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.

Seroprevalence of cytomegalovirus and its coinfection with Epstein-Barr virus in adult residents from Manaus: a population-based study

Abstract INTRODUCTION: This study assessed the seroprevalence of cytomegalovirus, associated factors, and Epstein-Barr virus coinfection among adult residents of Manaus. METHODS: Using a cross-sectional study design, we collected blood samples from 136 individuals in a household survey in 2016. Prevalence ratios were calculated using Poisson regression. RESULTS: Cytomegalovirus and Epstein-Barr virus seroprevalences were 67.6% (95% CI: 9.7-75.6%) and 97.8% (95% CI: 95.3-100.0%), respectively. Coinfection was observed in 66.2% (95% CI: 58.1-74.2%) of participants. Bivariate analysis showed no statistical association. CONCLUSIONS: Seroprevalences were high among participants and approximately 7 out of 10 individuals had cytomegalovirus and Epstein-Barr virus coinfection.

Detección del virus Epstein Barr en escolares adolescentes en la ciudad de Cali, Colombia / Detection of epstein barr virus in adolescent students in the city of cali, colombia

Objetivo: Detectar el virus Epstein-Barr en estudiantes de secundaria entre los 14 y 17 años de la ciudad de Cali, Colombia y su posible asociación con la edad, sexo y grado escolar. Métodos: Estudio retrospectivo de corte transversal en donde se analizaron 374 muestras de saliva, tomadas entre el año 2015 y 2016, mediante PCR convencional y PCR en Tiempo real. Se evalúo la asociación entre la detección del ADN viral y las características demográficas, además de un análisis de razón de oportunidades para evaluar la medida de la asociación. Resultados: El ADN viral fue detectado en el 45% (167/374) de las muestras orales, encontrándose una presencia viral mayor en los escolares de los grados octavo y noveno (p=0,004); en donde los estudiantes de 14 años presentaron un riesgo de 2,4 veces mayor para la detección del virus (IC 95%:1,12-4,9) en comparación con los estudias de más edad. Conclusión: En el presente estudio se evidencio la exposición del VEB en la cavidad oral de estudiantes de secundaria, lo cual hace necesario que se tomen acciones de vigilancia que permitan monitorear las implicaciones de estos hallazgos en la salud de los escolares.

Objective: To detect the Epstein Barr virus in adolescent students between 14 and 17 years old in the city of Cali, Colombia and its possible association with age, gender and school grade. Methods: Retrospective cross-sectional study where 374 mouthwash samples collected between the years 2015 and 2016 was analyzed through conventional and real-time PCR. Association between viral DNA detection and sociodemographic characteristics were evaluated. The odds ratio analysis was used to assess the extent of this association. Results: The viral DNA was present in 45% (167/374) of the samples, with a higher DNA detection in the students of eighth and ninth grades (p=0.004); where the 14 years old students present a 2.4 times higher risk of detecting the virus (IC 95%: 1,12-4.9) in comparison with older students. Conclusion: In the present study, the Epstein Barr virus exposition in the oral cavity was evidenced, which make necessary to take actions on surveillance that allow monitoring the implications of these fndings in the teenage student's health.

Análise comparativa do polimorfismo genético da glutationa transferase, do Helicobacter pylori e do vírus Epstein-Barr entre a área do tumor e as margens de ressecção proximal e distal do câncer gástrico / Comparative analysis of glutathione transferase genetic polymorphism, Helicobacter pylori and Epstein-Barr virus between the tumor area and the proximal and distal resection margins of gastric cancer

