巨噬细胞活化综合征的研究进展

巨噬细胞活化综合征是一种多见于儿童慢性风湿性疾病的严重、致命性并发症,其发病机制尚不完全清楚,目前仍没有统一的诊断标准,早期诊断有一定难度。文章综述了近几年巨噬细胞活化综合征发病机制的研究新进展以及早期诊断的生物学标志物。[临床儿科杂志,2012,30(5):496-498]     

儿童巨噬细胞活化综合征的发病机制与生物标志物研究进展

巨噬细胞活化综合征是一种继发于风湿免疫性疾病, 由多种原因引起的危及生命的综合征。巨噬细胞活化综合征是由于T细胞和巨噬细胞持续激活和增殖导致免疫过度刺激和致炎介质的瀑布样释放, 最终诱发细胞因子风暴和多器官衰竭。巨噬细胞活化综合征主要临床表现及实验室检查结果异常包括发热, 血细胞减少, 肝、脾、淋巴结肿大, 凝血障碍, 肝功能损害, 高铁蛋白血症, 高甘油三酯血症及骨髓噬血现象。该文从流行病学、发病机制、生物标志物方面的研究进展进行综述, 以期为巨噬细胞活化综合征的进展快、病死率较高的并发症的早期识别和诊断提供新思路。     

自身炎症性疾病与巨噬细胞活化综合征的亲疏

单基因缺陷自身炎症性疾病(AIDs)实体之间是异质性的,合并巨噬细胞活化综合征(MAS)少见。相似促炎性细胞因子谱研究AIDs-MAS、s JIA-MAS和HLH之间的临床与免疫病理机制可能会有新发现。     

细胞因子与全身型幼年特发性关节炎的研究进展

随着经济和医疗水平的发展, 慢性疾病成为影响儿童身心发展越来越突出的问题。其中, 幼年特发性关节炎是临床上常见的儿童风湿性疾病。细胞因子作为机体免疫反应的重要介质, 其在全身型幼年特发性关节炎及其并发症巨噬细胞活化综合征中的作用愈发受到重视。研究发现多种细胞因子在全身型幼年特发性关节炎及巨噬细胞活化综合征的发生与发展中起到致炎或抗炎的作用。该文就全身型幼年特发性关节炎及巨噬细胞活化综合征相关细胞因子的具体作用机制及临床意义归纳总结, 另对细胞因子相关药物治疗进展进行汇总, 通过探究全身型幼年特发性关节炎的发病机制, 以期为寻找新兴治疗靶点提供理论依据。     

重视对巨噬细胞活化综合征的认识

巨噬细胞活化综合征（macrophage activation syndrome,MAS）是一个严重危及生命的风湿性疾病并发症。以巨噬细胞过度活化为特点,临床表现为发热、肝、脾、淋巴结肿大,全血细胞降低,严重的肝脏损害,血管内凝血和神经系统受累。该病起病急、进展快、影响全身多个器官系统,如未及时诊断、治疗,病死率高。随着近年来对MAS认识的提高,国内外报道显示,风湿性疾病合并MAS并非少见。因此提高临床医生对该病的认识,对救治工作有重要意义。     

巨噬细胞活化综合征7例临床分析

巨噬细胞活化综合征(MAS)与噬血细胞综合征(HPS)属于异质同型性疾病,分类在继发性噬血细胞综合征中,是SOJIA严重而致命的并发症.病情进展迅速,可致多系统功能损伤.     

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现将2006年国内儿童风湿病诊断治疗的主要进展报道如下。1巨噬细胞活化综合征巨噬细胞活化综合征(MAS)是一种严重危及生命的风湿性疾病并发症。既往儿科临床对MAS认识不足,存在诸多误诊和漏诊。2006年《中华儿科杂志》编委会邀请部分儿科临床风湿免疫、血液、肾脏疾病专家和部分成人临床专家,在广州市召开“MAS专题研讨会”,对深入认识MAS起了重要推动作用[1]。本年度北京儿童医院、华中科技大学同济医院和天津儿童医院相继总结报道幼年特发性关节炎全身型(soJIA)并发MAS的临床表现、实验室特点、治疗和预后,从而对soJIA并发MAS有…     

