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.

Comparison of clinical features between chronic active Epstein-Barr virus infection and infectious mononucleosis in adult patients / 中华临床感染病杂志

Objective:To compare the clinical features between chronic active Epstein-Barr virus infection(CAEBV) and infectious mononucleosis(IM)in adult patients.Methods:Clinical data from 56 adult IM patients and 14 adult CAEBV patients admitted in the First Affiliated Hospital of Nanjing Medical University during January 2011 to December 2019 were enrolled. Clinical manifestations, laboratory indicators, treatment and outcomes were compared between two groups. Chi-square test and Mann-whitney U test were used to analyze data. Results:The average age of CAEBV patients was higher than that of IM patients [36.0(23.8, 50.5)years vs. 19.0(17.3, 22.8) years; U=90.0, P<0.05]. The symptoms of sore throat, throat congestion, tonsilla enlargement and lymphadenopathy in IM group were more common than those in CAEBV group( χ2=14.088, 16.875, 31.855 and 10.938, all P<0.01). However, the incidence of pulmonary infection, sleepiness/dysphoria and splenomegaly in CAEBV group were significantly higher than those in IM group( χ2=17.217, 5.809 and 6.254, P<0.05 or <0.01). The white blood cell counts, hemoglobin levels, platelet counts, alanine aminotransferase(ALT) and albumin in CAEBV group were significantly lower than those in IM group( U=47.0, 49.5, 158.5, 173.0 and 263.5, all P<0.01). The levels of neutrophil ratio, C-reactive protein, serum ferritin and EBV DNA load in CAEBV group were significantly higher than those in IM group( U=145.0, 140.0, 128.5 and 115.0, P<0.05 or <0.01). The proportions of CD3 + T cell counts and CD8 + T cell counts in CAEBV group were significantly lower compared to those in IM group( U=42.0 and 24.5, P<0.01); the proportions of CD4 + T cell counts, the CD4 + T/CD8 + T cell counts ratio and B lymphocytes in CAEBV group were significantly higher compared to those in IM group( U=29.0, 23.5 and 34.5, P<0.01). Fifty-six IM patients were all cured and discharged from hospital. In CAEBV group, 8 cases died, 3 cases were improved and 3 cases lost follow-up. Conclusions:Patients with IM represent a favorable prognosis, while the prognosis of CAEBV is relatively poor and complication with HLH may occur. For older patients with EBV infection complicated with pulmonary infection, lethargy/irritability, attention should be paid to monitor blood routine, liver function, serum EBV DNA load and peripheral blood lymphocyte subsets.

Case report of unrelated cord blood transplantation for the treatment of recurrent refractory Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis with intestinal perforation and literature review / 中华实用儿科临床杂志

Objective:To examine the clinical experience and efficacy of unrelated cord blood transplantation (UCBT) in the treatment of recurrent refractory Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) in children.Methods:The clinical data of a patient with recurrent refractory EBV-HLH and intestinal perforation who was treated by UCBT in Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University in September 2015 and finally cured were retrospectively analyzed.Meanwhile, literature was reviewed.Results:The patient, male, 1 year and 6 months, was admitted to the hospital with " fever for 15 days, rash for 9 days" as the main complaint, mainly manifested as high fever, large liver, spleen, lymph nodes, rapidly progressing pancytopenia, liver function damage, phagocytic blood cells on bone marrow smear, diagnosed as EBV-HLH in September 2015.The patient received chemotherapy according to the HLH-2004 protocol developed by the International Association of Cell Societies.During the treatment, he suffered two recurrence during the maintenance period, and a second-line rescue treatment was adopted, namely, " Pegaspargase, Doxorubicin liposome, Etoposide and Methylprednisolone" (L-DEP regimen) chemotherapy.The complete relief of diagnostic indexes for hemophagocytic lymphohistiocytosis was evaluated after chemotherapy.The patient developed sudden intestinal perforation and underwent emergency surgical surgery, enteroenterostomy.After the condition was stabilized, the patient was pretreated with the " Fludarabine+ Busulfan+ Cyclophosphamide" (Flu+ BU+ CY) therapy and then treated with UCBT, with intravenous nutritional support provided during the entire process.Neutrophil and platelet implantation was implemented on day 13 and day 35 after transplantation, respectively.The chimeric rate was 100%, and the implantation was a success.Hepatic veno-occlusive disease, fungal pneumonia and skin graft-versus-host disease (GVHD) Ⅱ occurred on the 15 th day, 22 nd day and 26 th day after transplantation, respectively.The corresponding symptoms improved after treatment.On day 49 after transplantation, phase Ⅱ " enterostomy fistula" was performed.The patient was followed up to 70 months after transplantation, and generally in good condition.His symptoms relieved, and no chronic GVHD and other comorbidities occurred. Conclusions:Allogeneic hematopoietic stem cell transplantation is the only possible effective means of treating relapsed refractory EBV-HLH in children.In the absence of a suitable sibling or unrelated donor, unrelated cord blood stem cells can be used as a graft source.Enterostomy after intestinal perforation is not contraindicated for transplantation.

