Publicação
Esofagite Eosinofílica - Uma Revisão Fisiopatológica
| Resumo: | Eosinophilic esophagitis (EoE) is a chronic disease, triggered by food antigens and mediated by a Th2 inflammatory response. The disease was first described about 3 decades ago and is characterized clinically by symptoms of esophageal dysfunction. EoE is also associated with atopic comorbidities and, histologically, there is an eosinophilic infiltrate in the esophageal tissue. The knowledge of this disease’s pathophysiology is still far from enlightened, however great progress has been made in understanding the genetic and molecular mechanisms behind it, allowing for the development of better methods of diagnosis, prediction of disease risk and of more effective treatments. The review of the research done in this area puts the findings of the various studies in perspective, brings up the inconsistencies between them, and allows a knowledge update, regarding the latest discoveries obtained in the area.The literature search was performed using the PubMed database and the equation of research "eosinophilic esophagitis/pathology OR eosinophilic esophagitis/ etiology", applying the inclusion filters of articles published only in Portuguese or English, between 1 of January 2008 to the present date and only articles with abstract available. Bibliographical references of those articles and other articles not included in the research, but with importance in the global knowledge of the subject, were also consulted.Despite the great relationship between eosinophilic esophagitis and allergic/atopic comorbidities, there is no classical immediate and immunoglobulin E (IgE) mediated response as a pillar of EoE pathophysiology. Genetic heritability appears to be low and suggests that the shared environment should be the biggest factor for disease risk, which includes early exposure to exogenous antigens and a microbiome alteration.There is an exaggerated Th2 inflammatory response to antigens, with deregulation of the expression of chemoattractant molecules, such as thymus stromal lymphopoetin and eotaxin-3, but also of epithelial barrier molecules, such as desmoglein, filaggrin, and calpain-14. Genetic studies confirmed the involvement and over-expression of calpain-14, of the thymic stromal lymphopoetin (and its membrane receptor) and revealed the implication of the STAT6 pathway.In all studies researched, there seems to be a consensus that, to develop EoE, a dysfunctional epithelial barrier with abnormal expression of desmoglein, filaggrin and other components is required. This dysfunction may exist as an initial triggering factor or caused by the existing inflammation. There is also a hypersensitivity of the epithelium, with exaggerated production of basophil and eosinophil chemoattractants, in the presence of interleukins such as IL-4, IL-5 and IL-13, which influence cell recruitment and inflammation. Eosinophils recruited into the tissue release toxic proteins that contribute to the inflammation of the esophagus and stimulate the production of extracellular matrix proteins, leading to long-term esophageal fibrosis. Future studies should focus on the molecular components already proven to be most important in the pathophysiology of the disease, in order to differentiate the initial and precipitating deregulations of the disease from the dysregulations that are a consequence of the active disease. |
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| Autores principais: | Nunes, Bruno André Puim |
| Assunto: | Esofagite eosinofílica Fisiopatologia Etiologia Hipersensibilidade alimentar Inflamação Eosinophilic esophagitis Physiopathology Etiology Food hypersensitivity Inflammation |
| Ano: | 2018 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso embargado |
| Instituição associada: | Universidade de Coimbra |
| Idioma: | português |
| Origem: | Estudo Geral - Universidade de Coimbra |
| Resumo: | Eosinophilic esophagitis (EoE) is a chronic disease, triggered by food antigens and mediated by a Th2 inflammatory response. The disease was first described about 3 decades ago and is characterized clinically by symptoms of esophageal dysfunction. EoE is also associated with atopic comorbidities and, histologically, there is an eosinophilic infiltrate in the esophageal tissue. The knowledge of this disease’s pathophysiology is still far from enlightened, however great progress has been made in understanding the genetic and molecular mechanisms behind it, allowing for the development of better methods of diagnosis, prediction of disease risk and of more effective treatments. The review of the research done in this area puts the findings of the various studies in perspective, brings up the inconsistencies between them, and allows a knowledge update, regarding the latest discoveries obtained in the area.The literature search was performed using the PubMed database and the equation of research "eosinophilic esophagitis/pathology OR eosinophilic esophagitis/ etiology", applying the inclusion filters of articles published only in Portuguese or English, between 1 of January 2008 to the present date and only articles with abstract available. Bibliographical references of those articles and other articles not included in the research, but with importance in the global knowledge of the subject, were also consulted.Despite the great relationship between eosinophilic esophagitis and allergic/atopic comorbidities, there is no classical immediate and immunoglobulin E (IgE) mediated response as a pillar of EoE pathophysiology. Genetic heritability appears to be low and suggests that the shared environment should be the biggest factor for disease risk, which includes early exposure to exogenous antigens and a microbiome alteration.There is an exaggerated Th2 inflammatory response to antigens, with deregulation of the expression of chemoattractant molecules, such as thymus stromal lymphopoetin and eotaxin-3, but also of epithelial barrier molecules, such as desmoglein, filaggrin, and calpain-14. Genetic studies confirmed the involvement and over-expression of calpain-14, of the thymic stromal lymphopoetin (and its membrane receptor) and revealed the implication of the STAT6 pathway.In all studies researched, there seems to be a consensus that, to develop EoE, a dysfunctional epithelial barrier with abnormal expression of desmoglein, filaggrin and other components is required. This dysfunction may exist as an initial triggering factor or caused by the existing inflammation. There is also a hypersensitivity of the epithelium, with exaggerated production of basophil and eosinophil chemoattractants, in the presence of interleukins such as IL-4, IL-5 and IL-13, which influence cell recruitment and inflammation. Eosinophils recruited into the tissue release toxic proteins that contribute to the inflammation of the esophagus and stimulate the production of extracellular matrix proteins, leading to long-term esophageal fibrosis. Future studies should focus on the molecular components already proven to be most important in the pathophysiology of the disease, in order to differentiate the initial and precipitating deregulations of the disease from the dysregulations that are a consequence of the active disease. |
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