Single-center "Argentine" analysis of post-transplant lymphoproliferative disorders: incidence, histopathological characteristics and EBV status

ABSTRACT Introduction: Post-transplant lymphoproliferative disorders (PTLDs) are a heterogeneous group of lymphoid proliferations occurring after solid organ or bone marrow transplantation. The primary aims of our study were to characterize cumulative incidence of PTLDs, clinical and pathological features according to the Epstein-Barr virus (EBV) status and survival. Methods: This was a retrospective cohort study on adult and pediatric patients, from January 2001 to December 2017. The cumulative incidence of PTLD was calculated by analyzing all the patients transplanted at our hospital, based on the database of the Organ Donation and Ablation Authority of Argentina (INCUCAI). The Kaplan-Meier method was used to plot the survival. Results: Fifty-eight cases of biopsy-confirmed PTLD were identified and 12 cases of clinical data were incomplete and these patients were excluded. The median age at the time of the PTLD diagnosis was 17.5 years (interquartile range [IQR] 9 - 57). The median interval between transplant and PTLD diagnosis was 39 months (IQR 9 - 113). The most commonly transplanted organ was the liver (24 cases, 52.2%), followed by kidney (20 cases, 43.5%). The Epstein-Barr encoding region in situ hybridization (EBER ISH) was positive in 29 (69.8%) of the 43 evaluable biopsies. The PTLD cumulative incidence was 1.84% (95%CI 1.77 - 1.91) for solid organ and 0.84% (95%CI 0.48 - 1.2) for bone marrow transplant patients. The overall survival rate at 5 years was 0.77 (95%CI 0.61 - 0.87). Subgroups by the EBV EBER status, transplant type, PTLD subtype and age group (adult vs. pediatric) showed no statistically significant association with the overall survival. Conclusion: The PTLD incidence was similar to that of previous series and the EBER did not appear as a relevant factor in our patient survival.

Seroepidemiología del virus de Epstein-Barr en estudiantes universitarios del Alto Paraná, Paraguay / Seroepidemiology of Epstein-Barr virus among university students from Alto Paraná, Paraguay

Introducción. La infección por el virus de Epstein-Barr (VEB) es la causa más frecuente de mononucleosis infecciosa, y también está asociada a varios tipos de cáncer. La prevalencia de la infección por este virus varía en diferentes poblaciones y no hay publicaciones sobre la epidemiología de esta infección en Paraguay. Objetivo. Describir la seroprevalencia de la infección por VEB en estudiantes universitarios y las características sociodemográficas asociadas. Materiales y Métodos. Estudio transversal en estudiantes de una universidad pública del departamento Alto Paraná, Paraguay. Se incluyeron 101 participantes, mediante muestreo de casos consecutivos. Se aplicó un cuestionario y se tomó muestras sanguíneas. Se determinó la presencia de anticuerpos por el método ELISA de captura de IgG específicos contra el antígeno de la cápside viral -VCA del VEB, además se evaluaron factores asociados a la seropositividad. Resultados. La seroprevalencia global fue 89,1% (90/101), asociado (p<0,025) a la condición socioeconómica baja (93,4%vs 76%, OR: 4.9 [IC 95%: 1,2 ­16,3]). Conclusión. La seroprevalencia contra el virus de Epstein-Barr es alta en estudiantes universitarios y está asociada a la condición socioeconómica baja. Palabras Clave: estudios seroepidemiológicos; anticuerpos; infecciones por virus de Epstein-Barr; estudiantes; Paraguay

Introduction. Infections by Epstein-Barr virus (EBV) is the most common cause of infectious mononucleosis and is also linked to multiple cancers. The prevalence of EBV infection varies in different populations and there is no publication about the epidemiology of this infection in Paraguay. Objective.To describethe seroprevalence among university students and associated sociodemographic characteristics. Material and Methods.Cross-sectional study in students from a public university in Alto Paraná, Paraguay.A total of 101 participants were recruited through consecutive sampling.Aquestionnaire was applied and blood samples were obtained. Antibodies were determined by Epstein-Barr Virus IgG anti-VCA capture ELISA method, and factors associated with seropositivity were evaluated. Results. The overall seropositivity was 89,1%(90/101), which was associated(p<0,025) with low socioeconomic status (93,4%vs 76%, OR: 4.9 [95% CI: 1.2 -16.3]). Conclusion. The seroprevalence to EBV is high in collegestudents which is associated to low socioeconomic condition. Key words: seroepidemiologic studies; antibodies; Epstein-Barr virus infections; students; Paraguay

