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Clinical Features and Risk Factors of Kawasaki Disease Complicated with Deep Neck Space Involvement: A Summary of 38 Cases
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摘要:
目的 对川崎病(Kawasaki disease, KD)合并颈深间隙受累(deep neck space involvement, DNSI)患儿的临床资料进行总结, 并分析KD患儿合并DNSI的危险因素。 方法 本研究为病例对照研究。研究对象为2018年1月—2020年12月深圳市儿童医院风湿免疫科住院治疗的KD合并DNSI患儿(DNSI组)及采用系统抽样法按1∶7比例选取的该时间段内单纯KD患儿(对照组)。比较两组临床资料差异, 采用多因素Logistic回归法分析KD患儿合并DNSI的危险因素。 结果 共入选符合纳入与排除标准的DNSI组患儿38例, 对照组患儿288例。DNSI组患儿中, 38例(100%)均存在发热伴颈部淋巴结肿大, 且颈部淋巴结肿大均在发病5 d内出现; 颈部淋巴结疼痛30例(78.9%), 颈部活动受限25例(65.8%)。相较于对照组, DNSI组患儿临床资料呈现出多种显著性变化: 在临床特征方面, DNSI组发病年龄更大, 住院时间更长, 颈部淋巴结肿大、颈部淋巴结疼痛、颈部活动受限、上气道阻塞的比例均更高(P均＜0.05);在实验室检测方面, DNSI组中性粒细胞计数及其百分比、C反应蛋白(C-reactive protein, CRP)、铁蛋白(ferritin, FER)、总胆汁酸、总胆红素、直接胆红素、球蛋白水平均更高, 血小板、淋巴细胞计数及其百分比均更低(P均＜0.05);在冠状动脉损害及治疗效果方面, DNSI组Kobayashi评分、Sano评分及激素治疗的比例均更高(P均＜0.05)。多因素Logistic回归分析显示, 颈部淋巴结疼痛(OR=5.523, 95% CI: 1.443~21.141, P=0.013)、颈部活动受限(OR=3.947, 95% CI: 1.044~14.928, P=0.043)、CRP(OR=1.016, 95% CI: 1.002~1.030, P=0.024)与FER(OR=1.004, 95% CI: 1.001~1.006, P=0.002)升高是KD合并DNSI的独立危险因素。 结论 多数KD合并DNSI患儿出现颈部淋巴结肿大、颈部淋巴结疼痛、颈部活动受限等临床症状, 血液学提示存在高强度炎症反应。以颈部疼痛及活动受限为主要临床表现并伴血清CRP与FER升高的KD患儿需警惕合并DNSI的可能性。 Abstract:Objective To summarize the clinical characteristics and explore the risk factors of Kawasaki disease(KD) with deep neck space involvement(DNSI). Methods This study was a case-control study. We reviewed KD complicated with DNSI patients in Department of Rheumatology and Immunology of Shenzhen Children's Hospital from January 2018 to December 2020 as DNSI group. Meanwhile, children with KD withoutDNSI during this period were selected by systematic sampling at a ratio of 1∶7 as control group. The clinical characteristics were analyzed by Chi-square test and the Mann-Whitney test and risk factors of KD complicated with DNSI were analyzed by Logistic regression. Results A total of 38 children in the DNSI group who met the inclusion and exclusion criteria and 288 children in the control group were selected. In the DNSI group, 38 children (100%) had fever and cervical lymph node enlargement, and the cervical lymph node enlargement occurred within 5 days of onset; 30 patients (78.9%) had cervical lymph node pain and 25 patients suffered (65.8%) limited movement of neck. Compared with the control group, the clinical data of children in the DNSI group showed a variety of significant