Lee Joo Young, Son Minji, Kang Jin Han, Choi Ui Yoon
a Department of Pediatrics , College of Medicine, The Catholic University of Korea , Seoul , Republic of Korea.
b Department of Pediatrics, St. Paul's Hospital, College of Medicine , The Catholic University of Korea , Seoul , Republic of Korea.
Postgrad Med. 2018 Mar;130(2):258-263. doi: 10.1080/00325481.2018.1416257. Epub 2017 Dec 14.
The enterovirus EV71 is a major pathogen of hand, foot, and mouth disease (HFMD) in children. Aseptic meningitis is the most common neurologic complication of EV71-induced HFMD. Lumbar puncture is a crucial procedure in the diagnosis of aseptic meningitis. It is often performed based on physicians' clinical suspicion. A diagnostic method that can aid in deciding whether this procedure should be performed is necessary. Cytokines are speculated to be associated with neurologic complications. In this study, we aimed to find an indicator of the presence of aseptic meningitis in children with EV71-induced HFMD.
This cross-sectional study included children with EV71-induced HFMD. The children underwent lumbar puncture due to suspected aseptic meningitis. They were categorized into an aseptic meningitis complicated group (n = 54) and uncomplicated group (n = 47) based on the results of cerebrospinal fluid examination. Healthy children were included as controls (n = 51). The sample serum levels of tumor necrosis factor-α, interferon-γ, interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, and IL-13 were detected using multiplexed fluorescent bead-based immunoassays.
The levels of all cytokines were significantly higher in children with EV71-induced HFMD complicated with aseptic meningitis than in children with uncomplicated EV71-induced HFMD and controls (p < 0.001). Binary logistic regression analysis demonstrated that IL-6 had the strongest association with aseptic meningitis of all cytokines examined. According to receiver operating characteristic analysis, the optimal cutoff value for IL-6 was 66 pg/mL with maximum sensitivity and specificity.
The results of this study suggest the association between higher production of cytokine and aseptic meningitis among children with EV71-induced HFMD. IL-6 was also suggested as an indicator of aseptic meningitis. Rapid measurement of IL-6 could be useful in deciding whether physicians should perform lumbar puncture on children.
肠道病毒71型（EV71）是儿童手足口病（HFMD）的主要病原体。无菌性脑膜炎是EV71所致手足口病最常见的神经系统并发症。腰椎穿刺是诊断无菌性脑膜炎的关键步骤。通常根据医生的临床怀疑进行操作。因此，需要一种有助于决定是否应进行该操作的诊断方法。细胞因子被推测与神经系统并发症有关。在本研究中，我们旨在寻找EV71所致手足口病患儿无菌性脑膜炎存在的指标。
本横断面研究纳入了EV71所致手足口病患儿。因疑似无菌性脑膜炎而接受腰椎穿刺。根据脑脊液检查结果，将他们分为无菌性脑膜炎并发症组（n = 54）和非并发症组（n = 47）。纳入健康儿童作为对照组（n = 51）。使用基于多重荧光微珠的免疫测定法检测样本血清中肿瘤坏死因子-α、干扰素-γ、白细胞介素（IL）-1β、IL-2、IL-6、IL-8、IL-10和IL-13的水平。
EV71所致手足口病合并无菌性脑膜炎患儿的所有细胞因子水平均显著高于未合并无菌性脑膜炎的EV71所致手足口病患儿及对照组（p < 0.001）。二元逻辑回归分析表明，在所检测的所有细胞因子中，IL-6与无菌性脑膜炎的关联最强。根据受试者工作特征分析，IL-6的最佳截断值为66 pg/mL，具有最大的敏感性和特异性。
本研究结果提示，EV71所致手足口病患儿细胞因子产生增加与无菌性脑膜炎之间存在关联。IL-6也被认为是无菌性脑膜炎的一个指标。快速检测IL-6可能有助于医生决定是否应对儿童进行腰椎穿刺。
