Pathological Types,Expression of Mismatch Repair Protein,Human Epidermal Growth Factor Receptor 2,and Pan-TRK,and Eostein-Barr Virus Infection in Patients With Colorectal Cancer Resected in Tibet / 中国医学科学院学报

Objective To study the pathological types,expression of mismatch repair protein,human epidermal growth factor receptor 2(HER2),and Pan-TRK,and Epstein-Barr virus(EBV)infection in patients with colorectal cancer resected in Tibet. Methods A total of 79 patients with colorectal cancer resected in Tibet Autonomous Region People's Hospital from December 2013 to July 2021 were enrolled in this study.The clinical and pathological data of the patients were collected.The expression of mismatch repair protein,HER2,and Pan-TRK was detected by immunohistochemical(IHC)staining,and detection of HER2 gene by fluorescence in situ hybridization(FISH)in the patients with HER2 IHC results of 2+ or above.EBV was detected by in situ hybridization with EBV-encoded small RNA. Results A total of 79 colorectal cancer patients were included in this study,with the male-to-female ratio of 1.26:1 and the mean age of(57.06±12.74)years(24-83 years).Among them,4 patients received preoperative neoadjuvant therapy.Colonic cancer and rectal cancer occurred in 57(57/79,72.15%,including 31 and 26 in the right colon and left colon,respectively)and 22(22/79,27.85%)patients,respectively.The maximum diameter of tumor varied within the range of 1-20 cm,with the mean of(6.61±3.33)cm.Among the 79 colorectal cancer patients,75(75/79,94.94%)patients showed adenocarcinoma.Lymph node metastasis occurred in 12(12/21,57.14%)out of the 21 patients with severe tumor budding,13(13/23,56.52%)out of the 23 patients with moderate tumor budding,and 2(2/31,6.45%)out of the 31 patients with mild tumor budding,respectively.The lymph node metastasis rate showed differences between the patients with severe/moderate tumor budding and the patients with mild tumor budding(all P<0.001).The IHC staining showed that mismatch repair protein was negative in 10(10/65,15.38%)patients,including 5 patients with both MSH2 and MSH6 negative,4 patients with both MLH1 and PMS2 negative,and 1 patient with MSH6 negative.Pan-TRK was negative in 65 patients.The IHC results of HER2 showed 0 or 1+ in 60 patients and 2+ in 5 patients.FISH showed no positive signal in the 5 patients with HER2 IHC results of 2+.The detection with EBV-encoded small RNA showed positive result in 1(1/65,1.54%)patient. Conclusions Non-specific adenocarcinoma of the right colon is the most common in the patients with colorectal cancer resected in Tibet,and 15% of the patients showed mismatch repair protein defects.EBV-associated colorectal carcer is rare,Pan-TRK expression and HER2 gene amplification are seldom.The colorectal cancer patients with moderate and severe tumor budding are more likely to have lymph node metastasis.

Dynamic monitoring of plasma Epstein-Barr Virus DNA load can predict the occurrence of lymphoproliferative disorders after haploidentical hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To determine the optimal cutoff value of Epstein-Barr virus (EBV) DNA load that can assist in the diagnosis of post-transplant lymphoproliferative disease (PTLD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: The data of patients with EBV infection after haplo-HSCT from January to December 2016 were retrospectively analyzed. Through constructing the receiver operating characteristic (ROC) curve and calculating the Youden index to determine the cutoff value of EBV-DNA load and its duration of diagnostic significance for PTLD. Results: A total of 94 patients were included, of whom 20 (21.3% ) developed PTLD, with a median onset time of 56 (40-309) d after transplantation. The median EBV value at the time of diagnosis of PTLD was 70,400 (1,710-1,370,000) copies/ml, and the median duration of EBV viremia was 23.5 (4-490) d. Binary logistic regression was used to analyze the peak EBV-DNA load (the EBV-DNA load at the time of diagnosis in the PTLD group) and duration of EBV viremia between the PTLD and non-PTLD groups. The results showed that the difference between the two groups was statistically significant (P=0.018 and P=0.001) . The ROC curve was constructed to calculate the Youden index, and it was concluded that the EBV-DNA load ≥ 41 850 copies/ml after allogeneic hematopoietic stem cell transplantation had diagnostic significance for PTLD (AUC=0.847) , and the sensitivity and specificity were 0.611 and 0.932, respectively. The duration of EBV viremia of ≥20.5 d had diagnostic significance for PTLD (AUC=0.833) , with a sensitivity and specificity of 0.778 and 0.795, respectively. Conclusion: Dynamic monitoring of EBV load in high-risk patients with PTLD after haplo-HSCT and attention to its duration have important clinical significance, which can help clinically predict the occurrence of PTLD in advance and take early intervention measures.

