Hybrid capture shotgun sequencing detected unexpected viruses in the cerebrospinal fluid of children with acute meningitis and encephalitis.

PURPOSE: Investigation of undiagnosed cases of infectious neurological diseases, especially in the paediatric population, remains a challenge. This study aimed to enhance understanding of viruses in CSF from children with clinically diagnosed meningitis and/or encephalitis (M/ME) of unknown aetiology using shotgun sequencing enhanced by hybrid capture (HCSS). METHODS: A single-centre prospective study was conducted at Sant Joan de Déu University Hospital, Barcelona, involving 40 M/ME episodes of unknown aetiology, recruited from May 2021 to July 2022. All participants had previously tested negative with the FilmArray Meningitis/Encephalitis Panel. HCSS was used to detect viral nucleic acid in the patients' CSF. Sequencing was performed on Illumina NovaSeq platform. Raw sequence data were analysed using CZ ID metagenomics and PikaVirus bioinformatics pipelines. RESULTS: Forty episodes of M/ME of unknown aetiology in 39 children were analysed by HCSS. A significant viral detection in 30 CSF samples was obtained, including six parechovirus A, three enterovirus ACD, four polyomavirus 5, three HHV-7, two BKV, one HSV-1, one VZV, two CMV, one EBV, one influenza A virus, one rhinovirus, and 13 HERV-K113 detections. Of these, one sample with BKV, three with HHV-7, one with EBV, and all HERV-K113 were confirmed by specific PCR. The requirement for Intensive Care Unit admission was associated with HCSS detections. CONCLUSION: This study highlights HCSS as a powerful tool for the investigation of undiagnosed cases of M/ME. Data generated must be carefully analysed and reasonable precautions must be taken before establishing association of clinical features with unexpected or novel virus findings.

Are corticosteroids safe in adolescent and adult patients with infectious mononucleosis? A retrospective cohort study.

BACKGROUND AND AIM: The use of systemic corticosteroids during Epstein-Barr virus (EBV)-induced infectious mononucleosis is a controversial but widespread practice. We aimed to investigate the frequency of complications in adolescents and adults with infectious mononucleosis in relation to the use of corticosteroids. METHODS: We reviewed the clinical records of 396 patients admitted to the hospital with infectious mononucleosis (52.0% male; median age, 19 years; range, 15-87 years), with a focus on both short-term (infectious and non-infectious) and long-term (hematological malignancies) complications in relation to corticosteroid use. RESULTS: A total of 155 (38.6%) patients received corticosteroids at some point during infectious mononucleosis. Corticosteroid use was significantly (P≤0.002) associated with sore throat, lymphadenopathy, leukocytosis, and with antibiotics use (mainly indicated after suspicion of tonsillar bacterial superinfection). Overall, 139/155 (89.7%) patients who were treated with corticosteroids also received antibiotics either before or during hospitalization, compared with 168/241 (69.7%) patients who did not. The frequency of short-term severe complications, either infectious (peritonsillar-parapharyngeal abscess or bacteremia) or non-infectious (splenic rupture, severe thrombocytopenia, myopericarditis, or lymphocytic meningitis) were similar in patients receiving and not receiving corticosteroids. After a median of 15 years of follow-up, only one Hodgkin's lymphoma was diagnosed, in a patient who was not treated with corticosteroids during infectious mononucleosis. CONCLUSIONS: The use of systemic corticosteroids during EBV-induced infectious mononucleosis is generally safe, at least with concomitant antibiotic therapy. However, this should not encourage the use of corticosteroids in this context, given that their efficacy has yet to be demonstrated.

Recommendations for the use of biomarkers for head and neck cancer, including salivary gland tumours: A Consensus of the Spanish Society of Medical Oncology and the Spanish Society of Pathology.

The treatment of head and neck and salivary gland tumours is complicated and is constantly evolving. Prognostic and predictive indicators of response to treatment are enormously valuable for designing individualized therapies, which justifies their research and validation. Some biomarkers, such as p16, Epstein-Barr virus, PD-L1, androgen receptors and HER-2, are already used routinely in clinical practice. These biomarkers, along with other markers that are currently under development, and the massively parallel sequencing of genes, ensure future advances in the treatment of these neoplasms. In this consensus, a group of experts in the diagnosis and treatment of tumours of the head and neck and salivary glands were selected by the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica - SEAP) and the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica - SEOM) to evaluate the currently available information and propose a series of recommendations to optimize the determination and daily clinical use of biomarkers.

