异型淋巴细胞IM

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,异型淋巴细胞IM,异型淋巴细胞IM异型淋巴细胞IM一、概述1. 定义 由EB病毒引起的一种急性或亚急性淋巴细胞良性增生的传染病。Self-limiting disorder of lymphoid tissue caused by infection with Epstein Barr virus (infectious mononucleosis). Characterised by the appearance of many large lymphoblasts in the circulation.,一、概述,1. 定义,由EB病毒引起的一种急性或亚急性淋巴细胞良性增生的传染病。,S,elf-limiting disorder of lymphoid tissue caused by infection with Epstein Barr virus (infectious mononucleosis). Characterised by the appearance of many large lymphoblasts in the circulation.,EB病毒,（Epstein-Barr virus，EBV ）,Epstein和Barr于1964年从非洲儿童恶性淋巴瘤(Burkitts lymphoma)细胞培养中最早发现,主要侵犯B细胞.,EBV属疱疹病毒亚科，外层有囊膜,囊膜内是核衣壳，它是20面体，有160个壳粒，最内层为大分子的双链DNA。,Epstein Barr Virus (EBV):Herpes Family (linear DNA virus HHV4),Surrounded by nucleocapsid and glycoprotein envelope.,EBV生物学性状,2. Infectious MononucleosisTransmission,“The Kissing Disease”,2. 发病情况,传染源：患者、隐性感染者,传播途径:,唾液,传播，偶尔输血感染,器官移植，性关系。,感染类型：,1.,初次感染 幼儿,潜伏感染,（隐性感染）,多见。,2.青春期原发性感染 50%引起传染性单核细胞增多症（,增殖性感染,）,3.非增殖性感染：潜伏感染引起细胞转化,恶性转化,传染性单核细胞增多症,青春期初次感染,非洲儿童恶性淋巴瘤（Burkitt瘤）,发病前有重度EBV感染,EBV引起细胞转化,血清学证据：患儿体内EBV-Ab水平高,瘤组织中EBV DNA和EBNA,鼻咽癌：,见于我国广东，广西，湖南,瘤组织中有EBV-DNA，EBNA,血清中EBV抗体增高,鼻咽癌治疗好转后，EBV抗体水平,EB病毒感染所致疾病,3. 发病机理：,唾液,EB,咽喉部,淋巴组织,病毒,淋巴结,良性增生,B细胞,T细胞,自制,3. Infectious MononucleosisPathogenesis,EBV infects the epithelium of the oropharynx and salivary glands.,Lymphocytes in the tonsilar crypts are directly infected - BLOODSTREAM.,Infected B cells and activated T cells proliferate and expand.,Polyclonal B cells produce antibodies to host and viral proteins.,Infectious MononucleosisPathogenesis,Memory B cells (not epithelial cells) are reservoir for EBV.,EBV receptor is CD21 (found on B cell surface),Cellular immunity (suppressor T cells, NK cells, cytotoxic T cells) more important than humoral immunity in controlling infection,Infectious MononucleosisPathogenesis,Infectious MononucleosisPathogenesis,IM World Distribution,4.,Maculopapular EBV Rash with Amoxicillin,Eyelid edema,Pharyngitis,Rash,Exudative pharyngotonsillitis,Lymphadenopathy,Cervical lymphadnopathy,Hepatosplenomegaly,Clinical manifestation of IM in children and adults,Frequency (%),Sign or symptom,Age 10%,）。