changes. In terms of clinical characteristics, the age of onset in the DNSI group was older, the hospital stay was longer and the proportions of cervical lymphadenopathy, cervical lymph node pain, limited neck movement and upper airway obstruction were all higher (all P < 0.05); in terms of laboratory tests, the neutrophil count and its percentage, C-reactive protein (CRP), ferritin (FER), total bile acid, total bilirubin, direct bilirubin, and globulin levels all increased, while platelet and lymphocyte counts and their percentages all decreased(all P < 0.05); in terms of coronary artery damage and treatment effect, the Kobayashi score, Sano score and the proportion of hormone therapy in the DNSI group all increased (all P < 0.05). Multivariate Logistic regression analysis showed that neck lymph node pain (OR=5.523, 95% CI: 1.443-21.141, P=0.013), limited cervical movement (OR=3.947, 95% CI: 1.044-14.928, P=0.043), higher CRP (OR=1.016, 95% CI: 1.002-1.030, P=0.024) and higher FER(OR=1.004, 95% CI: 1.001-1.006, P=0.002) were independent risk factors for KD combined with DNSI. Conclusions Most children with KD complicated with DNSI have clinical symptoms such as cervical lymph node enlargement, cervical lymph node pain, and limited cervical movement, and hematology shows that there is a high-intensity inflammatory response. For KD children with neck pain and limited cervical movement as the main clinical manifestations, accompanied by elevated serum CRP and FER, we should be alert to the possibility of DNSI. 作者贡献：朱晓娜负责设计课题并撰写论文；程雪莹、翁若航负责收集临床数据；夏宇、罗颖、何庭艳负责监督并指导数据分析；杨军负责修订论文。利益冲突：所有作者均声明不存在利益冲突 -
图 1 1例KD合并DNSI患儿颈部CT检查表现(箭头)
A.咽旁间隙软组织增厚、密度不均；B.咽后间隙软组织增厚；C.咽旁间隙模糊、密度不均
KD：川崎病；DNSI：颈深间隙受累表 1 两组患儿临床资料比较
指标 DNSI组(n=38) 对照组(n=288) P值 男性[n(%)] 26(68.4) 171(59.4) 0.371 发病年龄[M(P25, P75), 月] 41.0(19.2，59.2) 23.0(13.0，40.0) 0.002 发热时间[M(P25, P75), d] 4.0(3.0，5.8) 5.0(4.0，6.0) 0.267 住院时间[M(P25, P75), d] 10.0(8.0，12.8) 6.0(5.0，7.0) ＜0.001 结膜充血[n(%)] 34(89.5) 274(95.1) 0.144 口唇潮红、杨梅舌[n(%)] 37(97.4) 278(96.5) ＞0.999 颈部淋巴结肿大[n(%)] 38(100.0) 225(78.1) 0.003 颈部淋巴结疼痛[n(%)] 30(78.9) 57(19.8) ＜0.001 皮疹[n(%)] 28(73.7) 240(83.3) 0.216 肢端红肿/脱皮[n(%)] 24(63.2) 225(78.1) 0.066 肛周改变[n(%)] 14(36.8) 82(28.5) 0.382 咽痛[n(%)] 2(5.3) 5(1.7) 0.191 颈部活动受限[n(%)] 25(65.8) 32(11.1) ＜0.001 上气道阻塞[n(%)] 7(18.4) 9(3.1) ＜0.001 白细胞计数[M(P25, P75), ×109/L] 15.5(11.9，20.4) 14.4(11.2，18.2) 0.272 中性粒细胞计数[M(P25, P75), ×109/L] 12.9(8.2，14.9) 