Exploring atypical manifestations and multisystem involvement of Epstein-Barr virus infection in hospitalized pediatric patients from Mexico: insights from a tertiary hospital (2012-2022).

INTRODUCTION: Epstein-Barr virus (EBV) infection, with a global prevalence exceeding 95%, typically manifests in children as infectious mononucleosis. However, clinical practice frequently encounters diverse atypical presentations characterized by multisystem involvement, often resulting in an unfavorable clinical course. Our objective is to describe the clinical manifestations and results of EBV infection in a tertiary pediatric hospital in Mexico. METHOD: An observational, transversal, retrospective, and descriptive study that included a systematic review of medical records (2012-2022) of patients under 18 years of age with detectable EBV particles in peripheral blood. RESULTS: The study included 26 patients with a median age of 5 years and a male predominance of 53.8%. Predominant symptoms were fever (85%) and lymphadenopathy (35%). Sixty-five percent had severe and atypical manifestations, including pneumonia and hepatic, hematologic-oncologic, and autoimmune diseases. Anemia, thrombocytopenia and leukopenia were common, with lymphocytosis in 19% of cases. The median EBV viral load was 2816 copies/mL (range: 555-355,500 copies/mL). Four deaths related to EBV infection were reported. Viral load in these cases also varied widely from 594 to 121,000 copies/mL. Supportive care was administered to 85% of patients, while others received antiviral treatment, steroids, and rituximab. CONCLUSION: Atypical manifestations were common, especially in children with multisystem involvement. EBV should be considered as a potential contributor to a diverse spectrum of clinical presentations, emphasizing the need for comprehensive evaluation and awareness in clinical diagnosis.

INTRODUCCIÓN: La infección por el virus de Epstein-Barr (VEB) tiene una prevalencia mundial superior al 95%. Se considera que en los niños se manifiesta principalmente como mononucleosis infecciosa; sin embargo, en la práctica clínica, a menudo encontramos numerosas manifestaciones atípicas con compromiso multisistémico que llevan a un curso desfavorable. Nuestro objetivo es describir las manifestaciones clínicas y los resultados de la infección por VEB en un hospital pediátrico de tercer nivel en México. MÉTODO: Estudio observacional, transversal, retrospectivo y descriptivo, en el cual se revisaron sistemáticamente los expedientes médicos de pacientes menores de 18 años con una detección positiva de partículas de VEB en sangre periférica en el periodo 2012-2022. RESULTADOS: Se incluyeron 26 pacientes con una mediana de edad de 5 años y predominio de varones (53.8%). El 65% presentaron manifestaciones graves y atípicas, incluyendo enfermedades respiratorias, hepáticas, hematooncológicas y autoinmunitarias. Los síntomas más frecuentes fueron fiebre (85%) y linfadenopatía (35%). El 54% presentaron manifestaciones atípicas, incluyendo linfohistiocitosis hemofagocítica, neumonía y neoplasia. La anemia, la trombocitopenia y la leucocitopenia fueron comunes, mientras que el 19% presentaron linfocitosis. La media de la carga viral fue de 2816 copias/ml (555-355,500). Se informaron cuatro muertes atribuidas a la infección por VEB, con valores de carga viral de 594 a 121,000 copias/ml. El 85% de los pacientes recibieron solo tratamiento sintomático, mientras que otros recibieron antivirales, esteroides y rituximab. CONCLUSIÓN: Las manifestaciones atípicas se observaron comúnmente, en especial en niños con compromiso multisistémico. El VEB debe considerarse como un potencial factor contribuyente en el diagnóstico de una amplia gama de manifestaciones clínicas.

Age and Epstein-Barr viral load at diagnosis of post-transplant lymphoproliferative disease are associated with patient survival in kidney transplant recipients.