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

Infección por virus de epstein barr y debut de lupus eritematoso sistémico (LES) en un adolescente / Epstein barr virus infection and systemic lupus erythematosus (SLE) debut in an adolescent / Infecção pelo vírus Epstein Barr e início de lúpus eritematoso sistêmico (LES) em adolescente

Introducción: El lupus eritematoso sistémico (LES), prototipo de enfermedad autoinmune, cursa con empujes y remisiones. Dada la diversidad de presentaciones posibles, su diagnóstico y tratamiento son un reto para el clínico, y se requiere tener un alto índice de sospecha. Objetivo: presentar el caso clínico de un adolescente que debuta con LES a forma de anemia hemolítica, probablemente gatillado por infección por virus de Epstein Barr. Caso clínico: Varón de 14 años, sin antecedentes a destacar. Consulta por fiebre de 7 días de evolución de hasta 39º C, odinofagia, astenia y adinamia. Al examen físico se constata palidez cutáneo mucosa, ictericia, adenopatías cervicales y hepatoesplenomegalia. El laboratorio muestra anemia severa regenerativa con aumento de las bilirrubinas a expensas de la indirecta sin hepatitis. Prueba de Coombs positiva. Anticuerpos específicos para Epstein Barr positivos, con lo que se diagnostica anemia hemolítica secundaria a mononucleosis y se inicia tratamiento corticoideo. En la evolución agrega eritema malar y limitación en flexión de codos y rodillas. Se reciben anticuerpos antinucleares y anti ADN nativo positivos con hipocomplementemia severa. Con diagnóstico de LES se inicia hidroxicloroquina y azatioprina, manteniéndose la prednisona. Conclusiones: Muchos virus (hepatitis C, Parvovirus B19, Epstein Barr y Citomegalovirus) se han descrito como posibles inductores o simuladores de LES. Es necesario mantener un alto índice de sospecha para realizar un diagnóstico oportuno y tratamiento precoz.

Introduction: Systemic lupus erythematosus (SLE), prototype of autoimmune disease, progresses with flares and remissions. Given the diversity of possible presentations, its diagnosis and treatment are a challenge for the clinician, and a high index of suspicion is required. Objective: To present the clinical case of an adolescent who debuted with SLE in the form of hemolytic anemia, probably triggered by Epstein Barr virus infection. Clinical case: 14 - year - old male, with no history to highlight. Consultation for fever of 7 days of evolution of up to 39º C, odynophagia, asthenia and adynamia. Physical examination revealed mucous skin pallor, jaundice, cervical lymphadenopathy, and hepatosplenomegaly. The laboratory shows severe regenerative anemia with increased bilirubin at the expense of indirect without hepatitis. Positive Coombs test. Specific antibodies for Epstein Barr were positive, with which hemolytic anemia secondary to mononucleosis was diagnosed and corticosteroid treatment was started. In the evolution, it adds malar erythema and limitation in flexion of the elbows and knees. Positive antinuclear and anti-native DNA antibodies are received with severe hypocomplementemia. With a diagnosis of SLE, hydroxychloroquine and azathioprine were started, maintaining prednisone. Conclusions: Many viruses (hepatitis C, Parvovirus B19, Epstein Barr and Cytomegalovirus) have been described as possible inducers or mimics of SLE. It is necessary to maintain a high index of suspicion for timely diagnosis and early treatment.

Introdução: O lúpus eritematoso sistêmico (LES), protótipo de doença autoimune, evolui com impulsos e remissões. Dada a diversidade de apresentações possíveis, seu diagnóstico e tratamento são um desafio para o clínico, sendo necessário um alto índice de suspeição. Objetivo: apresentar o caso clínico de uma adolescente que iniciou com LES na forma de anemia hemolítica, provavelmente desencadeada por infecção pelo vírus Epstein Barr. Caso clínico: Homem de 14 anos, sem antecedentes a destacar. Consulta por febre de 7 dias de evolução de até 39º C, odinofagia, astenia e adinamia. O exame físico revelou palidez cutânea mucosa, icterícia, linfadenopatia cervical e hepatoesplenomegalia. O laboratório mostra anemia regenerativa grave com aumento da bilirrubina em detrimento da indireta sem hepatite. Teste de Coombs positivo. Anticorpos específicos para Epstein Barr foram positivos, com o qual foi diagnosticada anemia hemolítica secundária à mononucleose e iniciado tratamento com corticosteróides. Na evolução, acrescenta eritema malar e limitação na flexão dos cotovelos e joelhos. Anticorpos antinucleares e anti-DNA nativos positivos são recebidos com hipocomplementemia grave. Com diagnóstico de LES, iniciou-se hidroxicloroquina e azatioprina, mantendo-se prednisona. Conclusões: Muitos vírus (hepatite C, Parvovírus B19, Epstein Barr e Citomegalovírus) têm sido descritos como possíveis indutores ou mimetizadores do LES. É necessário manter um alto índice de suspeição para diagnóstico oportuno e tratamento precoce.