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.

Pneumonia por toxoplasmose em paciente imunocompetente / Toxoplasma pneumonia in an immunocompetent patient: case repor

Com grande distribuição mundial e incidência significativa, a toxoplamose é uma doença comum em mamíferos e pássaros, causada pelo protozoário Toxoplasma gondii. No homem, o parasitismo na fase proliferativa intracelular pode se apresentar sem sintomas, ou causar clínica transitória caracterizada por febre, fadiga e linfadenopatia. Por se tratar de patologia com sintomas inespecíficos e comuns a muitas outras, é fundamental a correta pesquisa de diagnósticos diferenciais, como citomegalovírus e Epstein-Barr. Relatamos o caso de um jovem e hígido, que desenvolveu pneumonia e, após confirmação sorológica para toxoplasmose e o tratamento adequado, apresentou melhora clínica.

With great worldwide distribution and significant incidence, toxoplamosis is a common disease in mammals and birds, caused by the protozoan Toxoplasma gondii. In humans, the parasitism in its intracellular proliferative phase may present no symptoms, or cause a transient condition characterized by fever, fatigue, and lymphadenopathy. Because it is a pathology with nonspecific symptoms that are common to many other conditions, it is fundamental to find the correct research of differential diagnoses, such as for Cytomegalovirus and Epstein Barr. We report a case of a young and healthy man who developed pneumonia and, after serological confirmation for toxoplasmosis and the appropriate treatment, presented clinical improvement

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

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

Identificación del Virus Epstein-Barr por Hibridación in situ en pacientes con Cáncer Gástrico que asisten al Instituto de Cancerología (Incan) de Guatemala / Identification of Epstein-Barr Virus by in situ Hybridization in Gastric Cancer patients attending the Cancer Institute (Incan) Guatemala

El Virus Epstein Barr (EBV) está relacionado como agente oncogénico en el desarrollo del cáncer gástrico, atribuyéndosele el 10 % de los casos de esta neoplasia a nivel mundial. No existen estudios previos que identifiquen la presencia EBV en los pacientes con cáncer gástrico en Guatemala, por lo que en este estudio se evaluó por hibridación in situ la presencia del micro ARN EBER (Epstein Barr ­encoded RNAs) de EBV en 71 pacientes con cáncer gástrico que asistieron al Instituto de Cancerología (Incan). Se determinó una prevalencia de 21.1 % (IC 95 % [10.9, 31.3] ) (15 pacientes), mayor que la reportada en otros estudios latinoamericanos. Se determinó asociación significativa entre la expresión del EBER del EBV, y el género masculino OR = 4.9 (IC 95 % [1.4, 17.5]) p < .05. Los factores asociados fueron, el padecer diarrea OR 5.7 IC 95 % [1.5, 12.6] p = .008, y la detección del anticuerpos de Helicobacter pylori séricos, OR 7.2 (IC 95 % [1.1, 18.9]) p = .03. Aun cuando la mayoría de los pacientes que expresan el EBER de EBV desarrollaron cáncer gástrico del tipo difuso 66.67 % no existe asociación significativa p = 0.13 OR = 2.5 (IC 95 % [1.1, 8.2]).

