Lymphoproliferative disorders after renal transplantation along 2 decades: a large longitudinal study of 21.546 recipients.

INTRODUCTION: Post transplant lymphoproliferative disorders (PTLD) are heterogeneous lymphoid proliferations in recipients of solid organs which seem to be related to Epstein Barr Virus (EBV). The use of antilymphocyte antibodies, EBV seronegativity in the recipient,acute rejection and CMV infection have been identified as classical risk factors. MATERIAL Y METHODS: We have studied in a retrospective observational study, the incidence of PTLD in a period of 22 years, its relationship with EBV, presence of classical risk factors and outcome in 21546 simple adult renal transplant recipients from cadaveric and living donors, transplanted in 21 hospitals from 1990 to 2009. RESULTS: A total of 275 recipients developed PTLD (1,2%),195 males (70,9%), 80 females (29,1%) aged 59.2 (p25 44.7 p75 68)years. Two hundred forty-five (89.0%) were 1st transplant recipients and 269 (97,8%) from cadaveric donors. EBV in the tissue was reported in 94 out of the 155 studied recipients (60.6%) and 86.0% of the proliferations were due to B lymphocytes. PTLD median appearance after transplant were 42.months (p25, 75, 12, 77, 5). One hundred eighty-eight recipients out of 275 patients (68.3%) had any classical risk factor and the use of antilymphocyte antibodies was the most frequent. During the follow-up, 172 patients died (62,5%) and 103 (37,5%) had a complete remission. The main cause of death was PTLD progression (n = 91, 52,9%), followed by sepsis (n = 24, 13,9%). The follow-up period post-transplant of the recipients was between 3 and 22 years. The incidence was 0,14% during the first year post-trasplant and 0.98% the cumulative incidence at 10 years. Patient survival after diagnosis was 51%, 44% and 39% after 1, 2 and 5 years, respectively. Finally, overall graft survival was 48%, 39% and 33% at the same periods. CONCLUSION: PTLD has a low incidence in renal transplant recipients. Most of the proliferations are due to B lymphocytes and seem to have a close relationship with EBV. PTLD can develop in the absence of classical risk factors. The prognosis is poor, mainly due to PTLD progression, but the survivors can even maintain their grafts.

Enfermedad linfoproliferativa difusa postrasplante renal: estudio longitudinal de 21.546 receptores durante 2 décadas en España / Lymphoproliferative disorders after renal transplantation along 2 decades: A large longitudinal study of 21.546 recipients

Introducción: La enfermedad linfoproliferativa difusa postrasplante (ELPD) es un grupo heterogéneo de enfermedades que se caracteriza por una proliferación de linfocitos después de un trasplante de órgano sólido y que presenta un espectro que comprende desde hiperplasias a agresivos linfomas. Material y métodos: Hemos evaluado, en un estudio observacional multicéntrico retrospectivo que incluye 21.546 receptores adultos de trasplante renal simple trasplantados en España de 1990 al 2009, la incidencia de ELPD durante un periodo de 22 años, su relación con el virus de Epstein-Barr, los factores de riesgo clásico y su pronóstico. Resultados: Un total de 275 receptores desarrollaron ELPD durante el seguimiento (1,2%), siendo 195 varones (70,9%) y 80 mujeres (29,1%), con una mediana de edad al diagnóstico de 59,2 (p25 44,7; p75 68) años. Doscientos cuarenta y cinco (89,0%) eran primeros trasplantes y 269 (97,8%) fueron de donante cadáver. Se objetivó virus de Epstein-Barr en el tejido proliferativo de 94 de los 155 casos estudiados (60,6%) y el 86,0% de las proliferaciones eran linfocitos B. La mediana del tiempo de desarrollo después del trasplante fue de 42 (p25 12; p75 77,5) meses. Un total de 188 receptores de 275 (68,3%) tenían algún factor de riesgo clásico. La incidencia anual fue de 0,14% el primer año y de 0,98% la acumulada en 10 años postrasplante. El periodo de seguimiento postrasplante de los receptores fue de 3 a 22 años. Durante el seguimiento 172 pacientes murieron (62,5%) y 103 (37,5%) tuvieron remisión completa. La causa de muerte más frecuente fue la progresión (n=91, 52,9%), seguida de la sepsis (n=24, 13,9%). La supervivencia del paciente después del diagnóstico fue del 51% al año, del 44% al segundo año y del 39% al quinto año. La supervivencia del injerto fue de 48, 39 y 33%, respectivamente. (AU)

Introduction: Posttransplant lymphoproliferative disorders (PTLD) are heterogeneous lymphoid proliferations in recipients of solid organs which seem to be related to Epstein-Barr virus. The use of antilymphocyte antibodies, Epstein-Barr virus seronegativity in the recipient, acute rejection and CMV infection have been identified as classical risk factors. Material and methods: We have studied, in a retrospective observational study, the incidence of PTLD in a period of 22 years, its relationship with Epstein-Barr virus, presence of classical risk factors and outcome in 21,546 simple adult renal transplant recipients from cadaveric and living donors, transplanted in 21 hospitals from 1990 to 2009. Results: A total of 275 recipients developed PTLD (1.2%), 195 males (70.9%), 80 females (29.1%), aged 59.2 (p25 44.7; p75 68) years. Two hundred forty-five (89.0%) were first transplant recipients and 269 (97.8%) from cadaveric donors. Epstein-Barr virus in the tissue was reported in 94 out of the 155 studied recipients (60.6%) and 86.0% of the proliferations were due to B lymphocytes. PTLD median appearance after transplant were 42 (p25 12; p75 77.5) months. One hundred eighty-eight recipients out of 275 patients (68.3%) had any classical risk factor and the use of antilymphocyte antibodies was the most frequent. During the follow-up, 172 patients died (62.5%) and 103 (37.5%) had a complete remission. The main cause of death was PTLD progression (n=91, 52,9%), followed by sepsis (n=24, 13.9%). The follow-up period post-transplant of the recipients was between 3 and 22 years. The incidence was 0.14% during the first year post-trasplant and 0.98% the cumulative incidence at 10 years. Patient survival after diagnosis was 51, 44 and 39% after one, 2 and 5 years, respectively. Finally, overall graft survival was 48, 39 and 33% at the same periods. (AU)