2011年国家级继续教育项目《儿童免疫性疾病研讨班》通知

2011年国家级继续教育项目《儿童免疫性疾病研讨班》[2011-06-01-087(国)]将于2011年6月3-5号在广东省广州市珠江新城召开,主题是儿科临床免疫相关性疾病的诊治。内容涉及多个交叉学科,主要包括小儿过敏性变态反应性疾病、自身免疫性疾病、免疫缺陷病、感染与免疫四个方面,包括幼年特发性关节炎及巨噬细胞活化综合征、系统性红斑狼疮、     

儿童系统性红斑狼疮合并巨噬细胞活化综合征2例报告

<正>系统性红斑狼疮(systemic lupus erythemato?sus,SLE)是临床常见的一种多系统损害的自身免疫性疾病。其临床表现多样,病情进展快、预后不良,已引起临床医生的广泛关注。巨噬细胞活化综合征(macrophage activation syndrome,MAS)是一种严重的自身炎症性疾病,病死率高达20%～30%~([1]),常继发于感染性疾病、恶性肿瘤和多种风湿性疾病,其原因是不受控制地产生促炎性细胞     

全身型幼年特发性关节炎及合并巨噬细胞活化综合征诊疗专家共识(2022版)

全身型幼年特发性关节炎(systemic juvenile idiopathic arthritis, sJIA)是幼年特发性关节炎的一个亚型, 是一种以高热和皮疹为主要特征, 可伴全身多脏器功能损害的炎症性疾病。巨噬细胞活化综合征(macrophage activation syndrome, MAS)是最常继发于sJIA的严重风湿性疾病并发症, 进展迅速, 诊治不及时可危及生命。sJIA合并MAS的病因目前尚不明确, 早期临床特征缺乏特异性, 容易漏诊或误诊, 延误治疗时机。虽然近年来对sJIA合并MAS的认识逐渐深入, 但如何及时、合理诊治该病, 仍是儿童风湿病医师面临的挑战。为进一步规范sJIA及其合并MAS的诊断、治疗、减停药方案, 改善疾病总体预后, 由中华医学会儿科学分会风湿病学组等4个儿童风湿病专业学术组织联合制定《全身型幼年特发性关节炎及合并巨噬细胞活化综合征诊疗专家共识(2022版)》, 以更好指导该类疾病的临床诊治。     

So-JIA并巨噬细胞活化综合征临床特征及穿孔素A91V基因分析(英文)

目的 分析幼年特发性关节炎-全身型(So-JIA)并巨噬细胞活化综合征(MAS)的临床特点、治疗及转归,并探讨穿孔素基因与So-JIA并MAS的关系.方法 回顾性分析广州市儿童医院2003年1月至2008年6月收治的14例So-JIA并发MAS患者的临床资料,对其中7例患者进行序列特异性引物-聚合酶链反应(SSP-PCR)分析穿孔素第2外显子第272C/T基因(A91V gene)多态性.结果 14例患儿9例为男性,5例为女性;年龄为4个月～12岁.临床表现以长期发热、骨髓噬血现象、血细胞减少为特征,可伴随有浅表淋巴结肿大、肝脾肿大、肝功能损害、脂代谢异常,糖皮质激素及免疫抑制剂治疗有效.其中出现急性呼吸窘迫综合征(ARDS)2例,出现多器官功能衰竭(MOF)3例,死亡3例.7例So-JIA并发MAS的患者穿孔素A91V基因均为野生型,未发现有突变基因.结论 MAS病情凶险,预后与早期诊断及治疗有关.MOF可能足其预后差的指征.未发现广东地区汉族So-JIA并MAS患儿与穿孑L素A91V基因多态性有关.     

幼年特发性关节炎全身型合并巨噬细胞活化综合征4例报告并文献复习

目的 总结巨噬细胞活化综合征(macrophage activation syndrome,MAS)的临床特征及误诊原因,以提高对该病的认识.方法 回顾性分析54例幼年特发性关节炎全身型(systemic onset juvenile idiopathic arthritis,SO-JIA)合并MAS患儿的临床症状、体征、辅助检查及病情进展、诊断、治疗及预后.结果 54例SOJIA患儿中4例并发MAS(7.4%).临床特征有:持续高热、肝脾淋巴结增大、肝功能急剧恶化、皮肤黏膜易出血、外周血三系减少、中枢神经系统功能障碍、血沉进行性下降.结论 MAS是SOJIA的一个致死性并发症,起病突然,进展迅速,病死率高.在临床工作中需提高对其的认识,避免误诊.     