Recommendations for the use of biomarkers for head and neck cancer, including salivary gland tumours: A Consensus of the Spanish Society of Medical Oncology and the Spanish Society of Pathology / Recomendaciones para el uso de biomarcadores para cáncer de cabeza y cuello, incluyendo tumores de glándulas salivares: consenso de la Sociedad Española de Oncología Médica y la Sociedad Española de Patología

The treatment of head and neck and salivary gland tumours is complicated and is constantly evolving. Prognostic and predictive indicators of response to treatment are enormously valuable for designing individualized therapies, which justifies their research and validation. Some biomarkers, such as p16, Epstein–Barr virus, PD-L1, androgen receptors and HER-2, are already used routinely in clinical practice. These biomarkers, along with other markers that are currently under development, and the massively parallel sequencing of genes, ensure future advances in the treatment of these neoplasms.In this consensus, a group of experts in the diagnosis and treatment of tumours of the head and neck and salivary glands were selected by the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica – SEAP) and the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica – SEOM) to evaluate the currently available information and propose a series of recommendations to optimize the determination and daily clinical use of biomarkers.(AU)

El tratamiento de los tumores de cabeza y cuello y de glándulas salivales es complejo, y evoluciona de forma constante. Los indicadores pronósticos y predictivos de respuesta al tratamiento son enormemente valiosos para diseñar terapias individualizadas, lo que justifica su investigación y validación. Algunos biomarcadores como p16, el virus de Epstein-Barr, PD-L1, los receptores de andrógenos o HER-2, ya se utilizan de manera rutinaria en la práctica clínica. Estos biomarcadores, junto con otros marcadores que están actualmente en desarrollo, y la secuenciación masiva de genes, aseguran los futuros avances en el tratamiento de estas neoplasias. En este consenso, un grupo de expertos en el diagnóstico y tratamiento de los tumores de cabeza y cuello y glándulas salivales seleccionado por la Sociedad Española de Anatomía Patológica (SEAP) y la Sociedad Española de Oncología Médica (SEOM) evalúan la información actualmente disponible y proponen una serie de recomendaciones para optimizar la determinación y utilización en la práctica clínica diaria de los biomarcadores.(AU)

Clinical and pathologic characteristics of gastric adenocarcinoma associated with Epstein-Barr virus in a region with a high incidence of gastric cancer in Colombia.

INTRODUCTION AND AIMS: Epstein-Barr virus (EBV) infection is an etiologic factor in EBV-associated gastric carcinoma (EBVaGC). The aim of our study was to describe the clinical and histopathologic characteristics of EBV infection in intestinal-type gastric adenocarcinoma samples. MATERIAL AND METHODS: Of 180 paraffin-embedded gastrectomy samples, 28 were studied. Chromogenic in situ hybridization was performed to detect EBV. Sociodemographic and histopathologic data were obtained from the patients' clinical histories. RESULTS: A total of 21.4% of the samples were positive for EBV. The predominant morphologic characteristic was the lace pattern, with dense inflammatory infiltration. Fifty percent of the EBVaGC+ patients were men, and the median age of the positive patients was 59 years (range: 50-75); 77.2% of the EBVaGC- patients were men, and the median age of the negative patients was 66 years (range: 34-89). Helicobacter pylori infection was associated with 10.7% of the EBVaGC+ patients and 53.6% of the EBVaGC- patients. In the EBVaGC+ patients, the cardia was the most frequent tumor location (17.9%), 7.1% had histologic grades 2 and 3, and 17.9% presented with Borrmann classification type III. In the EBVaGC- patients, the cardia and fundus were the most frequent tumor locations (71.4%), 35.7% had histologic grade 2, and 39.3% and 21.4% presented with Borrmann classification type III and IV, respectively. CONCLUSIONS: The present study describes the clinical and histopathologic characteristics associated with EBVaGC positivity. Those data may aid in the selection of cases that are candidates for analysis through molecular methods aimed at identifying EBV infection in intestinal-type gastric adenocarcinoma.

