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El virus Epstein-Barr es un virus gamma herpes que afecta exclusivamente a humanos; fue el primer virus oncogénico descrito y se ha relacionado con más de siete diferentes tipos de cáncer. Curiosamente, el intercambio de genes debido a infecciones virales ha permitido la evolución de los organismos celulares, favoreciendo el desarrollo de nuevas funciones y supervivencia del hospedero. El virus Epstein-Barr comparte cientos de millones de años de coevolución con la especie humana y más del 95% de la población adulta mundial se ha infectado en algún momento de su vida. La infección se adquiere principalmente durante la infancia, y en la mayoría de los casos aparece sin ninguna manifestación grave aparente. Sin embargo, en los adolescentes y la población joven-adulta, alrededor de un 10 a 30% evolucionan a mononucleosis infecciosa. Las células NK y T CD8+ son células citotóxicas cruciales durante las respuestas antivirales y se ha demostrado que controlan y eliminan la infección por el virus Epstein-Barr. No obstante, cuando se afecta su función efectora, el desenlace puede ser fatal. El objetivo de esta revisión es describir la infección por el virus Epstein-Barr y el papel decisivo de las células NK y T CD8+ durante el control y eliminación de la infección. Además, se discuten brevemente los principales defectos genéticos que afectan a estas células y conllevan a la incapacidad para eliminar el virus. Finalmente, se resalta la necesidad de elaborar una vacuna efectiva contra el virus Epstein-Barr y cómo podrían evitarse los procesos neoplásicos y enfermedades autoinmunes.

Copyright of Revista Alergia de Mexico is the property of Coleg. Mexicano de Inmunologia Clinica y Alergia A.C.; Soc. Lat. de Alergia, Asma e Inmunologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction and aims: Epstein-Barr virus (EBV) infection is an etiologic factor in EBV-associated gastric carcinoma (EBVaGC). The aim of our study was to describe the clinical and histopathologic characteristics of EBV infection in intestinal-type gastric adenocarcinoma samples. Material and methods: Of 180 paraffin-embedded gastrectomy samples, 28 were studied. Chromogenic in situ hybridization was performed to detect EBV. Sociodemographic and histopathologic data were obtained from the patients’ clinical histories. Results: A total of 21.4% of the samples were positive for EBV. The predominant morphologic characteristic was the lace pattern, with dense inflammatory infiltration. Fifty percent of the EBVaGC+ patients were men, and the median age of the positive patients was 59 years (range: 50–75); 77.2% of the EBVaGC− patients were men, and the median age of the negative patients was 66 years (range: 34–89). Helicobacter pylori infection was associated with 10.7% of the EBVaGC+ patients and 53.6% of the EBVaGC− patients. In the EBVaGC+ patients, the cardia was the most frequent tumor location (17.9%), 7.1% had histologic grades 2 and 3, and 17.9% presented with Borrmann classification type III. In the EBVaGC− patients, the cardia and fundus were the most frequent tumor locations (71.4%), 35.7% had histologic grade 2, and 39.3% and 21.4% presented with Borrmann classification type III and IV, respectively. Conclusions: The present study describes the clinical and histopathologic characteristics associated with EBVaGC positivity. Those data may aid in the selection of cases that are candidates for analysis through molecular methods aimed at identifying EBV infection in intestinal-type gastric adenocarcinoma. Resumen: Introducción y objetivos: La infección por virus de Epstein-Barr (VEB) es un factor etiológico de un subgrupo de cáncer gástrico (CaGVEB). El objetivo del estudio fue caracterizar la clínico-histopatología de la infección por VEB en muestras de adenocarcinoma gástrico de tipo intestinal. Material y métodos: 28 de 180 muestras de gastrectomías parafinizadas fueron estudiadas, se realizó hibridación in situ cromogénica para reconocimiento del VEB. Se obtuvieron datos sociodemográficos e histopatológicos de historias clínicas. Resultados: 21.4% de las muestras fueron positivas para VEB. La característica morfológica predominante fue patrón en encaje con denso infiltrado inflamatorio. De los pacientes CaGVEB+ 50% eran hombres, mediana de edad 59 años (rango 50–75), y de los CaGVEB−, 77.2% eran hombres, mediana de edad 66 años (rango 34–89). 10.7% de los CaGVEB+ y 53.6% de los CaGVEB− se asociaron a infección por Helicobacter pylori. Entre los CaGVEB+, la localización del tumor más frecuente fue cardias (17.9%) y entre los CaGVEB− fue cardias y fondo (71.4%). En la clasificación según grado histológico, los CaGVEB+ se asociaron a grados 2 y 3 (7.1%), y los CaGVEB- a grado 2 (35.7%). Para la clasificación Borrmann, 17.9% de los CaGVEB+ presentaron clasificación III, mientras que 39.3% y 21.4% de CaGVEB− presentaron clasificación III y IV, respectivamente. Conclusiones: Este estudio presenta características clínico-histopatológicas asociadas a CaGVEB+ que pueden contribuir con la selección de casos candidatos a ser estudiados por métodos moleculares dirigidos a la identificación de la infección por virus de Epstein-Barr en adenocarcinoma gástrico de tipo intestinal.

