Evaluation of herpesvirus members on hospital admission in patients with systemic lupus erythematous shows higher frequency of Epstein-Barr virus and its associated renal dysfunction / Avaliação de membros da família Herpesviridae na admissão hospitalar de pacientes com lúpus eritematoso sistêmico mostra maior frequência do vírus Epstein-Barr e sua disfunção renal associada

Abstract Introduction: Members of the Herpesviridae family have been described in patients with systemic lupus erythematous (SLE), but the clinical impact on renal function is not well known. Methods: HSV1, HSV2, VZV, EBV, CMV, HHV-6, HHV-7, and HHV-8 were evaluated by molecular biology on admission in blood samples from 40 consecutive SLE patients hospitalized for lupus activity. Results: Patients were 90.0% female, 77.5% non-white, with average age of 32.7 ± 13.6 years. We found positivity for EBV (65.0%), CMV (30.0%), HSV-1 (30.0%), HHV-6 (12.5%), and HHV-7 (7.5%). For all viruses, age, SLEDAI, hematological tests, ferritin, LDH, C-reactive protein, and erythrocyte sedimentation rate (ESR) were not significant. However, EBV positivity was a significant factor for higher serum creatinine (3.0 ± 2.8 vs. 0.9 ± 0.8; P = 0.001) and urea (86 ± 51 vs. 50 ± 46; P = 0.03). Moreover, positive cases for EBV only or with combined co-infections (66.7%-CMV; 58.3%-HSV-1) or negative for EBV only were evaluated by Kruskal-Wallis test again showed statistical significance for serum creatinine and urea (both P ≤ 0.01), with posttest also showing statistical differences for renal dysfunction and EBV presence (alone or in combined co-infections). The presence of EBV viral load was also significant for nephrotic-range proteinuria, renal flare, and the need for hemodialysis. Conclusion: Members of the Herpeviridae family (mainly EBV, HSV-1 and CMV) are common on hospital admission of SLE patients, reaching 65% for EBV, which seems to be associated with renal dysfunction and could reflect a previous association or overlapping disease, which is not well understood.

Resumo Introdução: Membros da família Herpesviridae tem sido descritos em pacientes com lúpus eritematoso sistêmico (LES), mas o impacto clínico na função renal não é bem conhecido. Métodos: Avaliou-se HSV1, HSV2, VZV, EBV, CMV, HHV-6, HHV-7, HHV-8 por biologia molecular na admissão em amostras sanguíneas de 40 pacientes com LES consecutivos hospitalizados por atividade lúpica. Resultados: Pacientes 90,0% mulheres, 77,5% não brancos, idade média 32,7 ± 13,6 anos. Encontramos positividade para EBV (65,0%), CMV (30,0%), HSV-1 (30,0%), HHV-6 (12,5%), HHV-7 (7,5%). Para todos os vírus, idade, SLEDAI, exames hematológicos, ferritina, LDH, proteína C reativa, velocidade de hemossedimentação não foram significativos. Entretanto, positividade para EBV foi estatisticamente significativo para creatinina (3,0 ± 2,8 vs. 0,9 ± 0,8; P = 0,001) e ureia (86 ± 51 vs. 50 ± 46; P = 0,03) séricas mais elevadas. Ademais, casos positivos para EBV isolado ou com coinfecções combinadas (66,7%-CMV; 58,3%-HSV-1) ou negativos apenas para EBV foram avaliados pelo teste Kruskal-Wallis e novamente mostraram significância estatística para creatinina e ureia séricas (ambas P ≤ 0,01), com pós-teste mostrando também diferenças estatísticas para disfunção renal e presença de EBV (sozinho ou em coinfecções combinadas). A presença de carga viral do EBV também foi significativa para proteinúria de faixa nefrótica, inflamação aguda, necessidade de hemodiálise. Conclusão: Membros da família Herpeviridae (principalmente EBV, HSV-1, CMV) são comuns na admissão de pacientes com LES, chegando a 65% para EBV, que parece associar-se à disfunção renal podendo refletir associação prévia ou doença sobreposta, o que não é bem compreendido.

Treatment-related fluctuations in Guillain-Barré syndrome​: clinical features and predictors of recurrence / Fluctuaciones relacionadas al tratamiento en el Síndrome de Guillain-Barré: características clínicas y predictores de recurrencia

ABSTRACT Background: A treatment-related fluctuation (TRF) in a patient with Guillain-Barré syndrome (GBS) is defined as clinical deterioration within two months of symptom onset following previous stabilization or improvements with treatment. Objective: To investigate the clinical characteristics and factors that could increase the risk of relapse of GBS in patients with and without TRFs. Methods: Retrospective review of medical records of patients (>18 years) with GBS evaluated between January/2006 and July/2019. Demographic and clinical characteristics, ancillary studies, treatment received, and the clinical course of patients with and without TRFs were analyzed. Results: Overall, 124 cases of GBS were included; seven (5.6%) presented TRFs. GBS-TRF cases were triggered more frequently by infectious mononucleosis (28.57 vs. 8.55%; p=0.01). GBS-TRF were initially treated with plasmapheresis more frequently than those without TRF (14.29 vs. 1.70%; p=0.0349). Combined treatment (71.43 vs. 4.27%; p<0.001) and corticosteroids (42.86 vs. 1.71%; p<0.001) were more commonly used in the GBS-TRF group. GBS-TRF patients presented a higher median initial disability score (4 vs. 2; p=0.01). Conclusions: Patients with GBS triggered by infectious mononucleosis and a high degree of initial disability have higher chances of developing TRFs. Although patients with TRF were treated with plasmapheresis more often, the total number was too low to suggest a link between plasma exchange and TRF.