Clinical characteristics of 111 patients with chronic active Epstein-Barr virus infection / 中华传染病杂志

Objective:To analyze the clinical features of chronic active Epstein-Barr virus infection (CAEBV) in order to reduce the rates of underdiagnosis and misdiagnosis of this disease.Methods:The CAEBV related literatures of PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, WanFang Database and Chongqing VIP since the first literature published (May 1987) until August 29, 2020 were searched. The clinical characteristics, laboratory examinations, outcome and causes of death of CAEBV patients were retrospectively analyzed. Statistical analysis was performed by Mann-Whitney U test, chi-square test or Fisher′s exact probability test. Results:A total of 111 patients aged 22.0 (10.0, 39.0) years were included from 46 articles. There were 64 cases (57.7%) in the age ≥18 years group and 47 cases (42.3%) in the age <18 years group. Fever, splenomegaly, hepatomegaly, and lymph node enlargement were common clinical manifestations, with incidences of 95.5%(106/111), 84.7%(94/111), 57.7%(64/111) and 56.8%(63/111), respectively. The incidences of rash and hepatomegaly in the age ≥18 years group were 3.1%(2/64) and 45.3%(29/64), respectively, which were both lower than those in patients aged <18 years group (27.7%(13/47) and 74.5%(35/47), respectively), while the incidence of abnormal liver biochemical indexes was higher (45.3%(29/64) vs 23.4%(11/47)). The differences were all statistically significant ( χ2=13.957, 9.436 and 5.643, respectively, all P<0.05). Of the 70 patients with follow-up outcomes, 38(54.3%) died and 32(45.7%) survived. The causes of death included gastrointestinal bleeding, severe infection, respiratory failure, liver failure, etc. The incidences of splenomegaly in the death and survival groups were 92.1%(35/38) and 68.8%(22/32), respectively. The difference was statistically significant ( χ2=6.266, P<0.05). Of 21 death and 17 survival cases in the age <18 years group, 15(71.4%) and two cases were combined hemophagocytic lymphohistiocytosis (HLH), respectively, with statistical significance ( χ2=13.527, P<0.01). Of the 90 patients whose HLH-related information was available, 38(42.2%) combined HLH and 52(57.8%) without HLH, with 36.8%(14/38) and 65.4% (34/52) of males, respectively. The difference of gender distribution was statistically significant ( χ2=7.187, P=0.007). The treatment regimens of the 111 CAEBV patients during the course of disease were various, but the detailed information was lacking. Conclusions:The clinical manifestations of CAEBV are diverse. CAEBV can be complicated with fatal complications, lacks of effective treatment, and shows poor prognosis. It is necessary to actively carry out related research to improve the understanding of the disease, and explore effective treatment and reduce mortality.

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.

EBV-positive T/NK-associated lymphoproliferative disorders of childhood: A complete autopsy report

Introduction: Epstein-Barr Virus (EBV)-associated systemic T-cell lymphoproliferative disorder of childhood is a rare but severe manifestation of chronic EBV infection. Despite several case reports characterizing this rare hematological neoplasm, the literature describes extensive heterogeneity in the presentation of this disease. Case presentation: Here we present a complete autopsy of a 16-year-old girl who ultimately succumbed to EBV-associated systemic T-cell lymphoproliferative disorder of childhood. Her clinical presentation demonstrated a non-specific pharyngitis with positive mono spot test, evolving into fulminant multi-organ failure, disseminated intravascular coagulopathy, sepsis, and ultimately death. Conclusions: Post-mortem findings included extensive hemorrhage, and infiltration of the liver, spleen, lymph nodes and bone marrow with neoplastic T-cells. There was extensive hemophagocytic lymphohistiocytosis (HLH) within these organs, suggesting overlap between the EBV-associated systemic T-cell lymphoproliferative disorder of childhood and EBV-associated HLH. We hope these findings provide a more comprehensive overview of several possible manifestations of EBV-associated systemic T-cell lymphoproliferative disorder of childhood.

