EB病毒感染及其相关性疾病

EB病毒（EBV）感染是儿科较为常见的病毒感染性疾病，不同的免疫状态有不同的临床表现。机体感染EBV后，可以产生传染性单核细胞增多症、EBV相关性噬血细胞综合征、慢性活动性EBV感染、X连锁淋巴组织增生性疾病及鼻咽癌、淋巴瘤等。免疫缺陷患者感染EBV后容易发生淋巴组织增殖性疾病。传染性单核细胞增多症是EBV感染最常见的临床表现形式，常合并一系列的并发症。     

EB病毒感染及其相关性疾病

EB病毒(EBV)感染是儿科较为常见的病毒感染性疾病,不同的免疫状态有不同的临床表现。机体感染EBV后,可以产生传染性单核细胞增多症、EBV相关性噬血细胞综合征、慢性活动性EBV感染、X连锁淋巴组织增生性疾病及鼻咽癌、淋巴瘤等。免疫缺陷患者感染EBV后容易发生淋巴组织增殖性疾病。传染性单核细胞增多症是EBV感染最常见的临床表现形式,常合并一系列的并发症。     

重症EB病毒感染相关疾病的现状和诊治进展

Epstein—Barr病毒，简称EB病毒（EBV），属于疱疹病毒，γ亚科，通过唾液的接触在人群中传播。该病毒被发现至今已有40多年的历史了。因其感染的普遍性及感染后终生潜伏而不能被机体免疫系统彻底清除，所以被称为“无处不在的成功病毒”。发展中国家2岁以下儿童EBV血清阳性转化率可达95％以上，由此可见一斑。在如此高的EBV血清阳性转化率下，大多数个体以“无症状”亚临床状态存在。对EBV致病性的认识，从最早的传染性单核细胞增多症（infectious mononucleosis，IM）到非洲高发的伯基特淋巴瘤，     

先天性EB病毒感染诊断与治疗:附3例报告

EB病毒(EBV)是由Epstein、Barr于1964年从Burkitt淋巴瘤细胞系中分离到的DNA病毒，主要与传染性单核细胞增多症、鼻咽癌等有关，在成人和儿童研究较多。而有关先天性EBV感染，国外报道不多，国内未见报道。我院新生儿科自2001年9月～2002年9月收治3例，经治疗取得一定效果，现报告如下。     

急性EB病毒感染患儿Toll样受体的变化

目的 探讨Toll样受体(TLRs)信号途径异常活化在急性EB病毒(EBV)感染免疫发病机制中的作用.方法 采用病例对照研究方法,选取急性EBV感染患儿15例,传染性单核细胞增多症(IM)患儿18例,同龄健康对照儿童25例,采用反转录-PCR(RT-PCR)及实时荧光定量PCR法检测其外周血单个核细胞TLRs(2、3、7、9)、TLR MyD88-依赖性途径转导分子髓样分化因子88(MyD88)、TNF受体相关因子6(TRAF6)、转化生长因子β激活性激酶1(TAKl)与MyD88-非依赖性途径转导分子β干扰素TIR结构域衔接蛋白(TRIF)、TNF受体相关因子3(TRAF3)、TANK结合激酶1(TBK1)、IL-1β、TNF-α及IFN-α、IFN-β mRNA的表达;应用ELISA法测其血浆IL-12、IFN-γ水平.结果 1.急性EBV感染组与IM组TLR2、TLR3、TLR7、TLR9表达均明显高于健康对照组(P均＜0.05),急性EBV感染组与IM组比较差异无统计学意义(P均＞0.05);TLR信号途径传导分子(MyD88、TRAF6、TAK1、TRIF、TRAF3、TBK1)在急性EBV感染组与IM组表达均较健康对照组显著升高(P均＜0.05).2.急性EBV感染组与IM组细胞因子IL-1β mRNA、TNF-α mRNA、IFN-αmRNA、IFN-β mRNA表达均较健康对照组显著升高(P均＜0.05),IM组IL-1β、TNF-α表达显著高于急性EBV感染组(P均＜0.05).3.急性EBV感染组和IM组血浆IL-12与IFN-γ水平均较健康对照组显著升高(P均＜0.05),IM组升高幅度均较EBV感染组显著(P均＜0.05).结论 TLR2、TLR3、TLR7、TLR9过度活化所致抗病毒反应/炎性反应失衡,可能是急性EBV感染导致体内免疫功能紊乱的原因之一.     