RESUMO Objetivo: comparar o polimorfismo dos genes Glutationa S-transferase teta 1 (GSTT1) e Glutationa S-transferase mu 1 (GSTM1) da área do tumor com as margens proximal e distal de espécimes de estômago ressecados de pacientes com câncer gástrico, e investigar a presença do DNA do vírus Epstein-Barr (EBV) e Helicobacter pylori. Métodos: coletamos prospectivamente amostras teciduais da área do tumor e das margens de ressecção proximal e distal dos estômagos de dez pacientes com adenocarcinoma gástrico submetidos à gastrectomia com linfadenectomia D2 e submetemos esses espécimes à extração de DNA. Comparamos a área do tumor com as margens proximal e distal dos estômagos ressecados para o polimorfismo dos genes GSTT1 e GSTM1 e investigamos a presença de DNA do EBV e H. pylori. Utilizamos o exon 5 do gene p53 como controle interno da reação de PCR multiplex. Resultados: em um paciente, detectamos genótipos GSTT1 e GSTM1 nulos na área do tumor, em contraste com a presença de ambos os genes nas margens proximal e distal. Encontramos DNA do EBV e H. pylori na área do tumor e também nas margens proximal e distal. Em outro paciente, a margem proximal foi negativa para GSTT1 e o DNA do EBV foi negativo na margem distal. Em três pacientes, o EBV-DNA foi negativo apenas na margem distal. Conclusão: este é o primeiro relato em que diferentes genótipos, infecção por EBV-DNA e H. pylori foram observados no mesmo paciente, indicando provável deleção desses genes em resposta à progressão tumoral e heterogeneidade intratumoral.

ABSTRACT Objective: to compare the polymorphism of the Glutathione S-transferase theta 1 (GSTT1) and Glutathione S-transferase mu 1 (GSTM1) genes from the tumor area with the proximal and distal margins of stomach specimens resected from patients with gastric cancer, and to investigate the presence of Epstein-Barr virus (EBV) DNA and Helicobacter pylori. Methods: we prospectively collected tissue specimens from the tumor area and from the proximal and distal resection margins of the stomachs of ten patients with gastric adenocarcinoma who underwent gastrectomy with D2 lymphadenectomy, and submitted these specimens to DNA extraction. We compared the tumor area with the proximal and distal margins of the resected stomachs for polymorphism of GSTT1 and GSTM1 genes and investigated the presence of EBV-DNA and H. pylori. We used the p53 exon 5 gene as an internal control of the multiplex PCR reaction. Results: in one patient, we detected null GSTT1 and GSTM1 genotypes in the tumor area, in contrast to the presence of both genes in the proximal and distal margins. We found EBV-DNA and H. pylori in the tumor area and also in the proximal and distal margins. In another patient, the proximal margin was negative for GSTT1, and EBV-DNA was negative in the distal margin. In three patients, EBV-DNA was negative only in the distal margin. Conclusion: this is the first report where different genotypes, EBV-DNA and H. pylori infection were observed in the same patient, indicating a probable deletion of these genes in response to tumor progression and intratumoral heterogeneity.

Diagnosing lymphoma in a setting with a high burden of infection: a pediatric case of Epstein-Barr virus-associated aggressive B-cell lymphoma with t(8;14) (q23;q32) and extensive necrosis mimicking tuberculosis

The association of lymphoma with necrotic granuloma can pose diagnostic challenges and delay treatment, especially in settings with a high burden of infection. In these settings, the timely use of cytogenetic and molecular methods is most relevant. Here, we report a case of B-cell lymphoma with t (8;14) in a 5-year-old male child. The lymphoma was associated with necrotic granuloma and was initially misdiagnosed as tuberculosis. Polymerase chain reaction was used to detect clonal lymphoproliferation and to rule out Mycobacterium tuberculosis infection. Tumor cells harbored Epstein-Barr virus and expressed CD20, CD10, BCL6, and Ki67 (30%), leading to the diagnosis of B-cell lymphoma with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma.

Síndrome de ativação macrofágica em paciente com artrite idiopática juvenil sistêmica / Macrophage activation syndrome in a patient with systemic juvenile idiopathic arthritis

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.

Machrophage activation syndrome (MAS) is a rare and potentially fatal disease, commonly associated with chronic rheumatic diseases, mainly juvenile idiopathic arthritis. It is included in the group of secondary forms of haemophagocytic syndrome, and other causes are lymphoproliferative diseases and infections. Its most important clinical and laboratorial manifestations are non-remitting fever, splenomegaly, bleeding, impairment of liver function, cytopenias, hypoalbuminemia, hypertriglyceridemia, hypofibrinogenemia and hyperferritinemia. The treatment needs to be started quickly, and the majority of cases have a good response with corticosteroids and cyclosporine. The Epstein–Barr virus is described as a possible trigger for many cases of MAS, especially in these patients in treatment with tumor necrosis factor (TNF) blockers. In these refractory cases, etoposide (VP16) should be administered, associated with corticosteroids and cyclosporine. Our objective is to describe a rare case of MAS probably due to EBV infection in a subject with systemiconset juvenile idiopathic arthritis, which achieved complete remission of the disease after therapy guided by 2004-HLH protocol.