RESUMEN Antecedentes: Una fluctuación relacionada al tratamiento (FRT) en un paciente con síndrome de Guillain-Barré (SGB) se define como un deterioro clínico dentro de los dos meses posteriores al inicio de los síntomas después de una estabilización previa o mejoría con el tratamiento. Objetivo: Investigar las características clínicas y los factores que podrían incrementar el riesgo de recaída, comparando pacientes con SGB, con y sin FRT. Métodos: Revisión retrospectiva de historias clínicas de pacientes (>18 años) con SGB evaluados entre enero/2006 y julio/2019. Se analizaron las características demográficas y clínicas, los estudios complementarios, el tratamiento recibido y la evolución clínica de los pacientes con y sin FRT. Resultados: Se incluyeron 124 casos de SGB en el total; 7 (5,6%) presentaron FRT. Los casos de SGB con FRT se desencadenaron con mayor frecuencia por mononucleosis infecciosa (28,57 vs. 8,55%; p=0,01). Los casos de SGB con FRT se trataron inicialmente con plasmaféresis con más frecuencia que aquellos sin FRT (14,29 vs. 1,70%; p=0,0349). El tratamiento combinado (71,43 vs. 4,27%; p<0,001) y los corticosteroides (42,86 vs. 1,71%; p<0,001) se utilizaron con mayor frecuencia en el grupo de SGB con FRT. Los pacientes con FRT presentaron una escala de discapacidad inicial mediana más alta (4 vs. 2; p=0,01). Conclusiones: Aquellos SGB desencadenados por mononucleosis infecciosa y un alto grado de discapacidad inicial tienen una mayor probabilidad de desarrollar FRT. Aunque los pacientes con FRT fueron tratados con plasmaféresis con mayor frecuencia, el número total fue demasiado bajo para sugerir un vínculo entre la plasmaféresis y FRT.

Extranodal nk/t-cell lymphoma, nasal type: case report

ABSTRACT Introduction: Extranodal NK/T-cell lymphoma, nasal type (ENKL), is a highly aggressive non-Hodgkin's lymphoma of unknown etiology. Clinical manifestations are usually nasal obstruction, epistaxis, and inflammatory signs. Diagnosis can be difficult to achieve and requires histo-pathology and immunohistochemistry studies. Radiotherapy and chemotherapy have been proposed as treatment, depending on the stage of the disease. Case presentation: A 44-year-old male patient, previously healthy, attended the outpatient service due to clinical nasal obstruction, secretion, edema, and facial erythema for 2 months. Facial cellulitis was initially diagnosed, but since there was no improvement with antibiotic treatment, the patient was referred to the emergency department of a higher complexity center, where complementary imaging showed a mass in the right nasal cavity. A histopathological analysis established that it was an ENKL, so radiotherapy was indicated; however, as a result of the advanced stage of this neoplasm, the patient died. Conclusion: Timely diagnosis of ENKL is crucial to improve life expectancy. Nevertheless, it may represent a clinical challenge due to its nonspecific presentation.

RESUMEN Introducción. El linfoma extranodal nasal de células T/natural killer (ENKL) es un linfoma no Hodgkin altamente agresivo y de etiología desconocida. Sus manifestaciones clínicas suelen ser obstrucción nasal, epistaxis y signos inflamatorios; sin embargo, el diagnóstico puede llegar a ser difícil, requiriendo histopatología e inmunohistoquímica para su detección. Como tratamiento se han propuesto radioterapia y quimioterapia, según el estadio de la enfermedad. Presentación del caso. Paciente masculino de 44 años de edad, previamente sano, quien asistió al servicio de consulta externa por cuadro clínico de 2 meses de evolución consistente en síntomas de obstrucción y secreción nasal, edema y eritema facial. Se realizó diagnóstico inicial de celulitis facial, pero dado que no hubo mejoría con el tratamiento antibiótico, el sujeto fue remitido al servicio de urgencias de una institución de mayor complejidad, donde se le practicaron imágenes complementarias que mostraron una masa en la cavidad nasal derecha; mediante análisis histopatológico se estableció que se trataba de un ENKL, por lo que se indicó radioterapia; sin embargo, a consecuencia del estadio avanzado de dicha patología, el paciente falleció. Conclusión. El diagnóstico oportuno de ENKL es crucial para mejorar la expectativa de vida de quienes lo padecen; sin embargo, puede representar un reto clínico debido a su presentación inespecífica.