EB病毒感染43例临床分析

EB病毒原发感染中,多数为传染性单核细胞增生症（IM）,该病毒与非洲儿重Burkitts淋巴瘤、鼻咽癌的发病有密切关系,与恶性组织细胞增多症似有密切关系,为了提高儿童EB病毒感染的诊断及预后,现将43例EB病毒感染患     

91例EB病毒相关疾病儿童血浆EB病毒DNA的检测

目的了解EB病毒(EBV)感染患儿外周血血浆中游离EBVDNA的拷贝数,确定EBV原发感染后外周血血浆中EBV游离DNA的拷贝数与发病天数及病情轻重的关系。方法应用荧光定量PCR方法,测定73例EBV原发感染和18例EBV相关重症疾病患儿外周血血浆中EBV游离DNA。结果①原发EBV感染患儿外周血血浆中EBV游离DNA随发病天数呈下降趋势,发病2周后很难检测到。②EBV相关重症疾病组患儿外周血血浆中EBV游离DNA阳性率明显高于原发EBV感染组,差异有显著性(89%vs16%,P<0.05)。结论原发EBV感染后随病程天数的增加,病毒复制水平逐渐下降。血浆中EBV游离DNA检测对评价EBV相关疾病的严重程度有一定参考价值。     

肺炎支原体感染致小儿传染性单核细胞增多综合征40例临床分析

传染性单核细胞增多症（传单）是一种由EB病毒感染引起的单核一巨噬系统急性增生性疾病，小儿期常见。由其他病毒和细菌感染、药物过敏引起者称传染性单核细胞增多综合征。肺炎支原体（MP）是介于病毒和细菌之间的一种病原体，MP感染可出现全身多系统的临床表现.     

91例EB病毒相关疾病儿童血浆EB病毒DNA的检测

目的:了解EB病毒（EBV）感染患儿外周血血浆中游离EBV DNA的拷贝数,确定EBV原发感染后外周血血浆中EBV游离DNA的拷贝数与发病天数及病情轻重的关系。方法:应用荧光定量PCR方法,测定73例EBV原发感染和18例EBV相关重症疾病患儿外周血血浆中EBV游离DNA。结果:①原发EBV感染患儿外周血血浆中EBV游离DNA随发病天数呈下降趋势,发病2周后很难检测到。②EBV相关重症疾病组患儿外周血血浆中EBV游离DNA阳性率明显高于原发EBV感染组,差异有显著性(89% vs 16%, P＜0.05）。结论: 原发EBV感染后随病程天数的增加,病毒复制水平逐渐下降。血浆中EBV游离DNA检测对评价EBV相关疾病的严重程度有一定参考价值。［中国当代儿科杂志,2009,11（11）：897-900］     

中山市儿童EB病毒感染情况分析

目的了解广东省中山市儿童EB病毒(EBV)感染情况及流行特征。方法回顾性分析2011至2013年经实时荧光定量PCR检测外周血中单个核细胞EBV-DNA的疑似EBV感染患儿的临床资料。结果 3 402例疑似EBV感染患儿中,EBV-DNA检出阳性409例,总阳性率为12.0%。其中2011年阳性率为8.1%,2012年为10.4%,2013年为19.5%,三年阳性率差异有统计学意义(P0.05);不同性别患儿间的差异无统计学意义(P0.05);不同年龄组间的差异有统计学意义(P0.05),以学龄前组为最高。EBV感染性疾病以传染性单核细胞增多症为最多(61.6%),其次为呼吸道感染(26.7%)、颈淋巴结炎(3.4%)、血小板减少性紫癜(2.4%)等。在部分EBV感染患儿中,检出MP-IgM阳性79例,CP-Ig M阳性47例,细小病毒B19-IgM阳性20例,单纯疱疹病毒IgM阳性11例,巨细胞病毒IgM阳性10例,风疹病毒Ig M阳性4例。结论中山市儿童EBV-DNA阳性年检出率呈上升趋势,EBV感染后以传染性单核细胞增多症最常见,但可累及多个系统。EBV感染后可能伴有多种病原抗体阳性。     

Epstein-Barr virus-associated Hodgkin''s disease in a patient with Wiskott-Aldrich syndrome

Wiskott-Aldrich syndrome is a primary immunodeficiency syndrome in which the majority of malignant complications are non-Hodgkin's lymphoma. We report here a Wiskott-Aldrich syndrome patient who developed Epstein-Barr virus-positive Hodgkin's disease in the bilateral pulmonary hilar lymph nodes. The treatment was successful as the patient achieved a complete response and event-free survival for more than 4 y. CONCLUSION: This case is very rare, but highly suggestive of the immune-mediated mechanisms in the pathogenesis of Epstein-Barr virus-associated Hodgkin's disease in an immunodeficiency patient.     

