牛痘样水疱病样皮肤淋巴瘤与慢性活动性EB病毒感染的关系

目的 报道6例牛痘样水疱病样皮肤淋巴瘤,并研究其与慢性活动性EB病毒感染的关系.方法 临床病理分析、皮损免疫组织化学染色、血清学分析、EB病毒编码RNA原位杂交、外周血EB病毒DNA测定.结果 6例患者皮损均为反复发作的丘疹、丘疱疹、坏死、痘疮样瘢痕,其中4例还伴有程度不同的颜面、手足水肿.所有患儿均有长期间断发热等症状.皮损病理可见表皮多房性水疱,真皮全层大量淋巴细胞浸润,细胞形态异形,可见病理分裂象.4例皮损病理免疫组化染色,可见大量CD56阳性细胞,散在的CD3和CD45RO阳性细胞,T细胞内抗原-1和粒酶B染色阳性,诊断为牛痘样水疱病样皮肤NK/T细胞淋巴瘤;2例组化染色CD3和CD45RO阳性,CD56阴性,诊断为牛痘样水疱病样皮肤T细胞淋巴瘤.6例皮损均可见EB病毒编码RNA原位杂交阳性肿瘤细胞,血清学检查EB病毒衣壳抗原IgG抗体滴度升高,其中2例滴度为1:5120,2例为1:2560,2例为1:1280;2例患者外周血EB病毒DNA拷贝数高于正常.6例患儿均证实患有慢性活动性EB病毒感染.结论 牛痘样水疱病样皮肤淋巴瘤主要表现为颜面手足肿胀、水疱、痘疮样瘢痕,病理表现主要为真皮异形淋巴细胞浸润和血管中心坏死,免疫表型以NK/T型多见.慢性活动性EB病毒感染与该型淋巴瘤发病密切相关.     

牛痘样水疱病样皮肤T细胞淋巴瘤

目的:根据3例种痘样皮肤T细胞淋巴瘤(hydroa vacciniforme-like CTCL)患者的临床表现、治疗及转归,进一步探讨该病的诊断和治疗.方法:分析3例hydroa vacciniforme-like CTCL患者的临床资料、实验室检查、治疗及转归.结果:3例患者均为幼年发病,皮损开始出现在曝光部位,反复发作,数月或数年后进展性或逐渐蔓延至非曝光部位,且伴有发热等全身症状.皮损组织病理显示真皮内致密的淋巴样细胞浸润达真皮下层甚至脂肪层,常侵犯血管;免疫组化组织病理显示浸润细胞以CD8(+)细胞为主;T细胞受体γ基因(TCRγ基因)呈单克隆性重排;EB(Epstein-Barr)病毒原位杂交(+).结论:该病与EB病毒感染有关.该病预后差,但干扰索治疗可改善症状.     

蚊咬超敏与儿童皮肤T/NK细胞淋巴瘤

儿童发生的皮肤T/NK细胞淋巴瘤在发生前可有蚊咬超敏现象,蚊咬超敏、慢性EBV感染、T/NK细胞淋巴瘤形成一个临床三联征,称之为HMB-EBV-NK病或Tokura-Ishihara病,属于儿童EBV阳性T细胞淋巴增殖性疾病。EB病毒慢性感染是蚊咬超敏和T/NK细胞型淋巴增殖性疾病共同的病因。在慢性EB病毒感染的基础上,蚊唾液腺变应原刺激CD4阳性T细胞反应,诱导EB病毒癌基因活化,进展为儿童皮肤T/NK细胞淋巴瘤。蚊咬超敏和儿童皮肤T/NK细胞淋巴瘤是EBV阳性T细胞淋巴增殖性疾病这一疾病谱系的不同阶段。     

Epstein-Barr病毒感染及相关皮肤疾病

EB病毒是一种人类疱疹病毒,其原发感染多无临床症状或导致传染性单核细胞增多症。原发感染后,EB病毒终身潜伏于健康人体的B淋巴细胞。但是,部分感染者发展为慢性活动性EB病毒感染,或者出现一些EB病毒相关的恶性疾病,如Burkitt's淋巴瘤、鼻咽癌、霍奇金淋巴瘤、牛痘样水疱病样淋巴细胞增生性疾病、NK/T细胞淋巴瘤、皮下脂膜炎样T细胞淋巴瘤、血管免疫母细胞T细胞淋巴瘤。本文将详述EB病毒感染的特点、机制,并讨论EB病毒相关皮肤疾病的临床、病理特征。     