A Boy with Chronic Active EBV Infection Presented as Mosquito Bite Hypersensitivity Progressed to Fatal Hemophagocytic Lymphohistiocytosis due to NK Cell Neoplasm / 임상소아혈액종양

Chronic active Epstein-Barr virus (CAEBV) infection is characterized by recurrent infectious mononucleosis (IM)-like symptoms and an unusual pattern of anti-EBV antibodies. We report a boy with CAEBV who progressed to aggressive hemophagocytic lymphohistiocytosis (HLH) with NK cell neoplasm. A 19-year-old adolescent boy was admitted with fever and a history of recurrent IM-like symptoms following mosquito bites since the age of 6 years. His condition was diagnosed as CAEBV with atypical lymphocytosis and an unusual pattern of anti-EBV antibodies. His symptoms subsided during treatment with steroids and cyclosporine, although the EBV genome load kept increasing for several years. He was re-admitted after follow-up loss for 8 years, and his clinical and laboratory findings confirmed HLH and high titer of the EBV genome. Bone marrow analysis with flow cytometry showed hemophagocytosis with compatible NK cell neoplasm. He rapidly progressed to pulmonary infection and expired soon after. We conclude that hematopoietic stem cell transplantation may be a potential therapeutic modality for treating CAEBV before serious EBV manifestations.

Epstein-Barr virus infection and respiratory-related diseases in children / 中华实用儿科临床杂志

Epstein-Barr virus (EBV) is a common viral pathogen in children.EBV infection can cause childhood tumors,immune-related diseases and respiratory-related diseases.The proportion of EBV infection in Chinese children is high and the age of primary infection is early.Its pathogenesis is closely related to B lymphocytes,natural killer cells and gene defects.Clinical EBV infection is not only associated with childhood tumors and immune-related diseases,but also causes respiratory-related diseases that deserve more attention.

Epstein-Barr virus infection and respiratory-related diseases in children / 中华实用儿科临床杂志

Epstein-Barr virus (EBV) is a common viral pathogen in children.EBV infection can cause childhood tumors, immune-related diseases and respiratory-related diseases.The proportion of EBV infection in Chinese children is high and the age of primary infection is early.Its pathogenesis is closely related to B lymphocytes, natural killer cells and gene defects.Clinical EBV infection is not only associated with childhood tumors and immune-related diseases, but also causes respiratory-related diseases that deserve more attention.

Clinical features of adult patients with chronic active Epstein-Barr virus infection / 中华内科杂志

Objective To investigate the clinical features of adult-onset chronic active Epstein-Barr virus infection (CAEBV). Methods A total of 21 adult patients with CAEBV who were admitted to the department of General Internal Medicine at Peking Union Medical College Hospital from January 2006 to January 2016 were retrospectively analyzed. Demographic data, disease duration, clinical manifestations, laboratory findings, treatments and prognosis were reviewed. Results Eighteen females and 3 males were enrolled with a mean age of 39 years. The most common clinical manifestations included fever in 20 patients, splenomegaly in 20 patients, lymphadenopathy in 18 patients, and hepatomegaly in 10 patients, followed by laryngopharyngeal disorders in 6 patients, pleural effusion and peritoneal effusion each in 5 patients, rash in 4 patients, interstitial lung disease in 3 patients, gastrointestinal hemorrhage in 2 patients, and peripheral neuropathy and pulmonary hypertension each in 1 patient. Six patients were complicated with hemophagocytic lymphohis-tioncytosis(HLH) that developed 5-17 (mean: 9) months following CAEBV onset, all of whom experienced hyperpyrexia, pancytopenia, lymphadenopathy, splenomegaly, and liver dysfunction, 3 with hepatomegaly. Nineteen of the 21 patients had received steroid therapy including 10 combined with immunosuppressive agents, 11 with antiviral therapy, and 8 with intravenous immunoglobulin. Thirteen patients died, including 10 of multiple organ failure, (including 6 of HLH) 2 of severe pulmonary infection, and 1 of lymphoma. Six patients remained on follow-up, yet 2 were missing. Conclusions CAEBV is expected with severe condition and poor prognosis, which is likely to be complicated with HLH. Clinical physicians should pay attention to adult patients with fever, hepatosplenomegaly and lymphadenopathy, which suggests possible CAEBV.

