Immunomodulatory therapy of eosinophil-associated gastrointestinal diseases.
Immunomodulatory therapy of eosinophil-associated gastrointestinal diseases.
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嗜酸性粒细胞相关胃肠道疾病的免疫调节治疗。
DOI：
10.1111/j.1365-2222.2008.03122.x
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发表时间：
2008-12
期刊：
影响因子：
--
通讯作者：
Prussin C
中科院分区：
文献类型：
--
作者：
Stone KD;Prussin C
嗜酸性粒细胞相关胃肠道疾病（EGID），包括嗜酸性粒细胞性食管炎（EE）和嗜酸性粒细胞性胃肠炎（EG），是一系列日益被认可的炎症性疾病，其特征为胃肠道症状和胃肠道嗜酸性粒细胞浸润。在一些患者中，显著的发病率与食管狭窄的发展相关。对食物过敏原的免疫介导的反应似乎驱动了一部分患者的炎症，特别是那些患有孤立性EE的患者，但饮食干预在EE中仍然很困难，并且在EG中效果较差。尽管这些疾病的发病率越来越高，医生对它们的认识也越来越高，但目前美国或欧盟监管机构都没有专门批准用于EGID的药物。缺乏安全有效的EGID治疗方法是这些患者护理的主要障碍，并强调了对新治疗方法的需求。本文简要讨论了目前可用的“标签外”药物治疗EGID，最显着的局部和全身皮质类固醇。EGID的发病机制研究提示了可能的治疗靶点，相反，机械靶向治疗的临床试验使人们深入了解疾病的发病机制。因此，EGID发病机制作为机械靶向免疫治疗的介绍进行了讨论。已被用于EGID，抗IgE（奥马珠单抗）和抗IL-5（SCH 55700/瑞利珠单抗和美泊利珠单抗）的两个生物类别，进行了讨论。由于EGID与哮喘和特应性皮炎的发病机制相似，目前在哮喘管理的早期试验中的生物疗法也被简要讨论为EGID的潜在治疗药物。鉴于目前治疗的不足和这些疾病的发病机制的快速发展的知识，EGID是一个理想的模型，用于翻译最近的进展，了解免疫发病机制为基础的治疗机制。还需要进一步了解发病机制中的早期事件以开发预防性和疾病改善治疗。
Eosinophil-associated gastrointestinal disorders (EGIDs), including eosinophilic esophagitis (EE) and eosinophilic gastroenteritis (EG), are a spectrum of increasingly recognized inflammatory diseases characterized by gastrointestinal symptoms and eosinophilic infiltration of the gastrointestinal tract. Significant morbidity is associated with the development of esophageal strictures in some patients. Immune-mediated reactions to food allergens appear to drive the inflammation in a subset of patients, especially those with solitary EE, but dietary interventions remain difficult in EE and are less effective in EG. Despite the increasing incidence of these disorders and their increased recognition by physicians, there are currently no medications that either United States or European Union regulatory agencies have specifically approved for use in EGIDs. This lack of safe and effective therapies for EGIDs is a major obstacle in the care of these patients and underscores the need for new therapeutic approaches. This review briefly discusses the currently available “off label” drug treatments for EGIDs, most notably topical and systemic corticosteroids. Pathogenesis studies of EGIDs suggest possible therapeutic targets, and conversely, clinical trials of mechanistically-targeted therapeutics give insight into disease pathogenesis. Thus, EGID pathogenesis is discussed as an introduction to mechanistically-targeted immunotherapeutics. The two biologic categories that have been used in EGIDs, anti-IgE (omalizumab) and anti-IL-5 (SCH55700/reslizumab and mepolizumab), are discussed. Since there are similarities in the pathogenesis of EGIDs with asthma and atopic dermatitis, biologic therapeutics currently in early trials for asthma management are also briefly discussed as potential therapeutic agents for EGIDs. Given the deficiencies of current therapeutics and the rapidly advancing knowledge of the pathogenesis of these disorders, EGIDs are an ideal model for translating recent advances in understanding immunopathogenesis into mechanistically-based therapeutics. Further understanding of the early events in pathogenesis is also needed to develop preventive and disease-modifying treatments.
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14.2
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