INTRODUCTION: This study investigated variables associated with mortality in kidney transplant recipients (KTRs) diagnosed with post-transplant lymphoproliferative disease (PTLD) and a simultaneous Epstein-Barr virus (EBV) viremia. METHODS: This was a retrospective cohort study enrolling KTRs diagnosed with PTLD between 2018 and 2020. Outcome: death within two years after diagnosis. RESULTS: Among 1,625 KTRs who collected EBV viremia (by PCR, 2018-2020) for any reason, 238 (14.6%) had a positive viral load and 41 (17.2%) simultaneous PTLD. These 41 patients were 40.1 years old at diagnosis and 8.6 years after transplantation; 26.8% were induced with rATG and 92.7% were maintained on tacrolimus and azathioprine (TAC/AZA) as immunosuppressive regimen. Lymph nodes (75.6%) was the most common site of PTLD, followed by the gastrointestinal tract (48.8%), with 61.0% at Lugano stage IV and 80.5% monomorphic PTLD. The mean EBV viral load was 12,198 IU/mL. One- and two-year patient survival post-diagnosis was 60.4% and 46.8%, respectively. In the Cox regression analysis, age at PTLD diagnosis (HR for each year = 1.039; p < 0.001) and EBV viral load (HR for each log = 1.695; p = 0.026) were associated with risk of death. CONCLUSION: This study suggests that in patients predominantly on TAC/AZA, PTLD with simultaneous EBV positive viral load is a late event, and worse survival is associated with older age and EBV viral load at diagnosis.

Extracavitary Primary Effusion Lymphoma Affecting the Oral Cavity: A Rare Case Report.

Primary effusion lymphoma (PEL) is an aggressive neoplasm often diagnosed in immunosuppressed patients demonstrating peritoneal, pleural, or pericardial effusions. This high-grade lymphoma is strongly associated with human herpesvirus 8 (HHV8) infection and most of the lesions also show the presence of Epstein-Barr virus in tumor cells, which lacks CD20 expression and reveals a plasmablastic morphology and phenotype. The extracavitary or solid variant of PEL is even rarer and usually affects the lymph nodes and is currently considered a clinical manifestation of the classic PEL. In the oral cavity, extracavitary PEL is extremely rare and only a few patients have been previously reported, with no detailed clinicopathological description. The recognition of oral extracavitary PEL is even more important given the occurrence of plasmablastic lymphoma in the oral mucosa, which shares many clinical, microscopic, and phenotypic features with PEL, therefore, demanding from pathologists the search for HHV8, especially in immunosuppressed patients, and an appropriate clinical evaluation. In this report, we aim to describe a very rare extracavitary PEL affecting the palate of a 36-year-old patient and to review the literature regarding the extracavitary presentation of this aggressive lymphoma. This report demonstrates the importance of searching for HHV8 infection in oral lymphomas with plasmablastic features.

Variation of Diagnostic Approaches and Treatment Practices for Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome Among Pediatric Subspecialists.

OBJECTIVE: To assess the diagnostic and treatment practices among a variety of subspecialists at pediatric institutions in the US. STUDY DESIGN: Using a web-based survey, we assessed the consultation, diagnostic, and treatment preferences of providers from the different pediatric subspecialties who care for pediatric patients with hemophagocytic lymphohistiocytosis (HLH)/macrophage activating syndrome (MAS). Domains included demographics, provider training level and specialty, experience and comfort level with the diagnosis and treatment of HLH/MAS, and institutional approaches toward the diagnosis and management of HLH/MAS. Participants also were given 2 case scenarios: one describing Epstein-Barr virus-associated HLH and another describing an underlying rheumatologic condition with MAS. RESULTS: Of 263 respondents, 23%, 29%, 39%, and 7% identified as hematology/oncology, rheumatology, general pediatrics/critical care/hospitalist, and allergy/immunology, respectively. For Epstein-Barr virus/HLH, hematology/oncology was the preferred first consultant by most respondents other than rheumatologists, of whom only 47% agreed. For MAS, 92% of respondents from all specialties favored a rheumatology consultation. Preferred diagnostic tests varied by subspecialty, with hematology/oncology more likely than rheumatology to order an infectious workup, natural killer cell function, soluble interleukin-2 receptor, bone marrow biopsy, and genetic testing. First-line therapy also varied, with hematology/oncology preferring dexamethasone and etoposide and rheumatology more often preferring methylprednisolone and anakinra. One-half of respondents were unaware of institutional algorithms for diagnosis and treatment of HLH/MAS. Most (85.6%) favored the development of treatment algorithms for HLH/MAS, and 90% supported a multidisciplinary approach. CONCLUSIONS: Current consulting patterns, diagnostic workup, and treatment approaches of HLH/MAS vary by specialty, highlighting the need for standardized management algorithms and institutional multidisciplinary HLH/MAS teams.

Hydroa vacciniforme-like lymphoproliferative disorder in Ecuadorian children: A case series.

