摘要
目的探讨与母亲风湿免疫性疾病相关的新生儿巨噬细胞活化综合征(macrophage activation syndrome,MAS)临床特点,提高对MAS的认识。方法回顾性分析本院收治的1例母亲成人Still病(adult onset still′s disease,AOSD)合并新生儿MAS患儿的临床资料,以"新生儿"、"巨噬细胞活化综合征"、"嗜血细胞性淋巴组织细胞增生症(hemophagocytic lymphohistiocytosis,HLH)"为关键词检索中国知网、维普、万方数据库、生物医学文献数据库(PubMed)和Embase数据库建库至2017年12月收录的文献,总结与母亲风湿免疫性疾病相关的MAS/HLH患儿的临床特点。结果本例患儿男,生后27d因持续发热、水样便、易激惹,以及明显的右侧腮腺和右侧颈部淋巴结肿大而就诊,其母亲罹患AOSD。病程中患儿因出现凝血功能障碍、多脏器功能损害、低纤维蛋白原血症和高铁蛋白血症诊断为MAS,血清抗SSA/Ro52kD和粪便轮状病毒抗原检测阳性,经静脉注射丙种球蛋白和激素治疗后症状迅速缓解,后续随访至2周岁体健。经文献检索共纳入母亲罹患自身免疫性疾病的新生儿MAS/HLH病例3例,结合本例共4例,患儿均有高热、肝脾肿大和多脏器功能受累,消化系统症状包括腹胀、腹泻、腹水,弥散性血管内凝血2例,精神意识改变1例,完全性房室传导阻滞1例,严重低血压1例,实验室检查均表现为血小板减少、肝酶增高和血清铁蛋白显著升高,4例患儿均行全基因组外显子测序,但未发现与疾病相关的基因变异。经激素、静脉注射丙种球蛋白和化疗等综合治疗后4例患儿临床症状均得以改善并最终停药,随访情况良好。结论风湿免疫性疾病孕母可能对胎儿产生触发MAS的致病性影响,其新生儿在出生早期如出现高热、肝脾肿大等表现,应及时考虑存在MAS的可能,早期诊断和有效治疗至关重要。
Objective To study the clinical characteristics of neonatal macrophage activation syndrome (MAS) associated with maternal rheumatic diseases and improve the understanding of neonatal MAS. Method Clinical data of MAS in a newborn infant with adult-onset Still′s disease (AOSD) mother was retrospectively studied. From the establishment day of databases (CNKI, VIP, Wanfang, Pubmed and Embase) to December 2017, literature were retrieved with key words including "newborn" , "macrophage activation syndrome" and "hemophagocytic lymphohistiocytosis (HLH)" . Clinical features of infant MAS/HLH with maternal rheumatic diseases were summarized. Result A 27-day-old boy with AOSD mother manifested with fever, watery stools, irritability, prominent enlargement of right parotid gland and right cervical lymphadenitis. The infant was diagnosed with MAS due to coagulopathy, multiple organ dysfunction, hypofibrinogenemia and increased levels of ferritin. Anti-SSA/Ro52kD and stool rotavirus antigen were positive. The infant recovered with intravenous immunoglobulin and steroids therapy. Follow-up at 2-year-old were normal. A total of 3 other cases of neonatal MAS/HLH were retrieved. All patients had high fever, hepatosplenomegaly and multiple organ dysfunction, impaired digestive system (abdominal distention, diarrhea and ascites), disseminated intravascular coagulation (2 cases), mental disorders (1 case), complete atrioventricular block (1 case) and severe hypotension (1 case). Laboratory results showed thrombocytopenia, elevated level of hepatic enzyme and serum ferritin in all patients. Targeted panel-based next generation sequencing were all negative for pathogenic gene mutations. After treatments of steroids, intravenous immunoglobulin and chemotherapy, all patients improved and ultimately cured. Conclusion In view of the impacts of the maternal rheumatic diseases on fetus, newborns with early onset high fever and hepatosplenomegaly should be suspected of MAS. Early diagnosis and effective treatment are crucial for clinical improvement.
作者
贝斐
金燕樑
孙建华
鞠慧群
黄华
Bei Fei;Jin Yanliang;Sun Jianhua;Ju Huiqun;Huang Hua(Department of Neonatology, Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China)