川崎病相关巨噬细胞活化综合征临床分析及诊断标准初探

Clinical analysis of Kawasaki disease associated with macrophage activation syndrome and a probe into its diagnostic criteria

目的分析川崎病相关巨噬细胞活化综合征（KD－MAS）的临床和实验室特点、治疗及转归，比较几种巨噬细胞活化综合征（MAS）诊断标准对KD－MAS的实用性。方法回顾性分析重庆医科大学附属儿童医院2007年9月至2017年9月收治的12例KD－MAS患儿的临床资料，评价不同MAS诊断标准对KD－MAS的实用性。结果男8例，女4例；中位年龄25个月。最常见诱因为感染（8例，66.7%）。12例（100.0%）均以高热为首发表现，常见临床表现有肝大（11例，91.6%）、脾大（8例，66.7%）和淋巴结大（7例，58.3%），8例（66.7%）伴中枢神经系统症状。实验室检查显示血红蛋白水平降低（11例，91.6%）、血小板水平下降（8例，66.7%）及白细胞水平下降（4例，33.3%）；天冬氨酸转氨酶（91.6%，11/12例）、三酰甘油（72.7%，8/11例）及铁蛋白（100%，9/9例）升高；11例（91.6%）红细胞沉降率（ESR）下降。10例行骨髓细胞学检查，8例提示噬血现象。12例患儿均符合2005年全身型幼年特发性关节炎发MAS诊断标准[SoJIA－MAS（2005）标准]，9例符合噬血细胞淋巴组织细胞增生症诊断标准（HLH－2009标准）。所有患儿予大剂量静脉丙种球蛋白（IVIG）冲击治疗，其中4例加用甲泼尼龙治疗，2例联合2种以上免疫抑制剂（地塞米松、环孢素或依托泊苷）治疗。治疗后6例（50.0%）好转，4例（33.3%）因肝性脑病死亡（含2例放弃）；2例失访。结论持续高热为KD－MAS最常见首发表现，血红蛋白、血小板下降及ESR加快，血清转氨酶及铁蛋白升高可能提示MAS发生，大剂量IVIG冲击无效时，联合糖皮质激素及免疫抑制剂治疗可能提高缓解率，早期严重的中枢神经系统症状可能提示预后不良。及早采用SoJIA－MAS（2005）标准可早期诊断。

ObjectiveTo analyze the clinical and laboratory characteristics, treatment, and outcomes of Kawasaki disease （KD） patients associated with macrophage activation syndrome （MAS） （KD-MAS） and to compare three diagnostic standards.MethodsTwelve cases of KD-MAS were reviewed retrospectively, who had been treated and therapied at the Children′s Hospital of Chongqing Medical University from September 2007 to September 2017.The clinical data were analyzed.And, the efficacy of different MAS diagnostic criteria for KD-MAS was evaluated.ResultsThe subjects included 8 males and 4 females, with a median age of 25 months.The capital trigger of MAS was infection（8 cases, 66.7%）. Unabating high fever had been the initial manifestation for 12 patients（100%）, other common clinical features including hepatomegaly（11 cases, 91.6%）, splenomegaly（8 cases, 66.7%）and lymphadenectasis（7 cases, 58.3%）. Besides, 8 patients （66.7%） had different degrees of central nervous system symptoms.Laboratory examination showed a decrease in hemoglobin （11 cases, 91.6%）, in thrombocytopenia （8 cases, 66.7%）, and white blood cells （4 cases, 33.3%）; while there was an increase were found in serum transaminase （11 cases, 91.6%）, triglyceride （72.7%, 8/11 cases） and serum ferritin （100%, 9/9 cases）. Eleven patients （91.6%） had decreased erythrocyte sedimentation rates （ESR）. Bone marrow cytology was performed in 10 cases, and 8 cases of them showed hemophagocytic phenomenon.All the patients were diagnosed by SoJIA-MAS（2005）criteria.All patients were treated with high-dose intravenous immunoglobulin （IVIG） treatment, among whom 3 cases were combined with methylprednisolone treatment, and 2 cases received with more than 2 kinds of immunosuppressive drugs （Dexamethasone and Ciclosporin or Etoposide）. Among the 12 patients, 2 patients lost to follow-up, 4 cases（33.3%） died due to hepatic encephalopathy, including 2 cases who withdrawn treatment the remaining 6 cases（50.0%）improved.ConclusionsProlonged high fever is the first manifestation of MAS in KD.Hemogram and ESR will decrease, elevated serum transaminase and ferritin may increase, which indicates MAS occurrence.If a high dose of IVIG therapy does not work, the combination of glucocorticoid and immunosuppressive for therapy may improve the remission rate.Severe central nervous system involvement may indicate a terrible prognosis.SoJIA-MAS （2005） can diagnose earliler by using preliminary diagnostic guidelines for macrophage activation system complicating systemic juvenile idiopathic arthritis.