32例噬血细胞综合征实验室检查及临床分析

目的分析继发性噬血细胞综合征(HPS)患者的实验室指标及临床特点,以提高对该病的认识。方法对2005年6月~2015年6月在广西肿瘤防治研究所治疗的32例继发性HPS患者的病因、临床表现、实验室特征、治疗及预后等进行分析。结果 32例患者中,血液系统肿瘤17例,单纯感染13例,自身免疫性疾病2例。临床上以发热(100%)、肝脾(87.5%)及淋巴结(43.8%)肿大为主要表现。实验室检查以血细胞减少(100%)、铁蛋白升高(96.9%)、自然杀伤细胞活性降低或缺失(96.9%)为主,纤维蛋白原降低(68.8%),甘油三酯升高(56.3%),81.3%的患者骨髓涂片检查可见噬血细胞现象。结论继发性HPS可由多种病因引起,临床表现多样,对可疑患者及时进行相关实验室检查有助于早期明确诊断;合并多脏器衰竭、DIC的患者预后不良。     

噬血细胞综合征临床特征与影响预后因素分析

目的:探讨噬血细胞综合症的临床特征及影响预后因素,为临床治疗提供依据。方法:选择2006年1月~2011年12月我院收治的噬血细胞综合症患儿26例,回顾分析所有患儿的临床表现、实验室检查、病因及转归等资料。结果:死亡10例,好转或痊愈16例。原发与继发性HPS转归情况比较,X2=7.825,P<0.05,差异有统计学意义。两组年龄(t=2.807)、肝肿大(t=2.817)、脾肿大(t=2.651)、白细胞计数(t=2.580)、血小板(t=2.814)、纤维蛋白原(t=2.984)、乳酸脱氢酶(LDH)(t=2.667)和丙氨酸转氨酶(ALT)(t=2.514)比较,差异有统计学意义,P<0.05。结论:儿童噬血细胞综合征病因复杂,临床特征多样,应结合患儿个体特征进行临床治疗。     

76例儿童隐球菌性脑膜炎临床分析

目的分析儿童隐球菌性脑膜炎临床特点。方法回顾性分析76例隐球菌性脑膜炎患儿临床资料。结果男47例,女29例,平均年龄(6.34±3.67)岁;主要临床表现为发热(100%)、头痛(78.95%)、呕吐(81.58%);首次脑脊液墨汁染色阳性46例(60.53%),首次脑脊液真菌培养阳性21例(27.63%),两性霉素B联合5-氟胞嘧啶抗真菌治疗好转率(74.19%),两性霉素B联合氟康唑治疗好转率(62.96%),差异无统计学意义(P=0.75)。结论儿童隐球菌性脑膜炎极易误诊、漏诊,反复、多次腰穿有助于早期诊断;两性霉素B联合5-氟胞嘧啶是抗真菌治疗首选方案,早期诊断、积极降颅压是改善预后的关键。     