Lymphoproliferative disorders arising in a background of immune deficiency/dysregulation correspond to a spectrum of disorders ranging from non-noxious hyperplasias to aggressive lymphomas, mainly of B-cell type. We describe a case of an Epstein-Barr virus-positive T-cell lymphoma, with a cutaneous presentation and unusual pathological features in a patient under immunosuppression with infliximab. A 60-year-old patient, with a history of ankylosing spondylitis and autoimmune hemolytic anemia, treated with infliximab and low-dose prednisone since 2013, presented with a 7 cm ulcerated, well-demarcated tumor on his left lower back and a 20 cm scaly, well-demarcated erythematous patch in the left scapular region. A skin biopsy revealed a diffuse infiltration of the superficial and deep dermis by atypical, intermediate-size lymphocytes that expressed CD2, CD3, CD56, TIA-1, Granzyme B, TCRδ, and EBER. There was no evidence of epidermotropism, vasculotropism, or necrosis. The fluor-d-glucose positron emission tomography showed a large splenic, hepatic, bone marrow, and nodal uptake. A diagnosis of an extranodal NK/T-cell lymphoma in association with immunosuppression was rendered. With this article, we aim to add awareness to the difficulty of diagnosis, the careful use of immunomodulators, clinical suspiciousness, and surveillance of possible consequences warranted in all patients under prolonged immunosuppression. [ABSTRACT FROM AUTHOR]

El linfoma No-Hodgkin T/NK nasal es una entidad infrecuente y agresiva, más prevalente en hombres y de presentación clínica inespecífica. Su diagnóstico se realiza a través de histopatología, sin embargo la sospecha clínica es fundamental para identificarlo entre los diferenciales. Se reporta el caso de un masculino joven con un cuadro clínico inespecífico que luego de tratamientos fallidos para otras condiciones, fue diagnosticado con un linfoma de células T/NK nasal.

Le virus d'Epstein-Barr ou virus EBV, découvert en 1964, est un virus à ADN double brin de la famille des Herpesviridae. Il s'agit d'un virus lymphotrope avec une capacité de transformation de la cellule infectée via l'utilisation de différentes protéines virales oncogènes. Il est l'exemple prototypique d'un virus possédant deux cycles réplicatifs ; un cycle lytique essentiellement mis en jeu au moment de la primo-infection et un cycle latent lui permettant de persister de manière prolongée dans les cellules hôtes que sont les lymphocytes B mémoires. Plus de 90 % de la population mondiale est séropositive pour EBV à l'âge adulte, avec une primo-infection majoritairement asymptomatique ou pauci-symptomatique. Néanmoins, l'infection par EBV peut parfois être responsable de complications sévères à la phase aiguë de primo-infection (formes tumorales ou hémophagocytaires) ou par l'induction de lymphoproliférations majoritairement B et de certains cancers (carcinome du nasopharynx, adénocarcinome gastrique, leiomyome et tumeur à cellules folliculaires dendritiques). Les facteurs de risque de ces complications sont de mieux en mieux compris grâce à la dissection des mécanismes immunopathologiques de la réponse anti-EBV permis par la découverte des gènes responsables de déficits immunitaires primitifs prédisposants aux infections EBV. Dans cette revue, nous proposons une mise au point sur les avancées récentes dans la compréhension physiopathologique à travers un panorama des situations devant alerter sur l'existence d'un déficit immunitaire sous-jacent ou une complication spécifique liée à EBV ainsi que les principes de leur prise en charge. Epstein-Barr virus (EBV), discovered in 1964, is a double-stranded DNA virus belonging to the Herpesviridae family. EBV has a lymphoid tropism with transforming capacities using different oncogenic viral proteins. This virus has two replication cycles: a lytic cycle mainly occuring during primary infection and a latent cycle allowing viral persistence into host memory B cells. More than 90% of adults are seropositive for EBV worldwide, with a past history of asymptomatic or mild primary infection. EBV infection can sometimes cause life-threatening complications such as hemophagocytic lymphohistiocytosis, and lead to the development of lymphoproliferative disorders or cancers. Risk factors associated with these phenotypes have been recently described through the study of monogenic primary immune deficiencies with EBV susceptibility. We here review the virological and immunological aspects of EBV infection and EBV-related complications with an overview of current available treatments. [ABSTRACT FROM AUTHOR]

Antecedentes: El linfoma de Hodgkin es una neoplasia maligna de células linfoides tipo B cuya característica histológica es la presencia de células de Reed-Sternberg en un medio inflamatorio. Caso clínico: Mujer de 37 años, con fiebre de hasta 40 °C desde cuatro meses atrás, disminución bilateral y progresiva de la agudeza auditiva, pérdida ponderal de 6 kg, linfadenopatía cervical, hepatoesplenomegalia y pancitopenia. Se corroboró neuropatía sensorial auditiva. La paciente desarrolló síndrome hemofagocítico, por lo que se descartaron procesos infecciosos o autoinmunes. La tomografía reveló hepatoesplenomegalia, ganglios cervicales torácicos y abdominales con pérdida del hilio graso; en los estudios de laboratorio se evidenciaron datos sugerentes de reactivación del virus de Epstein-Barr. Mediante biopsia de ganglio submandibular se concluyó que se trataba de linfoma de Hodgkin tipo clásico rico en linfocitos. Conclusión: La paciente descrita con síndrome hemofagocítico secundario a linfoma de Hodgkin clásico asociado a infección por Epstein-Barr constituye el primero caso reportado en la literatura latinoamericana.