Pronostico desfavorable de linfoma t/nk: reporte de casos

El linfoma de células T/NK tiene una frecuencia de presentación inusual, caracterizado por una progresión rápida y de mal pronóstico. Ocurrencia aludida a regiones de Asia y Latinoamérica por la fuerte incidencia de infección por el virus de Epstein- Barr. Su presentación puede ser nasal o en otra localización. Los esquemas de tratamiento suelen conllevar respuestas insuficientes, empero protocolos con base en L-Asparaginasa reflejarían mejores resultados. El presente reporte corresponde a 4 casos de este tipo de linfoma, 2 de tipo nasal y 2 de diversa presentación. Todos evolucionaron desfavorablemente, en parte por el mal pronóstico atribuido y también por el diagnóstico suscitado en etapas avanzadas de enfermedad concatenadas a dificultades económicas para sostener el tratamiento, factores intervinientes en nuestro medio.

NK/T cell lymphoma is an unusual neoplasm, characterized by fast progression and poor prognosis. It is present in regions of Asia and Latin America associated to a high incidence of Epstein-Barr virus infection. Its presentation can be nasal or in another location. Treatment schemes usually lead to insufficient responses, however protocols based on L-Asparaginase would reflect better results. This report concerns 4 cases of this lymphoma, 2 nasal type and 2 of a different presentation. Patients responses were unfavorable, partly due to the poor prognosis att r ibuted and also due to the diagnosis raised in advanced stages of the disease as well as to economic difficulties to sustain treatment, intervening factors in our country.

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

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

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

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

Acute Horner syndrome secondary to glandular fever due to Epstein Barr virus infection.

We present a clinical situation where a 47-year old female patient consulted with left partial ptosis and miosis that started, two weeks before, with an episode of glandular fever secondary to Epstein-Barr infection. Apraclonidine 0.5% and Phenylephrine 1% drop testing was performed with results consistent with suspected left Horner Syndrome (HS), with a probable postganglionic location. Magnetic Resonance Angiography (MRA) at the moment of the acute presentation did not show any image suggesting carotid arterial dissection but showed irregular narrowing of the left internal carotid artery on its paravertebral extracranial way, consistent to enlarged intra-carotid sheath lymphoid tissue. A week later, a Doppler ultrasound was performed, showing bilateral images compatible with internal carotid arterial dissection. When Postganglionar HS is suspected, the first aetiology to rule out is a carotid arterial dissection because of its potentially fatal outcome and for being a more described entity as postganglionic HS aetiology. However, it is also evidenced that a certain diagnose is not always possible. Furthermore, we describe the enlarged internal carotid artery sheath lymphoid tissue as a possible cause of sympathetic nerve disruption causing a Postganglionar HS, although not common.

Síndrome de Horner agudo secundario a mononucleosis infecciosa por virus de Epstein Barr / Acute Horner syndrome secondary to glandular fever due to Epstein Barr virus infection

Presentamos el caso clínico de una mujer de 47 años que consultó por miosis y ptosis del ojo izquierdo cuyo inicio coincidió, 15 días antes, con un episodio de mononucleosis infecciosa con serología positiva para virus de Epstein-Barr. Se realizaron test con colirios de apraclonidina al 0,5% y fenilefrina al 1%, que apoyaron el diagnóstico de síndrome de Horner(SH) izquierdo posganglionar. En el momento agudo se practicó una angiografía por resonancia magnética que descartó disección carotídea, pero evidenció una imagen de arrosariamiento de la arteria carótida interna izquierda a lo largo de su trayecto extracraneal paravertebral compatible con inflamación del tejido linfático de la capa adventicia de la arteria. Una semana más tarde la ecografía Doppler de troncos supraaórticos con la que se completó el estudio mostraba una imagen compatible con disección de la arteria carótida interna bilateral. Ante un caso de SH posganglionar la primera causa a descartar por su gravedad, y por ser una entidad más ampliamente descrita como etiología del SH de 3.ª neurona, es la disección carotídea. Sin embargo, con este caso ponemos de manifiesto que no siempre se puede llegar a un diagnóstico certero. Asimismo, describimos la inflamación del tejido linfático carotídeo como posible etiología de una lesión de la cadena simpática cervical como causa infrecuente de SH posganglionar (AU)

