Febre reumática – patogênese e vacina / Rheumatic fever – pathogenesis and vaccine

Há um amplo espectro de doenças causadas por estreptococos do grupo A (GAS), e estas são consideradas um problema de saúde pública em países em desenvolvimento, com aproximadamente 600 milhões de casos/ano. As infecções causadas por GAS podem ocasionar doenças invasivas como faringite e pioderma com seqüelas auto-imunes graves como a febre reumática (FR) e glomerulonefrite. A FR acomete principalmente crianças e jovens, inicia com poliartrite na maioria dos casos. Tem como sequelas principais a coreia de Sydenham e a doença reumática cardíaca (DRC), considerada a forma mais grave da doença e caracterizada por lesões cardíacas valvares progressivas e permanentes, que necessitam de cirurgias cardíacas para correção valvular, com alto custo para os Sistemas de Saúde, no mundo. A presente revisão descreve os principais mecanismos desencadeadores das lesões reumáticas no coração e o desenvolvimento da vacina contra o Streptococcus pyogenes para prevenção das principais sequelas decorrentes das streptococcias.

Group A streptococci (GAS) infections are considered a public health problem in developing countries, with about 600 million cases per year and are responsible for an wide spectrum of diseases, mainly invasive diseases as pharyngitis and pyoderma that lead to rheumatic fever (RF) and glomerulonephritis autoimmune sequelae. RF affects children and young adults, and presents differentmanifestations such as rheumatic heart disease (RHD), Sydenham chorea, erythema marginatum, subcutaneousnodules. RHD is considered the most serious complications leading to cardiac valvular lesions characterized byprogressive and permanent heart-valve damage, which entails high cost to the Healthy System around the world. In the present review we described the mechanisms that lead to rheumatic heart lesions and the development of avaccine against Streptococcus pyogenes.

Transtornos do espectro obsessivo-compulsivo e febre reumática: um estudo de transmissão familiar / Obsessive-compulsive spectrum disorders and rheumatic fever: a family study

A febre reumática (FR) é uma doença autoimune causada por anticorpos desenvolvidos contra o estreptococo beta hemolítico do grupo A (SBHGA). Estudos recentes amparam a noção de que a FR esteja associada ao transtorno obsessivo-compulsivo (TOC), independentemente da presença de outras manifestações no sistema nervoso central (ex.: coréia de Sydenham - CS). O TOC freqüentemente surge acompanhado por outros transtornos, como aqueles denominados de transtornos do espectro obsessivo (TEO), entre eles, a síndrome de Tourette (ST), o transtorno de tiques crônicos (TTC) e o transtorno dismórfico corporal (TDC). Alguns deles parecem apresentar uma relação geneticamente determinada. Um subgrupo de TOC é geneticamente relacionado à ST, podendo ser considerado uma expressão fenotípica alternativa de seu genótipo. Um recente estudo de famílias de portadores de TOC encontrou alta freqüência de TDC nos seus familiares de primeiro grau, além de transtornos de tiques. Neste estudo de famílias buscamos verificar a freqüência de TOC e TEO relacionados em familiares de portadores de FR, com ou sem CS e em um grupo controle, na tentativa de determinar se existe agregação familiar desses transtornos em famílias com FR. Foram avaliados 98 probandos e seus 381 familiares de primeiro grau (FPG). Dos 98 probandos, 31 eram portadores de FR sem CS, 28 tinham FR com CS e 39 eram controles sem FR recrutados em um ambulatório de ortopedia. Entrevistadores treinados avaliaram os sujeitos por meio de entrevistas semi-estruturadas (KSADS e SCID). Vinhetas clínicas foram elaboradas e avaliadas por psiquiatras independentes que faziam a melhor estimativa diagnóstica (best estimate diagnosis). Estes avaliadores eram cegos quanto a se os sujeitos eram probandos ou familiares e quanto ao grupo a que pertenciam. As comparações entre as freqüências dos transtornos entre os três grupos foram feitas por meio dos testes de Fisher, qui-quadrado, pelas Equações de Estimação...

Rheumatic fever (RF) is an autoimmune disease caused by antibodies against group A beta hemolytic streptococcus (GABHS). Some studies support the notion that RF be associated with obsessive-compulsive disorder (OCD) independent of its manifestations on the central nervous system (eg., Sydenham’s Chorea - SC). OCD is often accompanied by other disorders, which are known as obsessive-compulsive spectrum disorders (OCSD), such as Tourette syndrome (TS), chronic tic disorder (CTD) and body dysmorphic disorder (BDD). Some of those putative OCSD seem to share a genetic relationship. An OCD subgroup is genetically related to TS, being considered an alternative phenotype. A recent OCD family study found higher rates of BDD and tic disorders among first-degree relatives (FDR) of OCD probands. This is a family study that assessed the frequency of OCD and OCSD in first-degree relatives of RF probands (with and without SC) in order to verify if there was aggregation of those disorders in RF families. We assessed 98 probands and their 381 first-degree relatives. Of the 98 probands, 31 had RF without SC, 28 had RF with SC and 39 were controls without RF recruited in an orthopedic clinic. Trained interviewers assessed subjects with semi-structured interviews (KSADS and SCID). Clinical vignettes were elaborated and evaluated by independent psychiatrists that assigned best estimate diagnosis. These raters were blind to subject status regarding group and if they were probands or relatives. Comparisons between frequencies of disorders were done with Fisher and chi-square tests, generalized estimated equations (GEE), and Kaplan-Meier survival analyses. Results were considered statistically significant if their level of significance was less or equal to 0.05 (p, two-tailed). OCSD combined were more frequent in FDR of RF probands (with or without SC) than in FDR of controls (p=0.03). CTD was more frequent in FDR of SC probands than FDR of controls (p=0.05)...

Defective monocyte phagocytic function as a possible genetic marker for heumatic susceptibility

The activity of the monocyte phagocytic system in children with rheumatic heart disease [RHD], their parents, their normal siblings and in nonrheumatic families was investigated. Phagocytic activity of isolated monocytes was assessed using luminol-dependent chemiluminescence. The count per minute of emitted light was measured before and after stimulation with zymosan solution. The results indicate that one-third of the siblings of children with RHD were genetically free while two-thirds, as well as the parents, were heterozygous, and that children with RHD were homozygous for [a] mutant gene[s] responsible for the defective function of the monocyte phagocytic system. The findings are strongly suggestive of autosomal recessive inheritance