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 clínica y epidemiológica del carcinoma nasofaríngeo y su relación con el virus Epstein-Barr / Nasopharyngeal carcinoma and its relationship with the Epstein-Barr virus, clinical and epidemiological description

RESUMEN Fundamento: El carcinoma nasofaríngeo es el tumor maligno más frecuente del cavum. Estos tumores se diferencian de otros carcinomas epidermoide de la cabeza y cuello por su histología característica y su relación con el virus de Epstein-Barr. Objetivo: Caracterizar clínica y epidemiológicamente el carcinoma de nasofaringe y su relación con el virus Epstein-Barr, en el Instituto Nacional de Oncología y Radiobiología, Ciudad de la Habana, en el período de enero a diciembre de 2012. Metodología: Se realizó un estudio retrospectivo; se trabajó con un total de 16 historias clínicas. Se observaron variables como edad, sexo, tipo histológico, estadiamiento clínico, presencia del virus Epstein-Barr en el tumor, tratamiento aplicado, respuesta al tratamiento, recaída y estado del paciente. Resultados: El 50 % tenían entre 45-55 años de edad, 75 % eran hombres, el 50 % diagnosticados con tipo 3, 100 % negativo a la inmunohistoquímica para virus Epstein-Barr, predominó la etapa III con 43.75 %, el 56.25 % de los casos se trataron con radio-quimioterapia más quimioterapia, el 50 % tuvo respuesta completa, la recaída fue de 37.50 % y el 68.75 % de los pacientes estaba vivo a los 60 meses. Conclusiones: En esta pequeña población con carcinoma nasofaríngeo, la totalidad de la población fue negativa a la presencia de virus Epstein-Barr por técnicas de inmunohistoquímica, por lo que su negatividad se hizo representativa en los tipo 3 y etapas avanzadas y no tuvo impacto en la respuesta al tratamiento y la supervivencia global.

ABSTRACT Background: Nasopharyngeal carcinoma is the most common malignant tumor of the cavum. These tumors differ from some other epidermoid carcinomas of the head and neck by their histology features and their Epstein-Barr virus relationship. Objective: To describe clinically and epidemiologically the nasopharyngeal carcinoma and its relationship with the Epstein-Barr virus, at the National Institute of Oncology and Radiobiology, Havana City, from January to December 2012. Methodology: A retrospective study was conducted; with a total of 16 medical records. Variables such as age, sex, histological type, clinical staging, and presence of Epstein - Barr virus in the tumor, applied treatment, response to treatment, relapse and patient status were observed. Results: 50 % were between 45-55 years old, 75 % were men, 50 % diagnosed with type 3, 100 % negative to Epstein-Barr virus immunohistochemistry, stage III predominated with 43.75 %, 56.25 % of the cases were treated with radio-chemotherapy plus chemotherapy, 50 % had a complete response, relapse was 37.50 % and at 60 months 68.75 % of the patients were still alive. Conclusions: In this small population with nasopharyngeal carcinoma, the entire population was negative to the presence of Epstein-Barr virus applying immunohistochemical techniques, so its negativity became representative in type 3 and advanced stages and had no impact on the treatment response and overall survival.

Caracterización clínica y epidemiológica del carcinoma nasofaríngeo y su relación con el virus Epstein-Barr / Nasopharyngeal carcinoma and its relationship with the Epstein-Barr virus, clinical and epidemiological description

RESUMEN Fundamento: El carcinoma nasofaríngeo es el tumor maligno más frecuente del cavum. Estos tumores se diferencian de otros carcinomas epidermoide de la cabeza y cuello por su histología característica y su relación con el virus de Epstein-Barr. Objetivo: Caracterizar clínica y epidemiológicamente el carcinoma de nasofaringe y su relación con el virus Epstein-Barr, en el Instituto Nacional de Oncología y Radiobiología, Ciudad de la Habana, en el período de enero a diciembre de 2012. Metodología: Se realizó un estudio retrospectivo; se trabajó con un total de 16 historias clínicas. Se observaron variables como edad, sexo, tipo histológico, estadiamiento clínico, presencia del virus Epstein-Barr en el tumor, tratamiento aplicado, respuesta al tratamiento, recaída y estado del paciente. Resultados: El 50 % tenían entre 45-55 años de edad, 75 % eran hombres, el 50 % diagnosticados con tipo 3, 100 % negativo a la inmunohistoquímica para virus Epstein-Barr, predominó la etapa III con 43.75 %, el 56.25 % de los casos se trataron con radio-quimioterapia más quimioterapia, el 50 % tuvo respuesta completa, la recaída fue de 37.50 % y el 68.75 % de los pacientes estaba vivo a los 60 meses. Conclusiones: En esta pequeña población con carcinoma nasofaríngeo, la totalidad de la población fue negativa a la presencia de virus Epstein-Barr por técnicas de inmunohistoquímica, por lo que su negatividad se hizo representativa en los tipo 3 y etapas avanzadas y no tuvo impacto en la respuesta al tratamiento y la supervivencia global.

ABSTRACT Background: Nasopharyngeal carcinoma is the most common malignant tumor of the cavum. These tumors differ from some other epidermoid carcinomas of the head and neck by their histology features and their Epstein-Barr virus relationship. Objective: To describe clinically and epidemiologically the nasopharyngeal carcinoma and its relationship with the Epstein-Barr virus, at the National Institute of Oncology and Radiobiology, Havana City, from January to December 2012. Methodology: A retrospective study was conducted; with a total of 16 medical records. Variables such as age, sex, histological type, clinical staging, and presence of Epstein - Barr virus in the tumor, applied treatment, response to treatment, relapse and patient status were observed. Results: 50 % were between 45-55 years old, 75 % were men, 50 % diagnosed with type 3, 100 % negative to Epstein-Barr virus immunohistochemistry, stage III predominated with 43.75 %, 56.25 % of the cases were treated with radio-chemotherapy plus chemotherapy, 50 % had a complete response, relapse was 37.50 % and at 60 months 68.75 % of the patients were still alive. Conclusions: In this small population with nasopharyngeal carcinoma, the entire population was negative to the presence of Epstein-Barr virus applying immunohistochemical techniques, so its negativity became representative in type 3 and advanced stages and had no impact on the treatment response and overall survival.

