38例噬血细胞综合征病因分析

本研究探讨噬血细胞综合征(hemophagocytic syndrome,HPS)的病因及临床特点。回顾性分析38例HPS患者的临床资料,并且对家族性噬血细胞性淋巴组织细胞增多病(familial hemophagocytic lymphohistiocytosis,FHL)发病相关的穿孔素(prf1)和stx11基因外显子编码区片段进行突变筛查。结果表明:38例HPS病例中1例(2.63%)确诊为FHL,与感染性疾病相关14例(36.84%),与肿瘤相关10例(26.32%),与风湿免疫系统疾病相关7例(18.42%),病因不明6例(15.79%)。38例HPS患者中死亡9例,死亡率为23.68%,其中感染相关HPS患者4例死亡;肿瘤相关HPS患者2例死亡;风湿免疫相关HPS患者1例死亡;病因不明患者2例死亡。1例HPS患者发现穿孔素基因(prf1)突变,最终确诊为FHL。结论:HPS不是一种单一病因的疾病,原发疾病不同其转归各异。临床诊断HPS时必须重视原发疾病和病因学检查。穿孔素基因(prf1)及stx11基因外显子编码区片段突变检测对于FHL确诊具有重要作用。     

A Clinicopathological Study of 20 Patients With T/Natural Killer (NK)-Cell Lymphoma-Associated Hemophagocytic Syndrome With Special Reference to Nasal and Nasal-Type NK/T-Cell Lymphoma

We describe the clinicopathological features of 20 patients with T/natural killer (NK)-cell lymphoma-associated hemophagocytic syndrome (T/NK-LAHS). These patients were categorized into 2 groups according to the onset of hemophagocytic syndrome (HPS). Group 1 developed HPS during the clinical course, typically at the terminal phase of the disease. This group consisted of 7 patients with extranodal lymphoma arising in the nasal cavity, paranasal cavity, tonsils, or skin at presentation. In 5 of these patients, the preferred diagnosis was nasal and nasal-type NK/T-cell lymphoma, whereas the disease diagnoses in the remaining 2 patients were peripheral T-cell lymphoma of unspecified type and angioimmunoblastic T-cell lymphoma, respectively. Group 2 consisted of 13 patients whose disease corresponded to so-called malignant histiocytosis-like lymphoma, which is characterized by HPS at the initial presentation and the infiltration of the liver, spleen, and/or bone marrow without tumor formation. Nine of these 13 cases were found to have common histopathological features: CD56+, Epstein-Barr virus positivity, cytotoxic molecules, and nasal-type NK/T-cell lymphoma. The very poor prognosis of T/NK-LAHS may be partly explained by the finding that nasal and nasal-type NK/T-cell lymphoma, which is resistant to standard chemotherapy, made up the highest percentage (70%) of the cases.     

Two cases of reactive hemophagocytic syndrome: a patient with adult-onset Still's disease and a patient with herpes zoster and autoimmune abnormalities

We report two cases of bone marrow hemophagocytosis. One patient had adult-onset Still's disease, and the other had herpes zoster associated with potential autoimmune abnormalities. Our findings suggested a pos-sible role of cytokines and/or antibodies in the induction of hemophagocytosis in patients with connective tissue diseases and/or immune abnormalities. Received: November 28, 2000 / Accepted: March 12, 2001     

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.     

加强儿童噬血细胞综合征的早期诊断与干预研究

噬血细胞淋巴组织细胞增生症(hemophagocytic lymphohistiocytosis,HLH)是儿科临床上少见但病情凶险、病死率很高的疾病,分家族性、继发性和肿瘤相关性3种类型.其病因复杂,机制尚未完全阐明.有证据表明,该病的发生与编码免疫应答功能相关的蛋白基因缺陷有关,其基本发病机制是在免疫缺陷的基础上,伴有感染、肿瘤及坏死组织细胞等抗原的诱发下,导致细胞因子的大量释放,进而激活单核巨噬细胞发生吞噬现象和多脏器损伤.HLH-2004诊疗指南是当前诊治HLH的主要方法,细胞因子的快速测定有助于HLH的早期诊断.     