Transformación nodular angiomatoide esclerosante del bazo: reporte de caso / Sclerosing angiomatoid nodular transformation of the spleen: a case report

La transformación nodular angiomatoide esclerosante es una patología vascular benigna del bazo, desarrollada a partir de la pulpa roja, de etiología desconocida. Se postula que puede estar relacionada con la enfermedad por inmunoglobulina 4 y la infección por el virus de Epstein-Barr. La mayoría de los casos son asintomáticos, constituyendo hallazgos incidentales en estudios por imágenes. Presentamos el caso de un paciente masculino de 41 años con antecedentes de tiroidectomía por carcinoma papilar que consulta por fiebre. Recibió tratamiento sintomático y se realizó tomografía computarizada de abdomen por síntomas abdominales inespecíficos. La tomografía evidenció una imagen de aspecto sólido, con tenue realce periférico con el contraste que mide 62 por 52 por 51 milímetros en el polo inferior del bazo. Se realizó esplenectomía que midió 14 por 11 por 4 centímetros y pesó 284 gramos. Se identificó una formación nodular sólida, bien delimitada, con área central de aspecto fibroso, con tractos blanquecinos que delimitan áreas violáceas. La microscopía presentó nódulos coalescentes redondeados de aspecto angiomatoide, con proliferación vascular revestida por células endoteliales sin atipia, entremezclados con células ahusadas, infiltrado de linfocitos y macrófagos. El estroma entre los nódulos mostró proliferación miofibroblástica con linfocitos, plasmocitos y siderófagos. Inmunohistoquímica tuvo marcación positiva en los vasos para CD34 y CD31, sectores positivos para CD8 y negativos para CD34. Una célula positiva para inmunoglobulina 4 (IgG4) por campo de gran aumento. El estudio para Epstein-Barr por reacción en cadena de la polimerasa fue negativo. Para el diagnóstico los estudios de imagen son inespecíficos, por lo que la confirmación diagnóstica la da el estudio histopatológico. La esplenectomía es curativa sin casos reportados hasta la actualidad de transformación maligna o recidiva. No se conocen factores de riesgo y no se han comprobado factores desencadenantes, excepto la asociación de casos con IgG4 y virus de Ebstein-Barr. Por ser una entidad patológica recientemente descrita es necesario recopilar series grandes y revisar nuestros archivos, reevaluando algunos de sus diagnósticos diferenciales para lograr una mejor comprensión de la misma.

Sclerosing angiomatoid nodular transformation is a benign vascular pathology of the spleen, developed from the red pulp, of unknown etiology; it is postulated that it may be related to IgG4 disease and Epstein-Barr virus infection. Most cases are asymptomatic, constituting incidental findings in imaging studies. We present a 41-year-old male patient with a history of thyroidectomy for papillary carcinoma who consulted for fever, received symptomatic treatment and performed a computed tomography of the abdomen for nonspecific abdominal symptoms, the same evidence in the lower pole of the spleen a solid-looking image with faint Peripheral enhancement with contrast, measures 62x 52x51 mm. A splenectomy measuring 14x 11x4 cm and weighing 284 grams was performed, identifying a solid, well-defined nodular formation, with a central fibrous-looking area, with whitish tracts that delimited purplish areas. Microscopy: rounded angiomatoid-like coalescing nodules, with vascular proliferation lined by endothelial cells without atypia, interspersed with spindle cells, infiltrated by lymphocytes and macrophages. The stroma between the nodules shows myofibroblastic proliferation with lymphocytes, plasma cells, and siderophages. Immunohistochemistry: positive labeling in vessels for CD34 and CD31, positive sectors for CD8 and negative for CD34. One IgG4 positive cell per high power field. The study for Epstein-Barr by Polymesara Chain Reaction was negative. For the diagnosis, the imaging studies are nonspecific, so the diagnostic confirmation is given by the histopathological study. Splenectomy is curative with no reported cases of malignant transformation or recurrence to date. There are no known risk factors and no triggering factors have been proven, except the association of cases with IgG4 and Ebstein-Barr virus. As it is a recently described pathological entity, it is necessary to collect large series and review our files, reevaluating some of its differential diagnoses to achieve a better understanding of it