Encefalitis severa por el virus de Epstein-Barr en paciente inmunocompetente: reporte de caso / Severe encephalitis due to Epstein-Barr virus in an immunocompetent patient: case report

RESUMEN El virus de Epstein Barr (VEB) infecta a cerca del 90 % de las personas en la primera década de vida y, como los demás herpes virus, se mantiene en estado de latencia con riesgo de reactivaciones posteriores. La infección por VEB puede tener un curso asintomático o causar mononucleosis infecciosa (MI), especialmente en adolescentes y adultos. Rara vez, es responsable de infecciones en el sistema nervioso central como encefalitis, cerebelitis, mielitis, neuritis, encefalomielitis aguda diseminada y, más comúnmente, en relación con la infección por el virus de inmunodeficiencia humana (VIH), relacionado con el linfoma primario del sistema nervioso central (SNQ. La encefalitis por VEB no difiere en su presentación clínica de las demás encefalitis virales. Su diagnóstico se realiza mediante detección serológica de anticuerpos de respuesta aguda contra el virus o por reacción en cadena de la polimerasa (PCR) en líquido cefalorraquídeo (LCR). Las opciones terapéuticas en el momento son limitadas y con una baja evidencia de efectividad. A continuación, se presenta el caso de una mujer adulta, inmunocompetente, con clínica de encefalitis aguda severa y marcadas anormalidades en las neuroimágenes. El diagnóstico se hizo mediante la detección de ADN viral en LCR, apoyado por la exclusión de otros agentes patógenos y otras posibles etiologías mediante estudios microbiológicos, patológicos y serológicos.

SUMMARY Epstein Barr virus (EBV) infects about 90 % of people in the first decade of life and, like other herpes viruses, remains dormant with risk of subsequent reactivations. EBV infection can have an asymptomatic course or cause infectious mononucleosis (IM), especially in teenagers and adults. Rarely, it can be responsible for infections in the central nervous system such as encephalitis, cerebellitis, myelitis, neuritis, acute disseminated encephalomyelitis and, more commonly, primary lymphoma of the central nervous system (PLCNS) related to infection by human immunodeficiency virus (HIV). VEB encephalitis does not differ from other viral encephalitis in its clinical presentation. Its diagnosis is performed by serological detection of acute antibody response against the virus or by polymerase chain reaction (PCR) in cerebrospinal fluid (CSF). Treatment options are limited and with a low evidence of effectiveness. We report an unusual case of an immunocompetent mid adult woman, who presented clinically severe acute encephalitis and marked abnormalities in neuroimaging. The diagnosis was made by EBV DNA detection in CSF, supported by the exclusion of the presence of other pathogens and etiologies by microbiological and pathological studies.

Descarga de HSV-1, HSV-2, CMV y EBV en la saliva de receptores de trasplante de precursores hematopoyéticos de la Fundación HOMI - Hospital de la Misericordia, Bogotá, DC / Shedding of HSV-1, HSV-2, CMV, and EBV in the saliva of hematopoietic stem cell transplant recipients at Fundación HOMI - Hospital de la Misericordia, Bogotá, DC

Introducción. El trasplante de precursores hematopoyéticos es una alternativa en el tratamiento de diversas condiciones en la población pediátrica. La intensidad del acondicionamiento para el trasplante predispone al desarrollo de complicaciones en los receptores. Las infecciones por el virus herpes simple 1 (HSV-1), el virus herpes simple 2 (HSV-2), el citomegalovirus (CMV) humano y el virus de Epstein-Barr (EBV) son una causa importante de morbimortalidad en estos pacientes. La reactivación de infecciones latentes puede producir descargas virales asintomáticas detectables en la saliva, lo cual ayuda a determinar el comportamiento de dichas infecciones en pacientes con trasplante y a establecer el diagnóstico temprano de la reactivación. Objetivo. Evaluar el comportamiento de la descarga viral de HSV-1, HSV-2, CMV y EBV en la saliva de pacientes hospitalizados en la Unidad de Trasplante de la Fundación HOMI - Hospital de la Misericordia, entre enero y noviembre de 2012. Materiales y métodos. Se evaluaron muestras de saliva de 17 receptores de trasplante. La presencia de ADN de HSV-1, HSV-2, CMV y EBV en las muestras de saliva se detectó mediante reacción en cadena de la polimerasa convencional. Resultados. Se detectó el ADN del HSV-2 en la saliva de cuatro pacientes, del CMV en la de cuatro y del EBV en la de nueve, lo cual se asoció con leucopenia. Cuatro de los 17 pacientes presentaron cargas simultáneas de CMV y EBV. No se detectó el ADN del HSV-1. Conclusiones: Se demostró una descarga asintomática de HSV-2, CMV y EBV asociada a leucopenia en la saliva de los pacientes.

