neutrophil-predominant inflammation: 17(35%) compared to 17(19%) in patients with eosinophil-rich inflammation (p=0.04). Kaplan-Meier analysis showed higher flare-free survival in patients with eosinophil-predominant inflammation compared to mixed and neutrophil-predominant inflammation. Conclusion IBD patients with eosinophil-predominant inflammation phenotype might have reduced risk of disease flares and hospitalisation. Larger prospective studies to assess IBD outcomes in this subpopulation are warranted.
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Affiliation(s)
- Tarik Alhmoud
- Division of Gastroenterology and Hepatology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Anas Gremida
- Division of Gastroenterology and Hepatology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Diego Colom Steele
- Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Imaneh Fallahi
- Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Wael Tuqan
- Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Nina Nandy
- Division of Gastroenterology and Hepatology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Mahmoud Ismail
- Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Barakat Aburajab Altamimi
- Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Meng-Jun Xiong
- Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Audra Kerwin
- Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - David Martin
- Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
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12
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Licari A, Votto M, D'Auria E, Castagnoli R, Caimmi SME, Marseglia GL. Eosinophilic Gastrointestinal Diseases in Children: A Practical Review. Curr Pediatr Rev 2020; 16:106-114. [PMID: 31642786 DOI: 10.2174/1573396315666191022154432] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Revised: 09/11/2019] [Accepted: 09/18/2019] [Indexed: 12/15/2022]
Abstract
Primary eosinophilic gastrointestinal diseases (EGIDs) represent a heterogeneous group of disorders characterized by eosinophilic inflammation in the absence of known causes for eosinophilia, selectively affecting different segments of the gastrointestinal tract. While pediatric eosinophilic esophagitis (EoE) is a well-defined disease with established guidelines, Eosinophilic Gastritis (EoG), Eosinophilic Gastroenteritis (EoGE) and Eosinophilic Colitis (EoC) remain a clinical enigma with evidence based on limited anecdotal case reports. Large cross-sectional studies in the US defined a prevalence of EoG and EoGE ranging from 1,5 to 6,4/100.000 and from 2,7 to 8,3/100.000 subjects respectively, while the prevalence of EoC ranges from 1,7 to 3,5/100.000 subjects. Regarding the pathogenesis, it is hypothesized that EGIDs result from the interplay between genetic predisposition, intestinal dysbiosis and environmental triggers. Clinically, EGIDs might present with different and nonspecific gastrointestinal symptoms depending on the involved intestinal tract and the extension of eosinophilic inflammatory infiltrate. The diagnosis of EGIDs requires: 1. recurrent gastrointestinal symptoms, 2. increased eosinophils for high power field in biopsy specimens, 3. absence of secondary causes of gastrointestinal eosinophilia. No validated guidelines are available on the clinical management of patients with EGIDs. Evidence from case reports and small uncontrolled case series suggests the use of dietary and corticosteroids as the first-line treatments. Considering the clinical follow-up of EGIDs, three different patterns of disease course are identified: single flare, recurring course-disease and chronic course-disease. This review will focus on pediatric EGIDs distal to esophagus, including Eosinophilic Gastritis (EoG), Eosinophilic Gastroenteritis (EoGE) and Eosinophilic Colitis (EoC).
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Affiliation(s)
- Amelia Licari
- Department of Pediatrics, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Martina Votto
- Department of Pediatrics, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Enza D'Auria
- Department of Pediatrics, Vittore Buzzi Children's Hospital-University of Milan, Milan, Italy
| | - Riccardo Castagnoli
- Department of Pediatrics, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Silvia Maria Elena Caimmi
- Department of Pediatrics, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Gian Luigi Marseglia
- Department of Pediatrics, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
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13
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Fecal Eosinophil Cationic Protein Is a Diagnostic and Predictive Biomarker in Young Adults with Inflammatory Bowel Disease. J Clin Med 2019; 8:jcm8122025. [PMID: 31756948 PMCID: PMC6947361 DOI: 10.3390/jcm8122025] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Revised: 11/13/2019] [Accepted: 11/18/2019] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND AND AIMS Fecal biomarkers are important non-invasive markers monitoring disease activity in inflammatory bowel disease (IBD). We compared the significance of fecal eosinophil cationic protein (fECP) and fecal calprotectin (fCal). METHODS fECP and fCal were measured in patients with Crohn's disease (CD, n = 97), ulcerative colitis (UC, n = 53), Clostridioides difficile infection (CDI, n = 9), primary food allergy (PFA, n = 11), pollen-associated food allergy (n = 25) and non-inflammatory controls (n = 78). Results were correlated with clinical and endoscopic IBD activity scores. RESULTS fECP was significantly elevated in CD, UC, CDI and PFA compared to controls. fCal was significantly increased in CD, UC and CDI. fECP had lower diagnostic accuracy than fCal (area under the curve (AUC) = 0.88) in differentiating between endoscopically active and inactive patients with IBD (AUC = 0.77, ROC analysis). In contrast to fCal, fECP correlated negatively with age and levels were also elevated in clinically and endoscopically inactive patients with IBD <45 years (endoscopically inactive IBD vs controls; AUC for fECP = 0.86; AUC for fCal = 0.62). However, in those patients with low inflammatory activity (fCal <250 mg/kg), high fECP indicated the need for treatment modification or surgery (fECP <200 µg/kg = 22%; 200-600 µg/kg = 44%; >600 µg/kg = 82%) at month 48 of follow-up. CONCLUSIONS fECP is a diagnostic and prognostic marker in young patients with IBD in remission.
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Grandinetti T, Biedermann L, Bussmann C, Straumann A, Hruz P. Eosinophilic Gastroenteritis: Clinical Manifestation, Natural Course, and Evaluation of Treatment with Corticosteroids and Vedolizumab. Dig Dis Sci 2019; 64:2231-2241. [PMID: 30982212 DOI: 10.1007/s10620-019-05617-3] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2018] [Accepted: 04/08/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Eosinophilic gastroenteritis (EGE) is a rare, chronic inflammatory condition of the gastrointestinal tract. Little is known about its natural history and treatment outcomes. The aims of our analysis were to describe clinical presentation, response to current medical treatments, and to evaluate the response of refractory EGE to anti-integrin therapy. METHODS Patients with confirmed diagnosis of EGE fulfilling the diagnostic criteria: (1) the presence of gastrointestinal symptoms, (2) dense eosinophilic infiltration of the gastrointestinal mucosa, and (3) exclusion of other conditions leading to gastrointestinal eosinophilia were included in this analysis. In patients non-responding to corticosteroids and/or anti-TNF treatment the integrin blocker vedolizumab was used. RESULTS EGE patients (n = 22) were predominantly female (63%) with a median age at diagnosis of 41.5 years. The most frequent symptoms were abdominal pain (100%), diarrhea (59%), nausea/vomiting (36%), and bloating (27%). No pathognomonic endoscopic alterations were found. Eosinophilic infiltration was observed in the majority of patients in more than one segment. Patients were treated with systemic steroids, topical, and enteral release steroids in 21/22 (95%) patients, proton pump inhibitors in 7/22 (32%), TNFα inhibitors in 3/22 (14%), and vedolizumab in 4/22 (18%) patients. In 3/4 of steroid-refractory patients vedolizumab induced a clinical and histological improvement. CONCLUSIONS The combination of highly variable clinical presentation, subtle endoscopic abnormalities, and involvement of several GI segments undermines the difficulty to diagnose EGE and the need for structured biopsy sampling. Corticosteroids were efficient in the majority of patients to induce remission. Response to the integrin blocker vedolizumab suggests further assessment in refractory cases.
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Affiliation(s)
- Tanja Grandinetti
- Department of Gastroenterology and Hepatology, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland
| | - Luc Biedermann
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | | | - Alex Straumann
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
- Swiss EoE Clinic, Division of Gastroenterology, University Hospital Zurich, Zurich, Switzerland
| | - Petr Hruz
- Department of Gastroenterology and Hepatology, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.