Prevalence of epstein-barr virus infection in palatine tonsils hyperplasia through the immunoexpression of the LMP-1 marker / Avaliação da prevalência de infecção por epstein-barr vírus na hiperplasia de tonsilas palatinas através da imunoexpressão do marcador LMP-1

Introduction: LMP-1 (latent membrane protein 1) is a membrane protein found in EBV and can be identified through immunohistochemistry. Objectives: To evaluate the prevalence of EBV virus in tonsillar tissue samples correlating with tonsil size, age and gender. Methods: An LMP-1 immunohistochemical study was performed in slides from patients with tonsil hyperplasia. Results: The sample consisted of 120 slides, 66 were from male. The average tonsillar size was 6.0 cm2 (1.5-14.0) and the average age was 6.5 years (2-18). Overall, 72 patients were positive for the virus, the majority being male (51%) and preschoolers (51.4%). For comparative analysis, the sample was divided: group 1 (positive immunohistochemistry) and group 2 (negative immunohistochemistry). The average age was 6.74 years (± 4.14) and 6.19 years (± 3.82) for group 1 and 2, respectively. Group 1 had 37 preschoolers, 23 school-age children and 12 adolescents. Group 2 had 28 preschoolers, 14 school-age children and 6 adolescents (p=0.71). To evaluate the presence of virus, the slides were divided according to area: G (≥6cm²) and P (<6cm²). In G group, 54 slides were positive, while in P group, 18 were positive. Group 1 presented 54 of G group slides and 18 of P group slides, with no statistical difference, but with a tendency to positivity (p=0.09). Conclusion: Most of the sample was positive for the presence of Epstein-Barr virus. There was no difference in the virus presence or absence when correlated with the tonsillar size, age or sex

Introdução: LMP-1 (proteína latente de membrana-1) é uma proteína de membrana encontrada no Epstein-Barr vírus (EBV) e que pode ser identificadaatravés da imunoistoquímica. Objetivo: Avaliar a prevalência do EBV em amostras de tecido tonsilar correlacionando com o tamanho da tonsila, idade e sexo. Método: Realizou-se um estudo imunoistoquímico de LMP-1 para EBV em lâminas de pacientes com hiperplasia de tonsilas. Resultados: A amostra foi composta por 120 lâminas, sendo 66 (55%) de pacientes do sexo masculino. O tamanho médio tonsilar foi 6,0 cm2 (1,5-14,0) e a idade média 6,5 anos (2-18). Ao todo, 72 pacientes (60%) tiveram positividade para o vírus, a maioria meninos (51%) e pré-escolares (51,4%). A amostra foi dividida em: grupo 1 (imunoistoquímica positiva) e grupo 2 (imunoistoquímica negativa). A idade média foi de 6,74 anos (±4,14) e 6,19 anos (±3,82), para o grupo 1 e 2, respectivamente. O grupo 1 apresentou 37 pré-escolares, 23 escolares e 12 adolescentes. O grupo 2 foi composto por 28 pré-escolares, 14 escolares e 6 adolescentes, sem diferença estatística (p=0,71). Para avaliar a presença do EBV, as lâminas foram divididas de acordo com a área: G (≥6 cm²) e P (<6 cm²). No grupo G, 54 lâminas foram positivas, enquanto no grupo P, 18, sem diferença estatística, mas com tendência a positividade (p=0,09). Conclusão: A maior parte da amostra foi positiva para o Epstein-Barr vírus. Não houve diferença significante na positividade ou não do vírus quando correlacionada com o tamanho tonsilar, a idade e o sexo dos pacientes.

COVID-19 related acute genital ulcer: a case report

ABSTRACT Acute vulvar ulcer (Lipschütz's ulcer) is a rare lesion with local hyperimmunoreactivity triggered by infection, which is characterized by acute, painful, and necrotic ulcerations. This condition is usually found in non-sexually active adolescents, and it resolves spontaneously. We report a case of a 35-year-old woman who was diagnosed with COVID-19 who did not have severe symptoms, but had high levels of D-dimer for 9 days. The COVID-19 diagnosis was followed by the appearance of an acute, necrotic, extremely painful vulvar ulcer, although symptoms caused by COVID-19 had improved. We emphasize the importance of the differential diagnosis to exclude diseases such as Behçet's syndrome, Sexually Transmitted Infections, as well as the presence of viruses that generally trigger Lipschütz's ulcer, such as Epstein-Barr virus and cytomegalovirus. No treatment is usually necessary, however, in the present report due to the pain experienced by the patient, we successfully used oral prednisone.