儿童获得性再生障碍性贫血造血干细胞移植后Epstein-Barr病毒血症危险因素及预后分析

目的分析儿童获得性再生障碍性贫血(AA)异基因造血干细胞移植(allo-HSCT)后Epstein-Barr病毒(EBV)血症的危险因素、利妥昔单抗的干预效果及EBV相关疾病的临床转归。方法回顾性分析2010年4月至2018年3月于上海儿童医学中心完成allo-HSCT的257例AA患儿,根据是否发生EBV血症分为:EBV血症组(141例,单纯EBV血症组125例和EBV相关疾病组16例)和非EBV血症组(116例)。采用Cox回归分析危险因素,采用Kaplan-Meier法分析累积生存率,定性资料的组间比较采用卡方检验。结果(1)257例患儿行allo-HSCT后发生EBV血症为141例,发生率为54.86﹪(141/257),其中原发感染为5.67﹪(8/257),再激活为94.33﹪(133/141)。EBV血症的中位发生时间为移植后44 d(13~568 d),单纯EBV血症的移植相关死亡率为6.40﹪(8/125);EBV相关疾病的病死率为56.25﹪(9/16)。(2)利妥昔单抗抢先治疗EBV血症的有效率为88.73﹪(63/71)。(3)与单纯EBV血症组比较,EBV相关疾病组患儿生存率降低,差异有统计学意义(Log-rank P<0.001)。(4)多因素分析结果显示,使用全身照射治疗(TBI)预处理的患儿,发生EBV感染的风险是不使用TBI预处理的患儿1.717倍(95﹪的CI:1.160~2.542);患儿移植物中CD34阳性细胞≥3×10^6个/kg是<3×10^6个/kg患儿的1.775倍(95﹪的CI:1.089~2.894)。结论移植后EBV血症的发生和TBI的应用、输注CD34阳性细胞数大于3×10^6个/kg密切相关,EBV血症进展为EBV疾病后移植相关死亡率升高,对高危患儿应积极予以利妥昔单抗抢先治疗改善预后。     

280例呼吸道感染儿童呼吸道病毒病原学检出情况及流行规律分析

目的:了解呼吸道感染儿童呼吸道病毒病原学检出情况及其流行规律,为儿童呼吸道感染的预防、诊断及治疗提供病原学依据。方法:选取2016年1月-2017年12月期间中国人民解放军中部战区总医院收治的280例呼吸道感染患儿为研究对象,分析患儿呼吸道分泌物中呼吸道病毒的检出情况,并分析呼吸道感染儿童呼吸道病毒感染与年龄、季节、疾病类型的关系。结果:280例呼吸道感染患儿中共检出98份阳性标本,阳性率为35.00%,其中有2份标本中检出2种病毒感染,混合感染阳性率为0.71%;在所有病毒类型中,呼吸道合胞病毒(RSV)病毒感染阳性率最高。1岁患儿的病毒感染阳性率最高,与其他年龄段病毒感染阳性率比较差异有统计学意义(P0.05)。呼吸道感染患儿春季、冬季的病毒感染阳性率明显高于夏季、秋季(P0.05)。不同呼吸道感染疾病类型患儿病毒感染阳性率比较差异有统计学意义(P0.05),以喘息性肺炎、毛细支气管炎、肺炎患儿病毒感染阳性率较高。结论:RSV是呼吸道感染儿童呼吸道病毒感染的主要致病病原体,1岁的婴幼儿较易感染,春季、冬季为其高发季节,且以肺炎、毛细支气管炎、喘息性肺炎患儿的病毒感染阳性率较高。     

EB病毒抗体和DNA联合检测可提高儿童传染性单核细胞增多症的诊断灵敏度

目的评估EB病毒抗体VCA-IgM、VCA-IgG、EA-IgG、EBNA-1-IgG及EBV-DNA载量检测在儿童传染性单核细胞增多症(传单)中的诊断意义。方法用ELISA方法检测70例传单患儿和25例健康儿童血清中EBV四种抗体及PCR荧光定量法检测外周血单个核细胞EBV-DNA载量。结果传单患儿组EBV-DNA的阳性率为87.14%(61/70),对照组阳性率为8.00%(2/25),传单组与对照组EBV-DNA的阳性率比较差异有统计学意义(P<0.01)。EBV抗体检测中,传单组的VCA-IgM阳性率最高,达91.43%(64/70),对照组VCA-IgM全部阴性。传单组EB病毒VCA-IgM和EBV-DNA联合检测的阳性率97.1%。结论 EBV抗体和EBV-DNA载量检测对儿童传单的诊断有极高的价值,尤其是VCA-IgM抗体和EBV-DNA联合检测,可提高儿童传单的临床诊断的敏感性。     