Introduction: Hematopoietic stem cell transplantation in pediatric patients is an alternative treatment for different diseases. The conditioning regimen for transplant predisposes recipients to the development of infections. Viral infections by herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), human cytomegalovirus (CMV), and Epstein-Barr virus (EBV), are the most common, and the leading cause of morbidity and mortality among these patients. These viruses lie dormant in various cell types and the reactivation of latent infections may lead to asymptomatic viral shedding in saliva. The detection of these viruses in secretions may contribute to understand the behavioral dynamics of these viral infections in transplanted patients, and to the early diagnosis of reactivation. Objective: To assess HSV-1, HSV-2, CMV and EBV viral shedding in the saliva of patients admitted for hematopoietic stem cell transplantation at Fundación HOMI - Hospital de la Misericordia between January and November of 2012. Materials and methods: We evaluated stimulated saliva samples of 17 hematopoietic stem cell transplantation recipients weekly. We performed DNA extraction from saliva, and we evaluated the presence of DNA for HSV-1, HSV-2, CMV, and EBV by PCR. Results: While we detected HSV-2 and CMV DNA in the saliva of four patients, EBV DNA was detected in nine patients with leukopenia. In contrast, we did not detect HSV-1 DNA in saliva. Additionally, four out of the 17 patients showed a simultaneous shedding of CMV and EBV. Conclusions: By conventional PCR, we demonstrated asymptomatic HSV-2, CMV, and EBV viral shedding in saliva, associated with leukopenia.

Manifestação sistêmica atípica causada pelo vírus Epstein-Barr. Relato de caso / Atypical Systemic Manifestation caused by Epstein-Barr virus: case report

A infecção pelo vírus Epstein-Barr tem alta prevalência, ao passo que 90% da população mundial adulta já teve contato com ele. A primo-infecção geralmente ocorre na infância, apresentando- -se de forma subclínica. Com o avançar da idade, a incidência de infecção sintomática aumenta progressivamente, atingindo o pico entre 15 e 24 anos de idade. Em geral, trata-se de uma doença benigna, na qual a manifestação clínica mais comum é a mononucleose infecciosa. No entanto, a infecção pode acometer qualquer órgão ou sistema, e podem estar presentes tosse, dor abdominal, náuseas, vômitos, hepatoesplenomegalia, icterícia, entre outros. As complicações são raras e podem acometer o fígado, os rins, o sistema nervoso central, o coração, os pulmões e os genitais. Relatamos o caso de paciente adolescente previamente hígido com infecção por vírus Epstein-Barr e evolução para icterícia, pericardite e lesões importantes em orofaringe e genitais. O diagnóstico de infecção pelo Epstein-Barr foi feito por sorologia, e houve boa evolução do caso.

Epstein-Barr virus infection has a high prevalence, since 90% of the adult population worldwide have already had contact with the virus. The primary infection usually occurs in childhood, being subclinically presented. With aging. the incidence of a symptomatic infection progressively increases, reaching the peak between 15 and 24 years of age. In general, it is a benign disease,in which the most common clinical manifestation is Infectious Mononucleosis; however, the infection can occur in any organ or system, and cough, abdominal pain, nausea, vomiting, hepatosplenomegaly, jaundice, and other symptoms may be present. Complications are rare and can affect the liver, kidneys, central nervous system, heart, lungs and genitals. We report the case of a previously healthy adolescent patient with Epstein-Barr Virus infection and progression to jaundice, pericarditis, and important lesions in the oropharynx and genitals. The diagnosis of Epstein-Barr infection was made through serology, and the patient had good evolution.

Seguimiento con carga viral para virus Epstein- Barr en pacientes pediátricos con trasplante hepático / Follow up with viral load monitoring for Epstein-Barr virus in pediatric pacients with hepatic transplant

INTRODUCCIÓN: Los pacientes trasplantados son un reto desde todo punto de vista. La infección por el virus de Epstein-Barr es frecuente y su manejo suele ser difícil por la falta de medicamentos efectivos. Los pacientes con trasplante hepático tienen una alta incidencia de infección/reactivación por virus Epstein-Barr por el riesgo de primoinfección durante este periodo o la reactivación por inmunosupresión. OBJETIVOS: Describir los hallazgos obtenidos con el uso de la carga viral para el virus de Epstein-Barr en el seguimiento de los pacientes pediátricos sometidos a trasplante hepático en una institución de cuarto nivel en Medellín, Colombia. SELECCIÓN DE PACIENTES: Se revisaron siete historias clínicas de pacientes con trasplante hepáticos escogidos al azar, obteniendo de ellas los datos demográficos, motivo de trasplante, momento de la aparición de la de la carga viral positiva por el virus de Epstein-Barr, evolución de la carga viral, efectos de los medicamentos inmunosupresores y antivirales, y el desenlace de los pacientes. DESCRIPCIÓN DE CASOS: La edad promedio de los pacientes al momento del trasplante fue de 28,4 meses, el efecto de los medicamentos antivirales como gangiclovir, valganciclovir, inmunoglobulina contra citomegalovirus, no parece ejercer una disminución adecuada y sostenida de la carga viral. CONCLUSIONES: A pesar de las opciones terapéuticas disponibles para el herpes virus, según lo encontrado en la literatura actual y lo visto los pacientes evaluados, el grado de inmunosupresión parece ser el principal factor para el control de la replicación del virus de Epstein-Barr