We report the clinical and histopathological features of hydroa vacciniforme-like lymphoproliferative disorder in five indigenous and Mestizo children. All the children resided at higher altitudes, experiencing maximal solar exposure. All cases presented with prurigo along with Epstein-Barr virus infection. Histopathologic examination showed an atypical, CD30 + lymphocytic infiltrate with angiocentricity in all, while three cases demonstrated panniculitis-like infiltrate.

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.

Extraordinary Case: Unique Presentation of an Aggressive Epstein-Barr Virus-Positive Mucocutaneous Ulcer.

ABSTRACT: Epstein-Barr virus-positive mucocutaneous ulcer is a recent and unusual type of lymphoproliferation, mostly associated with various forms of immunosuppression. In most cases, they regress spontaneously, but an increasing number of reports describe a spectral behavior of the lesion, which ranges from a simple ulcer with eosinophilia to aggressive ulcers. In these cases, Epstein-Barr virus-related lymphomas are the main differential diagnosis. We report a unique observation of this rare disease with mandibular involvement. Due to bone erosion, the patient was treated with 6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) with complete healing of the ulcer on clinical examination and PET-scan control.

[Liver and colonic manifestation of active chronic infection by Epstein Barr virus]. / Manifestación hepática y colónica de la infección crónica activa por virus de Epstein Barr.

INTRODUCTION: Chronic active Epstein Barr virus infection (CAEBV) is a rare condition, where the body is unable to counteract Epstein Barr viral replication (EBV), leading the patient to a chronic state with variable symptoms. Early recognition of infrequent or atypical clinical manifestations is relevant due to the particularities of their management and prognosis. OBJECTIVE: to describe a case of CAEBV manifes ted with colitis and hepatitis, summarizing the clinical-pathological and endoscopic characteristics and their evolution. CLINICAL CASE: A 6-year-old girl, previously healthy, presented recurrent episodes of jaundice, hepatosplenomegaly, and fever. EBV hepatitis was diagnosed with a blood viral load of 328,000 copies / mL. Her liver biopsy revealed Epstein-Barr virus-encoded small RNAs (EBER). She evolved with mucosanguineous diarrhea and weight loss; the colonoscopy showed loss of the haustral pattern, multiple aphthous ulcers covered with fibrin, and 7 million copies of EBV / gram of tissue were found in the colon. T-cell lineage infection was identified, therefore Rituximab was started, with a decrease in viral load, complete resolution of diarrhea, and improvement in liver function tests. The definitive treatment was bone marrow transplantation. CONCLUSIONS: CAEBV is a serious disor der, little documented, and should be considered in the face of a prolonged or intermittent course of hepatitis, accompanied by general and gastrointestinal manifestations such as chronic diarrhea, hematochezia, and weight loss, since its outcome without treatment can be fatal.

Seropositivity for cytomegalovirus and PCR-EBV monitoring: Protective factors for posttransplant lymphoproliferative disorder in pediatric liver transplant.

BACKGROUND: PTLD is a clinical condition with high mortality. Monitoring EBV replication can be a useful tool to avoid the development of PTLD. MATERIALS AND METHODS: This was a retrospective analysis of 428 pediatric patients who underwent liver transplantation between 1989 and 2016. The patients were divided into 2 groups (transplanted before 2006, when PCR-EBV was not monitored, and after 2006, when PCR-EBV monitoring was started). Patients with continuous PCR measurements for EBV were evaluated for the impact of a reduction in immunosuppression or a change in immunosuppressants on the number of viral copies. A logistic regression model was applied to evaluate factors related to PTLD. RESULTS: The prevalence of PTLD was 4.2%. After monitoring patients with PCR for EBV levels, a predominance of the most severe, monomorphic form of lymphoproliferative disorder was observed (p = .009). The PTLD mortality was 5%. There was a change in the PCR level after tacrolimus reduction (p = .002) and after tacrolimus exchange for mTOR (p = .008). The number of EBV copies was significantly higher (p = .029) in patients who developed PTLD. In the multiple regression model, seropositivity for CMV was an independent protective factor for lymphoproliferative disorder (OR=0.09; 95% CI 0.02-0.42), reducing the chance of having PTLD adjusted by serology for EBV by 91%. CONCLUSIONS: Monitoring the EBV viral load by PCR seems to prevent the emergence of milder forms of lymphoproliferative disorder. Pretransplant seropositivity for CMV is a protective factor for PTLD.