苏浙闽地区婴幼儿急性腹泻患者病毒检测及 临床特征分析

目的分析苏浙闽地区婴幼儿急性腹泻患者常见病毒及患儿临床特征,为婴幼儿急性腹泻的流行病学研究和临床治疗提供参考。方法选取2010至2014年苏浙闽地区多家医院门诊就诊的急性腹泻患儿1 452例,采用ELISA法检测A组轮状病毒(HRV),多重PCR法检测诺如病毒(NoV)、肠道腺病毒(EAdV)和星状病毒(HAstV),并用RT-PCR法对A组轮状病毒阳性的样本进行G和P分型。结果 1 452例患儿中由常见病毒引起的急性腹泻患儿有707例,占总调查患者的48.69%。急性腹泻患儿常见病毒感染中单一病毒感染占90.10%(637/707),其感染病毒的构成以轮状病毒最多(47.52%,336/707),其次为诺如病毒(36.07%,255/707)以及星状病毒(2.40%,17/707)和肠道腺病毒(4.10%,29/707)。病毒感染腹泻患儿中多重感染者共70例,占9.90%(70/707),以A组轮状病毒合并诺如病毒感染最为常见,占多重感染者的68.57%(48/70)。226份A组轮状病毒阳性标本中,G分型以G1为优势分型,占33.19%;P分型中则以P [11]比例最高,占38.50%;G、P型组合以P [11]G11为主(38.50%)。结论 A组轮状病毒是引发婴幼儿急性腹泻的主要病毒,诺如病毒次之,且婴幼儿病毒性腹泻患者可合并多种病毒感染。不同地区腹泻患儿病毒感染阳性率有差异,轮状病毒基因型表现则具有多样性。     

慢性乙型重型肝炎预后的危险因素相关性分析

目的探讨影响慢性乙型重型肝炎患者预后的危险因素。方法收集浙江大学医学院附属第一医院345例慢性乙型重型肝炎患者临床资料,根据治疗结果分为好转组和恶化组,回顾性分析患者9项临床资料与预后间的相关性。结果患者年龄、重叠其他病毒感染、有无合并肝硬化以及是否抗病毒治疗2组间差异有统计学意义(P<0.05),而患者性别、嗜烟酒、并发糖尿病和高血压等因素在2组间差异无统计学意义(P>0.05)。结论年龄较大,重叠其他病毒感染,有肝硬化基础及未经抗毒治疗的慢性乙型重型肝炎患者预后较差。     

8209例住院儿童EB病毒感染情况分析

目的了解住院儿童EB病毒感染情况。方法采用ELISA法检测患儿血清中EBV-VCA-IgM和IgG抗体,分别从年龄、性别、季节、涉及的疾病等相关因素进行统计分析。结果 8 209例儿科住院病人EB病毒总体感染率为68.84%,近期感染率为14.76%,10~15岁组总体感染率最高为93.50%,各年龄组感染率差异有统计学意义(P0.05),感染率随年龄增长而逐渐增高;男童EB病毒感染率67.52%(3 308/4 899),女童为70.79%(2 343/3 310),女童感染率高于男童(P0.05);EB病毒感染存在季节差异,1-3月份感染率最高,7-9月份相对较低;EB病毒感染累及全身多系统而引起相应的疾病,1 212例近期感染患儿中传染性单核细胞增多症186例(15.35%)、支气管肺炎142例(11.72%)、急性扁桃体炎112例(9.24%)。结论 EB病毒感染在本地区住院儿童中占有一定比例,小儿EB病毒感染症状多样,可累及全身多系统,需提高对本病的认识,综合分析,早期诊断,早期治疗,同时加强护理,提高治疗效果。     

