Pathogenesis and Treatment of Anaphylaxis

我们评估了102例特发性过敏反应(IA)和抗原特异性过敏反应(SA)的患者，以探讨其发病机制并确定克隆性肥大细胞病的患者。在IA患者组中，15%的人患有克隆性肥大细胞疾病，8.5%的人被诊断为阿尔法-半乳糖综合征，12.8%的人被诊断为遗传性的α-胰蛋白酶血症。 在抗原诱导过敏反应的患者中，据报道，在欧洲队列中，那些有毒液过敏反应的患者克隆性肥大细胞疾病的患病率更高。到目前为止，在我们的蛇毒过敏患者队列中(n=8)，有6人被诊断为克隆性肥大细胞病。到目前为止，在登记的五名因食物或药物引起的过敏反应的患者中，没有一人被诊断为克隆性肥大细胞疾病。 在2020财年，我们继续在临床中心COVID限制之前接纳过敏反应患者。大多数患者住进住院部，并接受骨髓程序，试图阐明病因和评估他们的疾病的发病机制。与NIH临床中心的髓系核心设施合作，我们评估所有患者的骨髓抽吸和活检，根据目前WHO诊断系统性肥大细胞增多症的标准。我们将按照CC指南的允许恢复协议注册。 为IA患者确定一种治疗方案是具有挑战性的。奥马珠单抗被批准用于治疗严重哮喘，部分作用机制是下调嗜碱性粒细胞、肥大细胞和树突状细胞表面的IgE受体。据报道，奥马珠单抗可作为辅助疗法用于治疗哮喘以外的疾病，包括食物过敏和慢性荨麻疹。我们从我们的过敏反应方案中招募符合频繁事件标准的患者参加DBPC试验，以评估奥马珠单抗在这一患者群体中的疗效。2020财年，我们完成了稿件，并将提交出版。研究中的药物没有严重的不良反应，特别是药物引起的过敏反应。 在2020财年，我们与我们的特发性过敏患者群体一起撰写了Lyons等人的手稿。有特发性过敏反应的患者与无过敏反应的对照组和有克隆性肥大细胞病和过敏反应的患者相比，遗传性α-胰腺炎(HATS)的患病率更高。HATS还与基线血清类胰蛋白酶升高有关，并可能与严重过敏反应风险增加有关。AAAAI工作组在《过敏与临床免疫学杂志》上发表了关于肥大细胞激活综合征的报告，并在《过敏》杂志上发表了一本关于特发性过敏反应患者管理的实用指南，并考虑了从过敏研究中获得的见解。

We have evaluated 102 patients referred for idiopathic anaphylaxis (IA) and antigen-specific anaphylaxis (SA) to explore pathogenesis and identify patients with clonal mast cell disease. Within the patient group with IA, 15% had clonal mast cell disease, 8.5% were diagnosed with alpha-gal syndrome, and 12.8% were diagnosed with hereditary alpha-tryptasemia. Among patients with antigen-induced anaphylaxis, those with venom anaphylaxis in European cohorts have been reported to have a higher prevalence of clonal mast cell disease. In our cohort of patients referred for venom anaphylaxis to date (n=8), six have been diagnosed with clonal mast cell disease. Of the five patients enrolled with food or drug-induced anaphylaxis, thus far, none have been diagnosed with clonal mast cell disease. In FY 2020, we continued to admit patients with anaphylaxis prior to the Clinical Center COVID restrictions. Most patients are admitted to the inpatient unit and undergo a bone marrow procedure in an attempt to elucidate the etiology and evaluate the pathogenesis of their disease. In collaboration with the NIH Clinical Center's myeloid core facility, we assess all patient bone marrow aspirates and biopsies obtained based on the current WHO criteria to diagnose systemic mastocytosis. We will resume protocol enrollment as allowed by the CC guidelines. It is challenging to identify a therapeutic regimen for patients with IA. Omalizumab is approved for the treatment of severe asthma and in part acts through a mechanism that down regulates the IgE receptor on the surface of basophils, mast cells, and dendritic cells. Omalizumab has been reported to be useful as adjunct therapy in the treatment of diseases other than asthma including food allergy and chronic urticaria. We recruited patients from our anaphylaxis protocol that met criteria for frequent events to enroll in a DBPC trial to evaluate the efficacy of omalizumab in this patient population. In FY 2020, we completed the manuscript and will submit for publication. There were no serious adverse events attributed to the study drug, in particular drug-induced anaphylaxis. In FY 2020, we contributed to a manuscript by Lyons et al with our idiopathic anaphylaxis patient population. Patients with idiopathic anaphylaxis were found to a have higher prevalence of hereditary alpha tryptasemia(HaTS) when compared to controls without anaphylaxis and patients with clonal mast cell disease and anaphylaxis. HaTS also was associated with an elevated baseline serum tryptase and was possibly associated with an increased risk of severe anaphylaxis. Insights gained from the anaphylaxis study were considerd in the creation of a practical guide to the management of patients with idiopathic anaphylaxis published in Allergy and an AAAAI Work Group report on mast cell activation syndrome in the Journal of Allergy and Clinical Immunology.