血清S-100β水平和小兒危重病例量表評分預測手足口病并發腦炎患兒預后的價值研究

熊 燚，王 健，魏 笛，馮 亞

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·論著·

血清S-100β水平和小兒危重病例量表評分預測手足口病并發腦炎患兒預后的價值研究

熊 燚，王 健，魏 笛，馮 亞

目的探討血清S-100β水平與小兒危重病例量表(PCIS)評分對手足口病(HFMD)并發腦炎患兒預后評估的價值。方法選取2012年12月—2014年12月遵義市第二人民醫院收治的HFMD患兒190例為研究對象，根據是否并發腦炎，將患兒分為HFMD并發腦炎組(60例)和HFMD普通組(130例)。另選取同期本院體檢中心體檢健康的兒童40例為對照組。收集HFMD并發腦炎患兒入院24 h內各項資料，并依據PCIS對患兒進行病情危重程度評分，據此將患兒分為非危重、危重、極危重。患兒于入院后12 h、對照組體檢時抽取空腹靜脈血3 ml檢測S-100β水平及白細胞計數(WBC)，記錄HFMD患兒住院期間死亡情況。結果各組S-100β水平、WBC比較，差異均有統計學意義(P<0.05)；其中，HFMD并發腦炎組S-100β水平高于HFMD普通組及對照組，HFMD普通組與HFMD并發腦炎組WBC高于對照組(P<0.05)。HFMD并發腦炎組病死率為20%(12/60)，高于HFMD普通組的4.6%(6/130)(χ2=18.32，P<0.05)。不同危重程度的HFMD并發腦炎患兒S-100β水平及病死率比較，差異均有統計學意義(P<0.05)；其中危重者S-100β水平及病死率高于非危重者，極危重者S-100β水平及病死率高于非危重和危重者(P<0.01)。HFMD并發腦炎患兒S-100β水平與PCIS評分呈負相關(r=-0.478，P<0.01)。S-100β水平預測HFMD并發腦炎患兒死亡的受試者工作特征(ROC)曲線下面積為0.888〔95%CI(0.834,0.947),P<0.01〕,取臨界值為2.91 μg/L時，靈敏度為84.46%，特異度為82.50%。PCIS評分預測HFMD并發腦炎患兒死亡的ROC曲線下面積為0.873〔95%CI(0.808,0.938),P<0.01〕,取臨界值為69分時，靈敏度為83.10%，特異度為81.24%。結論血清S-100β水平和PCIS評分可特異反映HFMD并發腦炎患兒嚴重程度，對預測HFMD并發腦炎患兒預后具有較高的準確性。

手足口病；腦炎；S-100β；小兒危重病例量表；預后

熊燚，王健，魏笛，等.血清S-100β水平和小兒危重病例量表評分預測手足口病并發腦炎患兒預后的價值研究[J].中國全科醫學，2016，19(23)：2780-2784.[www.chinagp.net]

XIONG Y,WANG J,WEI D,et al.Values of serum S-100β level and pediatric critical illness scale in predicting hand-foot-mouth disease children complicated with encephalitis[J].Chinese General Practice，2016，19(23)：2780-2784.

手足口病(hand-foot-mouth disease，HFMD)是兒科常見急性傳染病，主要由多種腸道病毒感染引起[1]，該病好發于5歲以下兒童，主要臨床表現為發熱及手、足、口腔等部位出現皰疹，一般預后良好，但少數患兒可出現心肌炎、腦炎等嚴重并發癥，致使患兒病死率顯著增加。其中，HFMD并發腦炎病情發展迅速，是導致患兒死亡的主要原因之一[2]。因此，早期特異評估患兒預后，對于改善其生存率具有重要臨床意義。S-100β主要由神經膠質細胞合成分泌，腦損傷時腦脊液及血清中S-100β水平明顯升高，其可特異性反映腦損傷的嚴重程度[3]。小兒危重病例量表(PCIS)是臨床中常用的針對危重患兒病情嚴重程度評分系統之一,但其在HFMD并發腦炎患兒病情評估及預后判斷的臨床意義尚不完全明確。本研究擬通過探討HFMD并發腦炎患兒血清S-100β水平、PCIS與預后的關系，為HFMD并發腦炎患兒的早期診斷及預后評估提供更有價值的指標。