Esclerosis lateral amiotrífica asociada a sarcoma de kaposi, vih y serológica positiva para sífilis y el virus de epstein barr. A propósito de un caso / Amyotrophic lateral sclerosis associated with kaposi sarcoma, hiv and positive serological for syphilis and epstein barr virus. About a case

Las enfermedades de la neurona motora no se asocian frecuentemente al Virus de Inmunodeficiencia Humana. Según algunos autores, existe evidencia de que los retrovirus podrían participar de alguna manera en la fisiopatología de la Esclerosis Lateral Amiotrófica (ELA). Según teorías no probadas, la activación de antiguos genes virales incrustados en el genoma humano conduciría a la degeneración de las neuronas motoras. Básicamente, esta enfermedad comienza con una desmielinización, seguida de una degeneración axonal, y termina en una esclerosis glial (estado terminal) de la vía motora central. Sin embargo, es difícil entender cómo se produce la desintegración de la mielina, ¿podría deberse a una alteración en el metabolismo lipídico? Es lamentable que no se haya realizado una evaluación anatomopatológica completa en los casos estudiados y en los que nos ocupan, ya que no podemos considerar al sistema nervioso como completamente independiente de otros sistemas. Se presenta un hombre con enfermedad de la neurona motora VIH positiva (ELA) asociada con sarcoma de Kaposi. Se describe una infección por un parásito

Motor neuron diseases are not frequently associated to Human Immunodeficiency Virus According to some authors, there is evidence that retroviruses could participate in some way in the pathophysiology of Amyotrophic Lateral Sclerosis (ALS). According to unproven theories, activation of ancient viral genes embedded in the human genome would lead to degeneration of motor neurons. Basically, this disease starts as demyelination, followed by axonal degeneration, and ends up in glial sclerosis (terminal state) of the motor central pathway. However, it is difficult to understand how the disintegration of myelin occurs, could it be due to an alteration in lipid metabolism? It is unfortunate that a complete anatomopathological evaluation has not been carried out in the cases studied and in those that concern us, since we cannot consider the nervous system as completely independent of other systems. A man individual with HIV-positive motor neuron disease ALS) associated with Kaposi's sarcoma is presented. An infection with a parasite is described

Carcinoma tipo-linfoepitelioma pulmonar con expresión de virus de Epstein-Barr y PD-L1 / Pulmonary lymphoepithelioma-like carcinoma with ex pression of Epstein-Barr virus and PD-L1

Resumen El carcinoma tipo-linfoepitelioma pulmonar es una variante rara de carcinoma de células no pequeñas de pulmón, representa aproximadamente 0.7% de todos los casos. Está usualmente asociado con la infección por el virus de Epstein-Barr y es más prevalente en el Sureste de Asia; sin embargo, es extremadamente raro en Améri ca Latina. Informamos el caso de un hombre de 65 años de edad con un carcinoma tipo-linfoepitelioma pulmo nar, que se presentó con tos, disnea y pérdida de peso. La TAC de tórax mostró nódulo mal definido localizado en el pulmón derecho. Se realizó biopsia transtorácica de la lesión, y el estudio microscópico reveló células gran des poligonales dispuestas en mantos, infiltrados por abundantes linfocitos y células plasmáticas, alrededor del intersticio. Las células neoplásicas fueron positivas para citoqueratina 5/6 y p63, y negativas para Napsina A y el factor de transcripción tiroideo 1 (TTF-1). La expre sión de PD-L1 fue positivo (aproximadamente 100%) por inmunohistoquímica; así como el núcleo de las células neoplásicas mediante hibridación in situ para el RNA codificado por el virus de Epstein-Barr (EBER-ISH). El paciente recibió seis ciclos de un esquema combinado de quimioterapia basado en platino (gencitabina/cisplatino) más durvalumab. Presentó progresión de la enfermedad y finalmente murió 9 meses después del diagnóstico.

Abstract Pulmonary lymphoepithelioma-like carcinoma is a rare type of non-small cell lung cancer, it accounts for approximately 0.7% of all cases. It is usually associated with Epstein-Barr virus infection and is more prevalent in Southeast Asia; however, it is extremely rare in Latin America. We present a 65-year-old man with a primary pulmonary lymphoepithelioma-like carcinoma, who presented with cough, dyspnoea and weight loss. Com puter tomographic scan of the thorax showed a nodule localized in the right lung. A transthoracic biopsy of the lung lesion was made and the microscopic obser vation revealed large polygonal cells that proliferated in a nest pattern with infiltration by lymphocytes and plasma cells around the interstitium. The tumour cells were positive for citokeratin 5/6 and p63, and negative for Napsin A and thyroid transcription factor 1 (TTF-1). PD-L1 expression was positive (approximately 100%) in the immunohistochemical study, and the nuclei of the tumour cells were positive for EBV-encoded small RNA in-situ hybridization (EBER-ISH). The patient underwent six cycles of platinum-based combination (gencitabine/ carboplatin) chemotherapy plus durvalumab. He pre sented progression of the disease and finally he died 9 months after diagnosis.