INTRODUCTION: Transplant patients are a challenge from every point of view. Infection with Epstein- Barr virus is common and management is often hampered by the lack of effective medicaments available. Liver transplant patients have a high incidence of Epstein-Barr virus infection / reactivation because of the the risk of primary infection during this period or immunosuppression associated reactivation. OBJECTIVES: Describe the findings when using EBV viral load monitoring in liver transplant patients in an institution of the fourth level in Medellin, Colombia. SELECTION OF PATIENTS: Seven medical records from liver transplant patients were randomly chosen obtaining from them demographic data, cause of transplantation, time of the Epstein-Barr virus detection, viral load evolution, effects of immunosuppressive medications over them and the patient's outcome. DESCRIPTION OF PATIENTS: Average patient age at transplant was 28,4 months, the effect of antiviral drugs (gangiclovir, valganciclovir, cytomegalovirus immunoglobulin) seems not to be adequate and sustained in decreasing viral load. CONCLUSIONS: Although the therapeutic options available for Herpes virus , as found in current literature and seen in our patients, immunosupression degree seems to be the main factor for controlling EBV replication

Detecção do HPV e EBV por nPCR em líquen plano bucal e tecido normal de cavidade bucal / Detection of HPV and EBV by nPCR in oral lichen planus and normal tissue of oral cavity

O líquen plano caracteriza-se como uma doença inflamatória crônica mucocutânea relativamente comum na população. Possui etiologia incerta, sendo possivelmente associado a fatores genéticos, psicológicos e infecciosos, dentre os quais o último vem ocupando um maior destaque devido a uma possível correlação com o vírus do papiloma humano (HPV) e com o Epstein-Barr vírus (EBV). O HPV possui alguns tipos considerados oncogênicos associados ao câncer de colo de útero e fortemente associado ao carcinoma espinocelular (CEC) de orofaringe. O EBV pertence à família herpesvirus humano e está relacionado com o carcinoma nasofaríngeo, linfoma de Burkitt e linfoma não-Hodgkin e sua possível relação com o CEC vem sendo estudada. O objetivo deste estudo foi detectar a presença do DNA do HPV e do EBV em amostras de tecido fresco, plasma sanguíneo, saliva e células esfoliadas orais, extraídas de um grupo pareado por sexo e idade de pacientes portadores de líquen plano bucal (LPB) e de um grupo de pacientes sem lesões de LPB, além de correlacionar as variáveis epidemiológicas dos grupos estudados com a presença viral e verificar se as fontes materiais testadas por este estudo são fontes viáveis para detecção do HPV e do EBV. Foram avaliados 24 pacientes portadores de LPB (Grupo caso) e 17 pacientes sem lesões de LPB (Grupo controle). A extração de DNA das amostras foi realizada após confirmar a presença e integridade do DNA. Os resultados obtidos foram submetidos à análise estatística (Teste exato de Fisher e Teste do Qui-Quadrado Mantel-Haenszel, ambos, com nível de significância de 5%). A nPCR foi utilizada para detecção do HPV e do EBV. Obteve-se a positividade viral para o HPV em 41,7% das amostras teciduais, em 12,5% das amostras de células esfoliadas e em nenhuma amostra de plasma sanguíneo e saliva dos pacientes do Grupo caso e em 52,9% das amostras teciduais e de saliva, 47,1% e 58,8% amostras de células esfoliadas e plasma sanguíneo, respectivamente, no Grupo controle...

Lichen planus is characterized as a chronic inflammatory mucocutaneous disease relatively common in the population. It has uncertain etiology, possibly associated with genetic, psychological and infectious factors. The infectious factor has excelled due the possible correlation of lichen planus with human papilloma virus (HPV) and Epstein-Barr virus (EBV). HPV has some types considered oncogenic, associated with cervical cancer and strongly associated with squamous cell carcinoma (SCC) of oropharynx. EBV belongs to human herpesvirus family and is associated with nasopharyngeal carcinoma, Burkitt’s lymphoma and non-Hodgkin lymphoma. Its possible relation to SCC has been studied. The aim of this study was to detect the presence of the DNA of the HPV and EBV in fresh tissue samples, blood plasma, saliva and oral exfoliated cells extracted from a group of patients with oral lichen planus (OLP) paired by age and gender and from a group of patients without OLP lesions, and also correlate the epidemiological variables of the studied groups with the viral presence and verify that the source materials tested in this study are viable for HPV and EBV detection. It was evaluated 24 patients with OLP (Case group) and 17 patients without OLP lesions (Control group). DNA extraction of samples was performed after confirming the presence and integrity of DNA. The results were subjected to statistical analysis (Fisher’s exact test and Mantel-Haenszel 19 chi-square test, both with a significance level of 5%). The nPCR was used to detect the presence of HPV and EBV. Was obtained the viral positivity for HPV in 41.7% of tissue samples and in 12.5% of exfoliated cells samples. No samples of blood plasma and saliva were positive in the Case group. On the other hand, the Control group showed a viral positivity of 52.9% in fresh tissue and saliva samples, 47.1% and 58.8% in samples of exfoliated cells and blood plasma, respectively. Was found positivity for EBV in 62.5% of tissue...