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15
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Loktionov A. Eosinophils in the gastrointestinal tract and their role in the pathogenesis of major colorectal disorders. World J Gastroenterol 2019; 25:3503-3526. [PMID: 31367153 PMCID: PMC6658389 DOI: 10.3748/wjg.v25.i27.3503] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Revised: 05/22/2019] [Accepted: 06/01/2019] [Indexed: 02/06/2023] Open
Abstract
Eosinophils are currently regarded as versatile mobile cells controlling and regulating multiple biological pathways and responses in health and disease. These cells store in their specific granules numerous biologically active substances (cytotoxic cationic proteins, cytokines, growth factors, chemokines, enzymes) ready for rapid release. The human gut is the main destination of eosinophils that are produced and matured in the bone marrow and then transferred to target tissues through the circulation. In health the most important functions of gut-residing eosinophils comprise their participation in the maintenance of the protective mucosal barrier and interactions with other immune cells in providing immunity to microbiota of the gut lumen. Eosinophils are closely involved in the development of inflammatory bowel disease (IBD), when their cytotoxic granule proteins cause damage to host tissues. However, their roles in Crohn’s disease and ulcerative colitis appear to follow different immune response patterns. Eosinophils in IBD are especially important in altering the structure and protective functions of the mucosal barrier and modulating massive neutrophil influx to the lamina propria followed by transepithelial migration to colorectal mucus. IBD-associated inflammatory process involving eosinophils then appears to expand to the mucus overlaying the internal gut surface. The author hypothesises that immune responses within colorectal mucus as well as ETosis exerted by both neutrophils and eosinophils on the both sides of the colonic epithelial barrier act as additional pathogenetic factors in IBD. Literature analysis also shows an association between elevated eosinophil levels and better colorectal cancer (CRC) prognosis, but mechanisms behind this effect remain to be elucidated. In conclusion, the author emphasises the importance of investigating colorectal mucus in IBD and CRC patients as a previously unexplored milieu of disease-related inflammatory responses.
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16
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Bastan I, Rendahl AK, Seelig D, Day MJ, Hall EJ, Rao SP, Washabau RJ, Sriramarao P. Assessment of eosinophils in gastrointestinal inflammatory disease of dogs. J Vet Intern Med 2018; 32:1911-1917. [PMID: 30294803 PMCID: PMC6271348 DOI: 10.1111/jvim.15310] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Revised: 07/17/2018] [Accepted: 07/31/2018] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Accurate identification of eosinophils in the gastrointestinal (GI) tract of dogs with eosinophilic GI disease (EGID) by histological evaluation is challenging. The currently used hematoxylin and eosin (H&E) staining method detects intact eosinophils but does not detect degranulated eosinophils, thus potentially underrepresenting the number of infiltrating eosinophils. OBJECTIVE To develop a more sensitive method for identifying and quantifying both intact and degranulated eosinophils to diagnose EGID more accurately. METHODS Endoscopically obtained paraffin-embedded intestinal biopsy specimens from dogs with GI signs were examined. The study groups were dogs with eosinophilic enteritis (EE), lymphoplasmacytic and mixed enteritis, and control dogs with GI signs but no histologic changes on tissue sections. Consecutive sections were immunolabeled with monoclonal antibodies (mAbs) against the eosinophil granule protein eosinophil peroxidase (Epx) and stained by H&E, respectively. The number of eosinophils was manually quantified and classified as intact or degranulated. RESULTS The number of intact eosinophils detected in Epx mAb-labeled duodenal sections was significantly higher compared with that in H&E-stained sections, with a similar relationship noted in the colon and stomach. The Epx mAb allowed the unique assessment of eosinophil degranulation. The number of intact and degranulated eosinophils was significantly higher in duodenal lamina propria of the EE and mixed group compared to the control group. CONCLUSION Immunohistochemical detection of Epx provides a more precise method to detect GI tract eosinophils compared to H&E staining and could be used as an alternative and reliable diagnostic tool for assessment of biopsy tissues from dogs with EGID.
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Affiliation(s)
- Idil Bastan
- Department of Veterinary Clinical SciencesUniversity of MinnesotaSt. PaulMinnesota
| | - Aaron K. Rendahl
- Department of Veterinary and Biomedical SciencesUniversity of MinnesotaSt. PaulMinnesota
| | - Davis Seelig
- Department of Veterinary Clinical SciencesUniversity of MinnesotaSt. PaulMinnesota
| | - Michael J. Day
- Bristol Veterinary SchoolUniversity of BristolBristolUnited Kingdom
| | - Edward J. Hall
- Bristol Veterinary SchoolUniversity of BristolBristolUnited Kingdom
| | - Savita P. Rao
- Department of Veterinary and Biomedical SciencesUniversity of MinnesotaSt. PaulMinnesota
| | - Robert J. Washabau
- Department of Veterinary Clinical SciencesUniversity of MinnesotaSt. PaulMinnesota
| | - P. Sriramarao
- Department of Veterinary and Biomedical SciencesUniversity of MinnesotaSt. PaulMinnesota
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17
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Zammit SC, Cachia M, Sapiano K, Gauci J, Montefort S, Ellul P. Eosinophilic gastrointestinal disorder: is it what it seems to be? Ann Gastroenterol 2018; 31:475-479. [PMID: 29991893 PMCID: PMC6033761 DOI: 10.20524/aog.2018.0263] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Accepted: 03/13/2018] [Indexed: 12/14/2022] Open
Abstract
Background Eosinophilic gastroenteropathy is an uncommon condition whose causes can be numerous and non-specific. The aim of the study was to characterize the presence of gastrointestinal disorders in the adult Maltese population and assess the degree of association with atopic diseases. Methods Adult patients with gastrointestinal eosinophilia in the gastrointestinal tract on histology were identified and their clinical case notes were reviewed. Patients were interviewed and asked questions regarding asthma, allergic rhinitis, and eczema. Results Sixty-six patients (39 female) were recruited. The most common clinical symptoms were diarrhea (42.4%) and abdominal pain (33.3%). The sites involved were stomach (10.6%), colon (56.1%), small bowel (10.6%), small bowel and colon (18.2%), esophagus (1.5%), and esophagus and colon (1.5%). Forty percent had persistent lower gastrointestinal symptoms and a repeat ileocolonoscopy was performed within 12 months. These patients were diagnosed with ulcerative colitis (n=10; 47.6%), Crohn's disease (n=6; 28.6%), indeterminate colitis (n=1; 4.8%) or microscopic colitis (n=4; 19%). Allergic rhinitis was present in 39.4% of the study group, eczema in 26.1%, and asthma in 19.7%. These findings were compared with local data for atopic conditions and the study group was found to have a significantly higher prevalence of allergic rhinitis (P=0.002), but not of asthma (P=0.62) or eczema (P=0.19). Conclusions A high proportion of patients with eosinophilic gastrointestinal infiltration were subsequently diagnosed with inflammatory bowel disease. Patients persistently symptomatic or who do not respond to treatment should be reassessed to exclude inflammatory bowel disease, given its high prevalence in this group of patients.
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Affiliation(s)
- Stefania Chetcuti Zammit
- Division of Gastroenterology, Department of Medicine (Stefania Chetcuti Zammit, Pierre Ellul), Mater Dei Hospital, Malta
| | - Monique Cachia
- Department of Medicine (Monique Cachia, Karen Sapiano, Julia Gauci), Mater Dei Hospital, Malta
| | - Karen Sapiano
- Department of Medicine (Monique Cachia, Karen Sapiano, Julia Gauci), Mater Dei Hospital, Malta
| | - Julia Gauci
- Department of Medicine (Monique Cachia, Karen Sapiano, Julia Gauci), Mater Dei Hospital, Malta
| | - Stephen Montefort
- Division of Respiratory Medicine, Department of Medicine (Stephen Montefort), Mater Dei Hospital, Malta
| | - Pierre Ellul
- Division of Gastroenterology, Department of Medicine (Stefania Chetcuti Zammit, Pierre Ellul), Mater Dei Hospital, Malta
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18
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Loktionov A, Chhaya V, Bandaletova T, Poullis A. Inflammatory bowel disease detection and monitoring by measuring biomarkers in non-invasively collected colorectal mucus. J Gastroenterol Hepatol 2017; 32:992-1002. [PMID: 27787913 DOI: 10.1111/jgh.13627] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2016] [Revised: 10/12/2016] [Accepted: 10/22/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Non-invasive detection and monitoring of inflammatory bowel disease (IBD) is an important clinical challenge. Stool calprotectin is the most popular among available options, but the necessity of stool collection limits its acceptability. This study aimed to evaluate biomarker measurement in non-invasively collected colorectal mucus as a new tool for IBD detection and activity monitoring. METHODS Calprotectin, eosinophil-derived neurotoxin (EDN), and protein S100A12 were measured in colorectal mucus self-collected following defecation by 58 patients with IBD (before therapy), 50 patients with irritable bowel syndrome, and 33 healthy volunteers. Patients with IBD also collected samples at days 10, 20, and 30 of treatment for disease activity monitoring. RESULTS Protein biomarker levels were significantly (P < 0.001) higher in IBD patients than in irritable bowel syndrome and control groups. Calprotectin and EDN effectively detected IBD with a respective sensitivity and specificity of 0.76 and 0.92 for calprotectin and 0.83 and 0.94 for EDN. S100A12 was less sensitive. Calprotectin and EDN results were combined in a new test (CALEDN) that had a sensitivity of 0.91 and a specificity of 0.89. Repeated biomarker measurement during IBD treatment demonstrated a steady decline of calprotectin and EDN levels as well as CALEDN values in patients responding to applied therapy and lack of this pattern in non-responders. CONCLUSIONS Measuring calprotectin and EDN in non-invasively collected colorectal mucus presents a simple and efficient method for IBD detection and monitoring. Excellent performance of EDN for this purpose is reported for the first time. Combining calprotectin and EDN in one test improves IBD detection sensitivity.
