噬血细胞综合征临床分析

目的：探讨噬血细胞综合征(HPS)的常见病因及临床特点。方法：对40例确诊为HPS的患者采用单抗、骨髓活检等方法明确其病因及相关治疗、预后。结果：病因不明HPS占42．5％，淋巴瘤伴发HPS10例，2例死亡，各种感染(包括结核、伤寒、传染性单核细胞增多症等)相关11例，占27．5％，3例死亡，结缔组织病伴发HPS2例，1例死亡。结论：噬血细胞综合征病因复杂，其临床表现缺乏特异性，易导致误诊，需采用免疫学等多种方法积极寻找病因对治疗及预后致关重要。     

噬血细胞综合征30例临床分析

目的:探讨噬血细胞综合征(HPS)的临床特点、诊断、治疗以及预后的危险因素。方法:对我院30例HPS患者的病因、临床表现、实验室检查指标、治疗方案及临床转归进行回顾性分析。结果:30例HPS病因以感染最多见(30%),其中EB病毒感染达20%,然而病因不明者也高达56.7%。HPS临床表现为持续高热(100%)、脾肿大(93.3%)、全血细胞减少(83.3%)、乳酸脱氢酶(100%)及血清铁蛋白(100%)升高。肝功能损害(90%)及心肌酶谱(60%)升高也较为常见。30例经治HPS患者30d、100d、1年的生存率分别为36.7%、23.3%、10.0%。其中7例给予包含VP16的化疗方案,30d、100d、1年的生存率分别为85.1%、71.4%、42.9%。结论:HPS可由多种病因所致,EB病毒最为常见,临床表现多样。发热、血清铁蛋白、乳酸脱氢酶升高在诊断中的灵敏度较高。包含VP16的化疗方案是有效的治疗方案。     

血管免疫母细胞性T细胞淋巴瘤继发噬血细胞综合征1例

噬血细胞综合征(HPS)是一类由免疫系统紊乱所致的疾病,临床表现为高热,肝脾和(或)淋巴结肿大,全血细胞减少,肝功能异常和凝血功能障碍.病情常发展迅速,若不及时诊断及治疗,预后很差.我们近期收治1例成人血管免疫母细胞性T细胞淋巴瘤伴发噬血细胞综合征患者,现报告如下.     

自身免疫病合并噬血细胞综合征临床分析

目的 通过分析11例自身免疫病(AID)合并噬血细胞综合征(HPS)的临床特点,提高对该病的认识.方法 收集北京协和医院2004年1月-2009年6月住院的AID合并HPS者11例,回顾性分析其发生诱因、各系统受累表现、治疗及预后.结果 11例AID合并HPS患者中男性3例,女性8例,年龄12 74(30.7±18.3)岁.基础病:斯蒂尔病4例,系统性红斑狼疮(SLE)3例,干燥综合征(SS)、类风湿关节炎(RA)、韦格纳肉芽肿(WG)、克罗恩病(CD)各1例.诱发HPS因素:基础病活动4例,基础病活动并发感染6例,单纯感染1例.11例患者均有高热,其中肝脾肿大8例,淋巴结肿大7例,神经系统受累4例,并发弥漫性血管内凝血(DIC)4例.实验室检查:血细胞减少11例,肝功能异常11例,高甘油三酯血症5例,低纤维蛋白原血症9例,铁蛋白＞500 μg/L 6例,NK细胞活性降低4例.骨髓涂片均见吞噬血细胞现象.经大剂量糖皮质激素联合免疫抑制剂、积极抗感染、静脉人免疫球蛋白(IVIG)支持治疗,5例存活,6例死亡,合并DIC 4例均未存活(r=0.69,P=0.019).结论 AID并发HPS不易与活动性AID鉴别.合并DIC预后差、病死率高.糖皮质激素、免疫抑制剂及IVIG对HPS治疗有效,合并感染时加强抗感染治疗至关重要.     