1　對象與方法

1.1研究對象選取2012年12月—2014年12月遵義市第二人民醫院收治的HFMD患兒190例為研究對象，其中男105例，女85例；平均月齡(20.8±12.2)月。患兒均符合原衛生部制定的《手足口病診療指南(2010年版)》[4]診斷標準。排除非HFMD腸道病毒感染者，近3個月內有呼吸道感染、神經系統疾病及腦腫瘤、腦創傷史者。根據是否有神經系統受累如嗜睡、嘔吐、腦膜刺激征、腱反射減弱等表現，以及實驗室檢查和影像學特征[4]，確診HFMD并發腦炎患兒60例(HFMD并發腦炎組)，余130例為HFMD普通組。另選取同期本院體檢中心體檢健康的兒童40例為對照組。受試者監護人均簽署知情同意書，本研究方案由本院倫理委員會批準。

1.2方法

1.2.1PCIS評分收集HFMD并發腦炎患兒入院24 h內臨床資料，包括心率、血壓、呼吸頻率、氧分壓、pH值、Na+、K+、肌酐、血紅蛋白、胃腸系統(如應激性潰瘍、應激性潰瘍出血等)情況，每項計為4、6或10分，計算總分。危重程度評價標準：PCIS評分>80分為非危重，71～80分為危重，<71分為極危重。

1.2.2觀察指標患兒于入院后12 h及對照組體檢時抽取空腹靜脈血3 ml檢測S-100β水平及血常規。血清S-100β水平采用酶聯免疫試劑盒進行測定，試劑盒購自瑞士羅氏公司，操作過程嚴格按說明書進行，血常規采用全自動生化分析儀測定。記錄HFMD患兒住院期間死亡情況。

2　結果

2.1各組一般資料及血清S-100β水平、WBC比較各組性別、月齡比較，差異均無統計學意義(P>0.05)。各組S-100β水平、WBC比較，差異均有統計學意義(P<0.05)；其中，HFMD并發腦炎組S-100β水平高于HFMD普通組及對照組，HFMD普通組及HFMD并發腦炎組WBC高于對照組，差異均有統計學意義(P<0.05，見表1)。

表1各組一般資料及血清S-100β水平、WBC比較

Table 1Comparison of the general data and serum levels of S-100β,WBC among each group

組別例數性別(男/女)月齡(月)S-100β(μg/L)WBC(×109/L)對照組4024/1620.6±5.60.45±0.156.28±0.93HFMD普通組13071/5921.0±6.20.51±0.1811.32±0.92aHFMD并發腦炎組6034/2620.8±5.93.54±0.57ab11.72±0.73aF(χ2)值0.88c0.9721.4524.74P值>0.05>0.05<0.01<0.01

注：HFMD=手足口病，WBC=白細胞計數；與對照組比較，aP<0.01；與HFMD普通組比較，bP<0.01；c為χ2值

2.2各組病死率比較HFMD普通組治愈124例，治愈率為95.4%，6例患兒因病情加重死亡，病死率為4.6%。HFMD并發腦炎組治愈48例，治愈率為80.0%，死亡12例，病死率為20.0%。HFMD并發腦炎組患兒病死率高于HFMD普通組，差異有統計學意義(χ2=18.32，P<0.05)。

2.3不同危重程度的HFMD并發腦炎患兒S-100β水平及病死率比較不同危重程度的HFMD并發腦炎患兒S-100β水平及病死率比較，差異均有統計學意義(P<0.05)；其中危重者S-100β水平及病死率高于非危重者，極危重者S-100β水平及病死率高于非危重和危重者，差異均有統計學意義(P<0.01，見表2)。

表2不同危重程度的HFMD并發腦炎患兒S-100β水平及病死率比較

Table 2Comparison of the S-100β level and fatality rate among different critical illness degrees in the HFMD children complicated with encephalitis

危重程度例數S-100β(μg/L)病死率〔n(%)〕非危重262.74±0.341(3.8)危重243.92±0.32a4(16.7)a極危重105.46±0.25ab7(7/10)abF(χ2)值8.467.84cP值<0.05<0.05

注：與非危重者比較，aP<0.01；與危重者比較，bP<0.01；c為χ2值

2.4HFMD并發腦炎不同預后患兒S-100β水平及PCIS評分比較HFMD并發腦炎死亡患兒S-100β水平高于存活者，PCIS評分低于存活者，差異有統計學意義(P<0.05，見表3)。

Table 3Comparison of the S-100β level and PCIS score between different clinical prognosis in the HFMD children complicated with encephalitis

預后例數S-100β(μg/L)PCIS評分(分)存活483.12±0.8377±6死亡125.82±1.1261±4t值4.538.73P值<0.01<0.01