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Affiliation(s)
| | - Vivek Chhaya
- Department of Gastroenterology, St George's Hospital, London, UK
| | | | - Andrew Poullis
- Department of Gastroenterology, St George's Hospital, London, UK
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19
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Diny NL, Rose NR, Čiháková D. Eosinophils in Autoimmune Diseases. Front Immunol 2017; 8:484. [PMID: 28496445 PMCID: PMC5406413 DOI: 10.3389/fimmu.2017.00484] [Citation(s) in RCA: 115] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Accepted: 04/07/2017] [Indexed: 12/15/2022] Open
Abstract
Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs.
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Affiliation(s)
- Nicola L Diny
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
| | - Noel R Rose
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Daniela Čiháková
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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20
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Bastan I, Robinson NA, Ge XN, Rendahl AK, Rao SP, Washabau RJ, Sriramarao P. Assessment of eosinophil peroxidase as a potential diagnostic and prognostic marker in dogs with inflammatory bowel disease. Am J Vet Res 2017; 78:36-41. [PMID: 28029282 DOI: 10.2460/ajvr.78.1.36] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
OBJECTIVE To evaluate a method for identifying intact and degranulated eosinophils in the small intestine of dogs with inflammatory bowel disease (IBD) by use of a monoclonal antibody (mAb) against eosinophil peroxidase (EPX). ANIMALS 11 untreated dogs with IBD, 5 dogs with IBD treated with prednisolone, and 8 control dogs with no clinical evidence of gastrointestinal tract disease and no immunosuppressive treatment. PROCEDURES 4-μm-thick sections of paraffin-embedded tissues from necropsy specimens were immunostained with EPX mAb. Stained intact and degranulated eosinophils in consecutive microscopic fields (400X magnification) of the upper (villus tips) and lower (between the muscularis mucosae and crypts) regions of the lamina propria of the jejunum were manually counted. RESULTS Compared with control and treated IBD dogs, untreated IBD dogs had a significantly higher number of degranulated eosinophils in the lower region of the lamina propria. However, no significant differences were detected in the number of intact eosinophils in this region among groups. In the upper region of the lamina propria, untreated IBD dogs had a significantly higher number of degranulated and intact eosinophils, compared with control and treated IBD dogs. Number of degranulated and intact eosinophils did not differ significantly between control and treated IBD dogs. CONCLUSIONS AND CLINICAL RELEVANCE Immunohistologic analysis with EPX mAb yielded prominent granule staining that allowed reliable morphological identification of degranulated and intact eosinophils, which may provide a strategy for quantitative and selective evaluation of eosinophils in gastrointestinal biopsy specimens and a potential method to diagnose IBD and evaluate treatment outcome.
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21
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Zhang M, Li Y. Eosinophilic gastroenteritis: A state-of-the-art review. J Gastroenterol Hepatol 2017; 32:64-72. [PMID: 27253425 DOI: 10.1111/jgh.13463] [Citation(s) in RCA: 89] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/23/2016] [Indexed: 12/12/2022]
Abstract
Eosinophilic gastrointestinal disorders are a series of diseases that include eosinophilic esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilic enteritis, and eosinophilic colitis. Among these disorders, eosinophilic gastroenteritis is an uncommon and heterogeneous disease characterized by eosinophilic infiltration of the gastrointestinal tract in the absence of secondary causes, presenting with a variety of gastrointestinal manifestations. Up to now, epidemiology and pathophysiology of eosinophilic gastroenteritis are still unclear. Based on clinical manifestations and depth of eosinophilic infiltration into the gastrointestinal tract wall, eosinophilic gastroenteritis is classified into three different patterns including predominantly mucosal pattern, predominantly muscular pattern, and predominantly serosal pattern. For diagnosing eosinophilic gastroenteritis, it is necessary for clinicians to have a high degree of clinical suspicion. In addition to the gastrointestinal symptoms, other evidences such as laboratory results, radiological findings and endoscopy can also provide important diagnostic evidences for eosinophilic gastroenteritis. And these indirect pieces of information together with histological results will lead to a definitive diagnosis of eosinophilic gastroenteritis. To avoid specific allergen, dietary treatments can be considered as initial treatment strategy before drug treatment. Corticosteroids are the main medication for eosinophilic gastroenteritis and have a dramatic therapeutic efficacy. Yet other medications need to further verify their effects in clinical practice, and surgery should be avoided as far as possible.
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Affiliation(s)
- MingMing Zhang
- Department of Gastroenterology, Laboratory of Translational Gastroenterology, Shandong University, Qilu Hospital, Jinan, Shandong, China
| | - YanQing Li
- Department of Gastroenterology, Laboratory of Translational Gastroenterology, Shandong University, Qilu Hospital, Jinan, Shandong, China
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Frascoli M, Jeanty C, Fleck S, Moradi PW, Keating S, Mattis AN, Tang Q, MacKenzie TC. Heightened Immune Activation in Fetuses with Gastroschisis May Be Blocked by Targeting IL-5. THE JOURNAL OF IMMUNOLOGY 2016; 196:4957-66. [PMID: 27183609 DOI: 10.4049/jimmunol.1502587] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Accepted: 04/18/2016] [Indexed: 12/20/2022]
Abstract
The development of the fetal immune system during pregnancy is a well-orchestrated process with important consequences for fetal and neonatal health, but prenatal factors that affect immune activation are poorly understood. We hypothesized that chronic fetal inflammation may lead to alterations in development of the fetal immune system. To test this hypothesis, we examined neonates with gastroschisis, a congenital abdominal wall defect that leads to exposure of the fetal intestines to amniotic fluid, with resultant intestinal inflammation. We determined that patients with gastroschisis show high systemic levels of inflammatory cytokines and chemokines such as eotaxin, as well as earlier activation of CD4(+) and CD8(+) effector and memory T cells in the cord blood compared with controls. Additionally, increased numbers of T cells and eosinophils infiltrate the serosa and mucosa of the inflamed intestines. Using a mouse model of gastroschisis, we observed higher numbers of eosinophils and both type 2 and type 3 innate lymphoid cells (ILC2 and ILC3), specifically in the portion of organs exposed to the amniotic fluid. Given the role of IL-5 produced by ILC2 in regulating eosinophil development and survival, we determined that maternal or fetal administration of the anti-IL-5 neutralizing Ab, or a depleting Ab against ILCs, can both effectively reduce intestinal eosinophilia. Thus, a congenital anomaly causing chronic inflammation can alter the composition of circulating and tissue-resident fetal immune cells. Given the high rate of prenatal and neonatal complications in these patients, such changes have clinical significance and might become targets for fetal therapy.
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Affiliation(s)
- Michela Frascoli
- Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA 94143; Department of Surgery, University of California San Francisco, San Francisco, CA 94143
| | - Cerine Jeanty
- Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA 94143; Department of Surgery, University of California San Francisco, San Francisco, CA 94143
| | - Shannon Fleck
- Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143
| | - Patriss W Moradi
- Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA 94143; Department of Surgery, University of California San Francisco, San Francisco, CA 94143
| | - Sheila Keating
- Blood Systems Research Institute, San Francisco, CA 94118; and
| | - Aras N Mattis
- Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA 94143; Department of Pathology, University of California San Francisco, San Francisco, CA 94143
| | - Qizhi Tang
- Department of Surgery, University of California San Francisco, San Francisco, CA 94143
| | - Tippi C MacKenzie
- Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA 94143; Department of Surgery, University of California San Francisco, San Francisco, CA 94143; Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143;
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Leonel AJ, Silva EL, Aguilar EC, Teixeira LG, Oliveira RP, Faria AMC, Cara DC, Ferreira LAM, Alvarez‐Leite JI. Systemic administration of a nanoemulsion with tributyrin reduces inflammation in experimental colitis. EUR J LIPID SCI TECH 2016. [DOI: 10.1002/ejlt.201400359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
- Alda Jusceline Leonel
- Department of Biochemistry and ImmunologyUniversidade Federal Minas GeraisBelo HorizonteBrazil
| | - Elton Luiz Silva
- Department of Pharmaceutical Products, Faculty of PharmacyUniversidade Federal Minas GeraisBelo HorizonteBrazil
| | - Edenil Costa Aguilar
- Department of Biochemistry and ImmunologyUniversidade Federal Minas GeraisBelo HorizonteBrazil
| | | | - Rafael Pires Oliveira
- Department of Biochemistry and ImmunologyUniversidade Federal Minas GeraisBelo HorizonteBrazil
| | - Ana Maria Caetano Faria
- Department of Biochemistry and ImmunologyUniversidade Federal Minas GeraisBelo HorizonteBrazil
| | - Denise Carmona Cara
- Department of Morphology, Institute of Biological SciencesUniversidade Federal Minas GeraisBelo HorizonteBrazil
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24
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Lucendo AJ. Disease associations in eosinophilic oesophagitis and oesophageal eosinophilia. Best Pract Res Clin Gastroenterol 2015; 29:759-769. [PMID: 26552775 DOI: 10.1016/j.bpg.2015.06.010] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2015] [Revised: 06/07/2015] [Accepted: 06/18/2015] [Indexed: 01/31/2023]
Abstract
Eosinophilic infiltration into oesophageal tissue, typical of eosinophilic oesophagitis (EoE), has been described in several other conditions, including infections, hypersensitivity, and other autoimmune disorders. Since its description, EoE has been associated with an increasing number of diseases also characterized by tissue infiltration, including eosinophilic gastroenteritis and Crohn's disease. While an association between EoE and coeliac disease was previously reported, it is not supported by recent research. In contrast, EoE seems to be common in patients with a history of congenital oesophageal atresia, leading to hypotheses linking both disorders. The prevalence of EoE has also been shown to be eight times higher in patients with connective tissue disorders (CTDs), which has led to the proposal of an EoE-CTD phenotype, although this requires further assessment. This paper reviews the evidence of EoE's associations with several disorders, defining the common bases from an epidemiological, clinical, molecular and genetic perspective whenever possible.