The Epstein Barr Virus (EBV) is related, as an oncogenic agent, in the development of gastric cancer, accounting for 10 % of the cases of this neoplasm worldwide. There are no previous studies that identify the presence of EBV in patients with gastric cancer in Guatemala, so in this study the presence of the EBER micro EBV of EBV was evaluated by in situ hybridization in 71 patients with gastric cancer who attended the Cancer Institute (Incan). A prevalence of 21.1% (95 % CI [10.9, 31.3]) was determined (15 patients), higher than that reported in other Latin American studies. A significant association was found between the EBER expression of EBV, and the male gender OR = 4.9 (95 % CI [1.4, 17.5]) p < .05. The associated factors were diarrhea OR 5.7 95 % (CI [1.5, 12.6]) p = .008, and detection of Helicobacter pylori serum antibodies, OR 7.2 95 % CI [1.1, 18.9] p = .03. Although the majority of patients expressing EBV EBER developed gastric cancer of the diffuse type 66.67% there is no significant association p = 0.13, OR = 2.5 (95 % CI [1.1, 8.2]).

Síndrome de Alice no país das maravilhas e reativação de infeção por Epstein-Barr / Alice in wonderland syndrome and reactivation of infection by Epstein-Barr

INTRODUÇÃO: O síndrome de Alice no País das Maravilhas (SAPM) é uma entidade rara que pode ocorre no contexto de várias condições clínicas, sendo a infeção por vírus Epstein-barr (EBV) a mais comum nas causas infeciosas. Apresenta-se um caso de SAPM associado a infeção a EBV alertando para a necessidade de investigação etiológica destes casos. RELATO DE CASO: Criança de 8 anos, com síndrome de Asperger que, no contexto de amigdalite aguda e febre, surgiu com episódios paroxísticos de alguns minutos de metamorfopsias (macro e micropsia), distorção da perceção das vozes e sensação de medo. A ressonância magnética e o eletroencefalograma foram normais, e o exame citoquímico do líquor foi normal mas a polimerase chain reaction (PCR) foi positiva para vírus EBV. As serologias para EBV, repetidas 3 e 10 semanas após a avaliação inicial, confirmaram uma reativação da infeção por este agente. O doente ficou assintomático após 2 semanas e não houve recidivas. CONCLUSÕES: A investigação de metamorfopsias ou síndrome de SAPM é mandatória pois podem indiciar patologia grave, nomeadamente lesão cerebral ou epilepsia focal. Embora a doença seja rara a etiologia infecciosa deve ser excluída mesmo em doentes com perturbação prévia do comportamento.

INTRODUCTION: Alice in wonderland syndrome (AWS) is a rare condition which may occur as a sign of multiple conditions, with the most frequent infectious etiology being Epstein-barr virus (EBV) infection. We present a case of an AWS caused by EBV infection to alert for the need to investigate these cases. CASE REPORT: 8-year-old boy with Asperger syndrome who developed, in the context of tonsillitis and fever, brief paroxystic episodes of metamorfopsias (macro and micropsia), with voice perception distortion and fear. Physical exam was otherwise normal. Brian magnetic resonance and electroencephalogram were normal, liquor cytochemical exam was normal but Epstein-barr virus (EBV) polimerase chain reaction was positive. EBV blood serologies, repeated 3 and 10 weeks after the initial evaluation, confirmed the reactivation of this agent's infection. Symptoms succumbed 2 weeks after its beginning, with no relapses. CONCLUSIONS: Metamorfopsias or AWS impose etiological investigation because they may occur due to severe disease, namely cerebral lesion or focal epilepsy. Although it is a rare disease, infectious causes should be excluded, even in patients with previous disturbed behavior.

Epstein-Barr virus and skin

Abstract: Epstein-Barr virus is a DNA virus infecting human beings and could affect 90% of human population. It is crucial to take in account that in Latin America, unlike what happens in developed countries, the exposure to the virus is very early and therefore people have a much longer interaction with the virus. The virus is related to many diseases, mainly the oncological ones, and when the onset is in cutaneous tissue, it can present many clinical variants, as well acute as chronic ones. Among the acute ones are infectious mononucleosis rash and Lipschutz ulcers; the chronic presentations are hypersensivity to mosquito bites, hydroa vacciniforme, hydroa vacciniforme-like lymphoma, its atypical variants and finally nasal and extra-nasal NK/T-cell lymphoma. Although they are not frequent conditions, it is crucial for the dermatologist to know them in order to achieve a correct diagnosis.

