Atypical manifestations of Epstein-Barr virus in children: a diagnostic challenge / Manifestações atípicas do vírus de Epstein-Barr em crianças: um desafio diagnóstico

Abstract Objective: Clarify the frequency and the pathophysiological mechanisms of the rare manifestations of Epstein–Barr virus infection. Sources: Original research studies published in English between 1985 and 2015 were selected through a computer-assisted literature search (PubMed and Scopus). Computer searches used combinations of key words relating to "EBV infections" and "atypical manifestation. Summary of the findings: "Epstein–Barr virus is a herpes virus responsible for a lifelong latent infection in almost every adult. The primary infection concerns mostly children and presents with the clinical syndrome of infectious mononucleosis. However, Epstein–Barr virus infection may exhibit numerous rare, atypical and threatening manifestations. It may cause secondary infections and various complications of the respiratory, cardiovascular, genitourinary, gastrointestinal, and nervous systems. Epstein–Barr virus also plays a significant role in pathogenesis of autoimmune diseases, allergies, and neoplasms, with Burkitt lymphoma as the main representative of the latter. The mechanisms of these manifestations are still unresolved. Therefore, the main suggestions are direct viral invasion and chronic immune response due to the reactivation of the latent state of the virus, or even various DNA mutations. Conclusions: Physicians should be cautious about uncommon presentations of the viral infection and consider EBV as a causative agent when they encounter similar clinical pictures.

Resumo Objetivo: Esclarecimento da frequência e dos mecanismos patofisiológicos das manifestações raras da infecção por vírus de Epstein-Barr. Fontes: Estudos de pesquisas originais publicados em inglês entre 1985 e 2015 foram selecionados por meio de uma busca na literatura assistida por computador (Pubmed e Scopus). As buscas no computador usaram combinações de palavras-chave relacionadas a "infecções por VEB" e "manifestação atípica". Resumo dos achados: O vírus de Epstein-Barr é um herpesvírus responsável por uma infecção latente vitalícia em quase todo adulto. A infecção primária ocorre principalmente em crianças e se apresenta como síndrome clínica da mononucleose infecciosa. Contudo, a infecção por vírus de Epstein-Barr pode apresentar diversas manifestações raras, atípicas e de alto risco. Ela pode causar infecções secundárias e diversas complicações dos sistemas respiratório, cardiovascular, geniturinário, gastrointestinal e nervoso. O vírus de Epstein-Barr também desempenha um papel significativo na patogênese de doenças, alergias e neoplasias autoimunes. O linfoma de Burkitt é o principal representante das últimas. Os mecanismos dessas manifestações ainda não foram resolvidos. Portanto, as principais sugestões são invasão viral direta e resposta imune crônica devido à reativação do estado latente do vírus ou mesmo a diversas mutações do DNA. Conclusões: Os médicos devem tomar cuidado sobre apresentações incomuns de infecção viral e considerar o VEB um agente causador quando encontrarem situações clínicas semelhantes.

Safety and Efficacy of Prolonged Hydroxycarbamide Administration in Patients with Sickle Cell Disease in Northwestern Greece.

Hydroxycarbamide (HC) is a ribonucleotide reductase inhibitor which promotes fetal hemoglobin (HbF) induction and has proven efficacy in sickle cell disease (SCD) patients. Given its mechanism of action and prior reports of genotoxicity in animal models, concern exists regarding long-term safety in relation to its cytotoxic effects. The purpose of this study was to retrospectively analyze the long-term (range 3-20 years, median 11) HC-derived clinical and biological effects, in 30 SCD patients (age range 20-68 years) from one referral center. HC treatment resulted in significant reduction of painful crises and transfusions, increase of HbF and hemoglobin as well as drop of white blood cell count and lactate dehydrogenase values. During the long term follow up time the following disease complications were observed: pulmonary hypertension (2 patients), leg ulcers (1 patient) and renal impairment (1 patient). Seven patients discontinued HC therapy because of scheduled pregnancy (3), severe neutropenia (2) and non-compliance (2). One poor HC compliant patient died of pulmonary embolism. No case of malignancy was observed. This retrospective study of most prolonged administration of HC, provides data supporting the safety and the wellestablished usefulness of chronic administration of HC in SCD.