Meconium is a potent activator of complement in human serum and in piglets

Meconium aspiration syndrome (MAS) is a clinical condition in the newborn infant with a significant morbidity and mortality. The complex pathophysiology of MAS, leading to both pulmonary and systemic complications, is characterized by an incompletely understood inflammatory reaction. Treatment is symptomatic, mainly limited to airway cleaning and ventilatory support. In this study, we show for the first time that meconium is a potent activator of complement, a key mediator of inflammation. In vitro, meconium activated the alternative complement pathway in human umbilical cord serum as judged by a substantial increase in the alternative pathway convertase C3bBbP. The activation proceeded through C3 (C3bc) and the terminal C5-9 pathway (terminal SC5b-9 complement complex), whereas the classical and lectin pathways were not activated (C1rs-C1-inhibitor complexes and C4bc). The lipid fraction, containing, e.g. free fatty acids, and the water fraction, containing, e.g. bile acids, contributed equally to the complement activation. A blocking antibody to factor D (alternative pathway) completely inhibited the meconium-induced complement activation, whereas blocking antibodies to mannose-binding lectin (lectin pathway) and C2 (classical and lectin pathway) had no effect. In vivo, meconium induced systemic complement activation in a piglet model of MAS, paralleling the increase in lung dysfunction. In conclusion, meconium is a potent activator of the complement system both in vitro and in vivo. Complement may be important in the pathogenesis of MAS, and specific complement inhibition might be a possible treatment approach in MAS.     

Macrophage activation syndrome as the presenting manifestation of rheumatic diseases in childhood

We describe 3 patients who presented with features of macrophage activation syndrome (MAS) at the time of presentation of systemic lupus erythematosus (SLE), systemic juvenile idiopathic arthritis, and Kawasaki disease. Immunohistochemical studies in the patient with SLE demonstrated extensive expression of CD163 on hemophagocytic macrophages, suggesting a possible role as a marker of MAS.     

儿童风湿性疾病合并巨噬细胞活化综合征六例临床分析

目的巨噬细胞活化综合征（MAS）的诊断和治疗尚未得到统一,总结分析我院6例MAS患儿的临床资料,为临床救治工作提供参考。方法回顾性分析我院1998-2004年风湿性疾病合并MAS患儿的临床资料。结果共有6例（女4例,男2例）患儿符合MAS的诊断条件。发生MAS前,4例诊断幼年特发性关节炎全身型（SOJIA）,2例诊断系统性红斑狼疮和狼疮性肾炎。所有病例确诊MAS时疾病状态处于低活动期,主要的临床特征是：峰形热（5／6）或中高热（1／6）,肝脾肿大（6／6）,淋巴结病（6／6）,外周血3系减少（6／6）,明显的肝损伤（6／6）,弥漫性血管内凝血象（2／6）和中枢神经系统功能障碍（3／6）。低纤维蛋白原血症、肝酶升高和高甘油三酯血症均持续存在。3例骨髓涂片可见吞噬血细胞现象和浆细胞岛,其他3例未行此检查。3例患儿被证实存在感染,2例单纯疱疹病毒（HSV）和1例甲型肝炎病毒（HAV）。未发现药物相关因素。分别进行个体化治疗,重点在早期发现和联合抗病毒治疗,适度地联合免疫化疗（HLH-94或环孢素A）可以获得及时的缓解。1例SOJIA患儿严重肝损伤经连续性血液滤过／肾脏替代治疗联合免疫化疗获得迅速缓解。2例SOJIA患儿死于严重的内脏出血。结论MAS不仅见于SOJIA,还可以发生在儿科其他风湿性疾病的任何阶段,其发生率可能要高于以往的认识。感染可能是主要的触发因素。适时的免疫净化联合免疫化疗有益于严重肝损伤的恢复。     

全身型幼年特发性关节炎合并巨噬细胞活化综合征诊断和治疗

巨噬细胞活化综合征(MAS)是继发于风湿免疫性疾病基础上的噬血细胞性淋巴组织细胞增多症(HLH),也是儿科急性危重症,其中,以全身型幼年特发性关节炎(sJIA)相关MAS(sJIA-MAS)最为常见,且具有较高的病死率,早期诊断、及时治疗是改善预后的关键。虽然sJIAMAS和HLH具有相似的临床和实验室特征,但由于二者的基础疾病不同,因此诊断标准也有所差异。糖皮质激素和环孢素A是MAS的一线治疗药物,但仍存在较大挑战,生物制剂靶向药物逐步被提出作为难治性MAS的治疗选择,甚至作为MAS的一线药物。该文重点阐述sJIA-MAS的临床和实验室特征、生物标志物、分类标准及治疗进展。     