Epstein-Barr病毒相关移植后淋巴组织增生性疾病免疫治疗的最新进展

Epstein-Barr病毒相关的移植后淋巴组织增生性疾病(EBV-PTLD)是造血干细胞移植或实体器官移植后病死率极高的并发症。在过去的十年中,对于存在高危因素的患者,免疫治疗干预措施包括减少免疫抑制剂,CD20单克隆抗体(利妥昔单抗)单药治疗或与化疗相结合,输注EBV-特异性T细胞的过继免疫治疗,使得EBV-PTLD患者的存活率有了显著的提高。本文旨在对造血干细胞移植或实体器官移植后EBV-PTLD的高危因素、 临床表现及免疫治疗的最新进展进行总结。     

Epstein-Barr virus-associated haemophagocytic lymphohistiocytosis in Wiskott-Aldrich syndrome

A patient with Wiskott-Aldrich syndrome who developed Epstein-Barr virus-associated haemophagocytic lymphohistiocytosis (EBV-HLH) is described in this study. At 4 mo of age the patient developed fever associated with bicytopenia and splenomegaly. Analysis of a bone marrow specimen revealed extensive haemophagocytosis, and in situ hybridization for EBV of the bone marrow specimen using an EBV-encoded RNA probe was positive. Diagnosis of EBV-HLH was established and immunotherapy with HLH-94 protocol was started. HLH has been described in patients with other well-defined primary immunodeficiencies such as X-linked lymphoproliferative syndrome, Chediak-Higashi syndrome and Griscelli disease. Also, HLH was reported recently in severe combined immunodeficiency and DiGeorge syndrome.

Conclusion: The possibility of an underlying primary immunodeficiency should be considered in paediatric patients who present with HLH during infancy.     

儿童传染性单核细胞增多症并发EB病毒相关性噬血细胞综合征临床危险因素分析

目的 比较传染性单核细胞增多症(infectious mononucleosis,IM)和EB病毒相关性噬血细胞综合征(EBV-associated hemophagocytic syndrome,EBV-AHS)的临床特点,分析IM患儿发生EBV-AHS的临床危险因素.方法 回顾性比较我院2000年1月至2006年4月430例IM和EBV-AHS患儿临床症状、体征和实验室检查特点,采用Logistic回归分析IM患儿发生EBV-AHS的临床危险因素.结果 (1)本组IM病例中EBV-AHS发生率为3.72%(16/430),EBV-AHS组患儿热程明显长于IM组患儿,体温峰值、肝脏和脾脏肿大程度均较IM组患儿明显,但咽峡炎发生率(37.5%)显著低于IM组(91.1%),差异均有统计学意义.(2)EBV-AHS组外周血三系均低于IM组,且变异淋巴细胞升高不明显,其比例(中位数10%)显著低于IM组(中位数18%),差异亦有统计学意义.(3)EBV-ASH组肝功能损害显著重于IM组,尤其乳酸脱氢酶(LDH)(中位数为2128.5 U/L)和天冬氨酸氨基转移酶(AST)(中位数为489 U/L)水平升高显著高于IM组,且常伴有高胆红素血症及低白蛋白血症.(4)多因素Logistic回归分析发现:热程＞10 d(OR=8.097)、LDH进行性升高＞1000 U/L(OR=7.998)、低白蛋白血症(OR=7.838)、中性粒细胞＜1.5×109/L(OR=7.587)和血小板＜100×109/L(OR=7.190)是本组IM患儿发生EBV-AHS的临床危险因素,本组EBV-AHS病死率高达50%.结论 绝大多数IM患儿呈良性自限性过程,约3.7%患儿进展为EBV-ASH.热程＞10 d、LDH＞1000U/L、低白蛋白血症、中性粒细胞＜1.5×109/L、血小板＜100 x 109/L是IM患儿发生EBV-AHS的临床危险因素,该病预后凶险,病死率高,多次骨髓检查有助于及时诊断.     