Linfoma de Hodgkin clásico: diferentes caras, una misma entidad / Classic Hodgkin lymphoma: different faces, same entity

El linfoma de Hodgkin clásico es una neoplasia linfoide maligna derivada de las células B del centro germinal, que corresponde aproximadamente al 85 % de los casos de linfoma de Hodgkin. Esta entidad afecta principalmente a pacientes jóvenes, y cuenta con un excelente pronóstico gracias a los avances en los métodos diagnósticos para su estadificación y tratamiento. Su enfoque diagnóstico correcto y completo requiere de una historia clínica exhaustiva y una biopsia de ganglio linfático adecuada para el análisis e identificación de los hallazgos histopatológicos e inmunohistoquímicos característicos, ya que a diferencia de otros linfomas donde las células neoplásicas son una población importante o dominante, las células de Hodgkin y Reed-Sternberg generalmente representan menos del 10 % de la lesión tumoral. Aunque todavía falta mucho por entender sobre la naturaleza biológica de este linfoma y sus diferentes subtipos, en los últimos años se ha avanzado considerablemente en la comprensión de su linfomagénesis, especialmente cuando está relacionada con la infección por el virus de Epstein-Barr. Su alta heterogeneidad y posible superposición morfológica, obligan a continuar su estudio para poder identificarlo, al igual que a sus posibles diagnósticos diferenciales en aquellos casos donde se presente con una variante o patrón infrecuente. Este artículo pretende ofrecer una descripción integral resumida y actualizada sobre la fisiopatología, la clínica, el diagnóstico histopatológico con énfasis en aquellos patrones raros que podrían llegar a ser factores distractores y de confusión, y el pronóstico del linfoma de Hodgkin clásico, buscando lograr una mejor comprensión de la enfermedad

Classic Hodgkin lymphoma is a malignant lymphoid neoplasm derived from B cells in the germinal center, and accounts for approximately 85% of all Hodgkin lymphoma cases. This disease mainly affects young patients and has an excellent prognosis due to advances in diagnostic methods for staging and treatment. A correct and complete diagnostic approach requires a thorough clinical history and an adequate lymph node biopsy for the analysis and identification of characteristic histopathological and immunohistochemical findings. Unlike other lymphomas where neoplastic cells are an important or dominant population, Reed-Sternberg/ Hodgkin cells generally represent less than 10% of the tumor lesion. Although much remains to be understood about the biological nature of this lymphoma and its different subtypes, considerable progress has been made in understanding its lymphomagenesis in recent years, especially when it is related to Epstein-Barr virus infection. Its high heterogeneity and possible morphological overlap require ongoing study to identify it and its possible differential diagnoses in cases where it presents with a rare variant or pattern. This article aims to provide a comprehensive updated summary on the pathophysiology, clinical presentation, histopathological diagnosis, with emphasis on rare patterns that could become distracting and confusing factors, and prognosis of classic Hodgkin lymphoma, seeking to achieve a better understanding of the disease

Virus de Epstein-Barr: más que una mononucleosis infecciosa / Epstein-Barr virus: more than infectious mononucleosis

El virus de Epstein-Barr (VEB) fue el primer virus asociado a neoplasias en humanos. Infecta el 95 % de la población mundial, y aunque usualmente es asintomático, puede causar mononucleosis infecciosa y se relaciona con más de 200.000 casos de neoplasias al año. De igual forma, se asocia con esclerosis múltiple y otras enfermedades autoinmunes. A pesar de ser catalogado como un virus oncogénico, solo un pequeño porcentaje de los individuos infectados desarrollan neoplasias asociadas a VEB. Su persistencia involucra la capacidad de alternar entre una serie de programas de latencia, y de reactivarse cuando tiene la necesidad de colonizar nuevas células B de memoria, con el fin de sostener una infección de por vida y poder transmitirse a nuevos hospederos. En esta revisión se presentan las generalidades del VEB, además de su asociación con varios tipos de neoplasias, como son el carcinoma nasofaríngeo, el carcinoma gástrico, el linfoma de Hodgkin y el linfoma de Burkitt, y la esclerosis múltiple. Adicionalmente, se describen los mecanismos fisiopatológicos de las diferentes entidades, algunos de ellos no completamente dilucidados

Epstein-Barr virus (EBV) was the first virus associated with human cancer. It infects 95% of the world's population, and although it is usually asymptomatic, it causes infectious mononucleosis. It is related to more than 200,000 cases of cancer per year, and is also associated with multiple sclerosis and other autoimmune diseases. Despite being classified as an oncogenic virus, only a small percentage of infected individuals develop EBV-associated cancer. Its persistence involves the ability to alternate between a series of latency programs, and the ability to reactivate itself when it needs to colonize new memory B cells, in order to sustain a lifelong infection and be able to transmit to new hosts. In this review, the general characteristics of EBV are presented, in addition to its association with various types of cancers, such as nasopharyngeal carcinoma, gastric carcinoma, Hodgkin's lymphoma and Burkitt's lymphoma, and multiple sclerosis. Additionally, the pathophysiological mechanisms of the different entities are described, some of them not completely elucidated yet

Relato de caso: linfoma de células t/nk extranodal tipo nasal / Case Report: Extranodal Nk/T-Cell Lymphoma, N a s a l Ty p e / Reporte de caso: linfoma extranodal de células t/nk de tipo nasal

Introdução: O linfoma não-Hodgkin é dividido em linfomas de células B e linfomas de células T, e o linfoma extranodal de células T / NK do tipo nasal está dentro do último grupo.Relato de caso: Paciente do sexo masculino de 30 anos, relata que há 6 meses, de forma progressiva e de início insidioso, apresenta tumor cervical à direita de crescimento progressivo, pelo qual foi encaminhado ao ambulatório de cabeça e pescoço onde apresentou seus principais sinais e sintomas adenopatia cervical direita, sintoma B e tumoração ao nível da nasofaringe, envolvendo o teto, parede posterior e face lateral; se movimenta com auxílio, com extenso conglomerado linfonodal supraclavicular direito, eritematoso, com calor local, além de áreas de ulceração e secreção serosa.Conclusão: O diagnóstico e tratamento precoces desta doença são as únicas ferramentas para melhorar o mau prognóstico e o grave impacto na qualidade de vida dos pacientes que a padecem

Introduction: Non-Hodgkin's lymphomas are divided into B-cell lymphomas and T-cell lymphomas, and extranodal NK/T-cell lymphoma, nasal type, is in the latter group.Case report: A 30-year-old male patient, for six months, progressively and with an insidious onset, has had a right-sided cervical tumor with progressive growth. He came to a head and neck outpatient clinic where the main signs and symptoms detected were right cervical lymphadenopathy, B-symptoms, and a tumor in the nasopharynx affecting the roof, posterior wall, and lateral wall. The patient moves with assistance and has an enlarged, erythematous warm right supraclavicular lymph node conglomerate. In addition, he has some ulcerated areas with serous drainage.Conclusion: Early diagnosis and treatment of this disease are the only tools to improve these patients' poor prognosis and severely deteriorated quality of life.