Detecção do HPV e EBV por nPCR em líquen plano bucal e tecido normal de cavidade bucal / Detection of HPV and EBV by nPCR in oral lichen planus and normal tissue of oral cavity

O líquen plano caracteriza-se como uma doença inflamatória crônica mucocutânea relativamente comum na população. Possui etiologia incerta, sendo possivelmente associado a fatores genéticos, psicológicos e infecciosos, dentre os quais o último vem ocupando um maior destaque devido a uma possível correlação com o vírus do papiloma humano (HPV) e com o Epstein-Barr vírus (EBV). O HPV possui alguns tipos considerados oncogênicos associados ao câncer de colo de útero e fortemente associado ao carcinoma espinocelular (CEC) de orofaringe. O EBV pertence à família herpesvirus humano e está relacionado com o carcinoma nasofaríngeo, linfoma de Burkitt e linfoma não-Hodgkin e sua possível relação com o CEC vem sendo estudada. O objetivo deste estudo foi detectar a presença do DNA do HPV e do EBV em amostras de tecido fresco, plasma sanguíneo, saliva e células esfoliadas orais, extraídas de um grupo pareado por sexo e idade de pacientes portadores de líquen plano bucal (LPB) e de um grupo de pacientes sem lesões de LPB, além de correlacionar as variáveis epidemiológicas dos grupos estudados com a presença viral e verificar se as fontes materiais testadas por este estudo são fontes viáveis para detecção do HPV e do EBV. Foram avaliados 24 pacientes portadores de LPB (Grupo caso) e 17 pacientes sem lesões de LPB (Grupo controle). A extração de DNA das amostras foi realizada após confirmar a presença e integridade do DNA. Os resultados obtidos foram submetidos à análise estatística (Teste exato de Fisher e Teste do Qui-Quadrado Mantel-Haenszel, ambos, com nível de significância de 5%). A nPCR foi utilizada para detecção do HPV e do EBV. Obteve-se a positividade viral para o HPV em 41,7% das amostras teciduais, em 12,5% das amostras de células esfoliadas e em nenhuma amostra de plasma sanguíneo e saliva dos pacientes do Grupo caso e em 52,9% das amostras teciduais e de saliva, 47,1% e 58,8% amostras de células esfoliadas e plasma sanguíneo, respectivamente, no Grupo controle...

Lichen planus is characterized as a chronic inflammatory mucocutaneous disease relatively common in the population. It has uncertain etiology, possibly associated with genetic, psychological and infectious factors. The infectious factor has excelled due the possible correlation of lichen planus with human papilloma virus (HPV) and Epstein-Barr virus (EBV). HPV has some types considered oncogenic, associated with cervical cancer and strongly associated with squamous cell carcinoma (SCC) of oropharynx. EBV belongs to human herpesvirus family and is associated with nasopharyngeal carcinoma, Burkitt’s lymphoma and non-Hodgkin lymphoma. Its possible relation to SCC has been studied. The aim of this study was to detect the presence of the DNA of the HPV and EBV in fresh tissue samples, blood plasma, saliva and oral exfoliated cells extracted from a group of patients with oral lichen planus (OLP) paired by age and gender and from a group of patients without OLP lesions, and also correlate the epidemiological variables of the studied groups with the viral presence and verify that the source materials tested in this study are viable for HPV and EBV detection. It was evaluated 24 patients with OLP (Case group) and 17 patients without OLP lesions (Control group). DNA extraction of samples was performed after confirming the presence and integrity of DNA. The results were subjected to statistical analysis (Fisher’s exact test and Mantel-Haenszel 19 chi-square test, both with a significance level of 5%). The nPCR was used to detect the presence of HPV and EBV. Was obtained the viral positivity for HPV in 41.7% of tissue samples and in 12.5% of exfoliated cells samples. No samples of blood plasma and saliva were positive in the Case group. On the other hand, the Control group showed a viral positivity of 52.9% in fresh tissue and saliva samples, 47.1% and 58.8% in samples of exfoliated cells and blood plasma, respectively. Was found positivity for EBV in 62.5% of tissue...

Investigação do vírus Epstein-Barr em pacientes com Periodontite Crônica / Investigation of the Epstein-Barr virus in patients with chronic periodontitis

Introdução: Nos últimos anos, um número crescente de estudos sugere a participação dos herpesvírus na doença periodontal. Objetivo: Este trabalho investiga a relação entre a presença do herpesvírus Epstein-Barr (EBV) e a infecção periodontal em pacientes com periodontite crônica. Metodologia: Foram coletadas amostras de biofilme subgengival de sítios com profundidades de sondagem de 4 a 6 mm e > 7 mm, de 28 pacientes com periodontite crônica. Como controles, foram incluídos 16 indivíduos, sistemicamente saudáveis e sem doença periodontal. Adicionalmente, parâmetros clínicos de profundidade de sondagem (PS), nível clínico de inserção (NCI) e índice de sangramento à sondagem (SS) foram registrados. Resultado: Os resultados demonstraram médias de 2,7 mm PS, 1,7 mm NCI e 0,3% dos sítios apresentaram SS. A investigação do EBV no biofilme subgengival dos grupos foi realizada por meio da reação em cadeia da polimerase com primer espécie-específico. Os resultados da análise viral indicaram ausência de EBV em todas as amostras subgengivais analisadas. Conclusão: A partir destes resultados, não foi encontrada relação entre a presença do herpesvírus Epstein-Barr e a periodontite crônica.

Introduction: In recent years, a growing number of studies have suggested the participation of the herpes virus in periodontal disease. Objective: this study investigates the relationship between the presence of the Epstein-Barr herpes virus and periodontal infection in patients with chronic periodontitis. Methodology: subgingival biofilm samples were collected of subgingival sites with probing depths of 4 mm to 6 mm, and > 7 of 28 patients with chronic periodontitis. The control group consisted of 16 healthy subjects without clinical evidence of chronic periodontitis. Additionally, clinical parameters of probing depth, attachment level and Bleeding index were recorded. Result: the results showed averages of 2 mm probing depth, 1, 7 mm attachment level and 0.3 % bleeding on probing. Investigation of the herpes virus in the subgingival biofilm of the groups was performed using polymerase chain reaction with species-specific primer. Results of viral analysis indicated the absence of EBV in all subgingival samples analyzed. Conclusion: these results found no relationship between the presence of the Epstein-Barr herpes virus and chronic periodontitis.