成人噬血细胞综合征23例临床特征分析

目的：分析成人噬血细胞综合征（HPS）的临床特征,对比 HLH-2004诊断标准,以提高对本病的认识,早期诊断,减少误诊,提高存活率。方法回顾分析近5年收治的23例因肝功能异常入院最终确诊为噬血细胞综合征患者的病因、临床症状、体征、实验室检查结果及转归。结果23例患者原发病分析显示,恶性淋巴瘤9例,感染8例,风湿性疾病5例,其他原因1例。主要临床表现以持续发热（95．7％）、脾脏肿大（100．0％）及肝脏肿大（82．6％）为突出表现,其他表现为淋巴结肿大（73．9％）、黄疸（73．9％）、呼吸系统症状（52．2％）、多浆膜腔积液（56．5％）、中枢神经系统症状（47．8％）、皮疹（34．8％）、出血（21．7％）及肾功能损害（30．4％）。实验室检查以肝功能损害最为突出,主要是 LDH、AST 升高（100．0％）,血细胞减少（两种血细胞下降占30．4％、全血血细胞下降占69．6％）,纤维蛋白原（Fg）下降（82．6％）,PT 延长（47．8％）。死亡组患者的LDH 和AST水平明显高于存活组（t＝4．509、3．339,P＝0．003）,而死亡组患者的血小板计数和Fg水平明显低于存活组（t＝7．892、3．561,P＝0．002）。首次骨髓检查有噬血细胞现象14例,第2次或多次骨髓检查有噬血细胞现象9例。23例经治 HPS患者12周总体生存率为43．5％。结论 HPS可由多种病因引起,临床表现多样,病死率高。LDH 和AST升高,PLT和Fg降低是疾病的不良预后因素。骨髓的多次检查有助于及时诊断。     

儿童巨噬细胞活化综合征与其他噬血细胞综合征的临床比较分析

目的 观察儿童巨噬细胞活化综合征(MAS)与其他噬血细胞综合征(HPS)的临床特点,探究两者在临床特点、诊断、治疗及预后上的不同之处.方法 收集2006年1月至2009年3月所有HPS患儿共36例,分为MAS组13例,其他HPS 23例.运用t检验、χ2检验及Fisher精确概率法统计两者在临床特点、实验室指标、治疗方法及预后情况上的差异.结果 MAS患儿年龄明显大于其他HPS患儿[(7.7±1.3)岁和(2.6±0.5)岁,t=3.899,P＝0.004];而性别分布上差异无统计学意义.临床表现上MAS患儿中枢神经系统受累(69%和13%,P=0.001)、循环系统受累(23%和9%,P=0.047)及泌尿系统受累(38%和9%,P=0.033)更为常见且临床症状更为严重.在实验宅检查上,MAS患儿血清铁蛋白的增高、红细胞沉降率(ESR)的动态变化更为明显,其中铁蛋白增高[(9703±9819) μg/L和(4569μ1396) μg/L,t:2.854,P=0.015]、ESR动态变化[(53±32)mm/1 h和(20±14)mm/1 h,t=2.708,P=0.020].结论 MAS与其他HPS在发病年龄、病因、各系统的累及、临床表现的严重程度、一些实验室检查变化及治疗方法上有所差别.     

成人噬血细胞综合征肝损伤临床特点分析

目的研究成人噬血细胞综合征(hemophagocytic syndrome,HPS)患者肝损伤的临床特点。方法对33例成人HPS患者的病因、临床特点及实验室结果进行分析。结果 33例中,病因与感染相关17例(51.5%),与非感染相关8例(24.2%),另有8例(24.2%)未找到原发病。16例死亡,病死率为48.5%。所有患者均有不同程度肝损伤,突出表现为LDH和AST明显升高,ALB明显下降,TBIL升高以DBIL为主,并伴有不同程度的PA下降。但在死亡组和存活组间只有TBIL和PA差异有统计学意义[TBIL(307.3±182.2)μmol/L vs(137.0±153.7)μmol/L,P=0.013;PA(44.5±18.8)%vs(64.9±19.1)%,P=0.004]。结论肝损伤是HPS常见的器官损害,肝损伤程度可能与预后相关。     

弥漫大B细胞淋巴瘤继发噬血细胞综合征1例

噬血细胞综合征（HPS）又称噬血细胞性淋巴组织细胞增生症,是一组因遗传性或获得性免疫缺陷导致的以过度炎症反应为特征的疾病,其主要临床特征为持续发热、肝脾肿大、全血细胞减少、出凝血机制障碍以及中枢神经系统异常等.HPS临床少见,症状不典型,易误诊、漏诊,且肿瘤相关性HPS病情凶险,病死率高.2013年1月,笔者收治弥漫大B细胞淋巴瘤相关HPS患者1例.现报告如下.     