EBER + extranodal NK/T lymphoma in patient with idiopathic CD4 lymphocytopenia / Linfoma T/NK EBER positivo en paciente con linfocitopenia CD4 idiopática

Abstract Idiopathic CD4 lymphocytopenia (ICL) not related to HIV is an infrequent and severe condition with no etiology defined until now. The concomitant presence of an underlying disease, especially an oncohematological process, could be related to the immune physiopathology and the development of the im munosuppressive state. On the other hand, Epstein Barr virus is a well-known oncogenic pathogen described in the development of several types of lymphoma which might be reactivated in the ICL. There is still no specific treatment for this syndrome, so the therapeutic scope for these patients is the treatment of opportunistic diseases and the administration of specific antimicrobials as prophylaxis. We present a patient with an uncommon asso ciation of an ICL and an extranodal T/NK lymphoma with detection of VEB nuclear RNA by in situ hybridization (EBER). Diagnosis was challenging which led the health team to carry out many studies over several months

Resumen La linfocitopenia CD4 idiopática (ICL) no relacionada al HIV es una condición grave e infrecuente sin una etiología aún definida. La presencia de una enfermedad subyacente, especialmente un proceso oncohematológico, podría tener relación en la fisiopatología del proceso inmunológico. Por otro lado, el virus Epstein Barr (VEB) es bien conocido por ser un patógeno oncogénico descrito en el desarrollo de diversos tipos de linfomas, el cual podría ser reactivado en estados de inmunosupresión severa. No existe aún un tratamiento específico para este síndro me, por lo que el objetivo terapéutico en estos pacientes radica en el manejo profiláctico y activo de las distintas enfermedades oportunistas ante las cuales son susceptibles. Se presenta un paciente con un déficit grave de linfocitos CD4 de causa idiopática, y un diagnóstico posterior de linfoma T/NK extraganglionar con detección de RNA nuclear de VEB por hibridización in situ (EBER), una asociación poco descrita en la literatura médica.

Síndrome hemofagocítico: caracterización clínica y seguimiento de una cohorte pediátrica chilena / Hemophagocytic syndrome: clinical characterization and follow-up of a Chilean pediatric cohort

INTRODUCCIÓN: La linfohistiocitosis hemofagocítica (HLH en inglés) es un síndrome clínico grave, potencialmente fatal, caracterizado por una activación patológica del sistema inmune y una respuesta hiperinflamatoria extrema. Según su etiología se clasifica en primario (genético o familiar) y secundario (gatillado por causas infecciosas, oncológicas o reumatológicas). OBJETIVOS: Describir y analizar las características clínicas y laboratorio, tratamiento recibido y seguimiento en pacientes pediátricos con diagnóstico de HLH. PACIENTES Y MÉTODOS: Se describió una cohorte pediátrica en pacientes hospitalizados con diagnóstico de HLH en un centro terciario universitario entre enero de 2000 y febrero de 2019. RESULTADOS: Se reclutaron 23 pacientes pediátricos con una mediana de edad de 36 meses. Los hallazgos clínicos y de laboratorio más frecuentes fueron fiebre, citopenias e hiperferritinemia. La etiología más frecuente fue infecciosa (virus Epstein Barr/citomegalovirus) e inmunológica/reumatológica. La mortalidad global fue de 35%, sin diferencias significativas según etiología. DISCUSIÓN: Dada su alta mortalidad es relevante un alto índice de sospecha que permita instaurar terapia de forma precoz. Son necesarios estudios multicéntricos para determinar predictores clínicos y de laboratorio con valor pronóstico.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a severe syndrome, potentially lethal, with a pathological activation of the immune system and an extreme hyperinflammatory response. The etiology is classified in primary HLH (familiar or genetic) and secondary (infectious, oncological, and rheumatological diseases). AIM: To analyze clinical and laboratory characteristics, treatment, and follow-up rates in pediatric patients with HLH. METHODS: A pediatric cohort of patients with HLH diagnosis attending in a tertiary hospital between January 2000 to February 2019 was analysed. RESULTS: 23 hospitalized patients were recruited with a median of 36 months of age. The most frequent clinical and laboratory findings were fever, cytopenias, and hyperferritinemia. The most frequent aetiologies were infectious (Epstein Barr virus and citomegalovirus) and rheumatological diseases. The global mortality was 35%, there was no significant difference between etiologies. DISCUSSION: Considering the high mortality of HLH it is very important to have a high grade of suspicion that allows treating at an early stage. It would be important to determine clinical and laboratory predictors in multicentric studies.