Macrophage activation syndrome as initial presentation of systemic lupus erythematosus

Macrophage activation syndrome (MAS) is known to be a severe and potentially life-threatening complication of rheumatic disorder, especially systemic juvenille rheumatoid arthritis. It is very rare for MAS to be an initial presentation of systemic lupus erythematosus (SLE). Here, we report a 14-year-old girl in whom MAS developed as an initial presentation of SLE. With early diagnosis and administration of cyclosporine A, she had a fair outcome. Further testing showed positive anti-dsDNA about 8 months later.     

Etanercept for therapy-resistant macrophage activation syndrome

Macrophage activation syndrome (MAS) is a severe, potentially fatal complication of childhood rheumatic diseases, especially systemic onset juvenile idiopathic arthritis (SoJIA). We report a 4-year-old girl with probable SoJIA who presented with MAS. She did not respond to pulse methyl prednisolone and Cyclosporine A (CsA). She also failed to respond to intravenous immunoglobulin (IVIG) therapy. Etanercept was started, based on the observation of increased serum levels of tumor necrosis factor-alpha (TNF-alpha) in patients with MAS. Her condition improved following etanercept, suggesting that etanercept might have a therapeutic role in resistant MAS.     

巨噬细胞活化综合征的临床和实验室特征分析

目的分析巨噬细胞活化综合征(MAS)患儿诊断初期的临床和实验室特征,探索早期识别MAS的方法。方法回顾性分析21例MAS患儿的临床、实验室特征,以及治疗和转归。结果 MAS患儿的原发病包括全身型幼年特发性关节炎(SJIA)14例、川崎病(KD)5例和结缔组织病(CTD)2例。发生MAS的中位时间为19 d,以KD-MAS发生最快,CTD-MAS发生最晚(P=0.009)。前10位的临床症状依次为发热(95%),皮疹(86%),淋巴结肿大(67%),骨髓吞噬现象(63%),肺部病变(62%),浆膜腔积液(62%),肝肿大(52%),脑脊液异常(50%),中枢神经系统损害(43%)和脾肿大(38%)。实验室特征方面,血红蛋白降低;超敏C反应蛋白、血沉升高、血清铁蛋白明显升高;谷丙转氨酶、谷草转氨酶、乳酸脱氢酶和甘油三酯升高;纤维蛋白原降低,D-二聚体明显升高;IL-6、IL-10和IFN-γ明显升高。21例患儿中20例好转出院。结论风湿性疾病患儿如出现持续发热,肝功能损害,凝血功能异常,甚至多脏器损害,以及IL-10、IFN-γ明显升高和血清铁蛋白持续升高,要高度警惕MAS发生。     

Macrophage activation syndrome: a potentially fatal complication of rheumatic disorders.

AIMS: To review the precipitating events, clinical features, treatment, and outcome of macrophage activation syndrome (MAS). METHODS: Retrospective review of cases of MAS from a prospectively collected database of children with rheumatic diseases from 1980 to 2000. RESULTS: Nine patients (eight girls) were considered to have evidence of MAS. The primary diagnosis was systemic onset juvenile idiopathic arthritis in seven, enthesitis related arthritis in one, and chronic infantile neurological cutaneous articular syndrome in one. Mean age of onset was 5.7 years, and duration prior to MAS, 4.2 years. No medication was identified as a trigger. Eight had infections prior to MAS; specific infectious agents were identified in four. High grade fever, new onset hepatosplenomegaly, and lymphadenopathy were common clinical features. Platelet counts fell dramatically, from an average of 346 to 99 x 10(9)/l. Mean erythrocyte sedimentation rate (in three patients) fell from 115 to 28 mm/h. Eight had abnormal liver function during the disease course, and six had coagulopathy. Bone marrow examination supported the diagnosis with definite haemophagocytosis in four of seven. All received high dose steroids (eight intravenous, one oral), five cyclosporin, two cyclophosphamide, and one antithymocyte globulin. Two of three patients with significant renal impairment died. CONCLUSION: MAS is a rare and potentially fatal complication of childhood rheumatic disorders. Most of our patients were female, and most cases were preceded by infection. Bone marrow studies support the diagnosis. Deranged renal function may be a poor prognostic sign. Aggressive early therapy is essential.