Assessment of immunological changes in Epstein-Barr virus co-infection in Egyptian chronic HCV patients

Epstein-Barr virus (EBV) plays a major role in liver pathology. Similar to other members of the herpesvirus family, EBV establishes a persistent infection in more than 90% of adults. The aim of this study was to evaluate the impact of EBV and chronic hepatitis C co-infection (HCV) on biochemical and immunological responses in patients. The study was conducted in 62 patients and 33 apparently healthy controls. Patients were divided into three groups: group I, consisting of 31 patients with chronic hepatitis C infection (CHC), group II, consisting of eight patients with EBV infection and without HCV infection and group III, consisting of 23 patients with EBV and chronic HCV. The percentage of CD3+ cells, helper CD4+ cells and CD19+ B-cells was measured by flow cytometry. Human interferon-γ (IFN-γ) and interleukin (IL)-15 levels were measured by an ELISA. The levels of liver alanine aminotransferase and aspartate aminotransferase enzymes were higher in EBV/HCV patients compared to that in EBV and HCV mono-infected patients. EBV/HCV patients had significantly reduced percentages of CD3+ and CD4+ cells compared to EBV patients. Serum IFN-γ levels were significantly reduced in EBV/HCV patients (3.86 pg/mL) compared to CHC patients (6.76 pg/mL) and normal controls (4.69 pg/mL). A significant increase in serum IL-15 levels was observed in EBV/HCV patients (67.7 pg/mL) compared to EBV patients (29.3 pg/mL). Taken together, these observations suggest that HCV and EBV co-infection can potentiate immune response dampening in patients.

Infecção pelo vírus Epstein-Barr tem influência sobre o desenvolvimento do carcinoma de laringe? Detecção de EBV pelo Real-Time Polymerase Chain Reaction em tecidos tumorais de pacientes com carcinoma de laringe / Does Epstein-Barr virus infection have an influence on the development of laryngeal carcinoma? Detection of EBV by Real-Time Polymerase Chain Reaction in tumour tissues of patients with laryngeal carcinoma

O vírus Epstein-Barr (EBV) é um conhecido vírus carcinogênico. A associação entre EBV e alguns tumores sugere que também pode haver correlação entre carcinoma de laringe e EBV. OBJETIVO: O presente estudo pretende determinar o papel do EBV na etiologia do carcinoma de laringe. MÉTODO: Estudo prospectivo sobre EBV por reação em cadeia da polimerase em tempo real em tecidos tumorais de 25 pacientes com carcinoma de laringe e 17 pacientes com lesões benignas de laringe; análise da relação entre presença de DNA viral e tabagismo, etilismo, localização e diferenciação tumoral. RESULTADOS: Não houve diferenças significativas entre os grupos de controle e de estudo para positividade da PCR para EBV (p > 0,05). Não foi identificada relação estatisticamente significativa entre positividade para EBV e diferenciação tumoral, localização da neoplasia, tabagismo ou etilismo (p > 0,05). CONCLUSÃO: Nossos resultados sugerem que, a despeito de sua identificação em alguns carcinomas espinocelulares de laringe, a presença de EBV não teve qualquer influência na patogenia do carcinoma de laringe.

Epstein-Barr virus (EBV) is a well-known carcinogenic virus, and the association of EBV with some tumours suggests that there may also be an association between laryngeal carcinoma and EBV. OBJECTIVE: The aim of this study is to determine the role of EBV in the aetiology of laryngeal carcinoma. METHOD: Prospective investigation the EBV with real time polymerase chain reaction in tumour tissues of 25 patients with laryngeal carcinoma and 17 patients with benign laryngeal lesions, and investigation of the relationship between the presence of viral DNA and patients' smoking habits, alcohol consumption, localization and differentiation of the tumour. RESULTS: There was no significant difference between the control group and patient group in terms of EBV polymerase chain reaction positivity (p > 0.05). Also we couldn't find a statistically significant relationship between EBV positivity and differentiation of the tumour, localization of the tumour, smoking and alcohol consumption habits (p > 0.05). CONCLUSION: Our results suggest that, although EBV is present in some of the squamous cell laryngeal carcinomas, its presence has no effect on the pathogenesis of laryngeal carcinomas.