Lipschütz Ulcer: An Unusual Diagnosis that Should Not be Neglected

Abstract The diagnosis of genital ulcers remains a challenge in clinical practice. Lipschütz ulcer is a non-sexually transmitted rare and, probably, underdiagnosed condition, characterized by the sudden onset of vulvar edema along with painful necrotic ulcerations. Despite its unknown incidence, this seems to be an uncommon entity, with sparse cases reported in the literature. We report the case of an 11-year-old girl who presented at the emergency department with vulvar ulcers. She denied any sexual intercourse. The investigation excluded sexually transmitted infections, so, knowledge of different etiologies of non-venereal ulcers became essential. The differential diagnoses are extensive and include inflammatory processes, drug reactions, trauma, and malignant tumors. Lipschütz ulcer is a diagnosis of exclusion. With the presentation of this case report, the authors aim to describe the etiology, clinical course, and outcomes of this rare disease, to allow differential diagnosis of genital ulceration.

Rotura esplénica espontánea secundaria a mononucleosis infecciosa / Spontaneous splenic rupture secondary to infectious mononucleosis

Resumen La rotura esplénica es una complicación rara pero potencialmente fatal de la mononucleosis infecciosa. Presentamos el caso de una mujer de 18 años que consultó por dolor abdominal de siete días de evolución, asociado a fiebre y pérdida de conciencia brusca y transitoria. En el hemograma presentaba una anemia y linfocitosis. Se realizó una tomografía computada de abdomen y pelvis que mostró un extenso hemoperitoneo, con el bazo rodeado por un hematoma, y numerosas adenopatías cervicales, mesentéricas e inguinales. Se efectuó una laparoscopía que demostró abundante hemoperitoneo con coágulos a lo largo de la gotera parietocólica izquierda. El bazo estaba completamente decapsulado y rodeado por una colección hemática con sangrado en napa. Se realizó una esplenectomía total sin complicaciones. El estudio histopatológico esplénico mostró una atenuación de la pulpa blanca y expansión de la pulpa roja con áreas de hemorragia y necrosis. La IgM anti-cápside para virus de Epstein Barr fue positiva. La paciente evolucionó de manera favorable.

Abstract Splenic rupture is a rare but potentially fatal complication of infectious mononucleosis. We report the case of an 18-year-old woman, who presented a 7-day history of abdominal pain, sudden temporary loss of consciousness and fever. Admission blood tests showed anemia, and lymphocytosis. Computed tomography of the abdomen and pelvis demonstrated extensive hemoperitoneum and numerous cervical, mesenteric and inguinal enlarged lymph nodes. Laparoscopy was performed and abundant hemoperitoneum with blood clots along the left parietocolic gutter were observed. The spleen was completely decapsulated and surrounded by a hematoma and the subcapsular tissue was bleeding. Total splenectomy was performed without complications. Splenic histology demonstrated white pulp attenuation and expansion of the red pulp with focal hemorrhage and necrosis. IgM anti-viral capsid antigen of Epstein Barr virus was positive. The patient had a satisfactory recovery.

Cutaneous smooth muscle tumors associated with Epstein-Barr virus in an adult patient with HIV

Abstract Epstein Barr virus-associated smooth muscle tumors are an uncommon neoplasm that occurs in immunosuppressed patients of any age. Usually, it presents as multifocal tumors mainly in the spinal cord, epidural region, gastrointestinal tract and liver, upper respiratory tract and skin, the latest with few cases reported in the literature and related with human immunodeficiency virus infection and acquired immune deficiency syndrome. The authors present the first case of a Colombian adult patient with human immunodeficiency virus infection and multifocal Epstein Barr virus-associated smooth muscle tumors in the skin and epidural region, confirmed by histopathology, immunohistochemistry and in situ hybridization studies.

