TREATMENT OF EOSINOPHILIC ESOPHAGITIS WITH OMALUZIMAB

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 嗜酸性食管炎(EE)是一种日益被认识的疾病，其特征是吞咽困难、食物嵌塞或其他儿童和年轻人的梗阻性食道症状。 EE的病理生理学机制似乎是一种由过敏/特应性反应引起的疾病。62-85%的EE患者有过敏性疾病(食物过敏、特应性皮炎、哮喘、过敏性鼻炎或结膜炎)的个人和家族病史。EE发病率的上升可能与世界范围内的变态反应和哮喘流行有关。 目前EE的治疗针对的是减少食道过敏性炎症。口服和外用皮质类固醇、色甘酸钠、孟鲁司特和元素/消除饮食都被证明是有效的。然而，这些治疗都不是针对EE的特定病理生理机制，而且有些有明显的副作用。 EE和哮喘的共同发病机制表明，针对哮喘的治疗策略也可能对EE有效。具体地说，针对与哮喘相关的过敏免疫机制的药物可能是有效的。奥马珠单抗是一种新近开发的抗IgE抗体，已被证明可以减少吸入和口服皮质类固醇的使用，减少哮喘加重的频率，并改善过敏性哮喘患者的哮喘相关症状。此外，通过降低循环中的游离IgE水平，奥马珠单抗可抑制对多种不同过敏原的免疫反应。这一信息表明，奥马珠单抗可能是治疗EE的理想疗法，因为EE的特定过敏原鲜为人知，而类固醇治疗仅抑制急性炎症反应，而不改变疾病潜在的致病机制。证明奥马珠单抗在EE中的有效性可以作为其他嗜酸性粒细胞相关疾病的模型。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Eosinophilic Esophagitis (EE) is an increasingly recognized condition characterized by dysphagia, food impaction or other obstructive esophageal symptoms in children and young adults. The pathophysiology of EE appears to be an allergy/atopy mediated disease. A personal and family history of allergic diseases (food allergies, atopic dermatitis, asthma, allergic rhinitis or conjunctivitis) has been noted in 62-85% of patients with EE. The rising incidence of EE may be related to the worldwide allergy and asthma epidemic. Current treatment of EE is directed at decreasing esophageal allergic inflammation. Oral and topical corticosteroids, cromolyn sodium, monoleukast and elemental/elimination diets have all been shown to be effective. However, none of these treatments are directed at the specific pathophysiologic mechanism of EE and some have significant side effects. The shared pathogenetic mechanisms of EE and asthma suggest that therapeutic strategies directed at asthma may also be effective for EE. Specifically those targeted at the allergic immune mechanisms involved with asthma may be effective. Omalizumab is a recently developed anti-IgE antibody that has been shown to decrease the use of inhaled and oral corticosteroids, reduce the frequency of asthma exacerbations, and improve asthma related symptoms in patients with allergic asthma. In addition, by its ability to lower free circulating IgE levels, omalizumab inhibits the immune response to many different allergens. This information suggests that omalizumab may be an ideal therapy for EE where the specific allergens are seldom known and steroid treatment merely suppresses the acute inflammatory response without altering the unerlying pathogenetic mechanism of the disease. Demonstration of omalizumab effectiveness in EE may serve as a model for other eosinophil associated diseases.