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Affiliation(s)
- Alfredo J Lucendo
- Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Spain.
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25
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Travers J, Rothenberg ME. Eosinophils in mucosal immune responses. Mucosal Immunol 2015; 8:464-75. [PMID: 25807184 PMCID: PMC4476057 DOI: 10.1038/mi.2015.2] [Citation(s) in RCA: 144] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2014] [Accepted: 12/28/2014] [Indexed: 02/06/2023]
Abstract
Eosinophils, multifunctional cells that contribute to both innate and adaptive immunity, are involved in the initiation, propagation, and resolution of immune responses, including tissue repair. They achieve this multifunctionality by expression of a diverse set of activation receptors, including those that directly recognize pathogens and opsonized targets, and by their ability to store and release preformed cytotoxic mediators that participate in host defense, to produce a variety of de novo pleotropic mediators and cytokines, and to interact directly and indirectly with diverse cell types, including adaptive and innate immunocytes and structural cells. Herein, we review the basic biology of eosinophils and then focus on new emerging concepts about their role in mucosal immune homeostasis, particularly maintenance of intestinal IgA. We review emerging data about their development and regulation and describe new concepts concerning mucosal eosinophilic diseases. We describe recently developed therapeutic strategies to modify eosinophil levels and function and provide collective insight about the beneficial and detrimental functions of these enigmatic cells.
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26
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Debnath T, Mijan MA, Kim DH, Jo JE, Kim YO, Lee JJ, Pyo HJ, Lim BO. Anti-Inflammatory Effects of H
aliotis discus hannai
Ino on Dextran Sulfate Sodium-Induced Colitis in Mice. J Food Biochem 2015. [DOI: 10.1111/jfbc.12118] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Trishna Debnath
- College of Biomedical and Health Science; Department of Applied Biochemistry; Konkuk University; Chungju 380-701 Korea
| | - Mohammad Al Mijan
- College of Biomedical and Health Science; Department of Applied Biochemistry; Konkuk University; Chungju 380-701 Korea
| | - Da Hye Kim
- College of Biomedical and Health Science; Department of Applied Biochemistry; Konkuk University; Chungju 380-701 Korea
| | - Jeong Eun Jo
- College of Biomedical and Health Science; Department of Applied Biochemistry; Konkuk University; Chungju 380-701 Korea
| | - Young Ock Kim
- Department of Herbal Crop Research; NIHHS; RDA; Eumseong Korea
| | - Jeong Jun Lee
- Research and Development Center; Naturetech, Inc.; Jincheon ChungBuk Korea
| | - Han Jong Pyo
- Research and Development Center; Naturetech, Inc.; Jincheon ChungBuk Korea
| | - Beong Ou Lim
- College of Biomedical and Health Science; Department of Applied Biochemistry; Konkuk University; Chungju 380-701 Korea
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27
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Zezos P, Patsiaoura K, Nakos A, Mpoumponaris A, Vassiliadis T, Giouleme O, Pitiakoudis M, Kouklakis G, Evgenidis N. Severe eosinophilic infiltration in colonic biopsies predicts patients with ulcerative colitis not responding to medical therapy. Colorectal Dis 2014; 16:O420-30. [PMID: 25040651 DOI: 10.1111/codi.12725] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2014] [Accepted: 06/05/2014] [Indexed: 12/16/2022]
Abstract
AIM Eosinophils are potent proinflammatory cells that are involved in the pathogenesis of ulcerative colitis (UC). We evaluated the infiltration of eosinophils into the lamina propria in patients with active and inactive ulcerative colitis (UC) and investigated its clinical significance, among other variables, in predicting the outcome of medical treatment in active disease. METHOD We studied colorectal biopsy specimens from 18 UC patients with disease in long-standing remission, from 22 patients with active disease who responded to therapy (12 with complete response and 10 with partial response) and from 10 patients who were nonresponders. Demographic information was obtained at baseline, and clinical, endoscopic and laboratory data were obtained at baseline and 12 weeks post-treatment. We evaluated five histological features: mucosal ulceration; mucosal erosions; crypt abscesses; cryptitis; and eosinophilic infiltration of the lamina propria. The severity of these lesions was graded as: none or minimal; mild; moderate; or severe. Statistical analyses were performed between responders and nonresponders for differences in demographic, clinical, laboratory, endoscopic and histological parameters. RESULTS Laboratory, endoscopic and histological parameters were significantly improved after treatment only in the complete responders group. Analyses of baseline data revealed no significant differences in parameters between complete or partial responders and nonresponders, except for a less severe eosinophilic infiltration of lamina propria in complete responders (P < 0.05). Multiple logistic regression analysis showed that severe eosinophilic infiltration in colonic biopsies was the most significant predictor of poor response to medical therapy. CONCLUSION Assessing the severity of eosinophilic infiltration in the lamina propria of colonic biopsies in patients with ulcerative colitis could be a valuable predictive tool of response to medical therapy.
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Affiliation(s)
- P Zezos
- Division of Gastroenterology, 2nd Propaedeutic Department of Internal Medicine, "Hippokration" General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; Gastrointestinal Endoscopy Unit, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis, Greece
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28
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Jung Y, Rothenberg ME. Roles and regulation of gastrointestinal eosinophils in immunity and disease. THE JOURNAL OF IMMUNOLOGY 2014; 193:999-1005. [PMID: 25049430 DOI: 10.4049/jimmunol.1400413] [Citation(s) in RCA: 94] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Eosinophils have historically been considered to be destructive end-stage effector cells that have a role in parasitic infections and allergic reactions by the release of their granule-derived cytotoxic proteins. However, an increasing number of experimental observations indicate that eosinophils also are multifunctional leukocytes involved in diverse inflammatory and physiologic immune responses. Under homeostatic conditions, eosinophils are particularly abundant in the lamina propria of the gastrointestinal tract, where their involvement in various biological processes within the gastrointestinal tract has been posited. In this review, we summarize the molecular steps involved in eosinophil development and describe eosinophil trafficking to the gastrointestinal tract. We synthesize the current findings on the phenotypic and functional properties of gastrointestinal eosinophils and the accumulating evidence that they have a contributory role in gastrointestinal disorders, with a focus on primary eosinophilic gastrointestinal disorders. Finally, we discuss the potential role of eosinophils as modulators of the intestinal immune system.
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Affiliation(s)
- YunJae Jung
- Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229; and Department of Microbiology, Graduate School of Medicine, Gachon University, Incheon 406-799, Republic of Korea
| | - Marc E Rothenberg
- Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229; and
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29
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Walker MM, Powell N, Talley NJ. Atopy and the gastrointestinal tract--a review of a common association in unexplained gastrointestinal disease. Expert Rev Gastroenterol Hepatol 2014; 8:289-99. [PMID: 24450399 DOI: 10.1586/17474124.2014.881716] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
In addition to diseases conventionally associated with atopy there is increasing recognition that atopy is also linked to a spectrum of gastrointestinal (GI) manifestations, including food allergy, primary eosinophilic GI disease, functional gastrointestinal disorders, gluten interactions, gastroesophageal reflux disease and inflammatory bowel disease. These associations may be underpinned by shared genetic susceptibilities, initiation of related immune pathways and common patterns of exposure to environmental cues, including allergen/pathogen encounters and variations in the composition of the intestinal microbiota. Further scrutiny of GI diseases with prominent allergic-type immune responses may yet redefine treatment paradigms for these common and important atopy-associated diseases. Looking forward, interventions by manipulation of the microbiota or host immune responses hold promise, but there is still room for further exploration of this novel field of host susceptibility, host-microbe interactions and atopy-associated GI diseases.