Síndrome de Behçet ou úlcera de Lipschütz: desafio diagnóstico / Behçet's syndrome or Lipschütz ulcer: diagnostic challenge

A ocorrência de úlceras genitais em adolescentes e mulheres jovens tem impacto emocional para as pacientes e seus familiares, pela frequente associação com uma possível etiologia de transmissão sexual. Porém, úlcera de Lipschütz e síndrome de Behçet não têm etiologia infecciosa e devem ser lembradas como possíveis diagnósticos diferenciais. O diagnóstico dessas duas patologias é clínico e pode ser desafiador. Dessa forma, foi realizada uma revisão na literatura com o objetivo de comparar as duas entidades. A úlcera de Lipschütz é causada por uma vasculite local e caracteriza-se pelo surgimento súbito de úlceras na vulva ou vagina inferior. Já a doença de Behçet é causada por vasculite sistêmica, com episódios de remissão e exacerbação, que pode envolver quase todos os sistemas orgânicos. Em ambos os casos, é essencial o referenciamento para reumatologia. O tratamento objetiva suprimir exacerbações, controlar a dor e prevenir infecção secundária.(AU)

The occurrence of genital ulcers in adolescents and young women have an emotional impact for the patient and their families, due to the frequent association of its etiology with a sexually transmitted disease. However, Lipschütz ulcer and Behçet's syndrome do not have an infectious etiology and should be remembered as a possible differential diagnoses. As the diagnosis of these two pathologies is clinical and can be challenging, a review of literature was carried out. The objective of this review of literature was to compare both diseases. Lipschütz ulcer is caused by local vasculitis and is characterized by the sudden appearance of ulcers in the vulva or lower vagina. Behçet's syndrome is caused by systemic vasculitis, with episodes of remission and exacerbation, which can affect almost all organ systems. In both cases, referral to rheumatology is essential. Treatment aims to suppress exacerbations, control pain and prevent secondary infection.(AU)

Vías moleculares patogénicas del linfoma T/NK extranodal de tipo nasal asociadas con virus de Epstein Barr: Revisión narrativa / Molecular pathways related to Epstein Barr virus in extranodal NK/T cell lymphoma, nasal type: Narrative review

El virus de Epstein Barr (VEB) se encuentra presente en el 100% de los casos de linfoma T/NK extranodal de tipo nasal (ENKTL) y juega un papel importante en la etiopatogenia de esta enfermedad. El objetivo de esta revisión es actualizar el conocimiento de las vías moleculares genéticas y epigenéticas utilizadas por el VEB en la oncogenesis del ENKTL. Para ello se realizó una revisión de la literatura, en las bases de datos de PubMed y Google Scholar, sobre los mecanismos que utilizan las proteínas virales como la proteína de membrana latente (LMP1) y el antígeno nuclear Epstein Barr 1 (EBNA1) para activar proteínas antiapoptóticas del huésped y pro-teínas relacionadas a proliferación celular, a través de las vías moleculares JAK/STAT (Janus quinasas/señales de transducción y activación de proteínas de transcripción), NF-κB (el factor nuclear potenciador de las cadenas ligeras kappa de las células B activadas) EZHZ2 (Enhancer of Zeste 2 Polycomb repressive Complex 2) y PI3K/Akt (Fosfoinositido 3 quinasa/proteína quinasa B); también se revisó el papel de las proteínas virales BNLF2a, BILF y BDLF3 en la evasión inmune del virus. También LMP1 aumenta la expresión de PDL-1 (ligando de la muerte celular programada), contribuyendo a la disminución de la respuesta inmunológica. A nivel epigenético se abordan los cambios del perfil de metilación en las áreas promotoras de genes supresores de tumor y se explica la función de los miARN de VEB que participan inhibiendo genes supresores de tumor o activando genes que aumentan la proliferación.

Epstein Barr virus (EBV) is present in 100% of cases of nasal-type extranodal NK/T cell lymphoma (ENKTL). It plays an important role in the etiopathogenesis of this disease. The objective of this review is to update the knowledge of the genetic and epigenetic molecular pathways used by EBV in the oncogenesis of ENKTL. To this end, a literature review was carried out in the PubMed and Google Scholar databases on the mechanisms used by viral proteins such as latent membrane protein (LMP1) and Epstein Barr 1 nuclear antigen (EBNA1) to activate host antiapoptotic proteins avoiding cell death and activating cell proliferation, through the molecular pathways JAK/STAT (Janus kinases/signal transduction and activation of transcription proteins), NF-κB (the nuclear factor enhancing the kappa light chains of activated B cells) EZHZ2 pathways (Enhancer of Zeste 2 Polycomb repressive Complex 2) and PI3K/Akt (Phosphoinositide 3 kinase protein kinase B). The role of the viral proteins: BNLF2a, BILF and BDLF3 in the virus immune evasion. It is currently recognized that LMP1 increases the expression of PDL-1 (programmed cell death ligand), contributing to the decrease in the immune response. Thus, the epigenetic changes in the methylation profile in the promoter areas of tumor suppressor genes, was also reviewed. Finally role of EBV miRNAs participate in inhibiting tumor suppressor genes or activating genes that increase proliferation.