种痘样水疱病样EB病毒感染相关淋巴细胞增生性疾病临床与病理分析

目的介绍、普及种痘样水疱病样EB病毒感染相关淋巴细胞增生性疾病的相关内容。方法回顾我科2014年诊断的3例儿童期发病的种痘样水疱病样EB病毒感染相关淋巴细胞增生性疾病,分析其临床与病理特点。结果 3例患儿临床特点为面部、上肢曝光部位反复发生水疱、丘疹、溃疡、坏死、结痂,后皮疹累及躯干、下肢等非曝光部位,留有萎缩性瘢痕。疾病呈慢性进展。3例均伴发热、肝脾淋巴结受累。辅助检查:3例血液EB病毒Ig G抗体(Epstein-Barr virus-Ig G antibody,EBV-Ig G)均阳性、EB病毒脱氧核糖核酸(Deoxyribonucleic acid,DNA)复制活跃。组织病理:真皮及脂肪层弥漫或灶状分布较密集的淋巴细胞浸润,细胞有轻度异型性。免疫组化:CD4、CD8、CD56阳性表达不一;Ki-67阳性比例低,TIA、Gram B散在阳性。EB病毒编码RNA原位杂交(EBV-encoded RNA,EBER)均阳性。TCR基因重排阴性。结论本病组织病理特异性不高、免疫组化标志尚无标准、TCR基因重排阳性率低。因此,特征性的临床表现和EB病毒病原学检验的诊断权重要高于组织病理、免疫组化、TCR基因重排。是否进展为种痘样水疱病样皮肤T细胞淋巴瘤需密切随访。     

种痘样水疱病样EB病毒感染相关淋巴细胞增生性疾病的诊断与治疗2例

目的根据2例种痘样水疱病样EB病毒感染相关淋巴细胞增生性疾病患者的临床表现、治疗及转归,探讨该病的诊断和治疗。方法分析2例患者的临床资料、实验室检查、治疗及转归。结果 2例均为幼年发病,皮损开始出现在暴露部位,反复发作,数月或数年后进展至非暴露部位且伴有发热等全身症状,严重者出现肝功能异常及嗜血现象。皮损组织病理示真皮内致密淋巴样细胞浸润至脂肪层,侵犯血管,可见部分中等大小不典型异形淋巴细胞;免疫组化示浸润细胞以CD4+T细胞为主;皮损中EB病毒(Epstein-Barrvirus,EBV)原位杂交阳性,血清中EBV抗体阳性。结论该病与EB病毒感染有关,糖皮质激素联合静脉丙种球蛋白即可控制症状,尚无必要按"淋巴瘤"治疗,但需长期随访。     

儿童种痘样水疱病样淋巴组织增生性疾病15例临床、病理及预后分析

【摘要】 目的 分析儿童种痘样水疱病样淋巴组织增生性疾病（HVLPD）的临床特征及预后。方法 回顾2014—2018年重庆医科大学附属儿童医院皮肤科诊断的15例HVLPD的临床特点、组织病理、治疗转归情况。结果 15例患儿中男7例,女8例,发病年龄2 ~ 13岁,平均6.5岁。皮损主要表现为面部水肿,面部及四肢等曝光部位反复发生丘疹、水疱、溃疡、结痂,皮疹亦累及躯干等非曝光部位。13例患儿伴有发热,13例肝脾肿大,15例淋巴结肿大,1例出现肾功能衰竭,2例出现噬血综合征,1例出现淋巴瘤。实验室检查：15例血液EB病毒IgG均阳性、IgM均阴性,EB病毒DNA复制活跃。皮损组织病理：真皮及皮下组织血管及附件周围轻度至致密淋巴细胞浸润。免疫组化：15例中13例CD4、CD8阳性,7例CD56阳性;检测CD3的13例中12例阳性;检测T细胞内抗原1的11例中9例阳性;检测粒酶B的8例均阳性;检测Ki67的12例中11例增殖指数3% ~ 50%。15例患儿治疗方案相似,其中10例病情复发,2例病情稳定;2例发生噬血综合征,1例进展为淋巴瘤,后3例经化疗病情仍恶化死亡。结论 本病与慢性活动性EB病毒感染密切相关,免疫调节疗法如糖皮质激素、丙种球蛋白、干扰素等可缓解症状,临床表现、治疗效果及预后差异较大。     