Introducción:El linfoma no Hodgkin se divide en linfomas de células B y linfomas de células T; y en este último grupo se encuentra el linfoma extraganglionar de células T / NK de tipo nasal.Caso clínico: Un paciente masculino de 30 años refiere que durante 6 meses de forma progresiva, y con un início insidioso, presenta una tumoración cervical en el lado derecho de crecimiento progresivo, por lo que acude a la consulta externa de cabeza y cuello, donde los signos y síntomas principales fueron adenopatía cervical derecha, síntoma B, y una tumoración a nivel de nasofaringe, que afecta el techo, la pared posterior y la cara lateral. Se moviliza con ayuda, con un extenso conglomerado ganglionar supraclavicular derecho, eritematoso, con calor local. Además, también muestra algunas áreas de ulceración y secreción serosa. Conclusión: El diagnóstico y tratamiento precoz de esta enfermedad son las únicas herramientas para mejorar el mal pronóstico y el deterioro severo en la calidad de vida de los pacientes que la padecen

Síndrome mononucleósico con síndrome nefrítico agudo asociado en paciente pediátrica / Mononucleosis syndrome with associated acute nephritic syndrome in a pediatric patient

Resumen La mononucleosis infecciosa es un síndrome clínico de causa viral que generalmente tiene un curso benigno y autolimitado, caracterizado por fiebre, faringoamigdalitis y adenomegalias generalizadas, siendo la afectación de órganos o sistemas algo inusual. Se presenta el caso de una niña de ocho años con un síndrome mononucleósico por virus de Epstein-Barr y Citomegalovirus, con un síndrome nefrítico agudo hipocomplementémico secundario, sin deterioro de la función renal y evolución clínica favorable. La ausencia de un período de latencia entre el proceso infeccioso y la aparición de los síntomas de síndrome nefrítico, es un elemento clave en el diagnóstico diferencial con el síndrome nefrítico agudo postestreptocócico, que es la causa más común en niños.

Abstract Infectious mononucleosis is a clinical syndrome of viral cause that generally has a benign clinical picture, characterized by fever, pharyngotonsillitis, and generalized lymphadenopathy, being the affectation of organ or systems something unusual. We present the case of an eight-year-old girl with a mononucleosis syndrome due to Epstein-Barr virus and Cytomegalovirus, with a secondary hypocomplementemia acute nephritic syndrome, without deterioration of renal function and favorable clinical evolution. The absence of a latency period between the infectious process and the appearance of nephritic syndrome symptoms are a key element in the differential diagnosis with post-streptococcal acute nephritic syndrome, which is the most common cause in children.

Factores asociados a la presencia del virus de Epstein-Barr en la cavidad oral de adolescentes de la ciudad de Cali (Colombia) / Factors associated with the presence of the Epstein-Barr virus in the oral cavity of high school students from the city of Cali (Colombia)

IntroducciónEl virus de Epstein-Barr (VEB) está clasificado como carcinógeno del grupo 1. Su principal vía de transmisión es la oral, a través de la saliva. Determinamos la frecuencia de detección del VEB en la cavidad oral en estudiantes de secundaria en Cali (Colombia).Materiales y métodosEstudio transversal analítico para estimar la frecuencia de detección del genoma del VEB en la cavidad oral, las razones de prevalencia y su asociación con diversos factores en 1.565 individuos. Las variables analizadas fueron factores sociodemográficos, de higiene y salud oral, comportamiento sexual, consumo de cigarrillos e ingesta de alcohol. La asociación entre la detección y las variables evaluadas se realizó mediante un modelo de regresión lineal generalizado con vínculo logarítmico y distribución de Poisson con varianza robusta.ResultadosLa exposición al VEB en la cavidad oral fue del 38,40% (IC 95%: 36,02-40,84). La frecuencia de presentar exposición al VEB fue un 22% mayor en los varones, y el riesgo se incrementó según el comportamiento sexual. Se encontró asociación inversa con el grado escolar: los participantes de undécimo grado tuvieron un 27% menos frecuencia de exposición al VEB que los de grados inferiores (sexto a octavo). Cuando se utilizó el modelo logístico para estudiar la asociación entre la detección del VEB y las variables independientes, se sobreestimó la asociación. El rango de sobreestimación fue entre el 27-47% según el tipo de variable.ConclusiónLa frecuencia de detección del VEB en la cavidad oral de estudiantes sanos fue similar a la previamente descrita. Factores asociados al comportamiento sexual incrementan el riesgo de oportunidad para la exposición al VEB.

IntroductionThe Epstein-Barr virus (EBV) is classified as a group 1 carcinogen. The main route of EBV transmission is oral, through saliva. The present study aimed to determine the frequency of EBV detection in the oral cavity in high school students in the city of Cali (Colombia).Materials and methodsAnalytical cross-sectional study in order to determine the frequency of EBV detection in the oral cavity, the reasons for its prevalence and its association with several factors, in 1,565 individuals. The variables analyzed were sociodemographic factors, oral hygiene, oral health, sexual behavior, cigarrete smoking and alcohol intake. The association between the EBV detection and the variables evaluated was done through a generalized linear regression model with logarithmic linkage and Poisson distribution with robust variance.ResultsThe percentage of exposure to EBV in the oral cavity was 38.40% (CI 95%: 36.02-40.84). The frequency of presenting EBV exposure was 22% higher in men and the risk increased according to sexual behaviour. An inverse association with the school grade was found: the eleventh-grade participants had 27% less frequency of exposure to EBV than the lower grades (sixth to eighth). When analyzing the logistic model to study the association between EBV detection and independent variables, the association was overestimated. The overestimation ranged from 27 to 47% depending on the type of variable.ConclusionsThe frequency of EBV detection in the oral cavity of healthy students was similar to that previously described. Factors associated to sexual behavior increased the risk of opportunity to be exposed to EBV.

Factors associated with the presence of the Epstein-Barr virus in the oral cavity of high school students from the city of Cali (Colombia).