Arbovirus, herpesvirus, and enterovirus associated with neurological syndromes in adult patients of a university hospital, 2017-2018

Abstract INTRODUCTION: Herpesviruses, enteroviruses, and arboviruses are important because of their clinical relevance and ability to cause meningitis, encephalitis, meningoencephalitis, and other diseases. The clinical virology associated with diagnostic technologies can reduce the morbidity and mortality of such neurological manifestations. Here we aimed to identify the genomes of agents that cause neurological syndromes in cerebrospinal fluid (CSF) samples from patients with suspected nervous system infections admitted to the University Hospital of the University of Campinas, São Paulo, Brazil, in 2017-2018. METHODS: CSF samples collected from adult patients with neurological syndrome symptoms and negative CSF culture results were analyzed using polymerase chain reaction (PCR), reverse transcriptase-PCR, and real-time PCR, and their results were compared with their clinical symptoms. One CSF sample was obtained from each patient. RESULTS: Viral genomes were detected in 148/420 (35.2%) CSF samples: one of 148 (0.2%) was positive for herpes simplex virus-1; two (0.5%) for herpes simplex virus-2; eight (1.9%) for varicella-zoster virus; four (1%) for Epstein-Barr virus; one (0.2%) for cytomegalovirus; 32 (7.6%) for human herpesvirus-6; 30 (7.1%) for non-polio enterovirus; 67 (16.0%) for dengue virus, three (0.7%) for yellow fever virus, and 21 (5%) for Zika virus. CONCLUSIONS: The viral genomes were found in 35.2% of all analyzed samples, showing the high prevalence of viruses in the nervous system and the importance of using a nucleic acid amplification test to detect viral agents in CSF samples.

Lipschütz ulcer and Epstein-Barr virus infection: a case report / Úlcera de Lipschütz e infecção pelo vírus Epstein-Barr: um relato de caso

Aims: Lipschütz ulcer (LU), also known as acute vulvar ulcer, is a rare cause of vulvar ulcerations of nonvenereal origin. Our aim is to alert about this manifestation of the disease and to prevent unnecessary treatment. Case description: we present a 15 years old female, without relevant family and past history, admitted in the emergency room with a painful vulvar ulcer, preceded by five days of fever and sore throat. On physical examination, she had enlarged, and erythematous tonsils and bilateral anterior cervical lymphadenopathy and the genital examination revealed vulvar oedema and a deep ulcer with necrotic plaques in labium minus. The exclusion of transmitted sexual disease led to a diagnosis of Lipschütz ulcer. She started symptomatic treatment, oral antibiotic and corticoid therapy. She was discharged from the hospital after 6 days of admission and returned to a consult one month later when it was observed an almost complete resolution of the lesions. No recurrences occurred until 3 months. Conclusion: LU is a misdiagnosed pathology, probably because doctors, in general, are not familiarized with that, and since the diagnosis is made by exclusion. Infectious, such as Epstein-Barr Virus infections, are proposed etiologies.

Objetivo: a úlcera de Lipschütz, ou úlcera vulvar aguda, é uma causa rara de ulceração de origem não venérea. O nosso objetivo é alertar para essa manifestação da doença e prevenir tratamentos desnecessários. Descrição: adolescente, sexo feminino, 15 anos, sem história pessoal ou antecedentes familiares de relevo. Recorreu ao Serviço de Urgência por febre e odinofagia, com cinco dias de evolução, associada a uma úlcera vulvar dolorosa, que surgiu no próprio dia. O exame clínico revelou amígdalas hipertrofiadas e eritematosas, linfadenopatia cervical anterior, e o exame ginecológico apresentou edema da vulva e uma úlcera profunda, com placas necróticas nos lábios menores. A exclusão de uma doença sexualmente transmissível levou ao diagnóstico de úlcera de Lipschütz. Ficou internada no Serviço de Pediatria e iniciou tratamento sintomático, antibioterapia por sobreinfeção da úlcera e corticoterapia tópica. Teve alta após seis dias de hospitalização e foi reavaliada em consulta um mês depois, com resolução completa do caso. Não apresentou recorrência da úlcera até aos três meses seguintes. Conclusão: a úlcera de Lipschütz é uma doença subdiagnosticada, muito provavelmente porque os médicos não estão familiarizados com ela e por ser um diagnóstico de exclusão. A infeção pelo vírus Epstein-Barr é uma das etiologias propostas.

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.