Epstein-Barr virus-associated post-transplant lymphoproliferative disease after bone marrow transplantation mimicking graft-versus-host disease

In contrast to solid organ transplantation (Tx), the incidence of post-transplant lymphoproliferative disease (PTLD) after hematopoietic stem cell Tx (HSCT) is generally low. This risk, however, is significantly elevated in patients receiving human leukocyte antigen (HLA) mis-matched or T-cell-depleted grafts, or after treatment for severe graft-versus-host disease (GvHD). An 18-yr-old patient with positive Epstein-Barr virus (EBV) serology received a fully matched, unmanipulated bone marrow graft from an unrelated EBV-positive donor for treatment of acute myeloid leukemia (AML) in second complete remission. GvHD prophylaxis was performed with cyclosporin A (CsA) and a short course of methotrexate. Four months after Tx, the patient developed ulcerative tonsillitis that was unresponsive to antibiotic treatment. Diarrhea appearing simultaneously was interpreted as gastrointestinal GvHD and steroids were added to CsA. A few days later the patient was admitted to hospital because of generalized seizure and pneumonia. Despite reduction of immunosuppression, intensification of anti-viral treatment, and subsequent mechanical ventilation, the patient died of acute respiratory distress 6 days later. Autopsy demonstrated disseminated EBV-induced, multi-nodular lymphoma infiltration of the entire colon but no signs of GvHD. Moreover, both lungs, paratracheal lymph nodes, kidneys, thyroid gland, and liver were infiltrated with large B-cell non-Hodgkin's lymphomas. This case underlines the rapid and aggressive course of EBV-induced disseminated PTLD after HSCT, initially mimicking intestinal GvHD because of massive colonic lymphoma infiltration. Tissue biopsies should be performed early for establishing correct diagnosis, thus enabling specific therapy, e.g. infusion of donor leukocytes with cytotoxic T-lymphocytes.     

儿童EB病毒相关平滑肌肿瘤1例

7岁女性患儿,因双下肢疼痛1年余入院.腰椎MRI提示椎旁团块状软组织肿块;头颅MRI提示双侧海绵窦区结节状肿块;胸部CT示右肺下叶外基底段及左肺上叶前段高密度结节灶.腰椎病变组织病理活检示EB病毒相关平滑肌肿瘤.基因检测示ITK基因存在c.725_730delAGAGTA(p.K242_S243del)新发突变.治疗上...     

EB病毒感染相关噬血细胞综合征的诊治研究进展

噬血细胞综合征(hemophagocytic syndrome,HS)是一组病因及发病机制复杂.组织病理表现以良性组织细胞增生活化,伴随噬血细胞现象的一类综合征.HS分为原发性和继发性两大类,原发性是指家族遗传相关的免疫缺陷状态,继发性指后天获得所致,其中以EB病毒感染相关最为常见.EB病毒感染相关HS的病情进展快,病死率高,现就该病的诊治进展作一概述.     

Unusual evolution of an Epstein-Barr virus-associated leiomyosarcoma occurring after liver transplantation

We report the case of a child who developed, 2 yr after orthotopic liver transplantation (OLTx) for biliary atresia, a multi-focal hepatic tumor with lymphonodular metastases, identified as an Epstein-Barr virus (EBV)-associated leiomyosarcoma. Chemotherapy was given without tumor response. Subsequently, slow growth of the tumor was observed. Immunosuppression was tapered and stopped 9 yr after transplantation. At the present time, 12 yr after the discovery of the first hepatic lesions, the patient is alive and completely symptom-free, the abdominal masses are stable, and liver function tests are completely normal. Smooth muscle tumors are increasingly recognized in children with various immunodeficiencies occurring after organ transplantation. This unusual evolution of a clinically aggressive tumor into a stable disease after restoration of immunity confirms that the immune status of the patient is a crucial factor.     

肺炎支原体感染相关疾病的临床研究

目的进一步提高对肺炎支原体（MP）感染及相关疾病的认识。方法回顾性分析292例MP感染患儿的临床特点，特别是肺外多系统受累情况。结果292例均有呼吸系统表现，其中肺炎180例，呼吸道以外各系统受累140例（47．9％），包括：血液、循环、神经、消化、泌尿、皮肤、淋巴结等系统。结论MP感染与多种疾病有关，而且易造成多系统损害。因该病多无典型症状易造成误诊，对不明原因发热及多脏器受累的呼吸系统感染病例，应注意MP感染。