支气管鼻病毒感染与哮喘患儿发病的相关性

目的:探讨支气管鼻病毒感染与哮喘患儿发病的相关性。方法:选择2012年8月至2015年3月在医院治疗的45例哮喘急性发作期患儿为哮喘发作组和45例哮喘缓解期患儿为哮喘缓解组,并选择同期40例健康体检儿童作为正常组;采用PCR法对鼻病毒基因进行检测以判定患儿感染,采用全血细胞分析仪测定外周血嗜酸性粒细胞(EOS)计数,采用化学发光免疫分析仪测定血清总免疫球蛋白E(T-IgE),对T-IgE与EOS进行相关性分析。结果:哮喘发作组鼻病毒感染14例占31.11%,明显高于对照组0例占0.00%和哮喘缓解组3例占6.67%,差异均有统计学意义(P均0.05),而哮喘缓解组鼻病毒感染率较对照组无明显变化,差异无统计学意义(P0.05)。哮喘发作组和哮喘缓解组血清T-IgE与EOS明显高于正常组,差异有统计学意义(P0.05);而哮喘发作组血清T-IgE与EOS明显高于哮喘缓解组,差异有统计学意义(P0.05)。哮喘发作组鼻病毒感染患儿血清T-IgE与EOS明显高于非鼻病毒感染患儿,差异具有统计学意义(P0.05)。正常组患儿血清T-IgE与EOS无相关性(r=0.325,P0.05);哮喘发作组血清T-IgE与EOS正相关性(r=0.736,P0.05);哮喘缓解组血清T-IgE与EOS正相关性(r=0.613,P0.05);哮喘发作组鼻病毒感染患儿血清T-IgE与EOS无相关性(r=0.316,P0.05),非鼻病毒感染患儿血清T-IgE与EOS正相关性(r=0.674,P0.05)。结论:鼻病毒感染与儿童哮喘的严重程度有关,且患儿的血清T-IgE越高,越容易发生鼻病毒感染,导致哮喘病情加重。     

嗜血细胞综合征患儿外周血CD_4~+CD_(25)~+调节性T细胞变化及临床意义

目的观察嗜血细胞综合征(hemophagocytic syndrome,HPS)患儿外周血中调节性T细胞(RegulatoryTcells,Treg细胞)的变化,探讨其在HPS发病中的作用及临床意义。方法应用流式细胞仪检测17例初诊HPS患者(初诊组)、11例经诱导治疗后临床缓解者(缓解组)及20例健康人群(对照组)外周血中CD4+CD25+调节性T细胞。结果与对照组相比较,HPS患者初诊组及缓解组外周血CD4+CD25+调节性T细胞均升高(P0.05)。与初诊组相比较,缓解组CD4+CD25+Treg细胞降低(P0.05),但仍高于正常对照组(P0.05)。结论CD4+CD25+Treg细胞增多可能是HPS患者免疫功能受抑的重要原因之一,其变化对于HPS的预后判断有一定的意义。     

Hemophagocytic syndrome--should we consider it more often?

Hemophagocytic syndrome (HPS) is a rare condition characterized by overactive histiocytes, hepatosplenomegaly, fever and cytopenia, with two major types: familial, autosomal recessive genetic disease and acquired that can occur during systemic infections, immunodeficiency or malignancy. Inappropriate activation of macrophages by cytokines is the major mechanism of the disease. We report a case of an adult patient with HPS. After thorough clinical investigation, we have not been able to establish the underlying disease, and corticosteroids therapy was initiated empirically. After 8 months follow-up the patient is well with normal laboratory findings.     

Therapeutic trials for a rabbit model of EBV-associated Hemophagocytic Syndrome (HPS): effects of vidarabine or CHOP,and development of Herpesvirus papio (HVP)-negative lymphomas surrounded by HVP-infected lymphoproliferative disease

Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS), which is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD), is a distinct disease characterized by high mortality. Treatment of patients with EBV-AHS has proved challenging. To develop some therapeutic interventions for EBV-AHS, we examined the effectiveness of an antiviral agent (vidarabine) or chemotherapy (CHOP), using a rabbit model for EBV-AHS. Fourteen untreated rabbits were inoculated intravenously with cell-free virions of the EBV-like virus Herpesvirus papio (HVP). All of the rabbits died of HVP-associated (LPD) and hemophagocytic syndrome (HPS) between 21 and 31 days after inoculation. Furthermore, three HVP-infected rabbits treated with vidarabine died between days 23 and 28 after inoculation, and their clinicopathological features were no different from those of untreated rabbits, indicating that this drug is not effective at all to treat HVP-induced rabbit LPD and HPS. Three of the infected rabbits that were treated with one course, with an incomplete set of three courses, or with three full courses of CHOP treatment died of HVP-induced LPD and HPS with a bleeding tendency and/or with opportunistic infections. They died on the 26th, 62nd and 105th day after virus inoculation, respectively. CHOP treatment transiently suppressed the HVP-induced LPD and contributed to the prolonged survival time of two infected rabbits. However, it did not remove all of the HVP-infected cells from the infected rabbits, and residual HVP-infected lymphocytes caused recurrences of rabbit LPD and HPS. The most interesting finding of this experiment was observed in the infected rabbit with the longest survival time of 105 days: HVP-negative lymphomas surrounded by HVP-induced LPD developed in the larynx and ileum of this rabbit, causing an obstruction of the lumen. We concluded that these were not secondary lymphomas caused by CHOP treatment, because no suspicious lesions were detected in three uninfected rabbits that were treated with three courses of CHOP for 120 days. It is therefore necessary to clarify the mechanism by which HVP-negative lymphomas associated with HVP-induced LPD can develop. Our data from therapeutic trials using EBV-AHS animal models indicate that vidarabine is not effective as an agent to treat HVP-infected rabbits, and even the cytotoxic chemotherapy of CHOP is not sufficient to cure the HVP-infected rabbits or to prolong the survival time of infected rabbits. Further studies will therefore be required to develop better therapies to treat EBV-AHS.     

Viral load in Epstein-Barr virus-associated hemophagocytic syndrome

The viral load in peripheral blood from patients with Epstein-Barr virus (EBV)-associated hemophagocytic syndrome was measured by real-time quantitative PCR and compared with that in infectious mononucleosis. Patients with EBV-associated hemophagocytic syndrome generally had larger viral burdens, although it was difficult to differentiate EBV-associated hemophagocytic syndrome from infectious mononucleosis simply by viral load. The difference in viral load seemed to be clearer in peripheral blood mononuclear cells than in plasma.     

Determination of free and glucuronide conjugated 20-hydroxyarachidonic acid (20-HETE) in urine by gas chromatography/negative ion chemical ionization mass spectrometry

20-Hydroxy-arachidonic acid (20-HETE) was determined in urine by an isotope dilution assay using gas chromatography/mass spectrometry (GC/MS). After addition of 18O2-internal standard, 20-HETE was extracted from urine with hexane either directly or after treatment with glucuronidase. 20-HETE was derivatized to the pentafluorobenzylester and the sample was applied to thin layer chromatography with iso-octane/iso-propanol 9:1 (v/v) as the developing solvent. The corresponding zone was extracted and 20-HETE was hydrogenated. After derivatization to the trimethylsilylether, 20-HETE was determined by GC/MS using the [M-pentafluorobenzyl]- -ion in the negative ion chemical ionization mode. Excretion rates of free and glucuronide conjugated 20-HETE was determined in healthy children and in children with hyperprostaglandin-E-syndrome/antenatal Bartter syndrome (HPS/aBS) with or without indomethacin treatment. Compared to the controls, the HPS/aBS children showed higher excretion rates of 20-HETE, which were suppressed to normal values under indomethacin medication. Free and glucuronide conjugated 20-HETE do not correlate with PGE2 excluding any participation in HPS/aBS.     