INTRODUCTION: The Epstein-Barr virus (EBV) is classified as a group 1 carcinogen. The main route of EBV transmission is oral, through saliva. The present study aimed to determine the frequency of EBV detection in the oral cavity in high school students in the city of Cali (Colombia). MATERIALS AND METHODS: Analytical cross-sectional study in order to determine the frequency of EBV detection in the oral cavity, the reasons for its prevalence and its association with several factors, in 1565 individuals. The variables analyzed were sociodemographic factors, oral hygiene, oral health, sexual behavior, cigarrete smoking and alcohol intake. The association between the EBV detection and the variables evaluated was done through a generalized linear regression model with logarithmic linkage and Poisson distribution with robust variance. RESULTS: The percentage of exposure to EBV in the oral cavity was 38.40% (CI 95%: 36.02-40.84). The frequency of presenting EBV exposure was 22% higher in men and the risk increased according to sexual behaviour. An inverse association with the school grade was found: the eleventh-grade participants had 27% less frequency of exposure to EBV than the lower grades (sixth to eighth). When analyzing the logistic model to study the association between EBV detection and independent variables, the association was overestimated. The overestimation ranged from 27% to 47% depending on the type of variable. CONCLUSIONS: The frequency of EBV detection in the oral cavity of healthy students was similar to that previously described. Factors associated to sexual behavior increased the risk of opportunity to be exposed to EBV.

Infección del sistema nervioso central por el virus de Epstein-Barr: manifestaciones clínicas y pronóstico / Infection of the central nervous system by Epstein-Barr virus: clinical manifestations and prognosis

Introducción: El papel del virus de Epstein-Barr (VEB) en las infecciones del sistema nervioso central no siempre está claro. Nuestro objetivo fue describir las manifestaciones clínicas y la evolución de los pacientes con detección del VEB en el líquido cefalorraquídeo (LCR). Pacientes y métodos: Se revisaron las historias clínicas de todos los pacientes adultos con detección del VEB en el LCR por reacción en cadena de la polimerasa diagnosticados desde 2004 hasta 2020 sin enfermedad linfoproliferativa. Resultados: Se diagnosticó a 27 pacientes, 22 (81,5%) hombres, con una mediana de 54 años; 23 (82,1%) pacientes eran inmunodeprimidos, 16 positivos para el virus de la inmunodeficiencia humana (VIH). En 15 (55,6%) pacientes, el VEB se detectó en coinfección con otro microorganismo, y en 12, como único patógeno. De los 12 pacientes, tres (25%) eran inmunocompetentes, uno presentó un síndrome de Guillain-Barré, otro una encefalitis diseminada multifásica y otro una meningitis linfocitaria; y nueve (75%) inmunodeprimidos, de los que cuatro presentaron encefalitis que se resolvieron sin secuelas, y cuatro encefalopatía, dos de ellos positivos para el VIH, que presentaron secuelas (deterioro cognitivo moderado). Conclusiones: En nuestro estudio, el VEB produjo cuadros de encefalitis, meningitis, polirradiculomielitis y SGB, principalmente en inmunodeprimidos. En más de la mitad de los casos se asocia a otros patógenos, en donde el papel del VEB no está claro. En inmunocompetentes, las infecciones pueden ser graves y dejar secuelas, y en pacientes con VIH con encefalopatía sin encefalitis, el daño neurológico podría ser mayor, por lo que consideramos de interés realizar estudios que evalúen el pronóstico y el papel de los antivirales en la evolución de estos cuadros clínicos.(AU)

Introduction: The role of Epstein-Barr virus (EBV) in central nervous system (CNS) infections is not fully resolved. We wanted to describe the clinical manifestations of patients with EBV infection in cerebrospinal fluid. Patients and methods: We reviewed the clinical records of all adult patients EBV PCR-positive in cerebrospinal fluid, without lymphoproliferative disease, during 2004 to 2020. Results. We identified 27 patients, 22 (81.5%) were men, and median age was 54 years. Twenty-three (82.1%) patients were immunosuppressed, 16 HIV-positive. In 15 (55.6%) patients coinfection with another microorganism was diagnosed and in 12 (44.4%) patients it was detected as the only pathogen. Of the 12 patients, three (25%) was immunocompetent patients, one had Guillain Barré syndrome (GBS), another had disseminated multiphasic encephalitis, and another had lymphocytic meningitis; 9 (75%) immunosuppressed, 7 HIV-positive, 4 had encephalitis that resolved without sequelae and 4 had encephalopathy, two HIH-positive had moderate cognitive impairment as a sequela. Conclusions: In our study, EBV produced encephalitis, meningitis, polyradiculomyelitis and GBS, mainly in immunosuppressed patients. In more than half of the cases, it is associated with other pathogens where the role of EBV is unclear. In immunocompetent patient, the infection can be serious and leave sequelae and in HIV-positive patients with encephalopatic involvement without encephalitis, the neurological damage could be greater, so we consider it of interest to carry out studies to evaluate the prognosis as well as the role of antivirals in the evolucion of these clinical pictures.(AU)

Acute dacryocystitis retention syndrome due to Epstein-Barr virus.

A 4 year-old boy with no previous history of eye or nasolacrimal disease was referred due to a painful mass on his left inner canthus, of three days onset, with no improvement in spite of oral antibiotics. On examination eyelid oedema with periocular hyperaemia was noted. Lacrimal sac palpation was painful and tonsillar exudation was reported. He was admitted and started on intravenous (iv) antibiotics. Four days later, lacrimal signs started to improve, but his general condition become worse. Head and neck Computed Tomography scan (CT scan) showed a left lacrimal sac enlargement, suggestive of acute dacryocystitis and swollen laterocervical lymph nodes. Epstein Barr Virus (EBV) serology and PCR testing were positive. The child responded well after eight days, and was discharged with oral antibiotics. Acute dacryocystic retention (ADR) associated with EBV was suspected. Six months later, the patient remained asymptomatic with no tearing or other lacrimal symptoms.

