Therapeutic Role of Anakinra, an Interleukin-1 Receptor Antagonist, in the Management of Secondary Hemophagocytic Lymphohistiocytosis/Sepsis/Multiple Organ Dysfunction/Macrophage Activating Syndrome in Critically III Children
Therapeutic Role of Anakinra, an Interleukin-1 Receptor Antagonist, in the Management of Secondary Hemophagocytic Lymphohistiocytosis/Sepsis/Multiple Organ Dysfunction/Macrophage Activating Syndrome in Critically III Children
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DOI：
10.1097/pcc.0000000000000078
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发表时间：
2014-06-01
影响因子：
4.1
通讯作者：
Birmingham, James
中科院分区：
文献类型：
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作者：
Rajasekaran, Surender;Kruse, Katherine;Birmingham, James
目的：继发性噬血细胞性淋巴组织细胞增多症、巨噬细胞活化综合征和脓毒症具有相同的炎症表型，通常导致需要重症监护的多器官功能障碍综合征。本文的目的是描述我们的经验与阿那白滞素（Kineret），一种重组白细胞介素-1受体拮抗剂，在减少全身炎症中的作用。设计：回顾性病例系列。设置：海伦·德沃斯儿童医院的PICU（大急流城，MI）。2011年1月1日期间，我们机构8名推测患有继发性噬血细胞性淋巴组织细胞增生症的危重儿童的记录，干预措施：所有患者均接受阿那白滞素（Kineret）治疗，在某些情况下，全身性皮质类固醇作为继发性噬血细胞性淋巴组织细胞增生症的一线治疗。测量和主要结果：患者的中位年龄为14岁，中位儿科死亡风险评分为11.5。其中四人此前健康，四人患有潜在疾病，这些疾病可能使他们容易患上继发性噬血细胞淋巴组织细胞增生症。PICU转移指征为呼吸窘迫50%（4/8）、心血管不稳定37.5%（3/8）和胸痛（1/8）。5例患者（62.5%）接受了机械通气，62.5%（5/8）接受了血管活性药物输注。在治疗开始时和7天后对炎症标志物进行线性评估。开始阿那白滞素治疗时，基线C反应蛋白为206 +/- 50 mg/L（平均值+/- sem），下降67.1%至68 +/- 36 mg/L（p = 0.03）。铁蛋白降低63.8%至3，210 +/-1，178 ng/mL（p = 0.30），纤维蛋白原降低42%至158 +/- 41 mg/dL（p = 0.03）。中性粒细胞绝对计数（p = 0.38）和淋巴细胞绝对计数（p = 0.69）无显著变化。无感染归因于阿那白滞素治疗。一名患者在接受造血干细胞移植前chemotherapy.Conclusions：阿那白滞素治疗后很长时间内死亡，阿那白滞素可能是这些危及生命的疾病的一种有前途的治疗方法，这些疾病可能诊断不足，往往难以治疗。
Objectives: Secondary hemophagocytic lymphohistiocytosis, macrophage activating syndrome, and sepsis share the same inflammatory phenotype leading often to multiple organ dysfunction syndrome needing intensive care. The goal of this article is to describe our experience with anakinra ( Kineret), a recombinant interleukin-1 receptor antagonist, in decreasing the systemic inflammation.Design: Retrospective case series.Setting: The PICU at the Helen DeVos Children's Hospital (Grand Rapids, MI).Patients: The records of eight critically ill children presumed to have secondary hemophagocytic lymphohistiocytosis at our institution between January 1, 2011, and July 31, 2012, were reviewed.Interventions: All of the patients were treated with anakinra (Kineret) and in some cases systemic corticosteroids as first-line therapy for secondary hemophagocytic lymphohistiocytosis.Measurements and Main Results: Patients had a median age of 14 years and a median Pediatric Risk of Mortality score of 11.5. Four were previously healthy and four had underlying diseases that could have made them susceptible to secondary hemophagocytic lymphohistiocytosis. Indications for PICU transfer were respiratory distress 50% (4 of 8), cardiovascular instability 37.5% (3 of 8), and chest pain (1 of 8). Five of the patients (62.5%) were mechanically ventilated and 62.5% (5 of 8) received vasoactive infusions. Inflammatory markers were assessed linearly at the start of therapy and 7 days later. Baseline C-reactive protein was 206 +/- 50 mg/L (mean +/- sem) at the start of anakinra and decreased by 67.1% to 68 +/- 36 mg/L (p = 0.03). Ferritin decreased by 63.8% to 3,210 +/- 1,178 ng/mL (p = 0.30), and fibrinogen decreased by 42% to 158 +/- 41 mg/dL (p = 0.03). Absolute neutrophil count (p = 0.38) and absolute lymphocyte count (p = 0.69) did not change significantly. No infections were attributed to anakinra therapy. One patient died long after treatment with anakinra while receiving pre-hematopoietic stem cell transplant chemotherapy.Conclusions: Anakinra could represent a promising therapeutic approach in these life-threatening disorders that are likely underdiagnosed and often difficult to treat.