Weathering the storm: Improving therapeutic interventions for cytokine storm syndromes by targeting disease pathogenesis.
Weathering the storm: Improving therapeutic interventions for cytokine storm syndromes by targeting disease pathogenesis.
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DOI：
10.1007/s40674-017-0059-x
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发表时间：
2017-03
影响因子：
1.2
通讯作者：
Behrens EM
中科院分区：
文献类型：
--
作者：
Weaver LK;Behrens EM
细胞因子风暴综合征需要快速诊断和治疗，以限制由高炎症状态引起的发病率和死亡率，高炎症状态是这些破坏性疾病的特征。在这里，我们讨论目前的知识，指导我们的治疗决策和个体化治疗的患者细胞因子风暴综合征。首先，通常需要ICU级别的支持性护理来稳定患有暴发性疾病的患者，同时进行额外的诊断评估以确定细胞因子风暴的根本原因。当免疫激活是潜在疾病病理生理学的核心时，药物干预的重点应该是消除炎症的激发触发和启动个体化免疫抑制方案。需要监测临床反应，以确保治疗方案的改变可以在临床上得到保证。如果患者对最初的治疗干预反应不佳，可能需要升级免疫抑制，而病情好转的患者缓慢摆脱免疫抑制可能会限制与药物相关的毒性。在某些情况下，必须决定个别患者是否需要造血细胞移植以防止疾病复发。尽管采取了这些干预措施，但细胞因子风暴患者的发病率和死亡率仍然很高。因此，我们利用这篇综述来提出一个临床方案，以指导当前和未来为患有这些破坏性疾病的患者设计合理的治疗干预措施的尝试，我们认为这些措施可以加快疾病的诊断，限制与药物相关的毒性，并通过针对导致每个患者疾病的异质和动态机制来改善临床结果。
Cytokine storm syndromes require rapid diagnosis and treatment to limit the morbidity and mortality caused by the hyperinflammatory state that characterizes these devastating conditions. Herein, we discuss the current knowledge that guides our therapeutic decision-making and personalization of treatment for patients with cytokine storm syndromes. Firstly, ICU-level supportive care is often required to stabilize patients with fulminant disease while additional diagnostic evaluations proceed to determine the underlying cause of cytokine storm. Pharmacologic interventions should be focused on removing the inciting trigger of inflammation and initiation of an individualized immunosuppressive regimen when immune activation is central to the underlying disease pathophysiology. Monitoring for a clinical response is required to ensure that changes in the therapeutic regimen can be made as clinically warranted. Escalation of immunosuppression may be required if patients respond poorly to the initial therapeutic interventions, while a slow wean of immunosuppression in patients who improve can limit medication-related toxicities. In certain scenarios, a decision must be made whether an individual patient requires hematopoietic cell transplantation to prevent recurrence of disease. Despite these interventions, significant morbidity and mortality remains for cytokine storm patients. Therefore, we use this review to propose a clinical schema to guide current and future attempts to design rational therapeutic interventions for patients suffering from these devastating conditions, which we believe speeds the diagnosis of disease, limits medication-related toxicities, and improves clinical outcomes by targeting the heterogeneous and dynamic mechanisms driving disease in each individual patient.