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Mononucleose infeciosa e síndromes mononucleósicas: etiologia, fisiopatologia, diagnóstico e terapêutica
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A mononucleose infeciosa é uma a síndrome clínica caracterizada por febre, faringite e linfadenopatia cervical. É frequentemente observada em adolescentes e jovens adultos e resulta, maioritariamente, da infeção primária pelo vírus Epstein-Barr, um herpesvírus que infeta pelo menos 90% da população mundial. Transmitido pelo contacto com a saliva de indivíduos infetados, o vírus Epstein-Barr infeta as células epiteliais orofaríngeas e durante um período de incubação, de aproximadamente 6 semanas, a replicação viral adicional resulta em viremia, com infeção das células B no sangue periférico. O início da doença aguda é marcado por altas cargas virais na cavidade oral e no sangue do doente, desencadeando uma potente resposta imunológica tanto inata, onde se destaca o papel das células NK, como adaptativa, com a produção de anticorpos dirigidos contra antigénios virais e expansão marcada de linfócitos T CD8+. Esta resposta, embora fundamental no controlo da infeção, não a elimina e o vírus persiste de forma latente nas células B de memória. A mononucleose infeciosa é geralmente uma doença benigna e autolimitada, podendo, no entanto, originar diversas complicações severas e potencialmente fatais. A infeção pelo vírus Epstein-Barr tem sido ainda associada ao desenvolvimento de doenças autoimunes e malignidades. O diagnóstico de mononucleose infeciosa constitui um desafio dada a diversidade de condições que a mimetizam. De facto, embora menos comuns, são vários os agentes infeciosos responsáveis pelo aparecimento de síndromes mononucleósicas, os quais incluem diferentes agentes virais, bacterianos e parasitários. Determinados fármacos, sobretudo anticonvulsivantes, encontram-se também descritos como potenciais indutores de quadros clínicos semelhantes. Assim, um diagnóstico diferencial torna-se crucial para garantir que a terapêutica e medidas de controlo a instituir são adequadas a cada situação clínica. Um quadro clínico típico num adolescente ou jovem adulto, com um teste para a pesquisa de anticorpos heterófilos positivo, é geralmente suficiente para estabelecer um diagnóstico de mononucleose infeciosa. Porém os anticorpos heterófilos não são específicos e não se desenvolvem em alguns doentes. Deste modo, os testes serológicos específicos para o vírus Epstein-Barr apresentam-se como a melhor opção para confirmação diagnóstica definitiva. Presentemente, não existe tratamento específico aprovado para a mononucleose infeciosa, nem uma vacina profilática eficaz.
Infectious mononucleosis is a syndrome characterized by fever, pharyngitis and cervical lymphadenopathy. It is frequently observed in adolescents and young adults and it is mostly a consequence of the Epstein-Barr virus’s primary infection, a herpesvirus that infects at least 90% of the world population. Transmitted by the saliva of infected individuals, the Epstein-Barr virus infects the oropharyngeal epithelial cells and, during an incubation period of approximately 6 weeks, the additional viral replication results in viremia, with B cell infection in the peripheral blood. The onset of the acute illness is characterized by a high viral load both in the oral cavity and in the blood, triggering a powerful immunological response both innate, where NK cells play an important role, and adaptative, with the production of antibodies directed against viral antigens and the sharp expansion of T CD8+ lymphocytes. This response, although fundamental in controlling the infection, does not eliminate it and the virus remains in latent form in the memory B cells. Generally, mononucleosis is a benign, self-limiting condition. It can, however, result in many severe and potentially fatal complications. Furthermore, the Epstein-Barr virus infection has been associated with the development of autoimmune diseases and malignancies. The diagnosis of infectious mononucleosis is challenging, given the variety of illnesses that mimic it. There are several other infectious agents that may be responsible for the appearance of mononucleosis-like syndromes which include viral, bacterial and parasitic agents. Some drugs, mainly anticonvulsant drugs, can potentially produce similar clinical presentations in patients. Thus, a differential diagnosis is crucial as it ensures an adequate treatment and control measure to each situation. Typically, the combination of a standard clinical presentation with a positive heterophile antibodies test is enough to establish a diagnosis of infectious mononucleosis. Nevertheless, heterophile antibodies are not specific and consequently do not develop in some patients. Thus, the Epstein-Barr virus specific serological tests are a better option for a definite diagnosis. Currently, there isn’t any approved specific treatment for infectious mononucleosis nor is there an effective prophylactic vaccine available.
Infectious mononucleosis is a syndrome characterized by fever, pharyngitis and cervical lymphadenopathy. It is frequently observed in adolescents and young adults and it is mostly a consequence of the Epstein-Barr virus’s primary infection, a herpesvirus that infects at least 90% of the world population. Transmitted by the saliva of infected individuals, the Epstein-Barr virus infects the oropharyngeal epithelial cells and, during an incubation period of approximately 6 weeks, the additional viral replication results in viremia, with B cell infection in the peripheral blood. The onset of the acute illness is characterized by a high viral load both in the oral cavity and in the blood, triggering a powerful immunological response both innate, where NK cells play an important role, and adaptative, with the production of antibodies directed against viral antigens and the sharp expansion of T CD8+ lymphocytes. This response, although fundamental in controlling the infection, does not eliminate it and the virus remains in latent form in the memory B cells. Generally, mononucleosis is a benign, self-limiting condition. It can, however, result in many severe and potentially fatal complications. Furthermore, the Epstein-Barr virus infection has been associated with the development of autoimmune diseases and malignancies. The diagnosis of infectious mononucleosis is challenging, given the variety of illnesses that mimic it. There are several other infectious agents that may be responsible for the appearance of mononucleosis-like syndromes which include viral, bacterial and parasitic agents. Some drugs, mainly anticonvulsant drugs, can potentially produce similar clinical presentations in patients. Thus, a differential diagnosis is crucial as it ensures an adequate treatment and control measure to each situation. Typically, the combination of a standard clinical presentation with a positive heterophile antibodies test is enough to establish a diagnosis of infectious mononucleosis. Nevertheless, heterophile antibodies are not specific and consequently do not develop in some patients. Thus, the Epstein-Barr virus specific serological tests are a better option for a definite diagnosis. Currently, there isn’t any approved specific treatment for infectious mononucleosis nor is there an effective prophylactic vaccine available.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2019
Palavras-chave
Mononucleose infeciosa Vírus Epstein-Barr Doença do beijo Síndromes mononucleósicas Mestrado Integrado - 2019