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Affiliation(s)
- Marjorie M Walker
- School of Medicine & Public Health, University of Newcastle, Callaghan NSW 2308, Australia
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30
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Lied GA. Indication of immune activation in patients with perceived food hypersensitivity. Dig Dis Sci 2014; 59:259-66. [PMID: 24185686 DOI: 10.1007/s10620-013-2926-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2013] [Accepted: 10/16/2013] [Indexed: 12/15/2022]
Abstract
Majority of the patients with perceived food hypersensitivity have irritable bowel syndrome (IBS), and a significant proportion of IBS patients also attribute their gastrointestinal complaints to food items. Different factors such as disturbed intestinal fermentation, enteric dysmotility, post-infectious changes and altered microbial flora in the colon as well as psychological disturbances likely play a role in the pathophysiology and symptoms generation in patients with food hypersensitivity. In addition, a number of studies in these patient groups indicate that local, systemic and mucosal immune systems are activated. The question now is no longer intestinal immune activation, but how the immune system is activated in these patients. In the following review, the potential pathogenetic role of the immune system and evidence of immune activation are reported in patients with perceived food hypersensitivity.
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Affiliation(s)
- Gülen Arslan Lied
- Department of Clinical Medicine, University of Bergen, Bergen, Norway,
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31
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Däbritz J, Musci J, Foell D. Diagnostic utility of faecal biomarkers in patients with irritable bowel syndrome. World J Gastroenterol 2014; 20:363-375. [PMID: 24574706 PMCID: PMC3923012 DOI: 10.3748/wjg.v20.i2.363] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2013] [Revised: 11/12/2013] [Accepted: 11/30/2013] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a common functional gastrointestinal (GI) disorder characterized by unspecific symptoms. In clinical practice it is crucial to distinguish between non-inflammatory functional problems and inflammatory, malignant or infectious diseases of the GI tract. Differentiation between these involves the use of clinical, radiological, endoscopic, histological and serological techniques, which are invasive, expensive, time-consuming and/or hindered by inaccuracies arising from subjective components. A range of faecal markers now appears to have the potential to greatly assist in the differentiation of inflammatory bowel disease (IBD) and IBS. Faecal markers of neutrophil influx into the mucosa are reliable indicators of intestinal inflammation and their role has been mainly studied in discriminating IBD from non-IBD conditions (including IBS) rather than organic from non-organic diseases. Phagocyte-specific proteins of the S100 family (S100A12, calprotectin) are amongst the most promising faecal biomarkers of inflammation. Faecal leukocyte degranulation markers (lactoferrin, polymorphonuclear elastase and myeloperoxidase) have also been suggested as diagnostic tools for the differentiation of IBD and IBS. More recently, additional proteins, including granins, defensins and matrix-metalloproteases, have been discussed as differential diagnostic markers in IBD and IBS. In this review, some of the most promising faecal markers, which have the potential to differentiate IBD and IBS and to advance diagnostic practices, will be discussed.
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32
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2013 update on celiac disease and eosinophilic esophagitis. Nutrients 2013; 5:3329-36. [PMID: 23974065 PMCID: PMC3798906 DOI: 10.3390/nu5093329] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2013] [Revised: 07/31/2013] [Accepted: 08/01/2013] [Indexed: 02/06/2023] Open
Abstract
Celiac disease is a chronic, immune-mediated disorder, characterized by small intestinal inflammation and villous atrophy after the ingestion of gluten by genetically susceptible individuals. Several extraintestinal manifestations have been associated to celiac disease. Eosinophilic esophagitis is a primary disorder of the esophagus characterized by upper gastrointestinal symptoms, absence of gastroesophageal reflux disease and more than 15 eosinophils per high-power field in biopsy specimens. Both celiac disease and eosinophilic esophagitis are caused by aberrant, but distinct, immune responses to ingested antigens and can be responsive to restricted food intake. The aim of this review is to assess whether there is an association between these two pathologies. In the majority of the studies examined, including the studies in pediatric population, the prevalence of eosinophilic esophagitis in subjects with celiac disease was about 10-times that of the general population. We suggest searching for eosinophilic esophagitis in all children undergoing endoscopy for suspicious celiac disease.
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Abstract
PURPOSE OF REVIEW Inflammatory bowel diseases (IBDs, e.g., Crohn's disease and ulcerative colitis) are thought to be a consequence of an uncontrolled inflammatory response against luminal antigens, including commensal bacteria. The observed link between eosinophil levels and severity and remission rates in IBD has led to speculation that eosinophils may contribute to the antimicrobial inflammatory response in IBD. RECENT FINDINGS Eosinophils express the necessary cellular machinery (innate immune receptors, proinflammatory cytokines, antibacterial proteins, and DNA traps) to mount an efficient antibacterial response; however, the rapid decline in eosinophil numbers following acute systemic bacterial infection suggests a very limited role for eosinophils in bacterial responses. SUMMARY We describe the clinical evidence of eosinophil involvement in IBD, summarize the in-vitro and in-vivo evidence of eosinophil antibacterial activity and the biology of eosinophils focusing on eosinophil-mediated bactericidal mechanisms and the involvement of eosinophil-derived granule proteins in this response, and conceptualize the contribution of eosinophils to a response against commensal bacteria in IBD.
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Affiliation(s)
- Simon P Hogan
- Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
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34
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Pickert CN, Lorentz A, Manns MP, Bischoff SC. Colonoscopic allergen provocation test with rBet v 1 in patients with pollen-associated food allergy. Allergy 2012; 67:1308-15. [PMID: 22913618 DOI: 10.1111/all.12006] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/15/2012] [Indexed: 12/30/2022]
Abstract
BACKGROUND After consumption of fruits, nuts, and vegetables, several patients with pollen allergy experience gastrointestinal (GI) tract symptoms that are possibly caused by pollen-associated food allergy. The aim of this study was to evaluate the colonoscopic allergen provocation (COLAP) test using the recombinant birch pollen allergen Bet v 1 (rBet v 1) for in vivo diagnosis of pollen-associated food allergy manifesting in the GI tract. METHODS Thirty-four patients with a history of adverse reactions to food, GI tract symptoms, and birch pollen pollinosis and five healthy controls underwent COLAP test. Twenty minutes after endoscopic challenge of the cecal mucosa with rBet v 1, the mucosal wheal and flare reaction was registered semiquantitatively, and tissue biopsy specimens were examined for eosinophil mucosal activation. RESULTS The mucosal reaction to rBet v 1 was correlated with the presence of pollinosis (P = 0.004), history of adverse reaction to Bet v 1-associated food allergens (P = 0.001), and tissue eosinophils' activation (P < 0.001). A wheal and flare reaction in the COLAP test was observed in 13 of 16 patients (81%) with a history of GI tract symptoms associated with the ingestion of Bet v 1-related foods and in four of 18 (22%) patients with a negative history (P < 0.001). The control group did not develop visible mucosal reactions to rBet v 1. Systemic anaphylactic reactions did not occur. CONCLUSIONS The mucosal administration of rBet v 1 by COLAP test provides a new diagnostic tool that might support the diagnosis of Bet v 1-associated food allergy manifesting in the GI tract.
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Affiliation(s)
- C. N. Pickert
- Department of Gastroenterology, Hepatology and Endocrinology; Medical School of Hannover; Hannover; Germany
| | - A. Lorentz
- Department of Nutritional Medicine; University of Hohenheim; Stuttgart; Germany
| | - M. P. Manns
- Department of Gastroenterology, Hepatology and Endocrinology; Medical School of Hannover; Hannover; Germany
| | - S. C. Bischoff
- Department of Nutritional Medicine; University of Hohenheim; Stuttgart; Germany
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35
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Vilela EG, Torres HODG, Martins FP, Ferrari MDLDA, Andrade MM, Cunha ASD. Evaluation of inflammatory activity in Crohn’s disease and ulcerative colitis. World J Gastroenterol 2012; 18:872-81. [PMID: 22408345 PMCID: PMC3297045 DOI: 10.3748/wjg.v18.i9.872] [Citation(s) in RCA: 72] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2010] [Revised: 01/22/2011] [Accepted: 01/29/2011] [Indexed: 02/06/2023] Open
Abstract
Crohn’s disease and ulcerative colitis evolve with a relapsing and remitting course. Determination of inflammatory state is crucial for the assessment of disease activity and for tailoring therapy. However, no simple diagnostic test for monitoring intestinal inflammation is available. Noninvasive markers give only indirect assessments of disease activity. Histopathological or endoscopical examinations accurately assess inflammatory activity, but they are invasive, time consuming and expensive and therefore are unsuitable for routine use. Imaging procedures are not applicable for ulcerative colitis. The usefulness of ultrasound and Doppler imaging in assessing disease activity is still a matter of discussion for Crohn’s disease, and an increased interest in computed tomography enterograph (CTE) has been seen, mainly because it can delineate the extent and severity of bowel wall inflammation, besides detecting extraluminal findings. Until now, the available data concerning the accuracy of magnetic resonance enterography in detecting disease activity is less than CTE. Due to this, clinical activity indices are still commonly used for both diseases.