牛痘样水疱病与Epstein-Barr病毒潜伏感染的关系

牛痘样水疱病(hydroa vacciniforme)是一种较罕见的皮肤病,日光照射可诱发和加重皮肤损害。有研究发现,在牛痘样水疱病皮肤损害中,存在Epstein-Barr(EB)病毒感染的细胞,提示EB病毒潜伏感染可能与牛痘样水疱病的发病相关^[1]。本研究通过免疫组化、原位杂交、聚合酶链反应(PCR)方法分析牛痘样水疱病病理中浸润细胞的类型,并检测EB病毒的基因,以探讨牛痘样水疱病发病与EB病毒感染的关系。     

儿童种痘样水疱病样EB病毒感染相关淋巴细胞增生性疾病的诊断与治疗3例

目的:探讨儿童种痘样水疱病样EB病毒(Epstein-Barr virus,EBV)感染相关淋巴细胞增生性疾病的诊断与治疗。方法:回顾性分析我科收治的3例种痘样水疱病样EB病毒感染相关淋巴细胞增生性疾病患儿的临床资料、实验室检查、治疗及预后等临床资料,并对相关文献进行复习。结果:3例患儿幼年发病,均因面部、四肢等部位皮损反复发作而就诊,其中2例伴有发热、肝大及淋巴结肿大。皮损组织病理检查均提示真皮浅层、皮下组织及毛囊附属器周围有大量淋巴细胞浸润,部分有轻度异形,免疫组化示CD43、CD56、Ki-67阳性表达不一;3例患儿血液EBV抗体阳性,EBV-DNA复制活跃。通过糖皮质激素、抗病毒等药物等治疗后,有2例病情明显缓解,1例效果不佳。结论:种痘样水疱病样EB病毒感染相关淋巴细胞增生性疾病与EB病毒感染密切相关,具有特征性临床表现,通过糖皮质激素、抗病毒药物联合静脉丙种球蛋白治疗部分有效,但仍有发展为种痘样水疱病样皮肤T细胞淋巴瘤可能,需密切随访。     

伴有嗜酸性粒细胞增多的种痘样水疱病样EB病毒感染相关淋巴细胞增生性疾病

报告1例伴有嗜酸性粒细胞增多的种痘样水疱病样EB病毒感染相关淋巴细胞增生性疾病。患者男,18岁。发现全身淋巴结及肝脾大4个月,面部、四肢皮疹20d。皮损组织病理检查:真皮至皮下纤维脂肪层中可见多灶性浸润的淋巴样细胞。细胞小至中等大小,胞质透明,没有明显异形性。小血管增生,可见血管壁多量嗜酸性粒细胞浸润。根据患者病史及临床表现及组织病理,诊断为种痘样水疱病样EB病毒感染相关淋巴细胞增生性疾病。     

Epstein–Barr virus‐associated T‐cell lymphoproliferative disorder affecting skin and lung in an elderly patient

A 70‐year‐old man presented with papular skin lesions and was diagnosed with Epstein–Barr virus (EBV)‐associated T‐cell lymphoproliferative disorder (T‐LPD). The patient showed infiltration of a large number of EBV‐encoded RNA‐positive T cells in the skin and lung, presence of EBV load in the peripheral blood, and expansion of clonal EBV‐infected γδ T cells and CD8⁺ T cells in the blood and skin, as assessed by EBV‐terminal repeat Southern blot, T‐cell receptor polymerase chain reaction and flow cytometric analyses. In the Japanese or East Asian fatal cases of EBV‐associated T/natural killer (NK)‐LPD, there are two peaks in age at death, approximately 20 years and 60 years. The former age group is associated with chronic active EBV infection (CAEBV), and the latter group typically suffers from extranodal NK/T‐cell lymphoma. Our case is characterized not only by the unique skin and lung manifestations but also the late onset age of the disease, indicating that the skin manifestation of CAEBV can be seen even in elderly patients.     