Detecção de Epstein-Barr vírus no carcinoma da nasofaringe: implicações numa área de baixo risco / Epstein-Barr virus detection in nasopharyngeal carcinoma: implications in a low-risk area

Several studies have been published concerning Epstein-barr virus (EBV) infection and nasopharyngeal cancer (NPC) development. The incidences of histological types are different according to endemic or non-endemic regions. Latent EBV infection is found in almost all cases of NPC in endemic regions, but normally absent in type I carcinomas, more common in non-endemic regions. AIM: The purpose of this hospital-based study was to analyze the presence of EBV in nasopharyngeal tumor tissues and in peripheral blood of nasopharyngeal cancer patients and healthy individuals, in a low risk, non-endemic area. METHODS: EBV detection in samples of nasopharyngeal cancer patients and healthy individuals. RESULTS: This study indicates that the frequency of EBV positive cases in peripheral blood is higher in advanced tumor stages. CONCLUSIONS: The incidence rates of NPC have a distinct distribution. Since the prevalence of this disease is low in occidental countries, little is known about the biology of these tumors in non-endemic areas. We observed statistically significant differences in EBV detection between the NPC patient group and the control group. This study may help to understand the biological mechanisms of NPC and the correlation of EBV infection with this disease, in a low risk, non-endemic region.

Têm sido publicados vários estudos acerca da infecção por Epstein-Barr vírus (EBV) e o desenvolvimento de carcinoma da nasofaringe (NPC). As prevalências dos tipos histológicos e a presença de infecção latente pelo EBV são diferentes em regiões endémicas e não endémicas. OBJETIVO: O objectivo deste estudo consistiu na detecção de EBV em tecido tumoral da nasofaringe e sangue periférico de doentes com NPC e em indivíduos saudáveis, provenientes duma área não-endémica, de baixo risco. MÉTODOS: Detecção de EBV em amostras de doentes com carcinoma da nasofaringe e indivíduos saudáveis. Neste estudo de série foram avaliadas as implicações clínicas da presença de EBV circulante no sangue periférico de doentes com carcinoma da nasofaringe. RESULTADOS: Este estudo indica que a frequência de casos EBV positivos detectados no sangue periférico é superior em tumores de estádio mais avançado. CONCLUSÕES: Estes resultados indicam que se observam diferenças na pesquisa do vírus Epstein-Barr no grupo de doentes com NPC e no grupo controlo, sem tumor. Este estudo pode ajudar na compreensão dos mecanismos biológicos do cancro da nasofaringe e da correlação destes tumores com a infecção por EBV numa área não-endémica, de baixo risco.

Detecção do vírus Epstein-Barr em carcinoma espinocelular oral e mucosa oral na região de Araçatuba – SP, Brasil / Detection of Epstein-Barr virus in oral squamous cell carcinoma and oral mucosa in the region of Araçatuba – São Paulo, Brazil

O vírus Epstein-Barr (EBV) faz parte da família herpesvirus humano e está relacionado com doenças benignas e malignas de cabeça e pescoço e sua possível relação com o carcinoma espinocelular (CEC) oral tem sido estudada. O objetivo deste estudo foi detectar a presença do EBV em pacientes com CEC oral e mucosa normal, correlacionando os achados com as variáveis clínico-patológicas, fatores de risco e sobrevida. Foi aplicada a nested-PCR em peças parafinizadas de CEC oral, sendo 20 amostras de assoalho bucal, 25 de língua e 12 de orofaringe. Também foi utilizado grupo controle, sem carcinoma espinocelular, com 19 amostras de mucosa oral normal. O vírus foi encontrado em 10% das amostras de assoalho bucal e 12% de língua, não sendo detectado na orofaringe. Para as amostras de mucosa normal a prevalência foi de 15,79%. Não houve diferença estatisticamente significante entre a presença do vírus e as variáveis: localização anatômica, sexo, idade, tabagismo, etilismo, estadiamento clínico, gradação histológica, esvaziamento cervical e sobrevida. Os resultados sugerem que o EBV não participa isoladamente da carcinogênese oral

The Epstein-Barr virus (EBV) is part of human herpesvirus family being associated with benign and malignant diseases head and neck. Its possible relation with oral squamous cell carcinoma (OSCC) has been studied. The aim of this study was to detect the presence of EBV in patients with OSCC and normal mucosa, correlating the findings with clinicopathologic variables, risk factors and patient’s survival. Nested PCR was applies in paraffin embedded samples of OSCC being 20 samples of mouth floor, 25 tongue and 12 oropharyngeal. A control group composed of 19 normal oral mucosa samples was used. The virus was found in 10% of mouth floor samples, 12% of tongue not being detected in oropharynx. The prevalence in oral mucosa samples was 15.79%. There was no statistically significant differences between the virus presence and the variables: anatomical localization, gender, age, smoking, alcoholism, clinical stage, histological grade, neck dissection and patient’s survival. The results suggest that EBV alone did not have participation in carcinogenesis or oral SCC