,the Disease Causing Abnormal Lymphocytosis and other causes,ATLL,HCL,EHF,Dengue Fever,Alcohol,MM,AL,MDS,NHL,granuloma fungoides,Drug （Propranolol，Phenytoin，ect）,Psychosis,Virus：ADV，HPV-1，EBV，ect.,IM血象：I型异淋细胞,Downey 将本病的异型淋巴细胞分为三型：,型（泡沫型或浆细胞型） 细胞中等大学，多呈圆形，部分为不规则型或阿米巴型，核偏位，椭圆、肾形或分叶形，染色质粗网状或成堆排列。胞质少，嗜碱性，呈深蓝色，含有大小不等的空泡或呈泡沫状，可有少量细的嗜苯胺蓝颗粒。,IM血象：异淋II型淋巴细胞,型（不规则型或单核细胞样型） 胞体较型大，形态不规则，胞核圆形、椭圆形或不规则形，核染色质较型细致，亦成网状，胞质丰富，呈淡蓝色，无空泡，可有少数天青颗粒。,IM血象：Downey III型异型淋巴细胞, 型（幼稚型或幼淋巴样型） 胞体较大，直径1518um，核圆形或卵圆形，染色质细致均匀，呈网状排列，无浓集现象，可见核仁12 个，胞质蓝色，一般无颗粒，可有分布较均匀的小空泡。,2. 骨髓象bone marrow ：通常无特征性改变。,骨髓增生明显活跃,淋巴细胞可以增加，出现一定量的不典型淋巴细胞，不如血象明显。,粒系、红系、巨核系无明显变化,IM骨髓象,IM骨髓象,EBV分离培养困难,血清试验,serologic finding,（1）嗜异性凝集试验,heterophil agglutination test,（2）鉴别吸收试验,differential absorption test,（3）单斑试验,monospot test,（4）EBV抗体测定,antibody to EBV,(1) 嗜异性凝集试验（Pall-Bunell test，P-B试验） 属非特异性血清学试验。主要用于辅助诊断传染性单核细胞增多症。患者在发病早期，血清中出现一种能非特异地与绵羊红细胞发生凝集的异嗜性抗体。此抗体滴度在发病34周内达高峰，于恢复期迅速下降，不久消失。传单患者试验的阳性率达8095%.,若效价在1:64以上则可疑为传单，结合临床及异型淋巴细胞的出现，具有诊断价值；,效价在1:224以上则可诊断为传单。,少数病例（约10%）嗜异性抗体出现时间较晚或持续时间过短，而且接受皮质类固醇治疗后该反应可消失，故阴性者不能排除此病。,然而，在其他某些疾病如血清病、病毒性肝炎、风疹、结核病患者，也可呈阳性反应，此时应进一步作鉴别吸收试验。,Paul-Bunnell presumptive test,heterophile antibody,被不同細胞抗原所吸附的情形,抗體來源,綿羊,RBC,馬,RBC,牛,RBC,天築鼠腎臟,IM,Serum sickness,Forssman-indused,鉴别吸收试验,differential absorption test,：,疾病 嗜异性凝集素滴度,豚鼠肾细胞吸收后 牛RBC吸收,传单 不下降或部分下降 下降,血清病 下降 下降,其他疾病 下降 下降,Absorbed Heterophile Test (Davidsohn Differential),(3) 单斑试验（monospot test） 为测定嗜异性抗体的快速玻片凝集法。,试验中以甲醛化马红细胞代替嗜异性凝集试验中的绵羊红细胞，以牛红细胞抗原取代牛红细胞。,是诊断本病最常用的快速筛选试验。,抗原,antigen,抗体,antibody,EB病毒核抗原（EBNA） 在疾病早期出现，并长期存在,膜抗原（MA）,抗膜抗体是病毒的中和抗体，,其高峰出现虽然较晚，但以后可,持续终生,早期抗原（EA）,在疾病的急性期有80%的阳性率病,壳抗原（VCA）,IgM 抗体急性期阳性率最高，急性,期可首先出现，并很快达高滴定度，,是传单患者急性期诊断的重要指标，,以后在数周内消失。IgG抗体在发病,两星期达高峰，以后以低水平存在持,续终生，虽不能作为近期感染指标，,但可用作流行病学调查。,淋巴细胞决定抗原（LYDMA）,EBV,特异性抗原,：,潜伏感染：,EBV核抗原（EBNA）,增殖性感染：,早期抗原（EA ）,衣壳抗原（VCA）,膜抗原（MA）,抗EBV抗体的阳性率出现时间及持续时间,抗体,测定方法,滴度（1：）,阳性率（%）,出现时间,高峰,持续时间,VCA-IgG,IIF*,101280,100,病初,第12周,终身低滴度,VCA-IgM,IIF,10160,97,病初,第12周,23个月,VCA-IgA,IIF,1040,80,病初,第12周,近似VCA-IgM,EA-IgG,IIF,5320,5080,比抗VCA略晚,比抗VCA略晚,数月,抗EBNA,AGIF*,5160,100,恢复期后,恢复期后,终身,抗MA,IIF,恢复期后,恢复期后,终身,*,间接免疫荧光法 *抗补体荧光免疫法,PB/MNST,可用核酸杂交和PCR等方法检测细胞内EBV基因组及其表达产物,4. 肝功能测定,5. 脑脊液检查,6. 尿液检查,三、诊断及鉴别诊断,诊断,（1）血象,（2）嗜异性凝集试验、鉴别吸收试验,（3）抗EB病毒抗体检查,鉴别诊断,传单和急淋、传淋的鉴别,传单 急淋 传淋,发热 常持续13周 持续不规则发热 无或暂短发热,淋巴结肿大 有 有 无,脾肿大 2575%有 有 无,传染性 小 无 大,白细胞计数 中等度增多 从减少到极度 显著增多,增多,有诊断价值细胞 异型淋巴细胞 原淋、幼淋 正常成熟小淋巴,贫血 无 有 无,血小板减少 一般无 有 无,骨髓象 有异型淋巴 原淋+幼淋显著 正常小淋巴细胞,细胞 增多 增多,嗜异性凝集试验 阳性 阴性 阴性,预后 良好 不良 良好,四、治疗,7.