Hydroa vacciniforme-like eruptions in a patient with chronic active EB virus infection

We report a case of chronic active Epstein-Barr (EB) virus infection (CAEBV) associated with skin eruptions mimicking hydroa vacciniforme (HV) in a 4-year-old boy. The patient had repeated episodes of vesiculo-necrotic eruptions on the face, scalp, and bilateral forearms one year before the first visit to our department. General symptoms including fever, hepatosplenomegaly, abnormal liver function, and cervical lymph node swelling were noted three months before the first visit. At the first visit, small, bean-sized, erythemic papules with central necrosis were observed on the face and anterior chest wall. Thumb-sized ulcers with crust were present on the bilateral forearms. Histopathological examination of an erythematous lesion in the submandibular area revealed parakeratosis with a thick crust, mild spongiosis in the epidermis, and a dense infiltration of lymphoid cells into the dermis and perivascular space. Laboratory examination showed EBNA x 40, EBV VCA IgG x 1,280, and EBV DNA (PCR) 8 x 10(4). EBV-encoded small nuclear RNA (EBER) positive cells were detected in the dermis by an in situ hybridization (ISH) method. Large granular lymphocytes (65%) with the NK cell phenotype were found in the peripheral blood. A real time PCR method showed 171,741 copies/ micro g DNA in CD 16 positive cells. Although latent EBV infection-associated eruptions have been documented, detailed skin manifestations in CAEBV are less well known.     

Fatal natural killer cell lymphoma arising in a patient with a crop of Epstein-Barr virus-associated disorders

Natural killer (NK) lymphoma in Asia is frequently associated with latent Epstein-Barr (EBV) infection. Unlike the adult cases, EBV-associated NK/T cell lymphomas in children are often preceded by various EBV-related disorders, including chronic active EBV infection (CAEBV), hypersensitivity to mosquito bites (HMB), virus-associated haemophagocytic syndrome (VAHS), and hydroa vacciniforme (HV)-like eruptions. Here, we report a 14-year-old Japanese girl who sequentially developed all the symptoms related to EBV-associated NK/T cell lymphoproliferative disorders in a 12-year clinical course. Our observations confirm the spectrum of EBV-associated cutaneous disorders and indicate the importance of long-term follow-up.     

Hydroa vacciniforme-like Epstein-Barr virus-associated monoclonal T-lymphoproliferative disorder in a child

Hydroa vacciniforme (HV) is a chronic photosensitivity disorder induced by ultraviolet radiation. Hydroa vacciniforme-like lymphoma is a rare cutaneous T-cell lymphoma occurring mainly in childhood. Recent studies have demonstrated an association between chronic latent Epstein-Barr virus (EBV) infection and both the benign skin disorder and the lymphoma. The authors report a 6-year-old boy with chronic EBV infection, HV-like skin eruptions, and chronic hepatitis. Histopathologic examination of a skin biopsy specimen demonstrated epidermal ballooning degeneration and dense superficial and deep perivascular and periappendageal lymphoid cell infiltrates extending to the fat lobules. Some blood vessels in the deep plexus were infiltrated by predominantly CD4+ and TIA-1+ cytotoxic T cells. The EBV genomes were found within tissue from three skin biopsies and peripheral blood cells. Monoclonal T-cell receptor gene rearrangement was present in skin biopsy specimens. Although no lymphoma has been found during 2 years of follow-up treatment, the possibility of lymphoma developing out of the current smoldering stage is of concern. The clinical manifestations of lymphoproliferative disorder and chronic active EBV infection are discussed.     