The clinical characteristics of immunocompetent adults with chronic active Epstein-Barr virus associated enteritis / 中华内科杂志

Objective To investigate the clinical and pathological characteristics of chronic active Epstein-Barr virus associated enteritis(CAEAE). Methods The clinical data of 6 CAEAE patients in Peking Union Medical College Hospital were retrospectively analyzed from January 2010 to November 2017, including clinical manifestations, endoscopic, pathological features, medications and clinical outcome. Results The male∶female ratio was 4∶2 and the average age was 34 years old. All patients did not have personal and family history of immunodeficiency. The common symptoms consisted of fever (6/6), abdominal pain (6/6), hematochezia (6/6) and diarrhea (5/6). The most frequently affected sites were colorectum (5/6), followed by small intestine (3/6). Further serologic tests revealed a high load of serum Epstein-Barr virus (EBV) DNA. The main manifestations under endoscopy were multifocal or diffuse irregular ulcers. There was inflammation in the ulcer bases and surrounding areas, where EBV-encoded small RNA (EBER) was positive by in situ hybridization (6/6). The common complications were massive hemorrhage (3/6) and intestinal perforation (2/6). None of treatment agents including glucocorticoid, ganciclovir, foscarnet sodium and cytotoxic drugs was effective. All patients died within 0.5 to 13 months after diagnosis. Conclusions CAEAE in immunocompetent individuals is a rare disorder with poor prognosis. It is difficult to differentiate CAEAE from inflammatory bowel disease due to similar clinical and endoscopic manifestations.

Clinical analysis of chronic active epstein-barr virus infection in children / 中国综合临床

Objective To study the clinical characteristics of chronic active Epstein-Barr virus (EBV) infection (CAEBV) in children and to provide a basis for the diagnosis and treatment of CAEBV.Methods Clinical data,laboratory serology,pathological examination,treatment and follow-up results of 10 cases with CAEBV infection who were treated in Xijing Hospital of the Fourth Military Medical University from January 2008 to January 2016 were analyzed retrospectively.Results CAEBV major manifestations were continuous or intermittent fever,hepatomegaly,splenomegaly and lymphadenopathy,and others,including general fatigue,cough,hematemesis,diarrhea,skin rash,jaundice,sore throat,muscle joint pain,and so on.And with liver dysfunction,hematologic abnormality,and so on.All patients in anti-EB virus capsid antigen IgG (EBVCA-IgG)antibodies and EBEA-IgG antibodies had positive,while all patients in EBVCA-IgM antibodies had negative.The median load of EBV-DNA detected by real-time polymerase chain reaction(PCR) in the peripheral blood was 7.15× 105 copies/ml.Six of 10 cases CAEBV patients presented a poor clinical course,1 case died from intracranial hemorrhage,2 cases from respiratory failure,1 case from gastrointestinal bleeding,1 case from liver failure,1 case from severe multiple pathogens infection,rest 3 cases showed an improvement and 1 cases had a recurrence.Conclusion CAEBV infection has varieties of clinical features,with poor prognosis and high mortality.If the patients had unexplained fever,hepatomegaly,splenomegaly and lymphadenectasis,we should be timely detect virology and histopathological to diagnosis as early as possible.

A case of Epstein-Barr virus-positive primary cutaneous diffuse large B-cell lymphoma of the elderly / 中华皮肤科杂志

An 88?year?old man presented with multiple nodules and ulcers on both lower limbs for 6 months. Dermatological examination showed multiple dark purple hard nodules with central crusted ulceration. Histopathological examination revealed a diffuse infiltration of atypical lymphoid cells with large hyperchromatic nuclei in the dermis and subcutis, as well as small necrotic foci in some regions. Conspicuous mitoses were seen. The large lymphoid cells were positive for CD20, CD79a and Bcl?2. Epstein?Barr virus?encoded RNA was detected by in situ hybridization. These findings were consistent with Epstein?Barr virus?positive diffuse large B?cell lymphoma. The patient gave up systemic chemotherapy and died six months later.