We present a clinical situation where a 47-year old female patient consulted with left partial ptosis and miosis that started, two weeks before, with an episode of glandular fever secondary to Epstein-Barr infection. Apraclonidine 0.5% and Phenylephrine 1% drop testing was performed with results consistent with suspected left Horner Syndrome (HS), with a probable postganglionic location. Magnetic Resonance Angiography (MRA) at the moment of the acute presentation did not show any image suggesting carotid arterial dissection but showed irregular narrowing of the left internal carotid artery on its paravertebral extracranial way, consistent to enlarged intra-carotid sheath lymphoid tissue. A week later, a Doppler ultrasound was performed, showing bilateral images compatible with internal carotid arterial dissection. When Postganglionar HS is suspected, the first aetiology to rule out is a carotid arterial dissection because of its potentially fatal outcome and for being a more described entity as postganglionic HS aetiology. However, it is also evidenced that a certain diagnose is not always possible. Furthermore, we describe the enlarged internal carotid artery sheath lymphoid tissue as a possible cause of sympathetic nerve disruption causing a Postganglionar HS, although not common (AU)

Identificación de macrófagos y virus Epstein-Barr en biopsias de pacientes con Síndrome de Sjögren / Identification of macrophages and Epstein-Barr virus in salivary glands of Sjögren's syndrome patients

RESUMEN El síndrome de Sjögren (SS) es una enfermedad crónica mediada inmunológicamente. La presencia de macrófagos y el virus Epstein-Barr (VEB) se ha relacionado con su desarrollo y severidad. Los macrófagos contribuyen al proceso autoinmune local y la infección viral promueve el quiebre de la auto-tolerancia. Objetivos. Identificar la presencia de Macrófagos en el infiltrado inflamatorio y VEB en células inflamatorias, correlacionándolos con las características histológicas de glándulas salivales labiales. Metodología. En biopsias de glándulas salivales labiales (8 pacientes y 7 individuos controles) se realizó inmunohistoquímica antiCD-68 para identificar macrófagos. El conteo de macrófagos y células inflamatorias se efectuó en relación a su distribución en las glándulas salivales. La presencia del virus fue evaluada mediante hibridación in situ e inmunohistoquímica para LMP1. Se utilizó el test t no pareado y de Mann-Whitney para comparar los grupos, y coeficiente de correlación de Pearson para correlacionar con parámetros histológicos. Resultados. Se observó un mayor número de macrófagos en el infiltrado inflamatorio de pacientes (p=0,001**). Los macrófagos se distribuyeron difusamente en las glándulas de controles y en los focos inflamatorios de pacientes. En ambos grupos no se detectó la presencia del virus Epstein-Barr. Conclusión. Los pacientes con síndrome de Sjögren presentaron mayor presencia de macrófagos y su incremento es a expensas del foco inflamatorio.

ABSTRACT: Sjögren's syndrome (SS) is an immunologically mediated chronic disease of complex etiopathogenesis. Macrophages and Epstein-Barr virus are among the factors related to its development and severity. Macrophages contribute to the local autoimmune process and viral infection promotes the breakdown of self-tolerance. Objectives. Identify the presence of macrophages in the inflammatory infiltrate and Epstein-Barr virus in inflammatory cells, correlating them with the histological features of labial salivary glands. Methodology. In labial salivary glands biopsies of 8 patients and 7 control individuals, anti-CD-68 immunohistochemistry was performed to identify macrophages. The macrophages and inflammatory cells were counted in relation to their distribution in the salivary glands. The presence of the virus was evaluated by in situ hybridization for viral RNA and immunohistochemistry for latent membrane protein type 1. The comparison between both groups was made using the unpaired t-test and Mann-Whitney test. The correlations with histological parameters were established with the Pearson´s correlation coefficient. Results. A greater number of macrophages was observed in the inflammatory infiltrate of SS patients (p=0,001**). Macrophages in control individuals were diffusely distributed in the gland, while, SS in patients, they were mainly located in inflammatory foci. In both groups, no inflammatory or epithelial cells infected by the Epstein-Barr virus were identified. Conclusion. Patients with Sjögren's syndrome had a greater presence of macrophages and their increase is at the expense of the inflammatory focus.