Infección por Mycobacterium scrofulaceum en un niño de las Islas Galápagos - Ecuador / Mycobacterium scrofulaceum infection in a pediatric patient from the Galapagos Islands - Ecuador

Resumen Mycobacterium scrofulaceum es una micobacteria atípica de crecimiento lento que tiene como reservorio el ambiente. De forma ocasional causa enfermedad en humanos. Se presenta el caso de un niño de 10 años de edad con fiebre de cuatro meses de evolución, adenopatías cervicales, torácicas, abdominales e inguinales bilaterales, exantema, dolor abdominal y vómitos; con evidencia concomitante de serología positiva para el VEB y cultivo de los ganglios inguinales izquierdos con crecimiento de M. scrofulaceum. Es la primera comunicación de una infección causada por esta micobacteria en Ecuador, y que particularmente se presentó con un patrón de resistencia inusual.

Mycobacterium scrofulaceum is a slow-growing atypical mycobacteria with a reservoir in the environmen, and occasionally it causes disease in humans. The case of a 10-year-old patient with fever of four months of evolution is presented. Symptoms include bilateral adenopathies of neck, thorax, abdomen and inguinal region, rash, abdominal pain and vomiting; in addition, a positive serology for EBV and a culture of the left inguinal ganglia with growth of M. scrofulaceum were evidenced. Thus, this is the first report of human infection caused by the aforementioned mycobacterium in Ecuador, which it was particularly manifested with an unusual pattern of resistance.

Performance of the Real-Q EBV Quantification Kit for Epstein-Barr Virus DNA Quantification in Whole Blood

There has been increasing interest in standardized and quantitative Epstein-Barr virus (EBV) DNA testing for the management of EBV disease. We evaluated the performance of the Real-Q EBV Quantification Kit (BioSewoom, Korea) in whole blood (WB). Nucleic acid extraction and real-time PCR were performed by using the MagNA Pure 96 (Roche Diagnostics, Germany) and 7500 Fast real-time PCR system (Applied Biosystems, USA), respectively. Assay sensitivity, linearity, and conversion factor were determined by using the World Health Organization international standard diluted in EBV-negative WB. We used 81 WB clinical specimens to compare performance of the Real-Q EBV Quantification Kit and artus EBV RG PCR Kit (Qiagen, Germany). The limit of detection (LOD) and limit of quantification (LOQ) for the Real-Q kit were 453 and 750 IU/mL, respectively. The conversion factor from EBV genomic copies to IU was 0.62. The linear range of the assay was from 750 to 10⁶ IU/mL. Viral load values measured with the Real-Q assay were on average 0.54 log₁₀ copies/mL higher than those measured with the artus assay. The Real-Q assay offered good analytical performance for EBV DNA quantification in WB.

Familial Hemophagocytic Lymphohistiocytosis Type 2 in a Korean Infant With Compound Heterozygous PRF1 Defects Involving a PRF1 Mutation, c.1091T>G

No abstract available.

Epstein-Barr virus load in transplant patients: Early detection of post-transplant lymphoproliferative disorders / Carga de virus Epstein-Barr en pacientes trasplantados: detección temprana de desórdenes linfoproliferativos postrasplante