注：PCIS=小兒危重病例量表

2.5血清S-100β水平與PCIS評分的相關性分析HFMD并發腦炎患兒S-100β水平與PCIS評分呈負相關(r=-0.478，P<0.01,見圖1)。

注：PCIS=小兒危重病例量表

圖1HFMD并發腦炎患兒S-100β水平與PCIS評分相關性的散點圖

Figure 1Scatter diagram of the correlation between S-100β level and PCIS score of HFMD children complicated with encephatilis

2.6ROC曲線分析S-100β水平預測HFMD并發腦炎患兒死亡的ROC曲線下面積為0.888〔95%CI(0.834,0.947),P<0.01〕,取臨界值為2.91 μg/L時，靈敏度為84.46%，特異度為82.50%，陽性似然比為4.83，陰性似然比為0.19，Youden′s指數為66.96%(見圖2)。PCIS評分預測HFMD并發腦炎患兒死亡的ROC曲線下面積為0.873〔95%CI(0.808,0.938),P<0.01〕,取臨界值為69分時，靈敏度為83.10%，特異度為81.24%，陽性似然比為4.43，陰性似然比為0.21，Youden′s指數為64.34%(見圖3)。

圖2　S-100β水平預測HFMD并發腦炎患兒死亡的ROC曲線

Figure 2The ROC curve of the S-100β level for predicting death on the HFMD children complicated with encephalitis

圖3　PCIS評分預測HFMD并發腦炎患兒死亡的ROC曲線

Figure 3The ROC curve of the PCIS score for predicting death on the HFMD children complicated with encephalitis

3　討論

HFMD是由腸道病毒引起的兒童急性傳染病，大部分患兒病情較輕，預后良好，但少數HFMD重癥患兒可并發中樞神經系統損害，即腦炎的發生，從而導致其病死率顯著升高[5]。有研究報道，HFMD并發腦炎患兒較普通患兒病死率增加4.8%，且神經系統損害后遺癥發生率升高14.3%[6]。因此，就HFMD并發中樞神經系統損害的患兒，及早做出診斷，準確判斷其預后，對于降低其病死率及致殘率具有重要的臨床意義。

有研究證實，中樞神經系統損傷時血清及腦脊液中S-100β水平顯著升高，其可特異性判斷中樞神經系統損傷的嚴重程度及預后，從而受到廣泛關注[7]。S-100β是主要由神經膠質細胞合成及分泌的鈣結合蛋白，具有調節能量代謝、維持細胞膜完整性及參與細胞內信號傳導的作用。生理情況下，腦脊液及血液中S-100β水平較低，但中樞神經系統受到損傷時，神經膠質細胞膜結構完整性被破壞，S-100β從細胞質釋放入腦脊液，再通過已破壞的血-腦脊液屏障進入外周血[8]。因此，血清S-100β水平可作為評判中樞神經系統損傷的特異性標志物，同時其水平的變化可反映中樞神經系統損傷的程度及預后情況。本研究結果顯示，入院24 h內，HFMD并發腦炎患兒血清S-100β水平明顯高于普通HFMD患兒及健康兒童，而普通HFDM患兒與健康兒童間無差異，說明HFMD并發腦炎患兒中樞神經系統受到損害。同時，HFMD患兒WBC明顯高于健康兒童，說明其體內存在明顯的炎性反應，但WBC在HFMD并發腦炎組與HFMD普通組間無明顯區別，提示WBC缺乏特異性，不能完全反映病情嚴重程度。已有相關研究顯示，WBC對于評估炎癥感染嚴重程度特異性較低，并且無法準確反映其預后情況，這可能與外周血中WBC個體差異大，不穩定即易受各種因素影響有關[9]。血清S-100β水平在非危重、危重和極危重患兒間呈升高趨勢，其與PCIS評分呈明顯的負相關，提示HFMD并發腦炎患兒病情越危重，其血清S-100β水平越高，死亡風險越高，預后也越差。已有研究證實，PCIS評分與患者病死率呈負相關[10]。本研究發現，HFMD并發腦炎死亡患兒血清S-100β水平高于存活患兒，并且PCIS評分低于存活患兒。S-100β水平及PCIS評分預測HFMD并發腦炎患兒死亡的ROC曲線下面積>0.850，可作為判斷預后的有效指標，其中，S-100β取臨界值為2.91 μg/L和PCIS評分取臨界值為69分時對HFMD并發腦炎患兒預后不良的診斷準確性較高。