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.

A pediatric case of Bartonella henselae and Epstein Barr virus disease with bone and hepatosplenic involvement / Un caso pediátrico de enfermedad por Bartonella henselae y virus de Epstein Barr con afectación ósea y hepatoesplénica

Abstract Background: Cat scratch disease (CSD) is an infectious disorder caused by Bartonella henselae. The infection usually presents as local lymphadenopathy, fever, and mild constitutional symptoms. Systemic or severe disease is reported in 5-20% of patients with CSD. We report a case of disseminated CSD with osteomyelitis and hepatosplenic disease and a review of the literature. Case report: A previously healthy 5-year-old male presented with prolonged fever and abdominal pain, followed by low back pain. The serologic test showed positive IgG for B. henselae and IgM and IgG for Epstein Barr virus (EBV). The abdominal ultrasound showed hepatic and splenic hypoechoic lesions, and the magnetic resonance imaging (MRI) revealed spondylitis of the D6 vertebra. He received treatment with azithromycin for 4 weeks and rifampicin for 6 weeks. The symptoms disappeared, and the abdominal ultrasound was normal nine months later. Conclusions: Disseminated CSD is infrequent. The diagnosis requires a high rate of suspicion. Laboratory findings of Bartonella infection are often non-specific. Serologic test, polymerase chain reaction of B. henselae in blood or biopsied material of the site of involvement and imaging test can be performed to confirm the diagnosis. The diagnosis of disseminated B. henselae was based on significantly elevated blood titers, radiologic findings, and epidemiologic history. Treatment of CSD depends on the disease presentation. Azithromycin is used as a first-line agent for lymphadenopathy. The optimum treatment and its duration have not been established in atypical or complicated CSD, including patients with osteomyelitis and hepatosplenic disease.

Resumen Introducción: La enfermedad por arañazo de gato (EAG) es una patología infecciosa originada por Bartonella henselae. Habitualmente se presenta como linfadenopatía local, fiebre y síntomas constitucionales leves. El 5-20% de los pacientes con EAG manifiestan una afectación sistémica. Se presenta un caso de EAG diseminada, con osteomielitis y enfermedad hepatoesplénica, y se hace una revisión de la literatura sobre la EAG. Caso clínico: Paciente de sexo masculino de 5 años, previamente sano, que presentó fiebre prolongada y dolor abdominal, seguidos de dolor en la parte baja de la espalda. En la serología, presencia de IgG frente a B. henselae y de IgM e IgG frente al virus de Epstein-Barr. En la ecografía abdominal se observaron lesiones hipoecoicas en el hígado y el bazo, y la resonancia magnética mostró espondilitis de D6. Recibió tratamiento con azitromicina 4 semanas y rifampicina 6 semanas. Los síntomas desaparecieron y la ecografía abdominal a los 9 meses fue normal. Conclusiones: La EAG diseminada es infrecuente. El diagnóstico requiere un alto grado de sospecha. Los hallazgos de laboratorio en la infección por Bartonella suelen ser poco específicos. Para confirmar el diagnóstico pueden hacerse serología, reacción en cadena de la polimerasa para B. henselae en sangre o en biopsia de tejidos afectados, y estudios de imagen. El diagnóstico de EAG diseminada se basa en títulos elevados en la sangre, hallazgos radiológicos e historia epidemiológica. El tratamiento depende de la forma de presentación. En los casos de linfadenopatía se utiliza azitromicina. En la EAG atípica o complicada, que incluye osteomielitis y afectación hepatoesplénica, no están bien establecidos el tratamiento ni su duración.

A pediatric case of Bartonella henselae and Epstein Barr virus disease with bone and hepatosplenic involvement.