Síndrome hematofagocítico como manifestación inicial de linfoma de Hodgkin clásico / Hemophagocytic syndrome as the initial manifestation of Hodgkin lymphoma

Introducción: las histiocitosis son un grupo heterogéneo de enfermedades; una de ellas es el síndrome hematofagocítico (SHF). Sus causas pueden ser infecciosas, neoplásicas, autoinmunes o relacionadas a inmunodeficiencias adquiridas; el linfoma de Hodgkin clásico (LHc) es una causa poco frecuente. Se reporta el caso de un hombre inmunodeprimido de 35 años que ingresa al hospital febril y con insuficiencia respiratoria grave.Métodos: se recopiló información clínica pertinente y se revisó material de biopsia estudiado con tinción de hematoxilina ­ eosina, técnica inmunohistoquímica e hibridación in situ cromogénica. Resultados: estudios de laboratorio muestran pancitopenia, altera-ción de pruebas hepáticas, hipertrigliceridemia, hipoalbuminemia e hiperferritinemia. El estudio de médula ósea hematopoyética con mielograma y biopsia muestran hallazgos compatibles con LHc, signos de hemofagocitosis e infección por virus Epstein-Barr (VEB). Se diagnostica SHF como primera manifestación de LHc e infección por VEB. Conclusiones: a la fecha, se describen 74 pacientes re-portados con SHF como manifestación de LHc; en el 84% fue su primera manifestación. Si bien la presentación clínica presentada es infrecuente, se ha propuesto una asociación en hombres con inmunodeficiencia, SHF, LHc e infección por VEB; por lo que se sugiere una sospecha diagnóstica alta.

Introduction: histiocytosis are a heterogeneous group of diseases; one of them is the hemophagocytic syndrome (HS). Its causes can be infectious, neoplastic, autoimmune or related to acquired immunodeficiencies; classic Hodgkin lymphoma (cHL) is a rare cause.We present the case of an immunosuppressed 35-year-old male who was admitted with fever and acute respiratory failure. Methods:pertinent clinical reports and biopsy material were reviewed; including hematoxylin-eosin stained slides from formalin-fixed and pa-raffin-embedded tissue blocks and immunohistochemical and chromogenicin situhybridisation studies. Results:laboratory studies revealed pancytopenia, abnormal liver functions, hypertriglyceridemia, hypoalbuminemia e hyperferritinemia. Bone marrow aspiration smear and biopsy showed a malignant lymphoid neoplasm consistent with cHL, signs of hemophagocytosis, and Epstein-Barr virus (EBV) infection. HS, as an initial manifestation of cHL, was diagnosed.Conclusions:to our best knowledge, there are 74 reported cases of cHL with HS; in 84% it was the initial clinical manifestation. Though this is an unusual presentation, an association between immu-nodeficiency, HS, cHL, and EBV infection has been proposed; so a high diagnostic suspicion is suggested.

Síndrome de retención aguda lagrimal asociada a infección por virus de Epstein-Barr / Acute dacryocystitis retention syndrome due to Epstein-Barr virus

Varón de 4 años, sin antecedentes de obstrucción de vía lagrimal, que acude con una masa dolorosa en el canto interno del ojo izquierdo y febrícula de 3 días de evolución, sin mejoría con antibióticos orales por lo que se ingresa para estudio y tratamiento. En la exploración presenta edema palpebral con hiperemia periocular, dolor a la palpación del saco y exudado amigdalar. Se administran antibióticos por vía intravenosa. Tras 4 días de ingreso, el cuadro lagrimal mejora, empeorando el estado general con aparición de adenopatías cervicales. La tomografía computarizada órbito-cervical refleja un aumento del tamaño del saco lagrimal izquierdo compatible con dacriocistitis aguda y adenopatías cervicales. Serología y PCR positivas a virus de Epstein-Barr (VEB). Es dado de alta por resolución del cuadro a los 8 días con antibioterapia por vía oral. Se diagnostica de síndrome de retención aguda lagrimal asociado a VEB. A los 6 meses, continúa asintomático sin lagrimeo (AU)

A 4 year-old boy with no previous history of eye or nasolacrimal disease was referred due to a painful mass on his left inner canthus, of 3days onset, with no improvement in spite of oral antibiotics. On examination eyelid oedema with periocular hyperaemia was noted. Lacrimal sac palpation was painful and tonsillar exudation was reported. He was admitted and started on intravenous antibiotics. Four days later, lacrimal signs started to improve, but his general condition become worse. Head and neck computed tomography scan showed a left lacrimal sac enlargement, suggestive of acute dacryocystitis and swollen laterocervical lymph nodes. Epstein Barr virus (EBV) serology and PCR testing were positive. The child responded well after 8days, and was discharged with oral antibiotics. Acute dacryocystic retention associated with EBV was suspected. Six months later, the patient remained asymptomatic with no tearing or other lacrimal symptoms (AU)

Prevention and therapy of viral infections in patients with solid organ transplantation / Prevención y tratamiento de las infecciones virales en receptores de trasplante de órgano sólido

Solid organ transplantation (SOT) is the best treatment option for end-stage organ disease. The number of SOT procedures has been steadily increasing worldwide during the past decades. This trend has been accompanied by the continuous incorporation of new antimicrobial drugs and by the refinement of strategies aimed at minimizing the risk of opportunistic infection. Nonetheless, viral infections, which can occur at any stage of the post-transplant period, remain a clinical challenge that negatively impacts both patient and graft outcomes. This review offers an overview of the most relevant viral infections in the SOT population, with a focus on herpesviruses (cytomegalovirus, Epstein–Barr virus, varicella-zoster virus, and herpes simplex virus 1 and 2) and polyomaviruses (human BK polyomavirus). In addition, the currently recommended prophylactic and treatment approaches are summarized, as well as the new antiviral agents in different phases of clinical development.(AU)

El trasplante de órgano sólido (TOS) es la mejor opción para el tratamiento de la enfermedad orgánica terminal, con un incremento sostenido a lo largo de las últimas décadas. Esta tendencia ha estado acompañada por la constante incorporación de nuevos antimicrobianos y el perfeccionamiento de las estrategias destinadas a minimizar el riesgo de infección oportunista. No obstante, las infecciones virales, que pueden aparecer en cualquier momento de la evolución post-trasplante, siguen constituyendo un desafío clínico con un impacto negativo en la evolución del receptor como del injerto. La presente revisión ofrece una panorámica de las infecciones virales más relevantes en el receptor de TOS, con énfasis en los herpesvirus (citomegalovirus, virus de Epstein-Barr, virus varicela-zóster y virus herpes simplex 1 y 2) y poliomavirus (poliomavirus humano BK). Se repasan igualmente las estrategias de profilaxis y tratamiento actualmente recomendadas, así como los nuevos agentes antivirales en diversas fases de desarrollo clínico.(A)

Prevention and therapy of viral infections in patients with solid organ transplantation.