Copyright of Scientia Medica is the property of EDIPUCRS - Editora Universitaria da PUCRS and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Nasopharyngeal carcinoma (NPC) has a high incidence in some geographical areas, 67% of all cases being reported in Southeast Asia. Since Epstein-Barr virus (EBV) plays an important role in the development of this malignancy, viral biomarkers (EBV-specific antibodies, EBV DNA) are currently used. However, new diagnostic and prognostic biomarkers associated EBV infection have been evaluated and among them are EBV non-coding RNAs which are involved in multiple pathological processes: complex regulatory signaling networks for cell cycle control and intercellular communication, tumor progression, transcriptional regulation of gene expression by modulating mRNAs molecules expression, chromatin and nuclear structures organization, transposable elements silencing. Produced in tumor cells, these viral non-coding transcripts could be secreted as extracellular vesicles into peripheral bloodstream. EBV non-coding RNAs have several advantages as biomarkers, especially rapidity of detection and elevated levels in body fluids. Therefore, testing these circulating molecules is much more accessible. The signature of these non-coding RNAs might be used as potential biomarkers of diagnostic, prognostic, clinical outcome and therapeutic response. The aim of this minireview was to evaluate the potential of EBV non-coding RNAs as biomarkers in EBV associated NPC. [ABSTRACT FROM AUTHOR]

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Các nghiên cứu đã chứng minh gen Latent Membrance Protein 1 (LMP1) của virus Epstein-Barr (EBV) (LMP1 EBV) và sự đột biến gen LMP1 EBV liên quan có ý nghĩa đến sự phát triển khối u ác tính tại biểu mô vòm mũi họng ở các BN có nhiễm EBV. Mục tiêu nghiên cứu là xác định tần suất và đột biến mất đoạn 30 bp trên gen LMP1 EBV ở mẫu mô sinh thiết vòm của BN UTVMH. Thiết kế nghiên cứu mô tả cắt ngang được thực hiện trên 65 mẫu mô sinh thiết vòm của BN được chẩn đoán xác định là UTVMH tại Bệnh viện ung bướu Cần Thơ. Kỹ thuật Polymerase Chain Reaction (PCR) - phản ứng chuỗi polymerase với cặp mồi LMP1 (168373-168174) được sử dụng để phát hiện gen LMP1 EBV và kỹ thuật giải trình tự gen LMP1 để xác định kiểu đột biến gen LMP1. Kết quả cho thấy 61,5% (40/65) có gen LMP1 EBV ở mô sinh thiết vòm và 57,5% (23/40) có kiểu đột biến mất đoạn 30 bp trên gen LMP1. Kết luận, tần suất gen LMP1 EBV trong mẫu mô sinh thiết vòm của BN UTVMH tại Cần Thơ là 61,5% và mất đoạn 30 bp là kiểu đột biến phổ biến trên gen LMP1.

Copyright of Colon & Rectum is the property of Lavoisier and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Infectious mononucleosis is one of the major clinical manifestations of Epstein-Barr virus infection. In this syndrome, elevation of liver transaminase levels is common but cholestasis is rare, with few cases described in the literature. We present the case of a 14-year-old female adolescent, admitted to the Emergency Room with fever, odynophagia and cervical adenomegaly. She was treated with amoxicillin and two days later he presented with jaundice. The analytical evaluation was compatible with cholestatic hepatitis and abdominal ultrasound revealed hepatosplenomegaly without dilatation of the bile ducts. The diagnosis of Epstein-Barr virus infection was confirmed by the presence of serological markers. This case aims to raise awareness of a rare manifestation of a common infectious agent and, consequently, to the inclusion of acute Epstein-Barr virus infection in the differential diagnosis of pediatric cholestatic hepatitis.

Se presenta el caso de una paciente de 13 años de edad con un cuadro rápidamente progresivo de lupus eritematoso sistémico (LES) sin anticuerpos antinúcleo (AAN), asociado a infección por Virus Epstein-Barr (VEB) y síndrome antifosfolípido. Se hizo un abordaje terapéutico y diagnóstico conforme a las complicaciones que sufrió; como una bronconeumonía, sangrado digestivo alto, e insuficiencia renal, los cuales en ese sentido la llevaron a falla multiorgánica y consecuentemente a su fallecimiento. Se toma en cuenta los hallazgos más relevantes de la historia clínica enfocado en la asociación entre las diversas afecciones que conlleva una misma enfermedad, que es bien conocida, sin embargo, es poco frecuente verle manifestarse de esta manera.

Presentamos el caso de un paciente de 6 años de edad, con papiledema bilateral y paresia del vi par, diagnosticado de hipertensión intracraneal idiopática asociada a un episodio agudo de infección por el virus de Epstein-Barr.

A síndrome de ativação macrofágica (SAM) é uma doença rara e potencialmente fatal, normalmente associada às doenças reumáticas crônicas, em especial a artrite idiopática juvenil. É incluída no grupo das formas secundárias de síndrome hemofagocítica, cujas outras causas podem ser as doenças linfoproliferativas e infecções. As manifestações clínicas e laboratoriais mais importantes são a febre não remitente, esplenomegalia, hemorragias, disfunção hepática, citopenias, hipoalbuminemia, hipertrigliceridemia e hiperferritinemia. O tratamento deve ser iniciado rapidamente, e a maioria dos casos responde bem aos corticosteroides e à ciclosporina (CSA). O vírus Epstein-Barr (EBV) é descrito como possível gatilho para muitos casos de SAM, especialmente naqueles em tratamento com bloqueadores do fator de necrose tumoral (TNF). Nos casos refratários ao tratamento convencional, etoposide (VP16) deve ser administrado, em associação com corticosteroides e CSA. Nosso objetivo foi descrever um caso raro de síndrome hematofagocítica provavelmente secundária à infecção pelo vírus Epstein-Barr (EBV), em paciente com artrite idiopática juvenil sistêmica, confirmada pelas manifestações clínicas e laboratoriais típicas, mielograma e sorologia positiva contra o EBV, que atingiu remissão completa após inclusão no protocolo de tratamento HLH-04.