肝功能异常为主要临床表现的噬血细胞综合征10例临床分析

目的通过对10例以肝功能异常为主要临床表现的噬血细胞综合征病例进行分析,探讨本病的临床特点,提高对本病的认识。方法对10例患者的病史、临床表现和实验室检查结果进行综合分析。结果噬血细胞综合征（HPS）可表现为严重的肝功能损害,其特点为胆红素明显升高,以直接胆红素升高为主,以及ALT、AST及GGT升高。结论不明原因肝功能异常并伴有发热和血细胞减少的患者应警惕HPS,早期诊断和治疗。     

丙酮酸激酶缺乏症36例临床资料分析

目的:探讨丙酮酸激酶(PK)缺乏症的临床特点、诊断、治疗及预后。方法:回顾性分析36例PK缺乏症患者的临床资料。结果:临床表现:36例患者中23例有不同程度的贫血貌,12例有皮肤和(或)巩膜黄染,脾大18例,肝大8例,尿色加深13例。实验室检查:全血细胞减少8例,36例患者红细胞均有不同程度的减少,血红蛋白低于正常值35例,血红蛋白正常1例,31例网织红细胞百分比增加。溶血检查:36例患者均存在PK活性缺乏,其中2例合并遗传性球形红细胞增多症,合并嘧啶5'核苷酸酶缺乏症1例,合并地中海贫血1例,继发于骨髓增生异常综合征4例,继发于再生障碍性贫血4例,继发于骨髓纤维化1例。结论:PK缺乏症病情严重程度不一,临床容易误诊、漏诊,目前无有效治疗手段,其治疗手段尚需进一步研究。     

Autoimmune-associated hemophagocytic syndrome

Hemophagocytic syndrome (HPS) is a clinicopathological condition characterized by the activation of histiocytes with prominent hemophagocytosis in bone marrow and other reticuloendothelial systems. The occurrence of HPS is usually associated with underlying disorders such as infection and lymphoma. Recently, we described patients with autoimmune disease who developed HPS. In these cases there was no evidence of underlying infection and malignancy, and the occurrences of HPS were associated with active autoimmune disease. Based on these observations, we described autoimmune-associated hemophagocytic syndrome (AAHS). This disease entity is becoming better known, and case reports presenting features compatible with clinical AAHS are increasing. Here, we review the clinical aspects, mechanisms, diagnosis, and treatment of AAHS according to our data and that in the literature.     

Clinical features of 25 patients with cytomegalovirus infection complicating hematological diseases unrelated to allogeneic bone marrow transplantation

The clinical features of 25 cases of cytomegalovirus (CMV) infection complicating hematological diseases were analyzed. These cases did not undergo allogeneic bone marrow transplantation. 21 cases (84%) had a lymphoid tumor including 16 cases (64%) of malignant lymphoma and three cases of adult T-cell leukemia. All patients but one have received corticosteroid or antineoplastic agents before the occurrence of CMV infection. The types of CMV infections were interstitial pneumonia (23 cases), retinitis (2 cases), enteritis (one case), and persistent pyrexia (one case). Nine cases were diagnosed by histopathology and 5 of these 9 cases were discovered as having a CMV infection at autopsy. 20 cases were treated with ganciclovir for CMV infection, but only 9 cases improved. Of the 9 cases diagnosed by CMV-antigenemia, which had been introduced in the late 1994, 4 cases whose lymphoid tumor had been controlled responded to ganciclovir and survived but others with uncontrollable disease died. The present study indicates that the progress in the treatment of CMV infection was achieved in patients with controllable hematological disease but not in patients with refractory disease even after introduction of CMV-antigenemia.     

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.     

Hemophagocytic syndrome in kidney transplant recipients: report of four cases from a single center

BACKGROUND: The prognosis of hemophagocytic syndrome (HPS) in kidney transplant recipients is reported to be poor, however the optimal therapeutic approach is still unclear. PATIENTS AND METHODS: The clinical and follow-up data of the 4 patients with HPS (3 male, 1 female; age 39.7 +/- 11.3 years) among 368 kidney transplant recipients during a 5-year period were retrospectively analyzed. RESULTS: HPS developed 35-61 days in the post-transplant period. All 4 patients presented with fever. Hepatosplenomegaly and lymphadenopathy were observed only in the first patient. Laboratory tests revealed pancytopenia and hyperferritinemia in all patients, but elevated liver enzymes were observed in 3. Two patients had cytomegalovirus infection, and 1 had Epstein-Barr virus infection. Three patients died despite aggressive supportive therapy, however the fourth case survived after graft nephrectomy. CONCLUSION: HPS pathogenesis in kidney transplants appears to be related with the graft itself. Graft nephrectomy may be the preferable therapeutic approach for kidney transplant recipients with HPS resistant to standard supportive therapy.     