儿童噬血细胞淋巴组织细胞增生症23例临床分析

目的 研究HLH-2004方案诊断和治疗噬血细胞淋巴组织细胞增生症(HLH)患儿的效果和预后,分析HLH的相关病因.方法 23例(男14例,女9例)HLH患儿,平均年龄3.8岁,其中12例≤2岁.按HLH-2004诊断标准和治疗方案进行诊断和治疗,并进行可能病因的检查和分析其相关病因.结果 相关病因未明组13例(56.5%),病毒感染相关组5例(21.7%);这二组中有4例未治疗的患儿在诊断后2周内死亡,14例使用HLH-2004方案治疗,仅1例治疗过程中死于消化道出血合并深部霉菌感染,其余13例早期均能获得缓解,4例中途退出治疗并死于复发,9例完成治疗后随访1.5～2年无复发.淋巴瘤相关组3例(13.1%),其中2例为间变性大细胞性淋巴瘤(ALCL),开始使用淋巴瘤方案(COP)治疗,病情未获缓解,加用HLH-2004方案治疗获得快速缓解,再继续按淋巴瘤的化疗方案治疗.其他相关组2例(8.69%),其中系统性红斑狼疮(SLE)和坏死性淋巴结炎(HNL)各1例,均使用肾上腺皮质激素治疗后前者存活,后者死亡.3例诊断后未治疗的患儿全部死亡.结论 HLH-2004诊断标准有较强的诊断可行性.所有HLH患儿对HLH-21304方案免疫一化疗有较好的治疗反应,可获得快速缓解,依托泊苷很可能是关键药物.部分HLH与病毒感染、淋巴瘤、SLE和HNL相关,半数以上病因未明.     

A spectrum of neuroradiological findings in children with haemophagocytic lymphohistiocytosis

Background Haemophagocytic lymphohistiocytosis (HLH) is a rare multisystem disorder. CNS involvement is a frequent and poor prognostic component. Better neuroradiological surveillance may be beneficial for patient management and outcome. Objective To describe various neuroradiological findings in nine patients with HLH with an emphasis on correlation with disease activity and treatment response. Materials and methods Between 1996 and 2007, nine children with HLH with CNS involvement were identified in a single centre. Neuroradiological findings from CT, MRI, and proton MR spectroscopy, and the clinical records of the nine children were retrospectively reviewed. The frequency, distribution, characteristics of abnormal neuroradiological findings and changes during follow-up were correlated with clinical findings. Results Initial abnormal findings included multiple nodular or ring-enhancing parenchymal lesions, a laminated pattern of nodular parenchymal lesions on T2-weighted images, leptomeningeal enhancement, confluent parenchymal lesions, mild ventriculomegaly, and diffuse brain oedema. On follow-up imaging studies, haemorrhagic transformation and atrophy were seen where brain parenchymal lesions had been previously. These abnormal neuroradiological findings showed good correlation with clinical findings. Proton MR spectroscopy also demonstrated typical changes of metabolites during the course of the disease. Conclusion A spectrum of neuroradiological findings in children with HLH is well matched with the clinical course of the disease and, therefore, a comprehensive analysis of the findings is useful to monitor disease activity and treatment responses.     

Hemophagocytic lymphohistiocytosis (HLH) presenting on the 3rd day of life

Hemophagocytic lymphohistiocytosis (HLH) embraces the frequently indistinguishable conditions, namely familial hemophagocytic lymphohistiocytosis (FHLH), sporadic hemophagocytic lymphohistiocytosis (SHLH) and virus associated hemophagocytic syndrome (VAHS). The disease is very rare and invariably lethal. Evidence suggests that the disease may be due to an inherited defect in immunoregulation that predisposes to an uncontrolled proliferation of activated histiocytes in response to a stimulus such as viral infection. We report here a 3-day-old neonate with confirmed HLH who had a stormy course and a fatal outcome to the disease process, in spite of early chemotherapy. To our knowledge, we believe this is the youngest reported case of HLH from Middle East. No familial or infective cause could be attributed.     

血源播散性肺结核继发噬血细胞综合征1例

<正>1病例资料患者男性,28岁,主因“发热2个月,鼻衄及双下肢出血性皮疹10天”入院。2个月前,患者无明显诱因出现发热,体温39℃,弛张热型,伴乏力,不伴咳嗽、咳痰、腹痛、腹泻、尿急、尿频、尿痛等不适。自行口服退热药(具体不详)后可短暂退热,但效果不佳,遂于当地医院就诊,予“头孢菌素”及“地塞米松”静脉输液(具体剂量不详) 6 d,体温恢复正常,但停药后再次出现发热,体温波动于38.5～40℃,未再诊治。1个月余前就诊于外院,查血常规未见异常,胸片示“双肺纹理增多”,予莫西沙星口服2 d(具体剂量不详),患者体温波动于38.5～40℃。