High levels of circulating EBV load are used as a marker of post-transplant lymphoproliferative disorders (PTLD). There is no consensus regarding the threshold level indicative of an increase in peripheral EBV DNA. The aim of the study was to clinically validate a developed EBV quantification assay for early PTLD detection. Transversal study: paired peripheral blood mononuclear cells (PBMC), plasma and oropharyngeal lymphoid tissue (OLT) from children undergoing a solid organ transplant with (n = 58) and without (n = 47) PTLD. Retrospective follow-up: 71 paired PBMC and plasma from recipients with (n = 6) and without (n = 6) PTLD history. EBV load was determined by real-time PCR. The diagnostic ability to detect all PTLD (categories 1-4), advanced PTLD (categories 2-4) or neoplastic PTLD (categories 3 and 4) was estimated by analyzing the test performance at different cut-off values or with a load variation greater than 0.5 log units. The higher diagnostic performance for identifying all, advanced or neoplastic PTLD, was achieved with cut-off values of 1.08; 1.60 and 2.47 log EBV gEq/10(5) PBMC or 2.30; 2.60; 4.47 log gEq/10(5) OLT cells, respectively. EBV DNA detection in plasma showed high specificity but low (all categories) or high (advanced/neoplastic categories) sensitivity for PTLD identification. Diagnostic performance was greater when: (1) a load variation in PBMC or plasma was identified; (2) combining the measure of EBV load in PBMC and plasma. The best diagnostic ability to identify early PTLD stages was achieved by monitoring EBV load in PBMC and plasma simultaneously; an algorithm was proposed.

La carga alta del virus Epstein-Barr se utiliza como un marcador de desórdenes linfoproliferativos postrasplante (post-transplant lymphoproliferative disorders [PTLD]). El objetivo de este estudio fue validar clínicamente un ensayo de cuantificación del virus Epstein-Barr para la detección temprana de PTLD. Se efectuó un estudio transversal en el que se analizaron muestras pareadas de células mononucleares periféricas (CMP), de plasma y de tejido linfoide orofaríngeo de niños con trasplante de órgano sólido, con PTLD (n = 58) y sin PTLD (n = 47). En el seguimiento retrospectivo se incluyeron 71 muestras pareadas de CMP y de plasma de trasplantados, con PTLD (n = 6) y sin PTLD (n = 6). La carga viral se determinó por PCR en tiempo real. Se estimó la capacidad diagnóstica para detectar PTLD (categorías: todas vs. avanzadas vs. neoplásicas) analizando diferentes valores de corte o una variación de carga mayor de 0,5 logaritmos. El mayor desempeño diagnóstico para identificar todos los PTLD, los avanzados y los neoplásicos, se obtuvo con valores de corte de 1,08; 1,60 y 2,47 log copias/10(5) en CMP y de 2,30; 2,60 y 4,48 log copias/10(5) en células de tejido linfoide orofaríngeo, respectivamente. La detección del ADN del virus Epstein-Barr en el plasma mostró una especificidad alta, pero una sensibilidad baja (todas las categorías) o alta (categorías avanzadas o neoplásicas) para identificar PTLD. Se observó el desempeño diagnóstico más alto en las siguientes condiciones: 1) al identificar una variación de carga en CMP o en plasma; 2) combinando la medición de la carga viral en CMP y en plasma. La mejor capacidad diagnóstica para identificar las etapas tempranas de los PTLD se logró mediante el seguimiento simultáneo de la carga viral en CMP y en plasma; se propone un algoritmo.

Clinical presentation of hemophagocytic lymphohistiocytosis in adults is less typical than in children

OBJECTIVE: Hemophagocytic lymphohistiocytosis in adults is largely underdiagnosed. To improve the rate and accuracy of diagnosis in adults, the clinical and laboratory characteristics of hemophagocytic lymphohistiocytosis were analyzed in and compared between adults and children in a Chinese cohort. METHOD: Data from 50 hemophagocytic lymphohistiocytosis patients, including 34 adults and 16 children who fulfilled the 2004 hemophagocytic lymphohistiocytosis diagnostic criteria, were collected and analyzed. RESULTS: 1. Etiological factors: The proportion of Epstein-Barr virus infection was lower in adults compared with children, whereas fungal infection and natural killer/T cell lymphoma were more frequent in adults (P<0.05). 2. Clinical manifestations and laboratory findings: Over 90% of adults and pediatric patients presented with fever, thrombocytopenia and high serum ferritin levels. However, in adults, the proportions of hepatomegaly, splenomegaly and jaundice were much lower (P<0.01) than in children, and serous cavity effusion was more frequent in adult patients (P<0.05). More children had hemoglobin <90 g/L, total bilirubin >19 mmol/L and lactate dehydrogenase >500 U/L compared with adults (P<0.05). 3. The time interval from the onset of symptoms to clinical diagnosis was significantly shorter in pediatric patients than in adults (P<0.05). CONCLUSIONS: Certain clinical features were different between the two groups. The less characteristic clinical presentation of hemophagocytic lymphohistiocytosis in adults may make the disease more difficult to diagnose. Our findings suggest that hemophagocytic lymphohistiocytosis should be considered when an adult patient presents with the above-mentioned symptoms.