Profound CD4+ T lymphocytopenia in human immunodeficiency virus negative individuals, improved with anti-human herpes virus treatment / Linfocitopenia T CD4+ grave, en individuos negativos para virus de immunodeficiencia humana, mejoró con tratamiento antivirus herpes humanos

Lymphocytopenia and CD4+ T lymphocytopenia can be associated with many bacterial, fungal, parasite and viral infections. They can also be found in autoimmune and neoplastic diseases, common variable immunodeficiency syndrome, physical, psychological and traumatic stress, malnutrition and immunosuppressive therapy. Besides, they can also be brought into relation, without a known cause, with idiopathic CD4+ T lymphocytopenia. Among viral infections, the Retrovirus, specially the human immunodeficiency virus, is the most frequently cause. However, many acute viral infections, including cytomegalovirus and Epstein Barr virus can be associated with transient lymphocytopenia and CD4+ T lymphocytopenia. As is well known, transient lymphocytopenia and CD4+ T lymphocytopenia are temporary and overcome when the disease improves. Nonetheless, severe CD4+ T Lymphocytopenia associated with chronic infections by human herpes virus has not been reported. We describe 6 cases of human immunodeficiency virus negative patients, with chronic cytomegalovirus and Epstein Barr virus infections and profound lymphocytopenia with clinical symptoms of cellular immunodeficiency. These patients improved rapidly with ganciclovir or valganciclovir treatment. We claim here that it is important to consider the chronic human herpes virus infection in the differential diagnosis of profoundly CD4+ T lymphocytopenia etiology, when human immunodeficiency virus is absent, in order to start effective treatment and to determine, in future studies, the impact of chronic human herpes virus infection in human beings' health.

Múltiples enfermedades bacterianas, micóticas, parasitarias y virales pueden asociarse con linfocitopenia y linfocitopenia CD4+. También enfermedades autoinmunes, neoplásicas, inmunodeficiencia común variable, estrés físico, sicológico o traumático, la malnutrición y el tratamiento con inmunosupresores. Esta condición también se presenta sin causa aparente y es conocida como linfocitopenia T CD4+ idiopática. Entre las infecciones virales, los retrovirus, especialmente el virus de inmunodeficiencia humana, es la más frecuente causa, pero muchas otras infecciones virales agudas, entre ellas, la mononucleosis por citomegalovirus y por Epstein Barr virus, se asocian con linfocitopenia total y linfocitopenia T CD4+, que son transitorias y se recuperan cuando la enfermedad mejora. Una linfocitopenia grave asociada con infección crónica por virus herpes humanos y que mejore con el tratamiento de ellos, no ha sido publicada. Se describen 6 pacientes, negativos para virus de inmunodeficiencia humana, con linfocitopenia total y linfocitopenia T CD4+ graves y con manifestaciones clínicas de inmunodeficiencia celular, quienes respondieron rápidamente al tratamiento con ganciclovir o valganciclovir. Es importante considerar la infección crónica por virus herpes humanos en el diagnóstico diferencial de la etiología de la linfocitopenia T CD4+ en individuos no infectados por el virus de inmunodeficiencia humana, para iniciar un tratamiento efectivo de los pacientes y determinar en futuros estudios el impacto de la infección crónica por herpes virus en la salud humana.

An Adult Case of Chronic Active Epstein-Barr Virus Infection with Interstitial Pneumonitis

Chronic active Epstein-Barr virus (CAEBV) infection is characterized by persistent infectious mononucleosis-like symptoms, an unusual pattern of Epstein-Barr virus (EBV) antibodies, detection of the EBV genome in affected tissues or peripheral blood, and chronic illness that cannot be attributed to any other known disease. This is the first reported Korean case of an immunocompetent adult with CAEBV-associated interstitial pneumonitis. A 28-year-old female was admitted with a fever that persisted for 3 weeks. She had multiple lymphadenopathy, hepatosplenomegaly, pancytopenia, and elevated serum aminotransferase levels. Serology for antibodies was positive and chest computed tomography showed diffuse ground glass opacities in both lungs. Histopathology of the lung tissue showed lymphocyte infiltration, and EBV DNA was detected in those lymphocytes using in situ hybridization with an EBV-encoded RNA probe. After 1 month of hospitalization, she improved without specific treatment.