[Conjunctival mass as the first manifestation of Epstein Barr virus infection]. / Masa conjuntival como primera manifestación de infección por virus del Epstein Barr.

The Epstein Barr virus is an infectious disease with a high worldwide prevalence, which can present multiple systemic manifestations. The ophthalmological findings are the least frequent and nonspe cific and, therefore, its diagnosis is complicated and delayed; however, it should always be considered as a diagnostic possibility in the presence of atypical ocular and periocular inflammatory clinical pictures. OBJECTIVE: To describe the clinical case of a patient with the presence of a conjunctival mass as the first finding in Epstein Barr virus infection. CLINICAL CASE: A 4-year-old boy with a 4-day history of left upper eyelid edema and ptosis associated with a large, fast-growing, elevated, painful, and salmon-colored upper bulbar conjunctival mass with extension to the upper fornix associated with bilateral cervical and inguinal lymphadenopathy. Initially, a lymphoproliferative disorder was suspected, with blood count with lymphocytosis and atypical lymphocytes, elevated lactate dehydro genase, peripheral blood smear with an increase in white blood cells and some atypical lymphocytes, bone marrow aspirate with a predominance of granulocytes and predominantly CD8-positive T lym phocytes and an increase in Gamma-Delta T lymphocytes. The orbit CT scan showed thickening of the left upper eyelid with peripheral enhancement and the abdominal CT scan showed splenomegaly. Biopsy confirmed chronic Epstein Barr virus infection with positive IgM and indeterminate IgG anti bodies. Symptomatic management was indicated with satisfactory evolution and complete resolution of the conjunctival lesion and lymphadenopathy. CONCLUSION: Epstein Barr virus infection should be considered as a possible diagnosis in atypical ocular and periocular inflammatory manifestations in the pediatric population.

M1 Macrophage Polarization Prevails in Epstein-Barr Virus-Infected Children in an Immunoregulatory Environment.

Macrophages can be polarized toward a proinflammatory phenotype (M1) (CD68+) or to an anti-inflammatory one (M2) (CD163+). Polarization can be triggered by cytokines such as IFN-γ for M1, or IL-10 and TGF-ß, for M2. In the context of pediatric Epstein Barr virus (EBV) infection, little is known about macrophage polarization in EBV primary or persistent infection. When studying tonsils of patients undergoing primary infection (PI), healthy carrier (HC), reactivation (R), and not infected (NI), M1 profile prevailed in all infection status. However, an increase in M2 cells was observed in those patients with broader expression of latency antigens, in particular EBNA2. Tonsils from primary infected patients showed an increased IL-10 expression, whereas, unexpectedly, TGF-ß expression correlated with M1 marker. Furthermore, an inverse correlation was demonstrated between CD68 and IFN-γ. Therefore, in the context of asymptomatic infection in children, M1 macrophage polarization prevails, even in the presence of IL-10 and TGF-Ꞵ immunomodulatory cytokines, and it might be independent from lymphomagenesis process. Our finding indicates that macrophages may have a significant plasticity in response to different types of extrinsic stimuli, and further studies are required to investigate M1 polarization under anti-inflammatory stimuli. IMPORTANCE Most studies on Epstein Barr virus (EBV) primary infection have been performed in adolescents and young adult populations with Infectious Mononucleosis (IM) in developed countries. Furthermore, studies related to macrophage polarization were assessed in EBV-associated lymphomas, but little is known about macrophage polarization in the context of primary infection at the site of viral entry and replication, the tonsils. Therefore, the aim of this study was to characterize macrophage response in children undergoing EBV primary or persistent infection, in order to enlighten the role of macrophages in viral pathogenesis, in a population with a high incidence of EBV-associated lymphomas in children younger than 10 years old. This study may contribute to explain, at least in part, the asymptomatic viral infection in children from an underdeveloped region, given that M1 polarization pattern prevails, but in a regulatory environment.

Prevalence of Epstein-Barr Viral DNA among children at a single hospital in Suzhou, China.