Antecedentes: La infección severa por virus de Epstein-Barr puede estar asociada con inmunodeficiencias y también predisponer a otras infecciones virales, bacterianas y fúngicas. Se han descrito mutaciones específicas en proteínas que controlan la infección por virus de Epstein-Barr. Reporte de caso: Niña de siete años. Originaria de Nueva Jersey, Estados Unidos. Antecedentes perinatales sin importancia, sin endogamia. Hermano que falleció a los cuatro años con diagnóstico de linfoma difuso de células B grandes asociado con virus de Epstein-Barr. Presentó cinco episodios de neumonía a partir de los seis meses de edad; infecciones de las vías respiratorias superiores, aproximadamente de 10 a 15 episodios por año; otitis media recurrente a partir de los seis meses de edad; gastroenteritis infecciosa en dos ocasiones; herpes labial a los cuatro y seis años. En el examen físico se observó desnutrición aguda de intensidad leve; hipertrofia tonsilar derecha grado IV; adenomegalias cervicales no dolorosas bilaterales; hepatomegalia, 1 cm por debajo del borde costal; adenomegalias múltiples en la región inguinal. Los datos de laboratorios indicaron hemoglobina de 9.6 g/dL, leucocitos de 9300, neutrófilos de 7440, linfocitos de 1767, monocitos de 279, plaquetas de 209 000. Inmunoglobulinas IgG de 2240 mg/dL, IgM de 187 mg/dL, IgA de 826 mg/dL, IgE de 75.5 mg/dL, ferritina de 110 ng/mL y triglicéridos de 126 mg/dL. Desde 2014 se detectó un alto nivel de ADN de virus de Epstein-Barr en plasma con 296 199 copias/mL; en 2015 con 345 000 copias/mL y ese mismo año, la biopsia pulmonar indicó neumonitis intersticial linfoide asociada con virus de Epstein-Barr; en 2016 se detectó virus de Epstein-Barr en líquido cefalorraquídeo. Se realizó biopsia de ganglio linfático cervical en 2017, que reveló enfermedad linfoproliferativa asociada con virus de Epstein-Barr. La citometría de flujo fue normal y expresión de CD27 normal. La paciente ha recibido cinco ciclos de rituximab e inmunoglobulina intravenosa (1 g/kg/dosis), trimetoprima-sulfametoxazol, hidroxicloroquina y ciclosporina. Conclusiones: La fisiopatología implica a las células T, las células natural killer y las células B y otras proteínas para el control del virus de Epstein-Barr. CD27 es un marcador de la memoria de células B y T; su deficiencia debe ser considerada en todos los pacientes con hipogammaglobulinemia o causas inusualmente graves de la infección por virus de Epstein-Barr. El trasplante alogénico de células madre hematopoyéticas se considera una opción de tratamiento curativo; otras opciones de tratamiento, como rituximab, se han informado con el fin de controlar la infección por virus de Epstein-Barr.

Copyright of Revista Española de Quimioterapia is the property of Sociedad Espanola de Quimioterapia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Résumé Objectifs Le virus Epstein-Barr (EBV) joue un rôle dans la pathogenèse d’environ 40 % des syndromes lymphoprolifératifs (SLP) qui surviennent chez des patients sous traitement immunosuppresseur (TIS) pour une maladie rhumatismale, mais il n’y a pas encore de données issues de grandes cohortes. Nous avons souhaité identifier les caractéristiques clinicopathologiques, la prise en charge et les résultats de cette affection. Méthodes Nous avons passé en revue tous les cas publiés de SLP positifs pour l’ARN encodé de l’EBV (EBER), incluant dans notre analyse un patient dont le cas n’avait pas été publié mais dont le diagnostic avait été établi dans notre hôpital. Nous avons exclu les cas ne présentant pas d’affection rhumatismale sous-jacente, sans TIS spécifique ou pour lesquels il n’existait pas de données univoques. Résultats La majorité des 159 patients cumulés de notre cohorte présentaient une polyarthrite rhumatoïde (83 %) et recevaient du méthotrexate (75,4 %). Chez 68,5 % des patients, le SLP est apparu entre 40 et 70 ans, après une période de 13,3 ± 9,6 ans depuis l’apparition de la maladie rhumatismale et après 58,7 ± 47 mois de TIS. Les SLP étaient majoritairement dérivés de la lignée B (39 %), de stade I dans la classification d’Ann Arbor (38,3 %) et présentaient dans 63,1 % des cas une atteinte extranodale touchant principalement le système nerveux central (17,6 %). L’approche la plus fréquemment adoptée a été l’arrêt du TIS (93,3 %) associé, dans 38,3 % des cas, à une radiothérapie (RT) ou une chimiothérapie (CT). Au total, une rémission complète a été obtenue chez 61,7 % des patients (RC ; 30,2 ± 24,0 mois). Parmi les cas publiés de patients pour lesquels l’approche de première instance a consisté en l’arrêt seul du TIS, une RC a été obtenue dans 67,2 % des cas. Aucune différence démographique, clinique ou histologique significative n’a été observée entre les patients ayant obtenu une RC et les autres, ni entre ceux ayant atteint la RC par arrêt seul du TIS et les autres ( p > 0,05 pour toutes les comparaisons). Conclusions Cette étude examine toutes les preuves publiées relatives à des SLP induits par l’EBV chez des patients recevant un TIS pour une affection rhumatismale. [ABSTRACT FROM AUTHOR]