Human papillomavirus and Epstein Barr virus in oral hairy leukoplakia among HIV positive Venezuelan patients

Oral hairy leukoplakia (OHL) is commonly found in individuals infected with HIV, and represents the most frequent oral manifestation. The purpose of this study was to detect the presence of Human Papillomavirus (HPV) and Epstein Barr Virus (EBV) in OHL of HIV+ Venezuelan patients. We evaluated 21 HIV+ adult patients with clinically present OHL lesions: 11 under antiretroviral therapy, 10 without therapy, and 10 oral mucosal samples as controls. Nested-PCR was used to detect EBV and HPV infection. The INNO-LiPA HPV Genotyping v2 was applied to determine the HPV genotype. The EBV genome was found in 16/21 (76%) of the HIV+ patients with OHL. No difference was observed in EBV+ and EBV- patients related to antiretroviral therapy viral load and CD4+ T cell count. HPV-DNA was observed in 7/21 HIV positive cases (33%). The HPV genotypes detected were: 6, 11, 31, 33, 52, and 56/74. The most frequently HPV found was genotype 6 in 7/7, while two cases were HPV-11 and two HPV-52. Of the positive cases, 5/7 (71%) presented co-infection with more than one HPV genotype and 4/7 (57%) had HPV coinfection with high and low risk types. No case was EBV or HPV positive in the control group. In this study, a higher EBV prevalence was observed in OHL-HIV+ patients, confirming the etiologic role in this entity. A considerable number of cases were positive for HPV infection, and many patients presented coinfection with more than one HPV genotype as well as the presence of high oncogenic risk HPV in OHL.

El proposito del presente estudio fue detectar la presencia de virus papiloma humano (VPH) y Epstein Barr (VEB) en Leucoplasia Vellosa Oral (LVO) de pacientes VIH positivos. Se evaluaron 21 pacientes adultos VIH positivos con lesiones clinicas presentes de LVO y 10 casos controles de mucosa sana. Para el diagnostico molecular de VPH y EBV se utilizo Nested PCR. La determinacion de los genotipos se realizo mediante el kit HPV INNO-LiPA genotyping v2. La presencia de genoma de VEB se demostro en un alto porcentaje (76%) en 16/21 de los pacientes VIH positivos con LVO. No se observo relacion entre los pacientes VEB+ y VEBcon el uso de terapia antirretroviral, la carga viral y el contaje de celulas T CD4+. Se demostro la presencia de ADN-VPH en 7/21 (8%) de los casos VIH positivos. Los genotipos de VPH detectados fueron 6, 11, 31, 33, 52, 56/74. El genotipo 6 fue el mas frecuentemente observado en 7/7, dos casos fueron VPH 11 y dos VPH 52. De los casos positivos 5/7 (71%) presentaron coinfeccion con mas de un genotipo de VPH y en 4/7 (57%) se evidencio coinfeccion con tipos de alto y bajo riesgo oncogenico. En el presente estudio se observo una alta prevalencia de VEB en pacientes VIH positivos con LVO, confirmando el papel etiologico en esta entidad. Un considerable numero de casos fueron positivos para VPH. Se observo la presencia de coinfeccion con mas de un tipo viral, asi como la presencia de VPH de alto riesgo.

Detecção do vírus Epstein-Barr em tonsilites recorrentes / Detection of Epstein-Barr virus in recurrent tonsillitis

As tonsilites recorrentes têm sido objeto de muitos estudos. Eventos considerados na predisposição e causa incluem a utilização errônea de antibióticos em crises agudas, alterações da microflora, mudanças estruturais nas criptas epiteliais tonsilares e infecções virais. A infecção pelo vírus Epstein-Barr (EBV) ocorre freqüentemente na infância persistindo em linfócitos de tonsilas, podendo causar tonsilites recorrentes. Pouco se conhece sobre a persistência e reativação do EBV em pacientes imunocompetentes. Alguns métodos como a hibridização in situ, a reação em cadeia da polimerase (PCR) e a imuno-histoquímica têm sido utilizados no estudo da patogenia do vírus. OBJETIVO: Para caracterizar a associação do vírus Epstein-Barr com tonsilites recorrentes examinamos a presença do EBV pela PCR e por imuno-histoquímica usando como alvo a proteína viral LMP-1. FORMA DE ESTUDO: Estudo transversal com análise de prevalência amostral. MATERIAL E MÉTODOS: Foram selecionados 24 blocos parafinados de tonsilas, provenientes do Serviço de Anatomia Patológica, removidas de crianças de 2 a 12 anos com diagnóstico de tonsilite recorrente. Resultados: O genoma do EBV foi detectado em 13 (54,1%) e a LMP-1 em 9 (37,5%) dos casos. CONCLUSÃO: As tonsilas das crianças podem ser colonizadas pelo EBV e este pode estar associado à patogenia das tonsilites recorrentes.