OBJECTIVE: This study aimed to describe the prevalence of Epstein-Barr virus (EBV)-DNA among children in Suzhou, and to explore the association between plasma EBV load and disease diagnosis. METHODS: All children admitted to the Children's Hospital of Soochow University between January 2018 and September 2020 and subjected to the plasma EBV-DNA assay were included. The authors retrospectively collected demographic and discharge diagnostic information of the participants, and ascribed the disease distribution characteristics of children with positive plasma EBV-DNA by age and viral load. RESULTS: A total of 38,175 patients underwent plasma EBV-DNA PCR assay, of which 2786 (7.3%) had EBV-DNA in their plasma. Children aged 3-4 years had a high prevalence of EBV infection. Plasma EBV positivity was common with infectious mononucleosis (IM, 40.0%), respiratory infection (20.1%), atypical EBV infection (14.2%), acute leukemia (6.4%), hemophagocytic lymphohistiocytosis (HLH, 4.8%), and idiopathic thrombocytopenic purpura (ITP, 2.9%). With increasing age, plasma EBV positivity was more common in children with IM and atypical EBV infection. However, an inverse correlation was observed in children with respiratory infections and ITP. High levels of EBV loads were more likely to occur in HLH, IM, and atypical EBV infection, especially in HLH. However, lower viral loads were found in respiratory infection and acute leukemia. CONCLUSIONS: This is a large sample study that revealed the prevalence of plasma EBV-DNA levels in children of various ages and presenting illnesses.

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.

Pediatric hemophagocytic lymphohistiocytosis: A rarely diagnosed entity in a developing country.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is an exaggerated inflammatory reaction secondary to a host's inadequate immune response causing a self-perpetuating loop of altered regulation. Signs and symptoms of HLH are compatible with other common diseases and are nonspecific. Underdiagnosis makes it difficult to estimate the real incidence of HLH, especially in developing countries. METHODS: Retrospective, descriptive study of pediatric patients admitted to a high-complexity institution in Cali, Colombia between 2012 and 2019 with HLH diagnosis. Medical history review to complete an electronic database and a secondary, descriptive analysis was carried out. The study was approved by the Institutional Ethics Committee. RESULTS: Twenty-one patients were included. 52.4 % of the population was male with a median age of 9.3 years [IQR (3.0-13.7 years)]. More than half of patients (66.6 %) had viral disease at diagnosis, the most frequent being Epstein-Barr Virus (EBV) (52.3 %) and dengue (14.3 %). Three patients had confirmed gene mutations (G6PC3, XIAP, and UNC13D). 95 % of the patients were treated with the HLH 2004 protocol, half of them received incomplete protocol with intravenous immunoglobulin (IVIG) and/or systemic steroids, while the other half received the complete protocol including etoposide and cyclosporine. More than three-fourths (76.2 %) required admission to an ICU with a median stay of 14 days [IQR (11-37 days)] and a median hospital stay of 30 days [IQR (18-93 days)]. 14.3 % (n = 3) of patients died. CONCLUSIONS: HLH is a complex disease that requires multidisciplinary management with secondary HLH due to EBV infection being a common cause. There is increasing awareness of HLH diagnosis in developing countries such as Colombia which can offer earlier treatment options and better outcomes.

Atypical oral viral coinfection after allogeneic hematopoietic stem cell transplantation: Diagnosis and treatment challenge.

BACKGROUND: Viral reactivation in patients undergoing immunosuppressive therapy after hematopoietic stem cell transplantation (HSCT) is a serious complication associated with significant morbidity and mortality. Infections caused by human herpes viruses such as herpes simplex virus (HSV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) can result in oral lesions. CASE PRESENTATION: A 40-year-old male patient who had undergone HSCT presented with ulcerated lesions in different areas of the mouth, for 7 months. The lesions had evolved to painful exophytic nodules with an erythematous, ulcerated surface. They were present on the tongue margins and soft and hard palate. Histological, immunohistochemical (IHC), and polymerase chain reaction analyses were performed, and the results were compatible with HSV-1 and -2 and CMV infections. Treatment comprised five sessions of antimicrobial photodynamic therapy (aPDT) and oral valganciclovir. Thirty days after combined antiviral therapy and aPDT, the lesions were completely resolved. Patient was followed up for 12 months without recurrence. CONCLUSION: Diagnosis and treatment of atypical oral infections in immunosuppressed patients is challenging. Assessment of both clinical and laboratory findings is mandatory for a conclusive diagnosis. The use of local antimicrobial and systemic therapies contributes to positive clinical response in such cases.

Clinical Features and Prognostic Factors of Children with Chronic Active Epstein-Barr Virus Infection: A Retrospective Analysis of a Single Center.