綜上所述，血清S-100β水平及PCIS評分可特異反映HFMD并發腦炎患兒病情嚴重程度及預后，其對于指導患兒治療，降低病死率具有重要臨床意義。目前，HFMD并發腦炎患兒的早期診斷及預后判斷尚缺乏有效的標準。通過檢測HFMD并發腦炎患兒血清S-100β水平，同時結合PCIS評分可有效判斷其病情的嚴重程度及預后。本研究沒有進一步對HFMD并發腦炎患兒腦脊液、腦電圖等方面做同步檢測及觀察，且樣本量有限，研究結論可能存在一定的局限性，故需進一步加大樣本量、多中心綜合分析。

作者貢獻：熊燚進行課題設計與實施、資料收集整理、成文并對文章負責；王健、魏笛進行課題設計與實施、評估、資料收集整理；馮亞進行質量控制及審校。

本文無利益沖突。

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(本文編輯：吳立波)

Values of Serum S-100β Level and Pediatric Critical Illness Scale in Predicting Hand-foot-mouth Disease Children Complicated With Encephalitis

XIONGYi,WANGJian,WEIDi,FENGYa.

DepartmentofEmergency,theSecondPeople′sHospitalofZunyi,Zunyi563000,China

WANGJian，DepartmentofEmergency,theSecondPeople′sHospitalofZunyi,Zunyi563000,China；E-mail：wjzy02@163.com

ObjectiveTo investigate the value of serum S-100β level and pediatric critical illness scale(PCIS) in prognostic evaluating the hand-foot-mouth disease(HFMD) children complicated with encephalitis.Methods190 children with HFMD,whoP<0.05);the S-100β level of HFMD complicated with encephalitis group was higher than that of the HFMD general group and the control group,and the WBC of the HFMD general group and the HFMD complicated with encephalitis group was higher than that of the control group,which showed significant differences(P<0.05).The fatality rate of the HFMD complicated with encephalitis group was 20%(12/60),which was higher than 4.6%(6/130) in the HFMD general group,which showed significant differences(χ2=18.32，P<0.05).There was significant difference in the S-100β level and the fatality rate of the HFMD children complicated with encephalitis among different critical illness degrees(P<0.05);the S-100β level and the fatality rate of the critical illness cases were higher than those of the non-critical illness cases,and the S-100β level and the fatality rate of extremely critical illness cases were higher than those of the non-critical illness cases and critical illness cases,which showed significant differences(P<0.01).The S-100β level of the HFMD children complicated with encephalitis was negatively correlated with the score of PCIS(r=-0.478,P<0.01).The area under ROC curve of the HFMD children complicated with encephalitis,predicted as death through S-100β level,was 0.888〔95%CI(0.834,0.947),P<0.01〕,when the taken critical value was 2.91 μg/L,the sensitivity and the specificity were 84.46% and 82.50% respectively.The area under ROC curve of the HFMD children complicated with encephalitis,predicted as death through PCIS,was 0.873〔95%CI(0.808,0.938),P<0.01〕,and when the critical value was 69,the sensitivity and the specificity were 83.10% and 81.24% respectively.ConclusionThe serum S-100β level and PCIS score can reflect the severity degree of the HFMD children complicated with encephalitis,and have high accuracy in predicting the prognosis of the HFMD children complicated with encephalitis.

treatment in the Second People′s Hospital of Zunyi from December 2012 to December 2014,were enrolled as the research objects in this study.Based on whether children were complicated with encephalitis,we divided the children into HFMD complicated with encephalitis group(60 cases) and HFMD general group(130 cases).Other 40 children,who were regarded as healthy after physical examination in the physical examination center of this hospital at the same period,were included as the control group.We collected necessary information of the HFMD children complicated with encephalitis within the 24-hour after their being admitted into the hospital,and scored their critical illness condition based on PCIS，then divided the children as non-critical illness cases,critical illness cases and extremely critical illness cases.S-100β and WBC were detected by the extracted 3 ml fasting blood,which were got from HFMD children 12 h after their being admitted into the hospital and from the physical examination of control group.Also HFMD children′s death duration of hospital stay was recorded.ResultsThere were significant difference in S-100β level and WBC among the different groups(

Hand-foot-mouth disease;Encephalitis;S-100β;Pediatric critical illness scale;Prognosis

貴州省衛生廳科學技術基金項目(gzwkj2013-1-060)；遵義市科學技術基金項目[遵義市科合社字(2013)37號]

563000貴州省遵義市第二人民醫院急診科(熊燚，王健，魏笛)；貴州省遵義市紅花崗區疾病預防控制中心(馮亞)

王健，563000貴州省遵義市第二人民醫院急診科；E-mail：wjzy02@163.com

R 512.5

A

10.3969/j.issn.1007-9572.2016.23.008

2015-06-02；

2016-04-27)