Multiple sclerosis is a neurodegenerative and autoimmune disease of the central nervous system that mainly affects young people, especially women; its origin has been associated with infection caused by the Epstein-Barr virus. However, not all people who have suffered infection by this virus develop multiple sclerosis, so it would be important to know the role of genetic variability, especially the individual allelic variability of the human leukocyte antigen; as well as to determine the molecular mechanisms and the immunological links of the virus when it remains latent inside the B lymphocytes. Based on the above, it could be defined if the virus is a necessary condition to develop the disease or if there are other factors that need to be present, and thus be able to establish specific prevention and treatment strategies. But the most relevant thing is that the virus is a present condition to develop multiple sclerosis and is potentially preventable through the design of the respective vaccine. [ABSTRACT FROM AUTHOR]

O Linfoma Extranodal de Células NK/T tipo Nasal tem uma distribuição geográfica peculiar, ocorrendo mais frequentemente em países orientais e na população nativa de alguns países da América Central e da América do Sul. Sua localização preferencial é na cavidade nasal e nos seios paranasais, mas pode acometer outras estruturas da chamada região médio-facial. Tem um padrão de disseminação com "homing" característico, incluindo pele, testículo, SNC e trato digestivo. Este linfoma, menos frequentemente, pode acometer primariamente estas regiões. A maioria destas neoplasias apresenta um fenótipo NK, mas alguns poucos casos podem ter sua origem em células T verdadeiras, por este motivo é designado "linfoma NK/T". O genoma do vírus Epstein-Barr é detectado na maioria dos casos, sugerindo uma relação etiológica. Embora este linfoma seja sensível à radioterapia, apresenta mais frequentemente resistência a agentes quimioterápicos que outros linfomas. Uma possível explicação para a resistência é a usual expressão de glicoproteína-p. O prognóstico destes linfomas é pobre, sendo necessária a investigação de novas modalidades terapêuticas.Extranodal Nasal type NK/T-Cell Lymphoma has a peculiar geographic distribution, occurring more frequently in Eastern countries and in the native populations of some Central and South American countries. It is commonly found in the nasal cavity and paranasal sinuses, but may also compromise other structures in the mid-facial region. The disease has a characteristic homing dissemination pattern, including skin, testis, CNS and digestive tract. This lymphoma can, less frequently, primarily compromise these regions. The majority of these neoplastic diseases present an NK phenotype, but a few cases can be truly of T-cell origin, because of which it is designed "NK/T-cell lymphoma". The Epstein-Barr virus genome can be detected in most of the cases, suggesting an etiological relationship. Although this lymphoma is responsive to radiotherapy, it is more resistant to conventional chemotherapy than other lymphomas. A possible explanation for this is the frequent expression of the p-glycoprotein. The prognosis of these lymphomas is still poor, making further investigation of new therapies imperativ.

La pustulosis exantemática aguda generalizada (PEAG) es una rara afección de hipersensibilidad, inducida principalmente por drogas y se manifiesta por una erupción aguda de pústulas estériles, acompañada de fiebre, que regresa en pocos días luego de discontinuar el fármaco causante. Se comunica el caso de una paciente de 23 años de edad, sin antecedentes de psoriasis que consulta por fiebre y una erupción pustulosa generalizada, asociada a la ingesta previa de amoxicilina y ácido clavulánico en el contexto de una mononucleosis infecciosa, con resolución espontánea del cuadro. El cultivo microbiológico no objetivó gérmenes patógenos.Acute generalized exanthematous pustulosis (AGEP) is a rare skin eruption most commonly caused by medications. It is characterized by an acute eruption of sterile pustules and it is accompanied by an episode of fever, which regresses a few days after discontinuation of the drug that caused the condition. We report a case 23 year-old woman without history of psoriasis, that consults for fever and an acute generalized pustular eruption after amoxicillin, with clavulanic acid administration in a mononucleosis infection context, which resolved spontaneously. The microbiologic culture was negative for pathogenic germens.

Relato de dois casos de pacientes do sexo masculino com linfoma de Hodgkin (LH) e idades inferiores a 5 anos apresentando linfonodomegalias com evolução de alguns meses e seguimento em nosso serviço. Os estudos imuno-histopatológicos do tumor confirmaram linfoma de Hodgkin, esclerose nodular e positividade para o vírus Epstein-Barr (EBV) em material tumoral, em ambos os casos. Após período de 13 meses em remissão completa houve recidiva em um dos pacientes, mostrando doença agressiva. A análise laboratorial do tumor mostrou as mesmas características da doença inicial, e mantendo a positividade ao EBV. Uma exposição mais precoce e intensa ao EBV poderia aumentar o risco para formas muito precoces da doença e a inesperada evolução poderia estar ligada à associação do subtipo histológico e positividade ao EBV.The cases of two male under five-year-olds diagnosed with Hodgkin's lymphoma presenting as lymphadenopathy in evolution for some months and treated in our hospital are reported. Immunohistopathological findings of the tumors proved the existence of Hodgkin's lymphoma nodular sclerosis and positive Epstein-Barr virus in tumoral material in both cases. After 13 months of complete remission one of the patients relapsed and presented aggressive disease. Laboratorial analyses of the tumor showed the same characteristics as the initial disease including positive Epstein-Barr virus. Early and intense exposure to Epstein-Barr virus may increase the risk related to the very early development of the disease and the unexpected evolution may be connected to the association of the histological subtype and the positive Epstein-Barr virus.