OBJECTIVE: To analyze the clinical characteristics, prognosis factors and risk factors of chronic active Epstein-Barr virus infection in children. STUDY DESIGN: Observational analysis of baseline data and follow-up evaluation data of children with chronic active Epstein-Barr virus infection in our center between January 1, 2016 and December 31, 2019; they were followed through June 30, 2020. RESULTS: There were 96 children with chronic active Epstein-Barr virus infection (50 male and 46 female children), with the median age of 6.7 years (range from 0.6 to 17.6 years) at diagnosis. The median follow-up time was 16.5 months. The 3 most common clinical manifestations were fever, lymph node enlargement, and hepatomegaly or splenomegaly. Thirty-three patients (36.3%) also had a diagnosis of hemophagocytic lymphohistiocytosis (HLH). Epstein-Barr virus infected only T lymphocytes, natural killer cells, or both T- and natural killer-cell types in 15 (33.3%), 17 (37.8%), and 13 (28.9%), respectively. At the end of follow-up, 26 children had died, 60 survived, and 10 were lost to follow-up. Generally, progression-free survival was 69.8% ± 2.4%. The level of interleukin (IL)-6 and IL-10 and the combination of younger age and lower pathologic grade at diagnosis were independent prognostic factors by Cox regression analysis (P = .009 and .018, respectively). CONCLUSIONS: Children with lower levels of IL-6 and IL-10, or with younger age and lower pathologic grades, generally had favorable outcomes at the terminal point of follow-up, indicating better prognostic signs.

Herpesvirus encephalitis diagnosed by polymerase chain reaction at the National Institute of Neurology of Mexico.

The frequency of central nervous system infections due to herpesvirus have been studied in various populations; however, studies in Mexican mestizo patients are scant. This paper documents the frequency of herpesvirus encephalitis in Mexican mestizo patients from the National Institute of Neurology and Neurosurgery (NINN) of Mexico. To study the frequency of herpetic viral encephalitis at the NINN in the period from 2004 to 2009. We reviewed clinical records from patients with clinically suspected encephalitis; polymerase chain reaction assays were done for detection of herpesviruses in cerebrospinal fluid (CSF) samples. The total number of patients studied was 502; in 59 (12%), the diagnosis of herpetic encephalitis was confirmed by PCR-based testing of CSF. Of them, 21 (36%) were positive for herpes simplex virus type 1, 15 (25%) for Epstein-Barr virus, 10 (17%) for varicella zoster virus, 8 (14%) for cytomegalovirus, 3 (5%) for human herpesvirus 6, and 2 (3%) for herpes simplex virus 2. Our results show a varied frequency of viral encephalitis in mestizo patients due to herpesviruses in a tertiary neurological center and point out the importance of modern molecular technology to reach the etiological diagnosis in cases of encephalitis.

Hemophagocytic Lymphohistiocytosis Associated with Histiocytic Necrotizing Lymphadenitis: A Clinical Study of 13 Children and Literature Review.

OBJECTIVE: To analyze the clinical characteristics and prognosis of pediatric hemophagocytic lymphohistiocytosis (HLH) associated with histiocytic necrotizing lymphadenitis (HNL). STUDY DESIGN: We retrospectively collected the clinical data of all children with HNL-HLH enrolled in Beijing Children's Hospital from 2007 to 2019. The control patients with Epstein-Barr virus-associated HLH and simple HNL (not associated with HLH) were case matched (1:2). The clinical features and prognosis were analyzed by case-control study. Cases of HNL-HLH in the literature were reviewed. RESULTS: The male-to-female ratio of the 13 patients in our center was 9:4. The mean age of the patients at disease onset was 8.1 ± 1.2 years, younger than that of the 16 patients in the literature (P = .017). Clinical presentations, especially rash and splenomegaly, and laboratory examination of HNL-HLH group were statistically different from Epstein-Barr virus-HLH group, simple HNL group, and patients reported in the literature (P < .05). Three patients were treated with immunosuppressive drugs or chemotherapy owing to poor control of HLH. One patient died, and all 12 remaining patients survived, 2 of which developed autoimmune diseases. Kaplan-Meier survival curves showed no statistical difference among the 3 groups (P > .05). CONCLUSIONS: HNL-HLH is more common in school- and preschool-age children. Most patients have a favorable prognosis. Some patients suffer from relapses or develop autoimmune diseases. Prolonged follow-up should be carried out for patients with HNL-HLH.