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.

Tamizaje de infecciones por virus Epstein Barr en muestras de sangre mediante el uso de una PCR en tiempo real previo a la cuantificación de la carga viral / Screening for Epstein Barr virus infections in blood samples using real-time PCR previous to viral load quantification

El desorden linfoproliferativo postrasplante es una de las complicaciones más importantes producidas por el virus Epstein Barr (EBV) en pacientes trasplantados de órganos sólidos y de médula ósea ya que afecta la sobrevida del paciente y del injerto. En estos pacientes se han reportado altos niveles de carga viral en sangre periférica que preceden al desarrollo del desorden linfoproliferativo postrasplante. Por esto el monitoreo de la carga viral (CV) permite detectar pacientes en riesgo a desarrollar esta patología para iniciar una terapia preventiva. El objetivo de este trabajo fue desarrollar una técnica de PCR en tiempo real cualitativa (RT PCR) que permitiera ser utilizada como prueba de tamizaje previo a la determinación de CV EBV. De esta manera se podrían minimizar el costo que implicaría la utilización de un método cuantitativo comercial para todas las muestras que ingresaran al monitoreo viral. Teniendo en cuenta el desempeño de la RT PCR desarrollada, se estableció Ct ≤ 37 como valor límite para evitar amplificación inespecífica y seleccionar las muestras candidatas a la determinación de CV EBV. Dicho punto de corte presentó una sensibilidad diagnóstica relativa de 80%, una especificidad diagnóstica relativa de 85%, un valor predictivo positivo (VPP) de 53% y un valor predictivo negativo (VPN) de 95%. Para ello se consideró que valores de CV EBV< 4000 copias/ml sangre eran bajas o no presentaban riesgo de desarrollar complicaciones. El límite de detección LoD 95% fue de 280 copias de EBV/ml sangre (66 ­ 1184, IC 95%). Esta técnica demostró tener una buena performance analítica, ser de fácil implementación y el punto de corte seleccionado nos permitió realizar un buen tamizaje de muestras de pacientes trasplantados que resultaban ser candidatas a la determinación de CV, con la consiguiente disminución de costos (AU)

Post-transplant lymphoproliferative disorder is one of the main complications caused by the Epstein Barr virus (EBV) in solidorgan and bone-marrow transplantation patients affecting survival of both the patient and the graft. High levels of viral load (VL) in peripheral blood preceding the development of posttransplant lymphoproliferative disorder have been reported in these patients. Therefore, VL monitoring allows detection of patients who are at risk of developing this disease to start preventive treatment. The aim of this study was to develop a qualitative real-time PCR technique to use as an early screening test to determine EBV VL. This test may minimize costs related to the use of a commercial quantitative method for all the samples that enter for viral screening. Considering the performance of the RT PCR method developed, a Ct ≤ 37 was established as the cut-off limit to avoid unspecific amplification and select the samples that are candidates for EBV VL determination. This cut-off point had a relative diagnostic sensitivity of 80%, a relative diagnostic specificity of 85%, a positive predictive value (PPV) of 53% and a negative predictive value (NPV) of 95%. Thus, an EBV VL< 4000 copies/ml blood was considered to be low and not to be a risk for developing complications. The 95% limit of detection was 280 copies of EBV/ml blood (66­1184, 95%CI). The technique showed to be of good analytical performance and easy implementation. The cut-off point allowed a good screening of the samples of transplanted patients to detect those who are candidates for VL determination at a lower cost (AU)