Nasopharyngeal cancer is a disease with a heterogenous incidence related to Epstein-Barr virus infection whose main issue in the management of locally advanced disease are long-term relapses. We introduce the case of a 27 years old female patient with nasopharyngeal cáncer in clinical stage III, type III (WHO) or linfoepitelial carcinoma with in situ hybridation for Epstein Barr positive and viral charge in blood of 1500 copies/mL at diagnosis. The patient went through induction chemotherapy of DCF regimen (docetaxel, cisplatino, 5FU) for two cycles and accomplish complete clinical response and no detectable viral charge and the end of induction, following concurrent chemotherapy and radiotherapy with carboplatino 2AUC and IMRT at 6996 cGys dosis. In the present, patient is still in follow-up with negative controls. [ABSTRACT FROM AUTHOR]

The prevalence of Epstein-Barr virus (EBV) in patients with classical Hodgkin’s lymphoma (CHL) is geographically variable. In the present study the prevalence of EBV in CHL was assessed in adult patients from Ceará, Brazil. Thirty-seven cases were immunohistochemically evaluated for EBV using latent membrane protein (LMP1) antibody and for EBV latency-associated RNA (EBER1) using in situ hybridization (ISH). Sex and age did not differ among patients as to the frequency of CHL. Nodular sclerosis was the predominant histological subtype. LMP1 was found in Reed-Sternberg cells in 67.5% of the cases whereas ISH detected EBER1 in 75.6%. Regarding histological subtypes EBV infection rates were not found statistically different in nodular sclerosis (NS) and mixed cellularity (MC) subtypes (p = 0.66).A freqüência do vírus Epstein-Barr (EBV) em pacientes com linfoma de Hodgkin Clássico (LHC) sofre variabilidade geográfica. No presente estudo investigamos a freqüência do EBV em pacientes com LHC no estado do Ceará. Trinta e sete casos de linfoma de Hodgkin clássico foram avaliados por imuno-histoquímica para EBV usando o anticorpo monoclonal contra a proteína latente da membrana (LMP1) e pelo método de hibridização in situ para RNA associado ao EBV (EBER1). Não há diferença por sexo e idade dos pacientes no que concerne à freqüência de LHC. O subtipo histológico esclerose nodular foi predominante. LMP1 esteve presente em células Reed-Sternberg em 67,5% e pela hibridização in situ, através da sonda EBER, foi evidente em 75,6% dos casos. Não observamos predominância significativa da associação de EBV com os subtipos histológicos esclerose nodular (EN) e celularidade mista (CM) (p = 0,66).

Viral coinfection in the oral cavity associated to HIV infection was evaluated in 180 children from birth to 13 years of age of both sexes. The oral examinations were performed at the Pediatric AIDS Outpatient Clinic, São Lucas Hospital and Clinic Hospital, both in Porto Alegre, Brazil and at the School of Dental Medicine, University Hospital Center, State University of New York at Stony Brook, USA. The aim of this study was to identify the presence of viral infections in the oral cavity. PCR technique was used to determine opportunistic viral infections caused by CMV, EBV, and HSV in mucosal swabs. A high frequency of viral infection was detected in the oral cavity of HIV-infected children determined by the PCR technique. HIV-infected children with viruses had a favorable CD4+T lymphocyte count and unfavorable viral load.A relação entre a infecção pelo HIV e a presença de diferentes tipos de vírus na cavidade bucal foi estudada em 180 crianças HIV-positivo, com idades entre zero e 13 anos de idade, de ambos os sexos. Os exames foram realizados nos Ambulatórios de Aids Pediátrica dos Hospitais São Lucas e de Clínicas, ambos em Porto Alegre, RS, Brasil e no Centro Hospitalar Universitário da Universidade Estadual de Nova Iorque, em Stony Brook (EUA). O objetivo desta pesquisa foi usar a técnica da PCR para detectar a presença dos vírus CMV, EBV e HSV na cavidade bucal desses pacientes, independentemente da presença ou não de manifestações estomatológicas relacionadas aos mesmos. Pode-se concluir que foi alta a freqüência de vírus detectados na cavidade bucal das crianças da amostra através da técnica da PCR e que a contagem média de linfócitos T-CD4+ das crianças com a presença dos vírus encontrava-se próxima da normalidade, enquanto a Carga Viral do HIV encontrava-se elevada.

La mononucleosis infecciosa (MNI) es una enfermedad frecuente que afecta a niños y adolescentes y es causada por el virus Epstein-Barr. En la mayor parte de los casos (80%) se presenta como un cuadro agudo, caracterizado por fiebre, faringoamigdalitis y linfoadenopatías (forma anginosa). Con menor frecuencia, puede presentarse con poliadenopatías asociadas a fiebre baja y faringitis leve. La ultrasonografía (US) Doppler color ha demostrado ser de utilidad en el estudio de adenopatías en el niño y puede ser de utilidad en el diagnóstico de MNI. Objetivos: Describir los hallazgos de la US Doppler color en la MNI. Pacientes y Método: Se revisó en forma retrospectiva los antecedentes clínicos y estudios por imágenes de 10 niños con diagnóstico confirmado de MNI y en quienes se efectuó US como parte de su estudio. Resultados: El estudio US Doppler color de las adenopatías cervicales mostró hallazgos relativa-mente constantes en todos los pacientes: adenopatías bilaterales múltiples, ovaladas o semi-rredondeadas, con una razón largo-ancho < 2, hiper o isoecogénicas con respecto al músculo, sin necrosis o alteración de estructuras vecinas. Mostró además aumento de flujo vascular en todas las adenopatías. En los cuatro pacientes con US abdominal, se encontró hepatoesplenomegalia (3 pacientes) o esplenomegalia (1 paciente). En dos pacientes, el bazo mostraba un aspecto reticular y nodular fino, que podría ser secundario a la hiperplasia linfática reactiva, con compromiso fundamentalmente de la pulpa blanca, que ha sido descrita en el estudio histológico del bazo en pacientes con esta patología(9). Conclusiones: La MNI es una enferme-dad frecuente en el niño y en la mayoría de los casos el diagnóstico se sospecha clínicamente y se confirma con el estudio serológico específico. La US Doppler color muestra un aspecto relativamente constante en el estudio de las adenopatías periféricas en esta enfermedad y puede ser de utilidad en el diagnósticoInfectious mononucleosis is a common disease in children and in most cases, the diagnosis can be suspected with clinical findings alone and confirmed with serologic study. However, in some patients, clinical pesentation can be atypical. When presented with poliadenopahy, high-resolution color-Doppler ultrasonography (US) could be helpful in the differential diagnosis. We present the US characteristics of 10 children who presented with lymphadenopathy and had infectious mononucleosis, confirmed by serologic study. US findings were relatively constant in all patients. When sonographic findings are correlated with clinical and laboratory findings , a correct diagnosis can be suspected

