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Eosinophilic esophagitis: updates on key unanswered questions.
Fernandez-Becker, NQ, Raja, S, Scarpignato, C, Lynch, KL, Ahuja, NK, Horsley-Silva, JL
Annals of the New York Academy of Sciences. 2020;(1):30-42
Abstract
Eosinophilic esophagitis (EoE) is a clinicopathologic disease characterized by symptoms of esophageal dysfunction and esophageal eosinophilia. In the last decade, there has been a dramatic increase in its prevalence for reasons that are not completely understood. The underlying pathophysiology involves an antigen-mediated TH 2 immune response that draws eosinophils to the esophagus, causing mucosal inflammation, esophageal remodeling, and fibrosis. This ultimately leads to esophageal dysfunction that most commonly manifests as dysphagia. In this review, we will discuss updates on key questions regarding the diagnosis and treatment of EoE.
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Eosinophilic esophagitis in children: current knowledge to open new horizons.
Alterio, T, Cardile, S, Trayers, C, Valenti, S, Loddo, I, Mardare, R, Mosca, A, Nobili, V
Scandinavian journal of gastroenterology. 2019;(7):822-829
Abstract
Eosinophilic Esophagitis (EoE) is a chronic immune/antigen-mediated condition which is also driven by genetic and environmental factors. It has been deeply investigated over the last years and its incidence is widely increasing in childhood. Although atopic diseases are closely linked with EoE, it does not recognize a classical IgE-mediate immune pathogenesis but it is rather a T helper type 2 inflammatory process. Familial clustering supports genetic predisposition in EoE and recent advances in understanding the genetic basis for EoE may eventually translate into targeted management of the disease. EoE diagnosis is based on clinical symptoms, micro, and macroscopic findings along with exclusion of gastroesophageal reflux disease (GERD) evidence. Management of the disease encompasses both dietary and pharmacological solutions that need to be specifically targeted on patients' history, clinical symptoms, and diagnostic evaluations. New therapies, currently not available in children, may represent the basis for future therapeutic options in the next years.
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The antiprotease SPINK7 serves as an inhibitory checkpoint for esophageal epithelial inflammatory responses.
Azouz, NP, Ynga-Durand, MA, Caldwell, JM, Jain, A, Rochman, M, Fischesser, DM, Ray, LM, Bedard, MC, Mingler, MK, Forney, C, et al
Science translational medicine. 2018;(444)
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Abstract
Loss of barrier integrity has an important role in eliciting type 2 immune responses, yet the molecular events that initiate and connect this with allergic inflammation remain unclear. We reveal an endogenous, homeostatic mechanism that controls barrier function and inflammatory responses in esophageal allergic inflammation. We show that a serine protease inhibitor, SPINK7 (serine peptidase inhibitor, kazal type 7), is part of the differentiation program of human esophageal epithelium and that SPINK7 depletion occurs in a human allergic, esophageal condition termed eosinophilic esophagitis. Experimental manipulation strategies reducing SPINK7 in an esophageal epithelial progenitor cell line and primary esophageal epithelial cells were sufficient to induce barrier dysfunction and transcriptional changes characterized by loss of cellular differentiation and altered gene expression known to stimulate allergic responses (for example, FLG and SPINK5). Epithelial silencing of SPINK7 promoted production of proinflammatory cytokines including thymic stromal lymphopoietin (TSLP). Loss of SPINK7 increased the activity of urokinase plasminogen-type activator (uPA), which in turn had the capacity to promote uPA receptor-dependent eosinophil activation. Treatment of epithelial cells with the broad-spectrum antiserine protease, α1 antitrypsin, reversed the pathologic features associated with SPINK7 silencing. The relevance of this pathway in vivo was supported by finding genetic epistasis between variants in TSLP and the uPA-encoding gene, PLAU We propose that the endogenous balance between SPINK7 and its target proteases is a key checkpoint in regulating mucosal differentiation, barrier function, and inflammatory responses and that protein replacement with antiproteases may be therapeutic for select allergic diseases.
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Natural history of eosinophilic esophagitis: a systematic review of epidemiology and disease course.
Shaheen, NJ, Mukkada, V, Eichinger, CS, Schofield, H, Todorova, L, Falk, GW
Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus. 2018;(8)
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Abstract
Eosinophilic esophagitis is a chronic immune-mediated esophageal disorder. For its timely diagnosis, clinicians must recognize common symptoms, and understand differences in symptoms across patient groups. The aim of this study is to systematically review the epidemiology and natural history of eosinophilic esophagitis. The MEDLINE, Embase, and Cochrane databases were searched from 1974 to February 2017 for studies describing the epidemiology and natural history of eosinophilic esophagitis. Congress abstracts from 2014 to 2016 were also searched. Search results were screened against predetermined inclusion/exclusion criteria by two independent reviewers, and data extraction was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Of 1376 articles identified, 47 met the inclusion criteria: 20 on epidemiology and 27 on natural history. Incidence and prevalence of eosinophilic esophagitis varied widely across North America and Europe, and increased over time. Incidence increased 131-fold in the Netherlands (1996-2010), 20-fold in Denmark (1997-2006), and 5.1-fold in Calgary, Canada (2004-2008). The most commonly reported symptoms were emesis and abdominal pain in children, and dysphagia and food impaction in adults. Age at diagnosis was 5.9-12.0 years in children, and approximately 30 years in adults. Time between symptom onset and diagnosis was 1.2-3.5 years in children and 3.0-8.0 years in adults. Diagnostic delay was associated with an increased risk of endoscopic features of fibrostenosis. Symptoms of eosinophilic esophagitis differed significantly by age and race. In conclusion, there is an increasing incidence and prevalence of eosinophilic esophagitis. The considerable delay between symptom onset and diagnosis suggests that clinicians do not readily recognize the disease, which may have important clinical ramifications.
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Eosinophilic esophagitis: Update in diagnosis and management. Position paper by the Italian Society of Gastroenterology and Gastrointestinal Endoscopy (SIGE).
de Bortoli, N, Penagini, R, Savarino, E, Marchi, S
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2017;(3):254-260
Abstract
Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease of the esophagus characterized by symptoms related to esophageal dysfunction, as well as significant esophageal eosinophilia. The entity exists worldwide but has been most extensively studied in Western countries. However, a wide range of symptoms has been noticed such as chest pain or gastro-esophageal reflux disease-like symptoms. Upper gastro-intestinal endoscopy and esophageal biopsies are crucial for the diagnosis. Endoscopy might be normal or reveal typical patterns such as rings, furrows, exudates, edema, and stricture. Two to four biopsies should be performed both in the distal and in the proximal esophagus, and 15 eosinophils per high power field within the esophageal epithelium are the minimal threshold to diagnose eosinophilic esophagitis. Allergy testing is recommended, although its impact to orient treatment remains to be demonstrated. Eosinophilic esophagitis treatment includes medical treatment, diet and endoscopic dilation. Proton pump inhibitors are the first-line therapy as up to 50% of patients respond well to proton pump inhibitors irrespective of objective evidence of GERD. Topical viscous corticosteroids or elimination diet are the treatment of choice in case of unresponsiveness to proton pump inhibitors.