9.6(6.7，12.9) 0.008 中性粒细胞百分比[M(P25, P75), %] 78.5(69.1，86.3) 68.7(54.3，77.0) ＜0.001 淋巴细胞计数[M(P25, P75), ×109/L] 2.1(1.3，3.0) 3.5(2.2，4.8) ＜0.001 淋巴细胞百分比[M(P25, P75), %] 14.5(8.8，22.7) 23.5(16.7，34.8) ＜0.001 血红蛋白[M(P25, P75), g/L] 107.0(100.0，112.8) 107.0(101.0，113.0) 0.769 血小板[M(P25, P75), ×109/L] 341.5(279.2，392.5) 381.0(311.5，476.5) 0.032 CRP [M(P25, P75), mg/L] 95.0(72.1，113.3) 55.0(35.1，92.0) ＜0.001 PCT [M(P25, P75), μg/L] 1.2(0.4，2.2) 0.7(0.2，2.0) 0.090 ESR[M(P25, P75), mm/h] 76.0(64.0，87.0) 71.0(50.5，86.0) 0.098 ALT[M(P25, P75), U/L] 27.0(16.0，122.0) 32.0(16.0，86.0) 0.836 AST[M(P25, P75), U/L] 34.0(23.2，109.5) 32.0(23.0，49.2) 0.346 总胆汁酸[M(P25, P75), μmol/L] 15.5(7.5，41.9) 8.9(5.4，19.0) 0.006 总胆红素[M(P25, P75), μmol/L] 8.6(5.9，16.6) 6.6(5.0，10.3) 0.019 直接胆红素[M(P25, P75), μmol/L] 3.4(1.9，9.6) 2.6(1.5，4.5) 0.019 间接胆红素[M(P25, P75), μmol/L] 4.8(3.4，7.5) 4.1(2.8，6.7) 0.208 白蛋白[M(P25, P75), g/L] 35.8(31.7，38.1) 35.2(32.8，38.0) 0.957 球蛋白[M(P25, P75), g/L] 28.8(25.2，31.6) 26.6(24.0，29.2) 0.015 甘油三酯[M(P25, P75), mmol/L] 1.3(0.9，1.6) 1.3(1.0，1.6) 0.741 NA+[M(P25, P75), mmol/L] 134.4(132.8，136.4) 135.5(133.5，137.0) 0.072 K+[M(P25, P75), mmol/L] 4.0(3.8，4.3) 4.2(3.8，4.6) 0.102 FER[M(P25, P75), μg/L] 259.8(196.1，420.8) 166.2(116.8，248.4) ＜0.001 Kobayashi评分(x±s, 分) 3.45±2.21 1.32±1.33 ＜0.001 Sano评分(x±s, 分) 1.29±0.77 0.55±0.70 ＜0.001 IVIG治疗无反应[n(%)] 7(2.4) 10(3.1) 0.098 左心室射血分数[M(P25, P75), %] 64.0(62.0，68.0) 64.0(61.0，67.0) 0.547 心包积液[n(%)] 2(5.3) 8(2.8) 0.329 冠状动脉管壁回声异常[n(%)] 16(42.1) 137(47.6) 0.644 冠状动脉管壁欠光滑[n(%)] 4(10.5) 43(14.9) 0.631 冠状动脉管腔欠清晰[n(%)] 1(2.6) 11(3.8) ＞0.999 冠状动脉扩张[n(%)] 8(21.1) 49(17.0) 0.697 激素治疗[n(%)] 22(57.9) 49(17.0) ＜0.001 DNSI：同图 1；CRP：C反应蛋白；PCT：降钙素原；ESR：红细胞沉降率；ALT：谷丙转氨酶；AST：谷草转氨酶；FER：铁蛋白；IVIG：静脉注射丙种球蛋白 
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表 2 KD合并DNSI危险因素的多因素Logistic回归分析结果
指标 β值 SE值 Wald χ2值 OR(95% CI) P值 颈部淋巴结疼痛 1.709 0.685 6.225 5.523(1.443~21.141) 0.013 颈部活动受限 1.373 0.679 4.093 3.947(1.044~14.928) 0.043 中性粒细胞百分比 -0.004 0.024 0.034 0.996(0.949~1.044) 0.854 血小板 0.002 0.002 1.108 1.002(0.998~1.007) 0.293 CRP 0.016 0.007 5.064 1.016(1.002~1.030) 0.024 总胆红素 -0.009 0.015 0.408 0.991(0.963~1.020) 0.523 FER 0.004 0.001 9.893 1.004(1.001~1.006) 0.002 白细胞计数 0.039 0.047 0.674 1.039(0.948~1.140) 0.411 PCT -0.001 0.051 0.001 0.999(0.904~1.104) 0.981 ESR -0.009 0.016 0.333 0.991(0.961~1.022) 0.564 KD、DNSI：同图 1；CRP、FER、PCT、ESR：同表 1
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