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36
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Abstract
Inflammatory bowel diseases (IBD) are characterized by the invasion of leukocytes into the intestinal mucosa. However, a mixed inflammatory picture is observed that includes neutrophils, lymphocytes, monocytes, and eosinophils. To this day, the role of eosinophils in health and in disease remains unclear. Investigations into their function stem primarily from allergic diseases, asthma, and parasitic infections. This makes it even more difficult to discern a role for the fascinating eosinophil in IBDs because, unlike the lung or the skin, eosinophils reside in normal intestinal mucosa and increase in disease states; consequently, an intricate system must regulate their migration and numbers. These granulocytes are equipped with the machinery to participate in gastrointestinal (GI) inflammation and in the susceptible microenvironment, they may initiate or perpetuate an inflammatory response. A significant body of literature characterizes eosinophils present in the GI microenvironment where they have the potential to interact with other resident cells, thus promoting intestinal remodeling, mucus production, epithelial barrier, cytokine production, angiogenesis, and neuropeptide release. A number of lines of evidence support both potential beneficial and deleterious roles of eosinophils in the gut. Although studies from the gut and other mucosal organs suggest eosinophils affect mucosal GI inflammation, definitive roles for eosinophils in IBDs await discovery.
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37
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Katsanos KH, Zinovieva E, Lambri E, Tsianos EV. Eosinophilic-Crohn overlap colitis and review of the literature. J Crohns Colitis 2011; 5:256-61. [PMID: 21575892 DOI: 10.1016/j.crohns.2011.02.009] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2011] [Revised: 02/11/2011] [Accepted: 02/12/2011] [Indexed: 02/08/2023]
Abstract
Eosinophilic colitis is an idiopathic inflammation of the alimentary canal and is characterized by infiltration of the intestinal wall by eosinophils, massive submucosal edema, and peripheral eosinophilia. However, the presence of eosinophils in a colon biopsy requires thorough searching for secondary causes and eosinophilic colitis remains a diagnosis of exclusion. A 67-year-old male patient underwent a diagnostic ileocolonoscopy because of recurrent episodes of diarrhea for the last six months. Colonoscopy revealed a normal terminal ileum while in the entire colon an erythematous mucosa with very slight edema on a continuous pattern that was more pronounced in the left colon. The laboratory workup demonstrated eosinophils slightly elevated, biochemical tests were unremarkable and further clinical and laboratory workup was unremarkable. Histology showed overlapping findings of eosinophilic colitis and Crohn's colitis. Patient started on mesalazine 2.4 with very good results. A review of the literature shows that the spectrum of eosinophil involvement in inflammatory bowel disease as well as in eosinophilic colitis is largely varying, including also some exceptional cases that parallel the case described herein.
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Affiliation(s)
- Konstantinos H Katsanos
- 1st Division of Internal Medicine and Hepato-gastroenterology Unit, Medical School, University of Ioannina, GR 45110, Greece
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Waddell A, Ahrens R, Steinbrecher K, Donovan B, Rothenberg ME, Munitz A, Hogan SP. Colonic eosinophilic inflammation in experimental colitis is mediated by Ly6C(high) CCR2(+) inflammatory monocyte/macrophage-derived CCL11. JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 2011; 186:5993-6003. [PMID: 21498668 PMCID: PMC3423906 DOI: 10.4049/jimmunol.1003844] [Citation(s) in RCA: 86] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Recent genome-wide association studies of pediatric inflammatory bowel disease have implicated the 17q12 loci, which contains the eosinophil-specific chemokine gene CCL11, with early-onset inflammatory bowel disease susceptibility. In the current study, we employed a murine model of experimental colitis to define the molecular pathways that regulate CCL11 expression in the chronic intestinal inflammation and pathophysiology of experimental colitis. Bone marrow chimera experiments showed that hematopoietic cell-derived CCL11 is sufficient for CCL11-mediated colonic eosinophilic inflammation. We show that dextran sodium sulfate (DSS) treatment promotes the recruitment of F4/80(+)CD11b(+)CCR2(+)Ly6C(high) inflammatory monocytes into the colon. F4/80(+)CD11b(+)CCR2(+)Ly6C(high) monocytes express CCL11, and their recruitment positively correlated with colonic eosinophilic inflammation. Phenotypic analysis of purified Ly6C(high) intestinal inflammatory macrophages revealed that these cells express both M1- and M2-associated genes, including Il6, Ccl4, Cxcl2, Arg1, Chi3l3, Ccl11, and Il10, respectively. Attenuation of DSS-induced F4/80(+)CD11b(+)CCR2(+)Ly6C(high) monocyte recruitment to the colon in CCR2(-/-) mice was associated with decreased colonic CCL11 expression, eosinophilic inflammation, and DSS-induced histopathology. These studies identify a mechanism for DSS-induced colonic eosinophilia mediated by Ly6C(high)CCR2(+) inflammatory monocyte/macrophage-derived CCL11.
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MESH Headings
- Animals
- Antigens, Differentiation/genetics
- Antigens, Ly/analysis
- Antigens, Ly/immunology
- Bone Marrow Cells
- CD11b Antigen/immunology
- Chemokine CCL11/genetics
- Chemokine CCL11/immunology
- Chemokine CCL11/metabolism
- Colitis/chemically induced
- Colitis/immunology
- Colitis/metabolism
- Colon/immunology
- Dextran Sulfate/pharmacology
- Disease Models, Animal
- Enzyme-Linked Immunosorbent Assay
- Eosinophilia/immunology
- Female
- Gene Expression Regulation
- Inflammatory Bowel Diseases/immunology
- Inflammatory Bowel Diseases/metabolism
- Macrophages/cytology
- Macrophages/immunology
- Male
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Mice, Knockout
- Microscopy, Fluorescence
- Monocytes/drug effects
- Monocytes/immunology
- Polymerase Chain Reaction
- Receptors, CCR2/analysis
- Receptors, CCR2/immunology
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Affiliation(s)
- Amanda Waddell
- Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229
| | - Richard Ahrens
- Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229
| | - Kris Steinbrecher
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229
| | - Burke Donovan
- Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229
| | - Marc E. Rothenberg
- Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229
| | - Ariel Munitz
- Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229
- Department of Microbiology and Clinical Immunology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, 69978, Israel
| | - Simon P. Hogan
- Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229
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39
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Han ES, Oh JY, Park HJ. Cordyceps militaris extract suppresses dextran sodium sulfate-induced acute colitis in mice and production of inflammatory mediators from macrophages and mast cells. JOURNAL OF ETHNOPHARMACOLOGY 2011; 134:703-710. [PMID: 21277968 DOI: 10.1016/j.jep.2011.01.022] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/07/2010] [Revised: 01/14/2011] [Accepted: 01/16/2011] [Indexed: 05/30/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Cordyceps militaris is a well-known medicinal mushroom used for treatment of asthma, and other bronchial and lung inflammatory diseases. AIM OF THE STUDY To investigate the anti-inflammatory effects and mechanism of Cordyceps militaris extract on a murine model of acute colitis. MATERIALS AND METHODS We induced colitis using DSS for 1 week. The disease activity index (DAI) took into account body weight loss, diarrhea, and bleeding. Colon length and crypt length were measured using a microscope. Structural changes of the colon were observed by H&E staining. NO, iNOS, and TNF-α were determined using the Griess assay. iNOS protein was determined using western blotting and quantitative reverse-transcriptase polymerase chain reaction, respectively. Degranulated mast cells in colon tissue were stained using toluidine blue. The degree of degranulated RBL-2H3 cells was measured by the β-hexosaminidase assay. RESULTS Cordyceps militaris extract significantly attenuated DSS-induced DAI scores (e.g., body weight loss, diarrhea, gross bleeding). Cordyceps militaris extract also effectively prevented shortening of colon length and crypt length. Histological analysis indicated that Cordyceps militaris extract suppressed epithelial damage, loss of goblet cells, loss of crypts, and infiltration of inflammatory cells induced by DSS. In addition, Cordyceps militaris extract inhibited iNOS and TNF-α mRNA expression in colon tissue of DSS-induced colitis and in LPS-stimulated RAW264.7 cells. Cordyceps militaris extract suppressed degranulation of mast cells in the colon of mice with DSS-induced colitis and in antigen-stimulated mast cells. CONCLUSION These results suggest that Cordyceps militaris extract has anti-inflammatory activity in DSS-induced acute colitis by down-regulating production and expression of inflammatory mediators. These findings suggest that Cordyceps militaris extract might be applied as an agent for prevention or treatment of inflammatory bowel diseases (IBDs).