中医治疗,IM Treatment,Medical Care,:,self,-,limited illness : not require specific therapy,.,Inpatient therapy of medical and surgical complications may be required,.,Acyclovir,(10 mg/kg/dose IV q8h for 7-10 d),inhibit viral shedding from the oropharynx,clincal course is not significantly,IVIG,(400 mg/kg/d IV for 2-5 d),immune thrombocytopenia associated with,Andersson J et al.,J Infect Dis,.Feb 1986;153(2):283-90.,Cyran EM et al.,Am J Hematol,.Oct1991;38(2):124-9.,IM Treatment,Medical Care,:,Short-course corticosteroids,:,prednisolone,(1 mg/kg/d, max 60 mg/d for 7 d,and tapered over another 7 d),Marked tonsillar inflammation with impending airway obstruction,Massive splenomegaly,Myocarditis,Hemolytic anemia,Hemophagocytic syndrome,Seizure and meningitis,Surgical Care,:,Splenic rupture.,AAP. Red book2006;286-288.,Nelson. Textbook of Pediatrics17th ed;977-981.,Infectious Mononucleosis,Activity,:,depends on severity of the patients symptoms,.,Extreme fatigue : bed rest for 1-2 weeks,.,Malaise may persist for 2-3 months,.,Patients should not participate in contact sports or heavy lifting for at least 2-3 weeks,some authors recommend avoiding activities that may cause splenic trauma for 2 months,.,IM : Complication,Hepatitis,: 90% of patients,LFT : 2-3 times of NUL,in the second and third weeks of illness,45% of patients : elevated bilirubin, but jaundice occurs in only 5%,.,Mild thrombocytopenia occurs in approximately 50% of patients with infectious mononucleosis,.,Platelet count,: nadir approximately 1 week after symptom onset (100,000-140,000,/,cm,3.,), then gradually improves over the next 3-4 weeks,.,Mild thrombocytopenia occurs in approximately 50% of patients with infectious mononucleosis,.,IM : Complications,Hemolytic anemia,0.5-3%, associated with cold,-,reactive antibodies, anti,-,I antibodies, and with autoantibodies to triphosphate isomerase,mild and is most significant during the second and third weeks of symptoms,.,Upper airway obstruction,0.1-1%,due to hypertrophy of tonsils and other lymph nodes of Waldeyer ring,treatment with corticosteroids may be beneficial,IM : Complications,Splenic rupture,: 0.1-0.2%,Spontaneous or history of some antecedent trauma,.,occur during the second and third weeks,.,mild,-,to,-,severe