Histopathologic features seen in Gianotti-Crosti syndrome secondary to Epstein-Barr virus

BACKGROUND: Gianotti-Crosti syndrome (GCS) or infantile papular acrodermatitis presents as a symmetric erythematous lichenoid papular and papulovesicular eruption of the face, extremities, and buttocks, usually occurring in young children. GCS has been associated with hepatitis B and enteroviruses, as well as Epstein-Barr virus (EBV) and, rarely, cytomegalovirus. OBJECTIVE: The purpose of this study was to use immunohistochemical studies to determine the pattern of the lymphoid infiltrate and evidence for viral antigens in cases of EBV-associated GCS. METHODS: Routine histologic and immunohistochemical stains were evaluated in 3 patients with typical GCS. All 3 patients showed serologic evidence of an acute EBV infection. The immunohistochemical studies included monoclonal antibodies for CD3, CD4, CD8, CD20, TIA, S-100 protein, KP-1, EBV latent membrane antigen-1, and EBV-encoded nuclear antigen-2. RESULTS: All biopsy specimens showed minimal epidermal spongiosis with marked papillary dermal edema. The associated inflammatory infiltrate showed a mixed mononuclear cell infiltrate with rare eosinophils. Immunohistochemical stains for latent membrane antigen-1 and EBV-encoded nuclear antigen-2 were negative for EBV. The majority of mononuclear cells showed membrane staining for CD3, 30% to 40% of the CD3 mononuclear cells showed positive staining for CD4, and 50% to 60% showed positive staining with CD8. TIA(+) cells appeared to correspond to the CD8(+) cells. CONCLUSION: Although papillary dermal edema has been reported within the spectrum of histologic findings in GCS, it was marked and a consistent finding in the 3 cases in which EBV was the most likely etiologic agent. The presence of large numbers of cytotoxic T cells in the inflammatory infiltrate may have accentuated this histologic finding and may be a relatively distinctive histologic finding with GCS associated with EBV.     

Characterization of skin blister fluids from children with Epstein–Barr virus‐associated lymphoproliferative disease

Epstein–Barr virus (EBV)‐associated T‐ or natural killer (NK)‐cell lymphoproliferative disease (LPD) is a heterogeneous group of disorders characterized by chronic proliferation of EBV‐infected lymphocytes. Patients may present with severe skin manifestations, including hypersensitivity to mosquito bites (HMB) and hydroa vacciniforme (HV)‐like eruption, which are characterized by blister formation and necrotic ulceration. Skin biopsy specimens show inflammatory reactions comprising EBV‐infected lymphocytes. However, blister fluids have not been fully assessed in patients with this disease. Blister fluids were collected from three patients with EBV‐associated LPD: two with HMB and one with HV. Immunophenotyping of blister lymphocytes and measurement of tumor necrosis factor (TNF)‐α in blister fluids were performed. The patients with HMB and HV exhibited markedly increased percentages of NK and γδ T cells, respectively, in both peripheral blood and blister fluids. These NK and γδ T cells strongly expressed the activation marker human leukocyte antigen‐DR and were considered to be cellular targets of EBV infections. TNF‐α was highly elevated in all blister fluids. Severe local skin reactions of EBV‐associated LPD may be associated with infiltrating EBV‐infected lymphocytes and a high TNF‐α concentration in blister fluids.     

Epstein-Barr virus-related persistent erythema multiforme in chronic fatigue syndrome.

BACKGROUND--Erythema multiforme (EM) has been rarely reported in Epstein-Barr virus (EBV)-associated diseases; this includes patients with chronic fatigue syndrome who have chronic or recurrent and disabling illness and an abnormal antibody reactivity to EBV. We describe a patient fulfilling the chronic fatigue syndrome diagnostic criteria who had developed an unusually persistent EM resistant to corticosteroids therapy. The EBV DNA was studied in skin EM lesions, throat washings, peripheral mononuclear cells, and plasma. The EBV antigens were studied in skin EM lesions and in mononuclear cells. The patient was followed up to 2 years. OBSERVATIONS--The patient had abnormal titers of antibodies against various EBV antigens and by immunofluorescence she disclosed the EBV nuclear antigen and the viral capsid antigen in the blood vessels of the affected skin. The dot blot hybridization assay detected viral DNA in throat washings and mononuclear cells, but not in plasma. The presence of the viral genomic content in lesional skin is suggested by the autoradiographic signal and by the difference from appropriate control specimens. Skin lesions and constitutional symptoms cleared after acyclovir sodium therapy and recurred after discontinuation of this therapy. CONCLUSIONS--This is the first EM case in which evidence of the EBV causal role has been provided. The association with chronic fatigue syndrome suggests the EBV role in selected cases of this syndrome.