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Affiliation(s)
- Eun Su Han
- Department of Bioscience and Biotechnology, Konkuk University, 1 Hwayang-dong, Kwangjin-gu, Seoul 143-701, Republic of Korea
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Albert EJ, Duplisea J, Dawicki W, Haidl ID, Marshall JS. Tissue eosinophilia in a mouse model of colitis is highly dependent on TLR2 and independent of mast cells. THE AMERICAN JOURNAL OF PATHOLOGY 2010; 178:150-60. [PMID: 21224053 DOI: 10.1016/j.ajpath.2010.11.041] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/10/2010] [Revised: 07/22/2010] [Accepted: 09/09/2010] [Indexed: 12/20/2022]
Abstract
The mechanisms initiating eosinophil influx into sites of inflammation have been well studied in allergic disease but are poorly understood in other settings. This study examined the roles of TLR2 and mast cells in eosinophil accumulation during a nonallergic model of eosinophilia-associated colitis. TLR2-deficient mice (TLR2(-/-)) developed a more severe colitis than wild-type mice in the dextran sodium sulfate (DSS) model. However, they had significantly fewer eosinophils in the submucosa of the cecum (P < 0.01) and mid-colon (P < 0.01) than did wild-type mice after DSS treatment. Decreased eosinophilia in TLR2(-/-) mice was associated with lower levels of cecal CCL11 (P < 0.01). Peritoneal eosinophils did not express TLR2 protein, but TLR2 ligand injection into the peritoneal cavity induced local eosinophil recruitment, indicating that TLR2 activation of other cell types can mediate eosinophil recruitment. After DSS treatment, mast cell-deficient (Kit(W-sh/W-sh)) mice had similar levels of intestinal tissue eosinophilia were observed as those in wild-type mice. However, mast cell-deficient mice were partially protected from DSS-induced weight loss, an effect that was reversed by mast cell reconstitution. Overall, this study indicates a critical role for indirect TLR2-dependent pathways, but not mast cells, in the generation of eosinophilia in the large intestine during experimental colitis and has important implications for the regulation of eosinophils at mucosal inflammatory sites.
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Affiliation(s)
- Eric J Albert
- Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada
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41
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Hepburn IS, Sridhar S, Schade RR. Eosinophilic ascites, an unusual presentation of eosinophilic gastroenteritis: A case report and review. World J Gastrointest Pathophysiol 2010; 1:166-70. [PMID: 21607158 PMCID: PMC3097962 DOI: 10.4291/wjgp.v1.i5.166] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2010] [Revised: 09/28/2010] [Accepted: 10/05/2010] [Indexed: 02/06/2023] Open
Abstract
Eosinophilic ascites (EA) is a rare disorder of unknown etiology that has been reported in both adult and pediatric patients. It is a part of the syndrome of eosinophilic gastroenteritis, which is characterized by eosinophilic infiltration of any or all layers of the gut wall and may involve any segment of the gastrointestinal tract. Peripheral eosinophilia may or may not be present. We report a case of EA that developed post partum.
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Maltby S, Wohlfarth C, Gold M, Zbytnuik L, Hughes MR, McNagny KM. CD34 is required for infiltration of eosinophils into the colon and pathology associated with DSS-induced ulcerative colitis. THE AMERICAN JOURNAL OF PATHOLOGY 2010; 177:1244-54. [PMID: 20696776 DOI: 10.2353/ajpath.2010.100191] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Eosinophil migration into the gut and the release of granular mediators plays a critical role in the pathogenesis of inflammatory bowel diseases, including ulcerative colitis. We recently demonstrated that eosinophil migration into the lung requires cell surface expression of the sialomucin CD34 on mast cells and eosinophils in an asthma model. Based on these findings, we investigated a similar role for CD34 in the migration of eosinophils and other inflammatory cells into the colon as well as explored the effects of CD34 ablation on disease development in a dextran sulfate sodium-induced model of ulcerative colitis. Our findings demonstrate decreased disease severity in dextran sulfate sodium-treated Cd34(-/-) mice, as assessed by weight loss, diarrhea, bleeding, colon shortening and tissue pathology, compared with wild-type controls. CD34 was predominantly expressed on eosinophils within inflamed colon tissues, and Cd34(-/-) animals exhibited drastically reduced colon eosinophil infiltration. Using chimeric animals, we demonstrated that decreased disease pathology resulted from loss of CD34 from bone marrow-derived cells and that eosinophilia in Cd34(-/-)IL5(Tg) animals was sufficient to overcome protection from disease. In addition, we demonstrated a decrease in peripheral blood eosinophil numbers following dextran sulfate sodium treatment. These findings demonstrate that CD34 was expressed on colon-infiltrating eosinophils and played a role in eosinophil migration. Further, our findings suggest CD34 is required for efficient eosinophil migration, but not proliferation or expansion, in the development of ulcerative colitis.
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Affiliation(s)
- Steven Maltby
- The Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada
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43
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Silva AC, Levy L, Trindade JC, Mendonça P, Silva C, Lopes AI. Faecal and serum levels of eosinophil cationic protein in a healthy paediatric population. Scandinavian Journal of Clinical and Laboratory Investigation 2009; 67:757-66. [PMID: 17852809 DOI: 10.1080/00365510701308337] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND Eosinophil cationic protein (ECP) has been regarded as an excellent marker of eosinophil activation in various diseases where eosinophil-mediated inflammation plays a role. Recently, it has been suggested as a faecal marker of intestinal inflammation in several immune-mediated diseases with gastrointestinal expression. Owing to the scarcity of information at paediatric age, the establishment of reference values is necessary before further clinical studies. OBJECTIVE To determine faecal and serum ECP levels in healthy children and their association with other biological parameters, thereby providing background additional validation data for this age group. METHODS Faecal and serum ECP levels were available from healthy Caucasian children recruited at a regular outpatient clinic. Exclusion criteria were: chronic illnesses, acute illness, mucosal bleeding and recent pharmacological medication. Faecal and serum ECP levels and faecal a1AT were determined by commercial radioimmunoassay and serum IgE by fluoroenzyme immunoassay Uni-CAP. RESULTS Mean and median faecal ECP levels were 1.93 microg/g and 1.20 microg/g, respectively (range 0.41-22.20),while the corresponding serum ECP levels were 13.50 microg/L and 9.54 microg/L, respectively (range 0.20-74.8). The cut-offs found were 2.80 microg/g and 16.89 microg/L for faecal and serum ECP, respectively. A significant (p=0.001) increase in serum, but not in faecal, ECP levels was found among patients with high peripheral eosinophil blood count. Neither faecal nor serum ECP levels were influenced by serum IgE levels. CONCLUSIONS Faecal and serum ECP levels, as determined in the present study, add background information concerning reference levels at paediatric age for further studies indifferent clinical settings.
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Affiliation(s)
- A C Silva
- Paediatric Department, University Hospital de Santa Maria, Lisbon, Portugal.
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44
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Bischoff SC, Mailer R, Pabst O, Weier G, Sedlik W, Li Z, Chen JJ, Murphy DL, Gershon MD. Role of serotonin in intestinal inflammation: knockout of serotonin reuptake transporter exacerbates 2,4,6-trinitrobenzene sulfonic acid colitis in mice. Am J Physiol Gastrointest Liver Physiol 2009; 296:G685-95. [PMID: 19095763 DOI: 10.1152/ajpgi.90685.2008] [Citation(s) in RCA: 147] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Serotonin (5-HT) regulates peristaltic and secretory reflexes in the gut. The serotonin reuptake transporter (SERT; SLC6A4), which inactivates 5-HT, is expressed in the intestinal mucosa and the enteric nervous system. Stool water content is increased and colonic motility is irregular in mice with a targeted deletion of SERT. We tested the hypotheses that 5-HT plays a role in regulating intestinal inflammation and that the potentiation of serotonergic signaling that results from SERT deletion is proinflammatory. Rectal installation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) was used to induce an immune-mediated colitis, which was compared in SERT knockout mice and littermate controls. Intestinal myeloperoxidase and histamine levels were significantly increased, whereas the survival rate and state of health were significantly decreased in TNBS-treated mice that lacked SERT. Deletion of SERT thus increases the severity of TNBS colitis. These data suggest that 5-HT and its SERT-mediated termination play roles in intestinal immune/inflammatory responses in mice.
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Affiliation(s)
- Stephan C Bischoff
- Department of Nutritional Medicine and Immunology, University of Hohenheim, D-70593 Stuttgart, Germany.
