RESUMO
INTRODUCTION: Vasculitis entails heterogeneous origins; it starts with an inflammatory process that leads to small vessels' necrosis, hemorrhage, and ischemic lesion, and may further result in occlusion of the vascular lumen. Vasculitis' contribution to allograft rejection is still unclear. This study aims to investigate the incidence of vasculitis in the early stages of heart transplantation as well as to assess the intragraft genes' expression associated with vascular function and subsequently to verify the way in which it affects the outcome of the allograft. METHODS: In this retrospective study, 300 archive paraffin-embedded endomyocardial biopsies from 63 heart allograft recipients were assessed. Cellular rejection and vasculitis were diagnosed through histological analysis, and antibody-mediated rejection was performed with immunohistochemical C4d staining. The transcripts of ICAM, VCAM, VEGF, CCL2, IFNG, TGFB, TNF, ADIPOR1, and ADIPOR2 genes were examined through quantitative polymerase chain reaction using B2M for normalization. RESULTS: We observed a higher prevalence of severe vasculitis in the early period of post-transplant, and recovery was observed to take place around 1 year post-transplant. Additionally, vasculitis was found to be directly associated with acute cellular rejection and antibody-mediated rejection. The intense C4d capillary positivity predicts higher long-term cardiovascular disease mortality. In comparison with the vasculitis-free group, the group with severe vasculitis displayed reduced left ventricular ejection fraction and an upregulation of VCAM and IFNG associated with the downregulation of VEGF, ADIPOR1, and ADIPOR2. CONCLUSION: The vasculitis associated with the presence of C4d and the change in intragraft gene expression profile may contribute to poor allograft outcomes.
Assuntos
Perfilação da Expressão Gênica , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/mortalidade , Transplante de Coração/mortalidade , Vasculite/diagnóstico , Vasculite/mortalidade , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Transplante de Coração/efeitos adversos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Vasculite/etiologiaRESUMO
Systemic vasculitides were initially reported as acute, progressive, severe, and life-threatening diseases. The introduction of glucocorticoids and cyclophosphamide for the treatment of vasculitis improved survival dramatically, but morbidity has remained high. Damage develops as a consequence of recurrent or persistent active vasculitis or its treatment. It is defined as the accumulation of nonhealing scars that are unlikely to respond to immunosuppressive therapy. Damage assessment is essential in systemic vasculitis because it may facilitate patient stratification in clinical trials and possibly in clinical practice. Moreover, it may avoid unnecessary use of immunosuppressive therapy. The Vasculitis Damage Index, developed and validated in 1997, has been very useful in solving many matters in systemic vasculitis and is currently the only validated damage-assessment tool available. However, the vasculitis community has recognized that there is a growing need to improve the evaluation of damage in vasculitis. The development of a Combined Damage Assessment index, which would permit a more appropriate and standardized approach to disease assessment applicable to systemic vasculitis, has been proposed.
Assuntos
Vasos Sanguíneos/patologia , Vasculite/patologia , Humanos , Morbidade , Recidiva , Índice de Gravidade de Doença , Análise de Sobrevida , Taxa de Sobrevida , Vasculite/mortalidade , Vasculite/fisiopatologiaRESUMO
Granulomatose de Wegener (GW) é uma vasculite necrotizante granulomatosa sistêmica de pequenos vasos, que acomete principalmente o trato respiratório superior e rins. É enfermidade rara, tem altas taxas de morbidade e mortalidade, e pacientes com comprometimento renal têm pior evolução. Relatamos um caso desta relativamente rara enfermidade com o objetivo de revisar, na literatura, as opções terapêuticas, discutir o tratamento instituídoe suas complicações e enfatizar sua apresentação clínica. Paciente do sexo masculino, 69 anos, com quadro de rinossinusite crônica, epistaxe e ulceração de mucosa nasal acompanhadas de lesões purpúreas, hematúria, e insuficiência renal avançada de um mês de evolução apresentou ANCA-c positivo(até diluição de 1:640) e histologia renal com glomerulonefrite crescêntica esclerosante. Foi instituído tratamento agressivo com pulsoterapia(metilprednisolona), seguida de corticoterapia oral, porém, o paciente evoluiu para óbito com 15 dias do tratamento devido a choque séptico. Aapresentação clínica do paciente está de acordo com os relatos prévios da literatura, entretanto, o tratamento instituído foi diferente do recomendado: pulso de ciclofosfamida (CFA) e corticóide. Entretanto, questiona-se: a imunossupressão com CFA era a melhor opção terapêutica, diante da gravidade do processo infeccioso?
Wegener Granulomatosis (WG) is a rare disorder characterized by vasculitis of small arteries, arterioles and capillaries, necrotizing granulomatous lesionsof both upper and lower respiratory tract and glomerulonephritis. The entity carries high morbidity and mortality rates; renal involvement aggravates itsprognosis. A case of this relatively rare disease is reported aiming to review the literature regarding the therapeutic alternatives and discuss our treatmentchoice and the drug-associated complications emphasizing the clinical picture of the patient. A 69 year old man with chronic sinusitis, epistaxis, nasalulcerations, purpura, hematuria, and advanced renal insufficiency for one month, showed high c-ANCA level (positive until 1/640) and focal segmental glomerulonephritis with crescent formation and necrosis on renal histology. The patient was aggressively treated with methylprednisolone followed by oral corticosteroids. Despite 15 day therapy he died from septic shock. The patients clinical presentation agreed with the one found in previous studies, but the treatment chosen was different from the most frequent recommendation: cyclophosphamide and corticosteroids. Based on the course of the patient, a questions remains unanswered: would it be immunosuppressive therapy with cyclophosphamide the best choice in face of a severe infectious disease?