Association analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope and smoking status in Brazilian patients with rheumatoid arthritis

INTRODUCTION: Epstein-Barr virus exposure appears to be an environmental trigger for rheumatoid arthritis that interacts with other risk factors. Relationships among anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status have been observed in patients with rheumatoid arthritis from different populations. OBJECTIVE: To perform an association analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status in Brazilian patients with rheumatoid arthritis. METHODS: In a case-control study, 140 rheumatoid arthritis patients and 143 healthy volunteers who were matched for age, sex, and ethnicity were recruited. Anti-Epstein-Barr nuclear antigen-1 antibodies and anti-cyclic citrullinated peptide antibodies were examined using an enzyme-linked immunosorbent assay, and shared epitope alleles were identified by genotyping. Smoking information was collected from all subjects. A comparative analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status was performed in the patient group. Logistic regression analysis models were used to analyze the risk of rheumatoid arthritis. RESULTS: Anti-Epstein-Barr nuclear antigen-1 antibodies were not associated with anti-cyclic citrullinated peptide antibodies, shared epitope alleles, or smoking status. Anti-cyclic citrullinated peptide antibody positivity was significantly higher in smoking patients with shared epitope alleles (OR = 3.82). In a multivariate logistic regression analysis using stepwise selection, only anti-cyclic citrullinated peptide antibodies were found to be independently associated with rheumatoid arthritis (OR = 247.9). CONCLUSION: Anti-Epstein-Barr nuclear antigen-1 antibodies did not increase the risk of rheumatoid arthritis and were not associated with the rheumatoid arthritis risk factors studied. Smoking and shared epitope alleles were correlated with anti-cyclic citrullinated peptide-antibody-positive rheumatoid arthritis. Of the risk factors, only anticyclic citrullinated peptides antibodies were independently associated with rheumatoid arthritis susceptibility.

Síndrome de ativação macrofágica secundária à infecção aguda pelo vírus Epstein-Barr: [relato de caso] / Macrophage activation syndrome triggered by Epstein-Barr virus: [case report]

A síndrome de ativação macrofágica (SAM) ou síndrome hemofagocítica secundária (reativa) consiste de uma rara, grave e potencialmente fatal complicação das doenças reumáticas crônicas, particularmente da artrite idiopática juvenil de início sistêmico, doença de Still do adulto e lúpus eritematoso sistêmico. É caracterizada pela excessiva ativação dos macrófagos, resultando febre, hepatoesplenomegalia, linfadenomegalia, envolvimento neurológico, graus variáveis de citopenias, hiperferritinemia, distúrbio hepático, coagulação intravascular e freqüente falência de múltiplos órgãos. Também ocorre em associação com neoplasias, imunodeficiências e variedade de agentes infecciosos virais (sobretudo do grupo do herpes), bacterianos e fúngicos. Relatamos um caso de SAM decorrente de infecção viral aguda pelo vírus Epstein-Barr tratado com corticóide oral

The macrophage activation syndrome (MAS) or secondary haemophagocytic syndrome (reactive) is an uncommon, severe and life-threatening complication of chronic rheumatic diseases, especially systemic onset juvenile idiopathic arthritis, adult-onset Still disease and systemic lupus eritematosus. It is characterized by the excessive activation of macrophages, resulting in fever, hepatoesplenomegaly, lymphadenopathy, neurological involvement, variable cytopenias, hyperferritinemia, liver disease, intravascular coagulation, often resulting in fatal multiple organ failure. Besides chronic rheumatic diseases, it is also seen in a heterogeneous group of diseases like neoplasms, imunodeficiencies and viruses (especially the herpes group), bacteria and fungi infections. We describe a case report of one patient with MAS triggered by Epstein-Barr virus infection treated with oral corticosteroid.