Background: Cat scratch disease (CSD) is an infectious disorder caused by Bartonella henselae. The infection usually presents as local lymphadenopathy, fever, and mild constitutional symptoms. Systemic or severe disease is reported in 5-20% of patients with CSD. We report a case of disseminated CSD with osteomyelitis and hepatosplenic disease and a review of the literature. Case report: A previously healthy 5-year-old male presented with prolonged fever and abdominal pain, followed by low back pain. The serologic test showed positive IgG for B. henselae and IgM and IgG for Epstein Barr virus (EBV). The abdominal ultrasound showed hepatic and splenic hypoechoic lesions, and the magnetic resonance imaging (MRI) revealed spondylitis of the D6 vertebra. He received treatment with azithromycin for 4 weeks and rifampicin for 6 weeks. The symptoms disappeared, and the abdominal ultrasound was normal nine months later. Conclusions: Disseminated CSD is infrequent. The diagnosis requires a high rate of suspicion. Laboratory findings of Bartonella infection are often non-specific. Serologic test, polymerase chain reaction of B. henselae in blood or biopsied material of the site of involvement and imaging test can be performed to confirm the diagnosis. The diagnosis of disseminated B. henselae was based on significantly elevated blood titers, radiologic findings, and epidemiologic history. Treatment of CSD depends on the disease presentation. Azithromycin is used as a first-line agent for lymphadenopathy. The optimum treatment and its duration have not been established in atypical or complicated CSD, including patients with osteomyelitis and hepatosplenic disease.

Introducción: La enfermedad por arañazo de gato (EAG) es una patología infecciosa originada por Bartonella henselae. Habitualmente se presenta como linfadenopatía local, fiebre y síntomas constitucionales leves. El 5-20% de los pacientes con EAG manifiestan una afectación sistémica. Se presenta un caso de EAG diseminada, con osteomielitis y enfermedad hepatoesplénica, y se hace una revisión de la literatura sobre la EAG. Caso clínico: Paciente de sexo masculino de 5 años, previamente sano, que presentó fiebre prolongada y dolor abdominal, seguidos de dolor en la parte baja de la espalda. En la serología, presencia de IgG frente a B. henselae y de IgM e IgG frente al virus de Epstein-Barr. En la ecografía abdominal se observaron lesiones hipoecoicas en el hígado y el bazo, y la resonancia magnética mostró espondilitis de D6. Recibió tratamiento con azitromicina 4 semanas y rifampicina 6 semanas. Los síntomas desaparecieron y la ecografía abdominal a los 9 meses fue normal. Conclusiones: La EAG diseminada es infrecuente. El diagnóstico requiere un alto grado de sospecha. Los hallazgos de laboratorio en la infección por Bartonella suelen ser poco específicos. Para confirmar el diagnóstico pueden hacerse serología, reacción en cadena de la polimerasa para B. henselae en sangre o en biopsia de tejidos afectados, y estudios de imagen. El diagnóstico de EAG diseminada se basa en títulos elevados en la sangre, hallazgos radiológicos e historia epidemiológica. El tratamiento depende de la forma de presentación. En los casos de linfadenopatía se utiliza azitromicina. En la EAG atípica o complicada, que incluye osteomielitis y afectación hepatoesplénica, no están bien establecidos el tratamiento ni su duración.

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.

[EBV and immunodeficiency]. / EBV et immunodépression.

Epstein-Barr virus (EBV), discovered in 1964, is a double-stranded DNA virus belonging to the Herpesviridae family. EBV has a lymphoid tropism with transforming capacities using different oncogenic viral proteins. This virus has two replication cycles: a lytic cycle mainly occuring during primary infection and a latent cycle allowing viral persistence into host memory B cells. More than 90% of adults are seropositive for EBV worldwide, with a past history of asymptomatic or mild primary infection. EBV infection can sometimes cause life-threatening complications such as hemophagocytic lymphohistiocytosis, and lead to the development of lymphoproliferative disorders or cancers. Risk factors associated with these phenotypes have been recently described through the study of monogenic primary immune deficiencies with EBV susceptibility. We here review the virological and immunological aspects of EBV infection and EBV-related complications with an overview of current available treatments.

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.

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.