EBV与HCMV传染性单核细胞增多症患儿的实验室指标比较

目的观察EB病毒（EBV）与人类巨细胞病毒（HCMV）感染所致的传染性单核细胞增多症（IM）患儿超敏C-反应蛋白（hs-CRP）、白细胞（WBC）计数、嗜中性粒细胞比值（N）、异常淋巴细胞（异淋）、嗜异性抗体和血清酶的变化。方法选择70例确诊有EBV病毒感染且具备传染性单核细胞增多症临床特点的患儿（A组）进行实验室检测指标分析及总结;并与37例HCMV相关传染性单核细胞增多症患儿（B组）进行比较。结果与EB组（A组）比较,HCMV组（B组）感染患儿hs-CRP水平、肌酸激酶同功酶（CK-MB）、丙氨酸氨基转移酶（ALT）、外周血WBC计数、异型淋巴细胞增高程度较低（P〈0.05）,嗜异性抗体常为阴性,两组N值差异无统计学意义（P〉0.05）。结论 EBV与HCMV感染所致的传染性单核细胞增多症患儿的实验室指标变化不同,应重视IM患儿的实验室检查以辅助诊断。     

A clinical variant of familial Hermansky-Pudlak syndrome

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive inherited disease consisting of (1) partial oculocutaneous albinism (with nystagmus, strabism, and visual acuity loss), (2) platelet storage pool deficiency (with bleeding diathesis), and (3) disorder of "ceroid" metabolism with a multisystem tissue lysosomal ceroid deposition. HPS is less uncommon in Puerto Rico, where the most important studies have been performed, but is a very rare disease in Europe. HPS basic defect remains unknown, even if an HPS-causing gene was identified in chromosome segment 10q23-q23.3, and several mutations have been reported. The aim of this article is to discuss, on the basis of a review of relevant literature, a new familial HPS clinical variant observed in 2 young sisters (aged 16 and 23 years old, respectively), characterized by the typical symptoms of this syndrome. Our patients also suffered from diffuse interstitial pulmonary disease and an unexpectedly increased platelet aggregation and were prone to bacterial infections. Interestingly, we observed urinary tract abnormality in the younger HPS sister and a porencephalic cyst in the older HPS sister; both of these developmental defects have been reported in the Cross syndrome (or oculocerebral hypopigmentation syndrome). It seems that in our patients, an overlapping of the phenotypic manifestations of different rare syndromes may be present. The presence of ceroid-like autofluorescent material in urinary sediment together with the histologic aspects and the autofluorescence of oral mucosa biopsy are consistent with a ceroid-like lipofuscin storage. HPS should be carefully tested for in suspected cases to prevent the severe visual impairment, rapidly progressive pulmonary fibrosis, and other complications associated with this disorder.     

Hemophagocytic histiocytosis diagnosed by fine needle aspiration cytology of the spleen. A case report

BACKGROUND: Hemophagocytic histiocytosis (HPS) is an idiopathic, familial or secondary syndrome characterized by mature histiocytes causing intensive erythrophagocytosis. CASE: A 2-month-old male suffering from autoimmune hemolytic anemia, fever, jaundice and hepatosplenomegalia underwent fine needle aspiration cytology of the spleen. Aspiration was performed using a 23-gauge, short needle with a subcostal approach. The smear showed a monomorphous cell population of mature histiocytes with marginal nuclei and wide, well-defined cytoplasm. The cytoplasm was microvaculated and often contained > or = 1 erythrocytes and occasional lymphocytes. Immunostaining performed on cytospin samples showed diffuse positivity for alpha-1-antichymotrypsin and S-100. Differential diagnosis with malignant histiocytosis, Langerhans histiocytosis and sinus histiocytosis with massive lymphadenopathy was established. HPS was diagnosed because of the cytologic and immunocytochemical features and clinical data. CONCLUSION: HPS may be diagnosed using fine needle aspiration of the spleen when other biopsy samples have been unsuccessful. Cytologic, diagnosis of HPS should always be considered in a specific clinical setting, because early treatment can often save the patient's life.