abdominal pain below the left costal margin, sometimes with radiation to the left shoulder and supraclavicular area,.,Massive bleeding : Shock,IM : Complications,Hematologic complications,hemophagocytic syndrome,.,Immune thrombocytopenic purpura occurs and may evolve to aplastic anemia,.,accelerate hemolytic anemia in congenital spherocytosis or hereditary elliptocytosis,.,Disseminated intravascular coagulation associated with hepatic necrosis has occurred,.,IM : Complications,Neurologic complications,: EBV,.,A syndrome of chronic fatigue, myalgias, sore throat, and mild cognitive dysfunction occurring primarily in young adult females initially was attributed to EBV,.,Current data suggest that EBV is not the etiologic agent,.,Traditional Medical therapy,早期邪在卫分疏表达邪，清热解毒。方药：银翘散加减。,中期邪入气分清气解毒、化湿泄浊、化痰散结。方药：白虎汤加减。：黛蛤散+清肝化痰汤加减。,极期热灼营阴清营泄热、凉血养阴。方药：清营汤加减。,后期气阴两伤益气养阴，清热散结。方药：沙参麦冬汤加减。中成药：,双黄连注射液、清开灵注射液、穿琥宁注射液、醒脑静注射液等。,推拿疗法：,高热：清天河水、开天门、退六腑，推大椎，拿肩井、风池；肝脾肿大：清肝经、分腹阴阳；咽喉肿痛：揉金津、玉液；抽搐：掐人中、十宣，拿委中。,7. 疗效标准,1、治愈 患者全面符合下述标准,（1）症状与体征消失,（2）血象和肝功能等实验室检查恢复正常,（3）并发症治愈,（4）观察一个月无复发,2、好转 患者符合下述标准，并维持三个月以上,（1）症状与体征好转,（2）血象与肝功能等实验室检查好转,（3）并发症好转或治愈,3、无效 患者除下述标准外，血清学检查EB病毒早期抗体的存在也是预后不佳的依据,（1）症状与体征无好转或恶化,（2）血象与肝功能等实验室检查无好转或恶化,（3）并发症发生或恶化,五、预后,IM : Prognosis,Immunocompetent : full recovery in several months,.,The common hematologic and hepatic complications resolve in 2-3 months,.,Neurologic complications,Children :,resolve quickly,Adults : neurological deficits,All individuals develop latent infection,asymptomatic,.,六、防治,国内试验研制的EBV疫苗，用以预防传染性单核细胞增多症，并考虑用于非洲儿童恶性淋巴瘤和鼻咽癌的免疫预防。,IM : Prevention,Isolation is not required : low transmission,.,Avoid contact with saliva,.,Do not kiss children on the mouth,.,Maintain clean conditions : day care, avoid sharing toys,.,EBV can be transmitted by blood transfusion and by bone marrow transplantation,.,Vaccine development is proceeding, although the role of a vaccine is unclear,.,FEIGIN et al. Textbook of Pediatric Infectious Diseases5th ed;2004:1952-1957.,发热、咽痛、淋巴结肿大,急性感染性疾病,无皮疹,排除,急性皮疹性传染病,无腮腺肿大、疼痛,排除,流行性腮腺炎,无药物过敏史,排除,药物过敏引起的淋巴细胞增多,巨细胞病毒感染、传淋、急淋、急性扁桃体炎、结核,排除,鉴别,Thank you for your attention !,人有了知识，就会具备各种分析能力，,明辨是非的能力。,所以我们要勤恳读书，广泛阅读，,古人说“书中自有黄金屋。,”通过阅读科技书籍，我们能丰富知识，,培养逻辑思维能力；,通过阅读文学作品，我们能提高文学鉴赏水平，,培养文学情趣；,通过阅读报刊，我们能增长见识，扩大自己的知识面。,有许多书籍还能培养我们的道德情操，,给我们巨大的精神力量，,鼓舞我们前进,。,