Introduction In primary immunodeficiencies there is a failure in the anti-tumor defense. Common variable immunodeficiency (CVID) is one of the most common primary immunodeficiencies characterized by an alteration in the differentiation of B lymphocytes (BL). Epstein-Barr virus (EBV) is an ubiquitous virus that selectively infects the BL. In patients with immunodeficiency, uncontrolled proliferation of infected BL and the action of viral proteins promote the development of lymphomas. Clinical cases At the University Hospital Sant Joan de Deu, Barcelona, 28 patients were diagnosed with CVID from 2000 to 2013. This paper describes four patients who developed non-Hodgkin's lymphoma (NHL). The lymphoma was associated with EBV in two of the cases. Patients were < 18 years old, diagnosed with lymphoma between 4 and 13 years old. Two patients were treated with rituximab as monotherapy and achieved complete remission. Two patients were treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) and radiotherapy or rituximab and achieved complete remission. Conclusions Early detection of EBV infections and NHL in all patients diagnosed with CVID is recommended, regardless of age at diagnosis. [ABSTRACT FROM AUTHOR]

Résumé: Le virus d’Epstein-Barr virus (EBV) est un virus oncogène ubiquitaire avec une séroprévalence de plus de 90 %. À l’âge de 5 ans, la moitié des enfants a déjà rencontré cet herpesvirus. Il présente le plus haut pouvoir transformant chez l’homme, et induit une réponse immunitaire cellulaire majeure au moment de la primo-infection. Il est responsable de différentes lymphoproliférations B, essentiellement (lymphome de l’immunodéprimé, Hodgkin, Burkitt) et épithélioproliférations (carcinome nasopharyngé, carcinome gastrique). Les cellules infectées par le virus sont en phase de latence 0, I, II ou III ou en cycle réplicatif (ou lytique) selon l’étape naturelle de l’infection ou selon la pathologie associée. Le diagnostic virologique d’une pathologie EBV-induite se fait sur tissu par immunohistochimie ou par hybridation in situ (recherche des ARN non codants les EBERs). Il est possible également de quantifier l’ADN de l’EBV par PCR en temps réel (charge virale EBV) dans le sang périphérique (sang total), la moelle ou d’autres fluides biologiques, voire dans des tumeurs. La charge virale EBV est en particulier utilisée dans le suivi longitudinal des greffes de moelle ou d’organe afin de dépister plus précocement une Iymphoproiiferation et de proposer ainsi un traitement anticipé. [Copyright &y& Elsevier]

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Copyright of RPDI - Revista Portuguesa de Doenças Infecciosas is the property of Sociedade Portuguesa de Doencas Infecciosas e Microbiologia Clinica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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Abstract: We report a case of Epstein Barr virus-associated large B cell lymphoproliferative disorder, with an abdominal cutaneous localization, in an adult treated for 10 years with immunosuppressive agents for a dermatomyositis. This is the third case of immunosuppressive induced lymphoproliferative disorder localized to skin in a patient with dermatomyositis. Diagnosis was unexpectedly obtained by the histologic examination of surgical samples of skin necrosis possibly induced by edetate calcium disodium subcutaneous injections in calcinosis cutis. [Copyright &y& Elsevier]

Abstract: Purpose: To determine the level and prognostic significance of c-kit expression in the two age groups of North African nasopharyngeal carcinomas. Patients and methods: A retrospective study of 99 NPC specimens from Tunisian patients was investigated by immunohistochemistry. Immunohistochemical data were correlated with Epstein-Barr virus LMP1 expression and pathological, clinical and survival parameters. Results: c-kit was detected in 79% of the cases for patients under 30 years of age (juvenile form) but in only 56% of specimens in patients over 30 years (P =0.039) and was significantly over-expressed for patients with lymph node involvement (P =0.015). LMP1 score was 5.78 (±1.84) for c-kit negative tumors compared to 8,23 (±2.39) for c-kit positive tumors (P =0.002). Multivariate analysis including age, lymph nodes involvement and LMP1 expression as co-variables, showed that only age (P =0.027) and LMP1 expression (P =0.005) were significantly correlated to the c-kit expression. Conclusion: c-kit is highly expressed in the juvenile form of North African nasopharyngeal carcinomas. There is a significant association between LMP1 and c-kit expression. The contrasted levels of C-kit expression in the two age groups strengthen the hypothesis that these clinical forms result from distinct oncogenic mechanisms. [Copyright &y& Elsevier]

