儿童巨噬细胞活化综合征的临床特征

Clinical features of macrophage activation syndrome in children

目的总结儿童巨噬细胞活化综合征(MAS)的临床特征,为临床早期识别和诊断提供参考。方法纳入20例MAS患儿,回顾性分析其原发疾病、诱因、临床表现、实验室检查结果、治疗及预后等。比较继发于全身型幼年特发性关节炎(sJIA)和川崎病的MAS患儿的实验室检查结果和死亡情况。结果(1)川崎病是最常见的原发疾病(10例,占50%),其次为sJIA(7例,35%)。诱发因素中,感染是最常见的诱因,病原体以EB病毒最常见。(2)20例患儿均有高热,95%(19/20)的患儿还存在多系统损害表现,包括皮疹、肝脾肿大、浆膜腔积液、神经系统损害、肾脏和胃肠道损害、关节痛和/或肌痛、淋巴结肿大。(3)血清铁蛋白水平升高和外周血两系下降是最常见的实验室表现,共15例存在骨髓涂片异常(6例可见噬血细胞,9例可见吞噬细胞);接受可溶性CD25检查、自然杀伤细胞活性检查的患儿分别仅有5例、2例。与继发于川崎病的MAS患儿相比,继发于sJIA的MAS患儿的血沉、血清铁蛋白、γ-谷氨酰转移酶水平更高,而血红蛋白及血清肌酐水平更低(均P<0.05)。(4)3例患儿在确诊MAS后30 d内死亡,病死率达15%(3/20)。川崎病组的病死率为20%(2/10),高于sJIA组的14.29%(1/7),但差异无统计学意义(P>0.05)。结论对于风湿免疫性疾病患儿,一旦出现多系统受累,尤其是合并两系及以上血细胞减少及血清铁蛋白明显升高时,应高度警惕MAS的可能。临床上应积极完善病原学检查,寻找诱发因素,重视慢性EB病毒感染。组织学检查噬血现象及自然杀伤细胞活性、可溶性CD25、噬血相关基因检查有助于MAS的早期诊断。

Objective To summarize the clinical features of macrophage activation syndrome(MAS) in children,so as to provide references to early clinical recognition and diagnosis.Methods Twenty cases of MAS children were enrolled,and their primary diseases,inducement,clinical manifestations,laboratory examination results,treatment and prognosis were retrospectively analyzed.The results of laboratory examination and mortality were compared between the MAS children secondary to systemic juvenile idiopathic arthritis(sJIA) and to Kawasaki disease.Results(1) Kawasaki disease was the most common primary disease(10 cases,accounting for 50%),followed by sJIA(7 cases,35%).Among the inducing factors,infection was the most common inducement,and EB virus was the most common pathogen.(2) All the 20 children had hyperpyrexia,and 95%(19/20) of the children also had manifestations of multi-system damage,including rash,hepatosplenomegaly,serous effusion,nervous system damage,kidney and gastrointestinal damage,arthralgia and/or myalgia,and lymphadenectasis.(3) The elevated serum ferritin level and the decline of two cell lineages of peripheral blood were the most common laboratory manifestations.A total of 15 cases had abnormal bone marrow smears(6 cases with hemotophage,and 9 cases with phagocytes).There were only 5 children received soluble CD25 examination,and only 2 children received natural killer cell activity test.Compared with MAS children secondary to Kawasaki disease,MAS children secondary to sJIA obtained higher levels of erythrocyte sedimentation rate,serum ferritin,and γ-glutamyltransferase,whereas lower levels of hemoglobin and serum creatinine(all P0.05).Conclusion For children with rheumatic immune diseases,the possibility of MAS should be highly vigilant once there is multiple system involvement,especially when there is cytopenia involving two or more cell lineages,and serum ferritin is significantly increased.Clinically,it is necessary to conduct the etiological examination actively,search for the inducing factors,and pay attention to chronic EB virus infection.Histological examination of hemophagocytosis,natural killer cell activity,soluble CD25 and hemophagocytosis related genes examinations are helpful for early diagnosis of MAS.