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)

Úlcera de Lipschütz: reporte de un caso y revisión bibliográfica / Lipschütz Ulcer: a case report and a literature review

Resumen: ANTECEDENTES: Las úlceras de Lipschütz son lesiones vulvovaginales dolorosas, de aparición aguda y desaparición espontánea en 2 a 6 semanas, no dejan secuelas ni son recurrentes a largo plazo. Su etiopatogenia es incierta, alrededor de 70% se consideran idiopáticas. En los estudios más recientes se ha demostrado su asociación con agentes infecciosos, sobre todo con el virus de Epstein-Barr. El diagnóstico se establece por exclusión y su tratamiento se basa en el control sintomático, cicatrizantes, analgésicos y antisépticos. CASO CLÍNICO: Paciente de 15 años, con úlceras vulvares de aparición súbita acompañadas de cuadro catarral. Se indicó tratamiento local con cicatrizante, antiséptico y antiinflamatorio; al cabo de tres semanas se observó la desaparición de las lesiones y la negatividad de las pruebas que descartó el origen infeccioso. Se estableció el diagnóstico de úlcera de Lipschütz. CONCLUSIONES: La úlcera de Lipschütz es infrecuente y los niños son quienes más la padecen. Debido al carácter de desaparición espontánea y a la juventud de las pacientes, es decisivo establecer el correcto diagnóstico diferencial.

Abstract: BACKGROUND: Lipschütz Ulcers are painful, acute onset and self-limiting vulvovaginal lesions that can frequently be associated with prodromal symptoms, disappearing in 2-6 weeks without any sequelae. 70% of cases present idiopathic etiopathogenesis, and are related to Epstein-Barr virus, among others. The diagnosis is made by exclusion and its treatment is based on symptomatic control and the promotion of correct healing, using analgesics, cicatrizers and antiseptics. CASE REPORT: A 15-year-old girl reported the acute apparition of ulcerative vulvar lesions coinciding with systemic catarrhal symptoms. Local treatment with healing, antiseptic and anti-inflammatory lotions was prescribed, and after three weeks, she was reevaluated, observing the disappearance of the lesions and the negativity of the tests to rule out infectious origin, for which she was diagnosed with a Lipschütz ulcer. CONCLUSIONS: Lipschütz ulcer is rare and children are the ones who suffer most from it. Due to the spontaneous disappearance character and the youthfulness of the patients, it is decisive to establish the correct differential diagnosis.

Enfoque del paciente con adenopatías generalizadas. Importancia de la estrategia didáctica del estudio de casos clínicos: a propósito de un paciente con linfoma de Hodgkin asociado a una infección por el virus de Epstein-Barr

Se muestra el caso de un paciente con 56 años de edad, con un síndrome adenomegálico generalizado que presentó un linfoma de Hodgkin de celularidad mixta, asociado al virus de Epstein-Barr. El paciente previo al inicio del linfoma presentó episodios prolongados de estrés emocional, lo que posiblemente contribuyó a la disminución de la vigilancia inmunológica. El caso fue abordado por los estudiantes de quinto semestre en la asignatura Acto médico, una estrategia didáctica interdisciplinaria. Este artículo presenta los aspectos a tener en cuenta en el enfoque clínico de los pacientes con adenopatías desde una perspectiva integradora de la inmunología, la clínica y los diagnósticos diferenciales. Se resalta el valor del estudio de los casos clínicos con varios métodos diagnósticos como estrategia didáctica. Finalmente, se realiza una revisión de la literatura sobre el linfoma Hodgkin orientada al papel en el que participa la infección por el virus de Epstein-Barr, relacionada con la inmunosupresión por estrés.

SUMMARY We present the case of a 56-year-old patient with a generalized adenomegalic syndrome who presented a mixed cellular Hodgkin's lymphoma associated with Epstein Barr Virus. The patient had had great emotional stress prior to the onset of lymphoma, which possibly contributed to the decrease in immunological surveillance. The case was addressed by the students of the fifth semester in the subject "Medical Act", an interdisciplinary didactic strategy. We present the aspects to be taken into account in the approach of the clinician of patients with adenopathies from an integrative perspective of immunology, clinical and differential diagnoses; and the value of the study of clinical cases with several diagnostic approaches as a didactic strategy is highlighted. Finally, we present a literature review about Hodgkin lymphoma and the role which plays stress related Epstein Barr Virus infection.