Duplex realtime PCR method for Epstein-Barr virus and human DNA quantification: its application for post-transplant lymphoproliferative disorders detection

INTRODUCTION: The quantification of circulating Epstein-Barr virus (EBV) DNA is used to monitor transplant patients as an early marker of Post-Transplant Lymphoproliferative Disorders (PTLD). So far no standardized methodology exists for such determination. OBJECTIVE: Our purpose was to develop and validate a real-time PCR assay to quantify EBV DNA in clinical samples from transplant recipients. METHODS: A duplex real-time PCR method was developed to amplify DNA from EBV and from a human gene. The EBV load was determined in peripheral blood mononuclear cells (PBMC), plasma and oropharyngeal tissue from 64 non-transplanted patients with lymphoid-hypertrophy (Non-Tx), 47 transplant recipients without PTLD (Tx), 54 recipients with PTLD (Tx-PTLD), and 66 blood donors (BD). WinPEPI, version 11.14 software was used for statistical analysis. RESULTS: Analytical validation: the intra and inter-assays variation coefficients were less than 4.5% (EBV-reaction) and 3% (glyceraldehyde 3-phosphate dehydrogenase - GAPDH reaction). Linear ranges comprised 107-10 EBV genome equivalents (gEq) (EBV-reaction) and 500,000-32 human gEq (GAPDH-reaction). The detection limit was 2.9 EBV gEq (EBV-reaction). Both reactions showed specificity. Application to clinical samples: higher levels of EBV were found in oropharyngeal tissue from transplanted groups with and without PTLD, compared to Non-Tx (p < 0.05). The EBV load in PBMC from the groups of BD, Non-Tx, Tx and Tx-PTLD exhibited increasing levels (p < 0.05). In BD, PBMC and plasma, EBV loads were undetectable. CONCLUSIONS: The performance of the assay was suitable for the required clinical application. The assay may be useful to monitor EBV infection in transplant patients, in particular in laboratories from low-income regions that cannot afford to use commercial assays. .

Falla hepática fulminante por virus Epstein Barr: rol de los corticoides: caso clínico / Epstein Barr virus and acute liver failure: role of steroids: clinical case

La falla hepática fulminante (FHF) debida a Virus Epstein Barr (VEB) es poco frecuente en inmunocompetentes. La utilidad de los esteroides en este cuadro no ha sido definida y permanece muy controversial. Objetivo: Reportar el caso de una paciente con mononucleosis infecciosa por VEB que presenta FHF y es tratada con corticoides. Caso clínico: Escolar con cuadro de 2 sem de síntomas respiratorios altos, fiebre, adenopatías, con ictericia y orina oscura. Bilirrubina total: 9; B. Directa: 6,3; Fosfatasas Alcalinas: 523; GOT: 7.527; GPT: 6.537; Protrombina (PT): 17 por ciento INR: 4,7; Amonio 510 y glicemia 33. Ecografía abdominal hígado normal y esplenomegalia. Monotest Positivo. Se transfirió a centro de trasplante hepático (TH). Laboratorio de ingreso PT 21 por ciento; bilirrubina en 9,8; GOT 2717; GPT 3716 y amonio 177. EEG con enlentecimiento difuso compatible con encefalopatía grado 1. IgM VEB positiva, descartándose otras etiologías. Se activó para TH por FHF y mientras se administró Metilprednisolona por 5 días. Evolucionó con normalización de las pruebas hepáticas y mejoría clínica. Conclusión: En este caso el uso de esteroides se asoció a una rápida y favorable respuesta tanto clínica como de laboratorio sin presentar efectos secundarios negativos. Al igual que en otras presentaciones de infección grave por VEB, debiera considerarse el uso de esteroides en FHF por VEB.