Solid organ transplantation (SOT) is the best treatment option for end-stage organ disease. The number of SOT procedures has been steadily increasing worldwide during the past decades. This trend has been accompanied by the continuous incorporation of new antimicrobial drugs and by the refinement of strategies aimed at minimizing the risk of opportunistic infection. Nonetheless, viral infections, which can occur at any stage of the post-transplant period, remain a clinical challenge that negatively impacts both patient and graft outcomes. This review offers an overview of the most relevant viral infections in the SOT population, with a focus on herpesviruses (cytomegalovirus, Epstein-Barr virus, varicella-zoster virus, and herpes simplex virus 1 and 2) and polyomaviruses (human BK polyomavirus). In addition, the currently recommended prophylactic and treatment approaches are summarized, as well as the new antiviral agents in different phases of clinical development.

Linfohistiocitosis hemofagocítica secundaria a infección crónica activa por virus de Epstein-Barr en un hospital pediátrico en México: series de casos y revisión de la literatura / Hemophagocytic lymphohistiocytosis secondary to chronic active Epstein-Barr virus infection in a pediatric hospital in Mexico: case series and literature review

INTRODUCCIÓN: La linfohistiocitosis hemofagocitica (HLH) secundario está asociada a enfermedades malignas, genéticas o autoinmunes, pero también a infecciones principalmente EBV hasta en un 70%, sin embargo hay poca información. Esta entidad se caracteriza por un curso variable y recurrente que conlleva a una alta morbimortalidad con complicaciones potencialmente mortales. OBJETIVO: Describir las características clínicas y evolución de los pacientes pediátricos con diagnóstico de HLH secundario a CAEBV. RESULTADOS: Se incluyeron 7 pacientes, edad media al diagnóstico fue 52 meses con predilección al sexo masculino. Todos los pacientes fueron tratados con un régimen quimioterapéutico multiagente, que incluye corticosteroide, etopósido y Ciclosporina. Después del tratamiento 6 pacientes presentaron remisión y uno de ellos reactivación. La media de seguimiento fue 19 meses y la supervivencia libre de enfermedad (SLE) 16 meses. CONCLUSIÓN: Podemos observar que el curso clínico es variable en ocasiones fulminantes y con pobre respuesta al tratamiento. Un diagnóstico temprano, así como detectar los factores pronóstico podría ayudar a adaptar estrategias de tratamiento que cambiaría la evolución clínica.

INTRODUCTION: Secondary hemophagocytic lymphohistiocytosis (HLH) is associated with malignant, genetic or autoimmune diseases but also with infections mainly EBV in up to 70%, however there is little information. This entity is characterized by a variable and recurrent course that leads to high morbidty and mortality with life-threatening complications. OBJECTIVE: To describe the clinical characteristics and evolution of pediatric patients with a diagnosis of HLH secondary to CAEBV. RESULTS: 7 patients were included, mean age at diagnosis was 52 months with a predilection for males. All patients were treated with a multiagent chemotherapeutic regimen, including corticosteroid, etoposide, and cyclosporine. After treatment, 6 patients presented remission and one of them had reactivation. The mean follow-up was 19 months and disease-free survival (DFS) 16 months. CONCLUSION: We can observe that the clinical course is variable, sometimes fulminant and with poor response to treatment. An early diagnosis as well as detecting prognostic factors could help to adapt treatment strategies that would change the clinical course.

Factors associated with the presence of the Epstein-Barr virus in the oral cavity of high school students from the city of Cali (Colombia). / Factores asociados a la presencia del virus de Epstein-Barr en la cavidad oral de adolescentes de la ciudad de Cali (Colombia).

INTRODUCTION: The Epstein-Barr virus (EBV) is classified as a group 1 carcinogen. The main route of EBV transmission is oral, through saliva. The present study aimed to determine the frequency of EBV detection in the oral cavity in high school students in the city of Cali (Colombia). MATERIALS AND METHODS: Analytical cross-sectional study in order to determine the frequency of EBV detection in the oral cavity, the reasons for its prevalence and its association with several factors, in 1,565 individuals. The variables analyzed were sociodemographic factors, oral hygiene, oral health, sexual behavior, cigarrete smoking and alcohol intake. The association between the EBV detection and the variables evaluated was done through a generalized linear regression model with logarithmic linkage and Poisson distribution with robust variance. RESULTS: The percentage of exposure to EBV in the oral cavity was 38.40% (CI 95%: 36.02-40.84). The frequency of presenting EBV exposure was 22% higher in men and the risk increased according to sexual behaviour. An inverse association with the school grade was found: the eleventh-grade participants had 27% less frequency of exposure to EBV than the lower grades (sixth to eighth). When analyzing the logistic model to study the association between EBV detection and independent variables, the association was overestimated. The overestimation ranged from 27 to 47% depending on the type of variable. CONCLUSIONS: The frequency of EBV detection in the oral cavity of healthy students was similar to that previously described. Factors associated to sexual behavior increased the risk of opportunity to be exposed to EBV.