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45
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Fleischer DM, Atkins D. Evaluation of the patient with suspected eosinophilic gastrointestinal disease. Immunol Allergy Clin North Am 2009; 29:53-63, ix. [PMID: 19141341 DOI: 10.1016/j.iac.2008.09.002] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
This article focuses on the evaluation and management of eosinophilic gastrointestinal diseases other than eosinophilic esophagitis. Those diseases include eosinophilic gastritis, gastroenteritis, enteritis, and colitis. The diagnosis of eosinophilic gastrointestinal disease is primarily dependent on the clinical history and histopathology of multiple biopsy specimens after ruling out other causes of intestinal eosinophilia. The diagnosis of eosinophilic gastrointestinal diseases other than eosinophilic esophagitis is complicated by the lack of uniformly accepted diagnostic criteria. Treatment involves evaluation for food sensitivity, elimination diets, and the use of anti-allergy and anti-inflammatory medications with varying degrees of success. Little is known about the natural history of eosinophilic gastrointestinal diseases, underscoring the need for long-term follow-up studies of patients with these disorders.
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Affiliation(s)
- David M Fleischer
- Department of Pediatrics, Division of Pediatric Allergy and Immunology, National Jewish Health, University of Colorado Health Sciences Center, 1400 Jackson Street, J321, Denver, CO 80206, USA
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Shirai T, Komiyama A, Hayakawa H, Hashimoto D, Suda T, Chida K. Eosinophil-associated gastrointestinal disorders with asthma: immunohistochemical analyses. Intern Med 2009; 48:1315-21. [PMID: 19652438 DOI: 10.2169/internalmedicine.48.2053] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
We report 5 patients with eosinophil-associated gastrointestinal disorders (EGIDs) and asthma. All patients developed EGIDs while asthma remained clinically stable. Asthma severity was moderate persistent and severe persistent and 2 patients had intolerance to nonsteroidal anti-inflammatory drugs. By immunohistochemical analysis of the mucosa, eosinophils, macrophages, and T cells were found to be the major infiltrating cells. There was a lesser degree of infiltration of mast cells and B cells but no neutrophils. Compared with normal controls, increased counts of eosinophils and CD8+ T cells were found in the duodenum, and eosinophils, macrophages, and CD4+ T cells in the colon.
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Affiliation(s)
- Toshihiro Shirai
- Department of Respiratory Medicine, Shizuoka General Hospital, Shizuoka.
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47
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Ahrens R, Waddell A, Seidu L, Blanchard C, Carey R, Forbes E, Lampinen M, Wilson T, Cohen E, Stringer K, Ballard E, Munitz A, Xu H, Lee N, Lee JJ, Rothenberg ME, Denson L, Hogan SP. Intestinal macrophage/epithelial cell-derived CCL11/eotaxin-1 mediates eosinophil recruitment and function in pediatric ulcerative colitis. THE JOURNAL OF IMMUNOLOGY 2008; 181:7390-9. [PMID: 18981162 DOI: 10.4049/jimmunol.181.10.7390] [Citation(s) in RCA: 136] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Clinical studies have demonstrated a link between the eosinophil-selective chemokines, eotaxins (eotaxin-1/CCL11 and eotaxin-2/CCL24), eosinophils, and the inflammatory bowel diseases, Crohn's disease and ulcerative colitis (UC). However, the cellular source and individual contribution of the eotaxins to colonic eosinophilic accumulation in inflammatory bowel diseases remain unclear. In this study we demonstrate, by gene array and quantitative PCR, elevated levels of eotaxin-1 mRNA in the rectosigmoid colon of pediatric UC patients. We show that elevated levels of eotaxin-1 mRNA positively correlated with rectosigmoid eosinophil numbers. Further, colonic eosinophils appeared to be degranulating, and the levels positively correlated with disease severity. Using the dextran sodium sulfate (DSS)-induced intestinal epithelial injury model, we show that DSS treatment of mice strongly induced colonic eotaxin-1 and eotaxin-2 expression and eosinophil levels. Analysis of eosinophil-deficient mice defined an effector role for eosinophils in disease pathology. DSS treatment of eotaxin-2(-/-) and eotaxin-1/2(-/-) mice demonstrated that eosinophil recruitment was dependent on eotaxin-1. In situ and immunofluorescence analysis-identified eotaxin-1 expression was restricted to intestinal F4/80(+)CD11b(+) macrophages in DSS-induced epithelial injury and to CD68(+) intestinal macrophages and the basolateral compartment of intestinal epithelial cells in pediatric UC. These data demonstrate that intestinal macrophage and epithelial cell-derived eotaxin-1 plays a critical role in the regulation of eosinophil recruitment in colonic eosinophilic disease such as pediatric UC and provides a basis for targeting the eosinophil/eotaxin-1 axis in UC.
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Affiliation(s)
- Richard Ahrens
- Division of Allergy and Immunology, Department of Pediatrics, University of Cincinnati College of Medicine, CCHMC, Cincinnati, OH 45229, USA
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48
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Ooi CY, Day AS, Jackson R, Bohane TD, Tobias V, Lemberg DA. Eosinophilic esophagitis in children with celiac disease. J Gastroenterol Hepatol 2008; 23:1144-8. [PMID: 18070017 DOI: 10.1111/j.1440-1746.2007.05239.x] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS Eosinophilic esophagitis and celiac disease are distinct gastrointestinal disorders. The present study in children highlights the possible coexistence of these two conditions. This study also analyzes the epidemiological and clinical profiles of these patients. METHODS The medical records of patients diagnosed with celiac disease from 1 April 1999 to 31 March 2007 were reviewed. Patients with coincident histological diagnosis of eosinophilic esophagitis were retrospectively identified. The presenting symptoms, laboratory evaluations, endoscopic and histopathological findings, and treatment and follow-up outcomes of these patients were analyzed. RESULTS Of the 221 patients with celiac disease, seven (3.2%) were also diagnosed with eosinophilic esophagitis. A majority (6/7) presented with periumbilical pain and diarrhea. None had dysphagia. Each patient had abnormal celiac screening tests. Three patients had peripheral blood eosinophilia and elevated eosinophil cationic protein. Endoscopic changes of eosinophilic esophagitis and celiac disease were apparent in the majority of patients (6/7). A gluten-free diet was instituted in every patient. Topical corticosteroid therapy was started in one patient at diagnosis and in another patient after repeat endoscopic and histopathological evaluations. CONCLUSIONS Awareness of the potential coexistence of eosinophilic esophagitis and celiac disease should promote optimal diagnosis of these conditions. Routine esophageal biopsies may be warranted when investigating for celiac disease.
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Affiliation(s)
- Chee Y Ooi
- Department of Gastroenterology, Sydney Children's Hospital, Randwick, NSW, Australia
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Davies MJ, Hawkins CL, Pattison DI, Rees MD. Mammalian heme peroxidases: from molecular mechanisms to health implications. Antioxid Redox Signal 2008; 10:1199-234. [PMID: 18331199 DOI: 10.1089/ars.2007.1927] [Citation(s) in RCA: 432] [Impact Index Per Article: 25.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
A marked increase in interest has occurred over the last few years in the role that mammalian heme peroxidase enzymes, primarily myeloperoxidase, eosinophil peroxidase, and lactoperoxidase, may play in both disease prevention and human pathologies. This increased interest has been sparked by developments in our understanding of polymorphisms that control the levels of these enzymes, a greater understanding of the basic chemistry and biochemistry of the oxidants formed by these species, the development of specific biomarkers that can be used in vivo to detect damage induced by these oxidants, the detection of active forms of these peroxidases at most, if not all, sites of inflammation, and a correlation between the levels of these enzymes and a number of major human pathologies. This article reviews recent developments in our understanding of the enzymology, chemistry, biochemistry and biologic roles of mammalian peroxidases and the oxidants that they generate, the potential role of these oxidants in human disease, and the use of the levels of these enzymes in disease prognosis.
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Affiliation(s)
- Michael J Davies
- The Heart Research Institute, Camperdown, University of Sydney, Sydney, Australia., Faculty of Medicine, University of Sydney, Sydney, Australia.
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50
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Abstract
Eosinophils and gastrointestinal tract interact in an intimate and enigmatic relationship. Under inflammatory conditions, eosinophil infiltration in the gastrointestinal tract is a common feature of numerous eosinophilic gastrointestinal disorders (EGIDs). EGIDs are disorders, for which the diagnosis is relatively difficult. Nevertheless, some common laboratory techniques are currently used for their diagnosis and disease monitoring. Besides eosinophils, mast cells and T cells have also been suggested to play a role in the pathogenesis of these disorders. Here, we review the pathogenesis and common laboratory approaches applied for their diagnosis, in particular eosinophil and mast cell markers.
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Affiliation(s)
- Sébastien Conus
- Department of Pharmacology, University of Bern, Bern, Switzerland.
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