Subcutaneous panniculitis-like T-cell lymphoma: definition, classification, and prognostic factors: an EORTC Cutaneous Lymphoma Group Study of 83 cases

In the WHO classification, subcutaneous panniculitis-like T-cell lymphoma (SPTL) is defined as a distinct type of T-cell lymphoma with an aggressive clinical behavior. Recent studies suggest that distinction should be made between SPTL with an alpha/beta T-cell phenotype (SPTL-AB) and SPTL with a gammadelta T-cell phenotype (SPTL-GD), but studies are limited. To better define their clinicopathologic features, immunophenotype, treatment, and survival, 63 SPTL-ABs and 20 SPTL-GDs were studied at a workshop of the EORTC Cutaneous Lymphoma Group. SPTL-ABs were generally confined to the subcutis, had a CD4-, CD8+, CD56-, betaF1+ phenotype, were uncommonly associated with a hemophagocytic syndrome (HPS; 17%), and had a favorable prognosis (5-year overall survival [OS]: 82%). SPTL-AB patients without HPS had a significantly better survival than patients with HPS (5-year OS: 91% vs 46%; P<.001). SPTL-GDs often showed (epi)dermal involvement and/or ulceration, a CD4-, CD8-, CD56+/-, betaF1- T-cell phenotype, and poor prognosis (5-year OS: 11%), irrespective of the presence of HPS or type of treatment. These results indicate that SPTL-AB and SPTL-GD are distinct entities, and justify that the term SPTL should further be used only for SPTL-AB. SPTL-ABs without associated HPS have an excellent prognosis, and multiagent chemotherapy as first choice of treatment should be questioned.     

13例噬血细胞综合征的临床特征分析

目的：分析噬血细胞综合征（HPS）患者的临床特征,进一步提高对本病的认识。方法：回顾性分析13例HPS患者的临床资料。结果：13例患者均表现为持续性或间歇性高热,均有脾肿大,2例为巨脾,9例同时肝肿大;4例患者发病时伴随消化系统症状;13例患者均表现为血象3少或2少;7例有高甘油三酯血症,4例有低纤维蛋白原血症;8例患者出现铁蛋白升高,其中4例高于2000ug／L,并伴有多器官功能衰竭;4例患者进行外周血流式细胞术分型,NK细胞均明显低于正常;所有患者骨髓象中均发现组织细胞增多,比例为2．O％～18．0％,存在吞噬血小板和红细胞现象;13例检查了EBV相关抗体,其中12例IgG,1例IgM和IgG抗体均为阳性;有6例患者进行了化疗,其中5例使用VP方案,1例使用CHOP方案化疗6个疗程,病情缓解;2例患者未进行化疗,病情好转。结论：HPS常呈动态发展过程,在发病初期极易误诊,应积极进行骨髓细胞学、免疫分型及可溶性白细胞介素-2受体（sL-2R）水平等检查,努力寻找病因和诱因;部分诊断指标可能在疾病发展过程中才显现,早期治疗有助于改善预后。

Abstract：

Objective.. To analyze the clinical features of patients with hemophagocytic syndrome （HPS）and enhance understanding of the disease further. Methods.. Clinical data of 13 patients diagnosed with HPS were analyzed retrospectively. Results： Thirteen patients showed persistent or intermittent high fever, splenomegaly, two cases with massive splenomegaly, nine cases had hepatomegaly at the same time. Four cases had the symptom of gastrointestinal system; 13 cases showed less for the blood cells, as three or two less; 7 cases with hypertrigliceridemia, 4 cases with hypofibrinogenemia. Ferritin increased in 8 cases, and 4 above 2000ug/L, 4 cases developed to multiple organ failure; four cases were examined for the peripheral blood flow type, their NK cells were significantly lower than normall increased histiocytosis in bone marrow were found in all patients, ratio from 2. 0% to 18. 0%, phagocytosis of platelets and red blood cells in the histiocytes were common; 13 cases were examined EBV-related antibodies, 12 cases were IgG, 1 case was IgM and IgG antibodies positive; 6 cases were treated with the chemotherapy, of which 5 cases used the VP regimen, one case used CHOP with 6 courses, then got remission; patients had no chemotherapy, and improved too. Conclusions.. HPS often has the dynamic development process, easily misdiag nosed in early stages of disease. The examinations of bone marrow cytology, flow immunophenotyping and sL-2R level should be carried out actively, and try to search for the causes and incentives. Some diagnostic criteria may become apparent during the development of the disease. Early treatment can help improve patiats＇ prognosis.     

