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可溶性白细胞介素-2受体水平作为重症登革热患儿噬血细胞性淋巴组织细胞增生症的标志物

Soluble Interleukin-2 Receptor Level as a Marker of Hemophagocytic Lymphohistiocytosis in Children With Severe Dengue.

作者信息

Singh Dhirendra, Raghunathan Veena, Dhaliwal Maninder, Rastogi Neha, Chadha Ritu, Yadav Satya Prakash

机构信息

Medanta the Medicity Hospital, Gurgaon, India.

出版信息

Front Pediatr. 2021 Oct 27;9:721857. doi: 10.3389/fped.2021.721857. eCollection 2021.

Abstract

Dengue induced-hemophagocytic lymphohistiocytosis (HLH) is increasingly recognized as an important cause of secondary HLH. Early identification of dengue HLH and directed therapy for HLH may help to alter the outcomes in critically ill patients. Soluble interleukin-2 receptor (IL2R) is a useful inflammatory marker and is seen to correlate with HLH disease activity. There is scarcity of data on IL2R in pediatric dengue patients with HLH. All patients (age < 18 years) with severe dengue confirmed by positive dengue IgM ELISA admitted to PICU were retrospectively enrolled. Patientswere screened for presence of HLH according to HLH 2004 criteria. Hemogram, ferritin, fibrinogen, liver, and renal function tests were noted. Patients who met four or more HLH criteria were treated with steroids and IL2R levels were sent to confirm the diagnosis of HLH. Out of 15 patients, nine patients met the criteria of HLH. IL2R levels were high in all HLH patients (mean 51,711, range 18,000-98,715 pg/mL). Mean ferritin levels were high in the HLH group as compared to non-HLH group (mean ferritin 34,593 vs. 3,206 ng/mL; -value 0.004). Liver dysfunction was notably higher in the HLH group compared to non-HLH group (mean alanine aminotransferase 6,621 U/L vs. 165.6 U/L; -value 0.04, mean aspartate aminotransferase 2,145 U/L vs. 104.2 U/L; 0.04, bilirubin level 4.2 mg/dL vs. 0.7 mg/dL; -value 0.03). Four patients in the HLH group had acute kidney injury (AKI) and two required renal replacement therapy in the form of sustained low efficiency dialysis (SLED). Requirement for invasive ventilation was exclusively seen in HLH group and three patients developed ARDS. Two patients each in HLH and non-HLH group had shock requiring vasoactive therapy in addition to fluids. Mean days of ICU and hospital stay were higher in HLH group vs. non-HLH group but not statistically significant (6.4 vs. 4.4; -value 0.32 and 8.44 vs. 5.6; -value 0.18 days, respectively). All children in HLH group received steroids as per HLH protocol. In the HLH group, seven survived while two died. In the non-HLH group, all five patients survived. We concluded that IL2R levels are high in dengue HLH and useful for definitive diagnosis. Early recognition of this condition in severe dengue and prompt steroid therapy improves chances of better outcome.

摘要

登革热诱发的噬血细胞性淋巴组织细胞增生症(HLH)越来越被认为是继发性HLH的一个重要病因。早期识别登革热HLH并针对HLH进行定向治疗可能有助于改变重症患者的预后。可溶性白细胞介素-2受体(IL2R)是一种有用的炎症标志物,且被发现与HLH疾病活动相关。关于患有HLH的儿童登革热患者的IL2R数据匮乏。对入住儿科重症监护病房(PICU)且登革热IgM酶联免疫吸附测定(ELISA)呈阳性确诊为重症登革热的所有患者(年龄<18岁)进行回顾性纳入。根据2004年HLH标准对患者进行HLH筛查。记录血常规、铁蛋白、纤维蛋白原、肝功能和肾功能检查结果。符合四项或更多HLH标准的患者接受类固醇治疗,并检测IL2R水平以确诊HLH。15例患者中,9例符合HLH标准。所有HLH患者的IL2R水平均较高(平均51,711,范围18,000 - 98,715 pg/mL)。与非HLH组相比,HLH组的平均铁蛋白水平较高(平均铁蛋白34,593 vs. 3,206 ng/mL;P值0.004)。与非HLH组相比,HLH组的肝功能障碍明显更高(平均丙氨酸转氨酶6,621 U/L vs. 165.6 U/L;P值0.04,平均天冬氨酸转氨酶2,145 U/L vs. 104.2 U/L;P值0.04,胆红素水平4.2 mg/dL vs. 0.7 mg/dL;P值0.03)。HLH组有4例患者发生急性肾损伤(AKI),2例需要以持续低效透析(SLED)形式进行肾脏替代治疗。仅在HLH组出现有创通气需求,3例患者发生急性呼吸窘迫综合征(ARDS)。HLH组和非HLH组各有2例患者除补液外还需要血管活性药物治疗以纠正休克。HLH组的平均重症监护病房(ICU)住院天数和住院总天数均高于非HLH组,但差异无统计学意义(分别为6.4天vs. 4.4天;P值0.32和8.44天vs. 5.6天;P值0.18天)。HLH组的所有儿童均按照HLH方案接受类固醇治疗。HLH组中,7例存活,2例死亡。非HLH组的所有5例患者均存活。我们得出结论,登革热HLH患者的IL2R水平较高,对明确诊断有用。在重症登革热中早期识别这种情况并及时进行类固醇治疗可提高获得更好预后的机会。

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