Recurrent tonsillitis has been the subject of frequent investigation. Misuse of antibiotic therapy in acute tonsillitis, changes to the tonsillar microflora, structural changes to the tonsillar crypts, and viral infections have been listed as predisposing or causal factors for recurrent tonsillitis. Epstein-Barr virus (EBV) infection usually occurs in early childhood and may persist in tonsillar lymphocytes, thus leading to the onset of recurrent tonsillitis. Little is known about the persistence and reactivation of EBV strains in immunocompetent patients. Methods such as in situ hybridization, polymerase chain reaction (PCR), and immunochemistry have been used to study the pathogenesis of the EBV. AIM: this study aims to characterize the association between EBV and recurrent tonsillitis by investigating the presence of EBV through PCR and immunohistochemistry, using viral protein LMP-1 as a target. STUDY DESIGN: this is a cross-sectional study with analysis of sample prevalence. MATERIALS AND METHOD: twenty-four paraffin-embedded tonsil specimens from the Pathology Service were selected. The specimens were removed from children aged between 2 and 12 years diagnosed with recurrent tonsillitis. RESULTS: EBV genome was detected in 13 (54.1%) specimens, whereas viral protein LMP-1 was found in 9 (37.5%) specimens. CONCLUSION: children's tonsils can be colonized by EBV and such colonies may be associated with the pathogenesis of recurrent tonsillitis.

Preliminary study on Epstein-Barr virus infection in patients with drug eruption / 中华皮肤科杂志

Objective To explore the role of Epstein-Barr virus (EBV) infection in the etiology of drug eruption. Methods PCR-Southern blot was used to detect EBV-specific DNA fragment BamH I -W in peripheral blood mononuclear cells of 32 patients with drug eruption and 30 age- and sex-matched normal controls. The mRNA expression of EBV lyric gene BZLF1 in EBV DNA-positive samples was measured by RT-PCR and Southern blot. ELISA was performed to detect EBV virus capsule antigen (VCA)-specific IgM. Results The positivity rate of EBV DNA was significantly higher in patients with drug eruption than in normal controls (78.13% (25/32) vs 10.00% (3/30), P < 0.01), while no significant difference was noted between patients with severe and mild drug eruption (P > 0.05). The expression of BZLF1 mRNA was detected in 3 out of 25 EBV DNA-positive patients; of the 3 patients, 1 suffered from mild drug eruption, and 2 from severe drug eruption. EBV VCA-specific IgM was observed in 6 of 32 patients with drug eruption, but not in any normal controls. No significant difference in the positivity rate of EBV VCA-specific lgM existed between patients with severe and mild drug eruption (P > 0.05). Conclusions There is an active infection of EBV in patients with drug eruption. EBV infection is probably an environmental factor affecting the development of drug eruption.

A case of adolescent Kawasaki disease with Epstein-Barr virus-associated infectious mononucleosis complicated by splenic infarction / 소아과

Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology that affects children. There are few reports that describe the Epstein-Barr virus (EBV) as the possible infectious agent of KD. Here, we describe a case of KD in a 15-year-old boy complicated with giant coronary artery aneurysms, pericardial effusion, and splenic infarction. The clinical course of KD was refractory to intravenous gamma globulin and aspirin. Our patient also showed typical findings of concomitant EBV-associated infectious mononucleosis, such as hepatosplenomegaly and generalized lymphadenopathy, with EBV-positive atypical lymphoid hyperplasia. He improved dramatically after receiving intravenous methylprednisolone followed by oral prednisolone. Ultimately, the coronary artery aneurysms remained as the only sequelae. We report a rare case of adolescent KD with EBV-associated infectious mononucleosis and splenic infarction.