Prenylated Rab acceptor domain family member 1 (PRAF1), a transmembrane protein whose precise function is unknown, localizes to the Golgi complex, post-Golgi vesicles, lipid rafts, endosomes, and the plasma membrane. VAMP2 and Rab3A are SNARE proteins that interact with PRAF1, and, as part of a SNARE complex, PRAF1 may function in the regulation of docking and fusion of transport vesicles both in the Golgi complex and at the plasma membrane. Alternately, PRAF1 may function as a sorting protein in the Golgi complex. In addition to interacting with SNARE proteins, PRAF1 interacts with rotaviral, retroviral, and herpes viral proteins. The function of viral protein interaction is unknown, but PRAF1 may enhance rotaviral and retroviral assembly. In contrast, PRAF1 may inhibit the herpes virus life cycle. [ABSTRACT FROM AUTHOR]

Coregulation of lymphoid-specific gene sets is achieved by a series of epigenetic mechanisms. Association with higher-order chromosomal structures (nuclear subcompartments repressing or favouring gene expression) and locus control regions affects recombination and transcription of clonotypic antigen receptors and expression of a series of other lymphoid-specific genes. Locus control regions can regulate DNA methylation patterns in their vicinity. They may induce tissue- and site-specific DNA demethylation and affect, thereby, accessibility to recombination-activating proteins, transcription factors, and enzymes involved in histone modifications. Both DNA methylation and the Polycomb group of proteins (PcG) function as alternative systems of epigenetic memory in lymphoid cells. Complexes of PcG proteins mark their target genes by covalent histone tail modifications and influence lymphoid development and rearrangement of IgH genes. Ectopic expression of protein noncoding microRNAs may affect the generation of B-lineage cells, too, by guiding effector complexes to sites of heterochromatin assembly. Coregulation of lymphoid and viral promoters is also possible. EBNA 2, a nuclear protein encoded by episomal Epstein-Barr virus genomes, binds to the cellular protein CBF1 (C promoter binding factor 1) and operates, thereby, a regulatory network to activate latent viral promoters and cellular promoters associated with CBF1 binding sites. [ABSTRACT FROM AUTHOR]

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Epstein–Barr virus (EBV) is a B-lymphotropic human herpes virus that infects B lymphocytes and is associated with a broad spectrum of benign and malignant diseases. B cell infection by EBV causes indefinite cell proliferation that results in the development of immortalized lymphoblastoid cell lines (LCLs). We found that SNU-1103, a latency type III EBV-transformed LCL developed from a Korean cancer patient, resisted the G1 arrest that was normally caused by serum starvation. Western blot analyses revealed several alterations in the expression of key regulatory cell cycle proteins involved in the G1 phase. High expression of cyclin D2 and time-dependent increases in cyclin-dependent kinase 6 (CDK6) and cyclin D3 were observed in SNU-1103 during serum starvation. Very unexpectedly, in SNU-1103, the key G1 phase CDK inhibitor p21[sup Cip1] was expressed at a consistently high level, while p27[sup Kip1] expression was increased. Of three pRb family proteins, pRb expression was reduced and it became hypophosphorylated in SNU-1103 during serum starvation. Instead, p107 and p130 were expressed at consistently high levels in SNU-1103 during serum starvation. In conclusion, compared with an EBV-negative BJAB cell line, multiple cell cycle regulatory proteins were abnormally or inversely expressed in SNU-1103 during serum starvation.Key words: Epstein–Barr virus, lymphoblastoid cell line, B lymphocyte, serum starvation, cell cycle proteins.Le virus Epstein–Barr (EBV) est un herpèsvirus B-lymphotrope humain qui infecte les lymphocytes B et est associé a de nombreuses maladies bénignes ou malignes. L'infection des lymphocytes B par EBV engendre une prolifération cellulaire illimitée, ce qui entraîne le développement de lignées cellulaires lymphoblastiques (LCL) immortalisées. Nous avons noté que les cellules SNU-1103, une LCL obtenue à partir de cellules tumorales d'un Coréen transformées par le EBV latent de type III, ne s'arrêtent pas en phase G1 comme le font normalement les cellules cultivées en absence de sérum. Des transferts de type Western montrent plusieurs modifications de l'expression d'importantes protéines de régulation du cycle cellulaire qui interviennent au cours de la phase G1. Une forte expression de la cycline D2 et une augmentation de la CDK6 et de la cycline D3 en fonction du temps sont notées dans les cellules SNU-1103 cultivées en absence de sérum. Il est très surprenant de constater que l'inhibiteur p21[sup Cip1] de la CDK, essentiel au cours de la phase G1, est constamment exprimé à taux élevé dans les cellules SNU-1103 et que l'expression de p27[sup Kip1] est augmentée. Pour ce qui est de trois protéines de la famille de pRb, l'expression de pRb est réduite et pRb devient hypophosphorylée dans les cellules SNU-1103 cultivées en absence de sérum. Par contre, les protéines p107 et p130 sont toujours exprimées à taux élevé dans les cellules SNU-1103 cultivées en absence de sérum. En conclusion, comparativement à la lignée de cellules BJAB non infectée par EBV, de nombreuses protéines de régulation du cycle cellulaire sont exprimées de façon anormale ou inverse dans les cellules SNU-1103 cultivées en absence de sérum.Mots clés : virus Epstein–Barr, lignée cellulaire lymphoblastique, lymphocyte B, absence de sérum, protéines du cycle cellulaire.[Traduit par la Rédaction] [ABSTRACT FROM AUTHOR]