Successful treatment of hemophagocytic syndrome in a patient with T cell lymphoma,EBV infection,and bone marrow necrosis: A case report

Rationale:Hemophagocytic syndrome (HPS) is associated with a high mortality rate, and Epstein–Barr virus infection and hematological malignancies, especially T/natural killer cell lymphomas, are the most common causes; however, due to the complexity of clinical manifestations, the diagnosis is usually delayed. There are few reports of lymphoma-associated HPS (LAPS) in combination with bone marrow necrosis, and there is still no standard treatment for LAPS.Patient concerns:A 64-year-old man developed a fever, mild jaundice, fatigue, and bone pain. Positron emission tomography and bone marrow biopsy with immunohistochemistry were performed.Diagnosis:Imaging analysis and bone marrow examinations were compatible with HPS, T-cell lymphoma, and bone marrow necrosis.Interventions:The patient received combination therapy of rituximab and Cyclophosphamide, epirubicin, vincristine, glucocorticoid, etoposide.Outcomes:The patient achieved complete remission and a disease-free survival of 52 months.Lessons:HPS and its potential diseases should be diagnosed and treated as soon as possible. Clinicians should be aware of the presence of lymphoma in patients with HPS. Rituximab plays an important role in the prognosis of HPS, particularly Epstein–Barr virus positivity. Cyclophosphamide, epirubicin, vincristine, glucocorticoid remains an effective regimen for the treatment of T-cell LAPS. This study provides a better understanding of the diagnosis and treatment of LAPS.     

原发性肺黏膜相关淋巴组织淋巴瘤4例临床病例分析

目的 总结原发性肺黏膜相关淋巴组织(MALT)淋巴瘤的临床表现、影像学特点、诊断手段、治疗方法及预后,提高临床诊治水平.方法 回顾性分析4例经病理确诊的原发性肺MALT淋巴瘤的临床资料并随诊分析预后.结果 4例原发性肺MALT淋巴瘤患者均为老年女性,为原发性肺非霍奇金淋巴瘤的最常见类型.其中3例为查体发现,1例因咳嗽、咳痰和痰中带血就诊.发病时间为7个月至5年.肺部体征无特异性.血炎症指标和肿瘤相关指标多为正常.影像学以肿块影和结节为主要表现.患者肺通气和弥散功能正常.经胸腔镜、CT引导下肺穿刺、开胸手术获取病变组织而确诊.病理表现为弥漫浸润生长的小淋巴细胞,可见淋巴上皮增生.治疗主要是化疗和手术.随访1～8.8年,1例随访4.5年时可疑复发,其余3例均病情稳定.结论 肺原发性MALT淋巴瘤为少见病,好发于老年女性,起病隐匿,临床表现不典型.诊断须靠有经验的病理专家作出.治疗尚无指南,无症状者可采取“观察等待”策略,待肿瘤进展或出现症状时,首选苯丁酸氮芥化疗,联合利妥昔单抗与否均可.预后良好,但复发率高.     

肺黏膜相关淋巴组织淋巴瘤临床特征分析

目的：提高肺黏膜相关淋巴组织淋巴瘤诊治水平。方法回顾性分析江西省人民医院及南昌大学第二附属医院自2005年1月至2015年1月确诊的8例肺黏膜相关淋巴组织淋巴瘤的临床表现、影像学特点、诊断手段、误诊情况、治疗及预后。结果8例肺黏膜相关淋巴组织淋巴瘤中男6例,女2例,年龄38~75岁,中位年龄65岁。主要症状：咳嗽(5例)、咳痰(4例)、发热(2例)、胸闷(4例)、乏力(3例)、消瘦(3例),无症状2例。胸部 CT 表现：双肺分布5例,单肺分布3例,实变影5例,肿块及结节影4例,斑片状浸润影3例,支气管充气征5例,钙化1例,空洞2例。确诊方法：经气管镜活检1例,CT 引导下经皮肺穿刺5例,外科手术2例。误诊分析：5例误诊为细菌性肺炎,1例误诊为肺真菌病,1例误诊为肺癌,1例误诊为肺转移癌。治疗及预后：2例外科手术患者术后未行放化疗,4例转入血液内科行化疗(CHOP 方案),2例放弃治疗。8例患者随访时间2~105个月,2例死亡,6例存活。结论肺黏膜相关淋巴组织淋巴瘤临床表现不典型,容易误诊,诊断需要组织病理活检。