Acute liver failure (ALF) due to Epstein Barr Virus (EBV) is rare in immunocompetent patients. The role of steroids in this case is not well defined and remains controversial. Case report: 7 years old female presenting with unspecific respiratory symptoms for 2 weeks, fever, lymphadenopathy, jaundice and dark brown urine. Total bilirubin: 9 and direct: 6.3, alkaline phosphatases: 523; AST: 7.527, ALT: 6.537; Prothrombin (PT): 17 percent, INR: 4.7; ammonium 510 and glucose 33. Abdominal ultrasound: normal liver and splenomegaly. Monotest Positive. She was transferred to a liver transplant centre (LT). Lab results at admission: PT 21 percent, bilirubin 9.8, AST 2717, ALT 3.716 and ammonium 177. EEG with diffuse and slowing conductivity consistent with encephalopathy. Positive IgM EBV, other aetiologies were ruled out. She was activated for LT due to ALF and while in waiting list methylprednisolone was administered for 5 days. She evolved with normalization of liver tests and clinical improvement. Conclusion: In this case the use of steroids was associated with a rapid and favourable clinical and laboratory response without negative side effects. As in other presentations of serious infection by EBV, should consider the use of steroids in ALF due to EBV.

Evaluation of reactive Epstein-Barr virus (EBV) in Iranian patient with different subtypes of multiple sclerosis (MS)

OBJECTIVES: Epstein-Barr virus has been recently associated with the onset of multiple sclerosis, yet understanding how it elicits autoimmunity remains elusive. We investigated the relation between Epstein-Barr virus reactivation and disease development in different subtypes of multiple sclerosis. METHODS: In the present research, we have determined the Epstein-Barr virus-DNA load by quantitative real-time polymerase chain reaction and Epstein-Barr virus antibody levels by EIA technique in both multiple sclerosis patients (n = 78) and healthy controls (n = 123). RESULTS: Our results demonstrated increased titer of both anti-Epstein-Barr virus-IgG and IgM antibodies in patients (91.02% vs 82.11% in controls, p < 0.001 and 14.1% vs 4.06% in controls, p < 0.001, respectively). Overall, Epstein-Barr virus reactivation was found in 68.75% of subtypes of multiple sclerosis, 4.54% of multiple sclerosis primary subtype, and in only 3.25% of healthy control subjects. Moreover, in samples of patients with disease relapse (exacerbation) cell free viral DNA was elevated in contrast to other patients (p < 0.001). CONCLUSIONS: These findings provide further support for the detrimental effects of Epstein- Barr virus in the reactivation of multiple sclerosis attacks.

Comparative analysis of presence of Cytomegalovirus (CMV) and Epsteinbarr virus -1 (EBV-1) in cases of chronic periodontitis and aggressive periodontitis with controls.

Aim : The aim of the present study was to evaluate the presence of Cytomegalovirus (CMV) and Epsteinbarr virus -1 (EBV-1)viruses in sub gingival plaque of chronic periodontitis (groupA), aggressive periodontitis patients (group B), periodontally healthy controls (group C) and to compare the clinical parameters between virus negative and positive sites in each of these groups. Materials and Methods : Sixty subjects were included in the study and equally divided into the 3 groups (group A - 20, group B - 20, group C - 20). Sub gingival plaque samples were obtained from the 3 deepest periodontal pocket sites in case of subjects suffering from periodontitis, and from one random bleeding site per quadrant in healthy groups. Clinical parameters like plaque index (PI), gingival index (GI), pocket depth (PD) and clinical loss of attachment (CAL) were recorded. Viral Deoxyribonucleic acid (DNA) was extracted using Proteinase-K DNA Extraction method, and the presence of CMV and EBV-1 was detected by polymerase chain reaction and 2% agarose gel. Results: Results of our study showed a 45% prevalence of CMV and EBV-1 in Aggressive periodontitis cases. Prevalence of CMV in chronic periodontitis and healthy subjects was 20% and 10%, respectively; while for EBV-1 it was 25% and 0%, respectively. In terms of comparison of the clinical parameters with virus presence, both CMV and EBV-1 positive sites showed a significantly higher mean pocket depth compared to virus negative sites. Conclusion: Our studyshowed that the prevalence of EBV1 was higher in chronic and aggressive periodontitis subjects compared to controls and the prevalence of CMV was higher in aggressive periodontitis patients. The virus positive sites showed higher pocket depth compared to virus negative sites.