Síndrome Hemofagocítico en Niños Reporte de Caso / Hemophagocytic Syndromein children: a case report

Introducción:El síndrome hemofagocítico (SHF) es reconocido como un conjunto de signos clínicos y hallazgos laboratoriales que tienen un grave compromiso en la salud y vitalidad de los niños con una incidencia de 1.2 casos/millón/año. Puede pasar subdiagnosticado y confundido con sepsis de foco inespecífico Caso clínico:Niño de 4 años de edad, sin antecedentes de importancia. Ingresado desde el servicio de emergencia por presentar 20 días de fiebre y dolor abdominal. Requirió intubación por franca falla respiratoria y el ingreso a la Unidad de Cuidados Intensivos Pediátricos. Con hipotensión e insuficiencia hepática, pancitopeniay esplenomegalia. Evolución: Se descartaron infecciones bacterianas con policultivos, SARS-Cov 2negativo,se descartaron inmunodeficiencias congénitas y adquiridas.TORCHnegativo, VDRL no reactivo.La prueba de Epstein Barr fue positivo para IgM.Se determinó endocarditis con derrame pericárdico global. Estudio de biopsia medular normocromía, normocitosis, pancitopenia y blastos <5%, sin infiltración tumoral. Se estableció el Diagnóstico de SHFse inicióciclosporina y corticoterapia.Requirió ventilación mecánica por 20 días con período de pronación de 36 horas. Fue dado de alta a pediatríay posteriormente a domicilio, para control por consulta externa. Conclusión: El diagnóstico del SHF es inusual y subestimado al momento de la evaluación clínica. En el presente reporte se asocia a la presencia del Virus Epstein Barr

Introduction: Hemophagocytic syndrome (HPS) is recognized as a set of clinical signs and laboratory findings that have a serious compromise on the health and vitality of children with an incidence of 1.2 cases / million / year. It can be underdiagnosed and confused with sepsis with a non-specific focus. Clinical case: 4-year-old boy, with no significant history. Admitted from the emergency service due to 20 days of fever and abdominal pain. She required intubation due to frank respiratory failureand admission to the Pediatric Intensive Care Unit. With hypotension and liver failure, pancytopenia and splenomegaly. Evolution: Bacterial infections were ruled out with polycultures, SARS-Cov 2 negative, congenital and acquired immunodeficiencies were ruled out. Negative TORCH, non-reactive VDRL. The Epstein Barr test was positive for IgM. Endocarditis with global pericardial effusion was determined. Medullary biopsy study normochromia, normocytosis, pancytopenia, and blasts <5%, without tumor infiltration. The diagnosis of SHF was established, cyclosporine and corticosteroid therapy were started. He required mechanical ventilation for 20 days with a 36-hour pronation period. He was discharged to pediatrics and later at home, for outpatient control. Conclusion: The diagnosis of HHS is unusual and underestimated at the time of clinical evaluation. In this report it is associated with the presence of the Epstein Barr Virus

Caracterización molecular de las variantes del virus de Epstein-Barr detectadas en la cavidad oral de adolescentes de Cali, Colombia / Molecular characterization of Epstein-Barr virus variants detected in the oral cavity of adolescents in Cali, Colombia

Introducción. El virus de Epstein-Barr (EBV) es un virus ubicuo y oncogénico, asociado con el desarrollo de enfermedades como la mononucleosis infecciosa, el linfoma de Burkitt, el carcinoma nasofaríngeo y otras neoplasias. Actualmente, se reconocen dos subtipos: EBV-1 y EBV- 2, que tienen diferencias genéticas con sus antígenos nucleares (Epstein-Barr Nuclear Antigens, EBNA). Debido a la gran heterogeneidad y variabilidad encontradas en la proteína LMP1 del virus, se han descrito variantes asociadas con ciertas enfermedades o con regiones geográficas específicas. Objetivo. Identificar y caracterizar molecularmente las variantes del EBV detectadas en la cavidad oral de 84 adolescentes de Cali, Colombia. Materiales y métodos. Se hizo la amplificación por reacción en cadena de la polimerasa (Polymerase Chain Reaction, PCR) convencional, así como la purificación y la secuenciación del gen EBNA3C se realizó para subtipificar el virus y del dominio C-ter de la proteína LMP1 para identificar variantes. Además, se llevó a cabo un análisis filogenético y de variantes nucleotídicas de las secuencias obtenidas comparadas con variantes patogénicas y geográficas reportadas en el GenBank (National Center for Biotechnology Information, NCBI). Resultados. El subtipo viral predominante fue el EBV-1 (79 %); el 72,6 % se agrupó con la variante patogénica Raji, derivada de linfocitos B de un paciente con linfoma de Burkitt; el 13,7 % se relacionó con una variante de origen geográfico del Mediterráneo y otro 13,7 % no se agrupó con ninguna de las variantes de referencia. Conclusiones. Este es el primer estudio que reporta variantes del gen LMP1-EBV en Cali, Colombia. Se requieren nuevos estudios para caracterizar la variante sin identificar y determinar si es patogénica o si es una variante geográfica presente exclusivamente en la ciudad.

Introduction: The Epstein-Barr virus (EBV) is an ubiquitous and oncogenic virus associated with the development of diseases such as infectious mononucleosis, Burkitt's lymphoma, nasopharyngeal carcinoma, and other neoplasms. Currently, two types are recognized: EBV-1 and EBV-2, which have genetic differences with their EBNA nuclear antigens. Likewise, due to the high degree of heterogeneity and variability found in the LMP1 protein of the virus, variants associated with pathogenesis or specific geographic regions have been described. Objective: To identify and characterize molecularly EBV variants detected in the oral cavity of 84 adolescents in Cali, Colombia. Materials and methods: Conventional PCR amplification, purification, and sequencing of the gen EBNA3C were carried out to typify the virus and the C-ter domain of the LMP1 protein to identify variants. We also conducted a phylogenetic and nucleotide variant analysis of the obtained sequences versus pathogenic or geographic variants reported in GenBank-NCBI. Results: The predominant viral subtype was EBV-1 (79%); 72.6% was grouped with the pathogenic variant Raji, derived from B lymphocytes of a patient with Burkitt>s lymphoma, 13.7% was related to a variant of Mediterranean origin, and 13.7% was not grouped with any of the reference variants. Conclusions: This is the first time that variants of LMP1-EBV have been identified in Cali, Colombia. Additional studies are necessary to characterize the unidentified variant and to determine if it is pathogenic or if it is just an isolate present in the city of Cali.