RESUMO
Microscopic polyangiitis is a rare autoimmune disease of unknown etiology, characterized by inflammation and necrosis of blood vessels. It forms a part of the antineutrophil cytoplasmic antibody-associated vasculitides-a heterogeneous group of disorders characterized by vasculitis. It is a systemic disease affecting multiple organs. The patients may present with a wide variety of symptoms. Ocular manifestations may present as its initial clinical symptoms, necessitating a multidisciplinary approach for reducing the morbidity and mortality. Early diagnosis aids in the formulation of appropriate treatment and prevention of further complications. Aggressive treatment, including surgery, is often necessary to limit structural damage and preserve visual function. We present the case of an 82-year-old woman who initially presented with peripheral ulcerative keratitis that led to the diagnosis of microscopic polyangiitis.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Úlcera da Córnea , Granulomatose com Poliangiite , Poliangiite Microscópica , Idoso de 80 Anos ou mais , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/etiologia , Olho , Feminino , Humanos , Poliangiite Microscópica/complicações , Poliangiite Microscópica/diagnósticoRESUMO
INTRODUCTION: ANCA-associated vasculitis (AAV) is an infrequent disease in childhood. International literature about pediatric vasculitis is scarce, and it mainly refers to other systemic vasculitides with a higher incidence in childhood, such as IgA vasculitis and Kawasaki disease. OBJECTIVE: To describe the clini cal and laboratory characteristics of a series of pediatric cases with AAV. PATIENTS AND METHOD: Re trospective, descriptive study of patients with diagnosis of AAV treated at a tertiary health center from Santiago, Chile, between 2000 and 2020. Electronic medical records were reviewed collecting epidemiological, laboratory, images, and biopsies data. RESULTS: There were five cases of pediatric pa tients with AAV, with varying degrees of severity, and the age range at the onset was 5.5 to 13.5 years. We observed frequent renal involvement in microscopic polyangiitis (MPA) and eye involvement due to orbital pseudotumor in patients with granulomatosis with polyangiitis (GPA), an infrequent manifestation in the international pediatric literature. Patients were treated according to recommen dations extrapolated from clinical trials in adult populations, showing excellent clinical response to induction therapy with systemic corticosteroids and cyclophosphamide or rituximab. During main tenance therapy, most of the patients were stable on rituximab, azathioprine, or methotrexate. No patient developed organ damage and all cases achieved discontinuation of the corticosteroid therapy. CONCLUSION: This report describes the clinical characteristics of AAV in a series of pediatric patients. In this series, renal involvement was common in MPA and eye involvement due to orbital pseudotu mor in GPA. The clinical response with treatment according to recommendations extrapolated from the adult population was favorable.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Granulomatose com Poliangiite , Poliangiite Microscópica , Adolescente , Adulto , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Anticorpos Anticitoplasma de Neutrófilos/uso terapêutico , Criança , Pré-Escolar , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/tratamento farmacológico , Humanos , Poliangiite Microscópica/complicações , Poliangiite Microscópica/diagnóstico , Poliangiite Microscópica/terapia , Rituximab/uso terapêuticoRESUMO
Lung involvement is one of the most common clinical features in ANCA-associated vasculitides (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). In this review, we detail the five main presentations of pulmonary involvement in AAV: necrotizing granulomatous inflammation, tracheobronchial inflammation, pulmonary capillaritis, interstitial lung disease (ILD) and asthma with their clinical, radiological and therapeutic characteristics. The prevalence of these manifestations is variable according to the subtype of AAV, necrotizing granulomatous inflammation and tracheobronchial inflammation being defining features of GPA whereas ILD is primarily seen in patients with MPA, especially in association with ANCA directed against myeloperoxydase (MPO-ANCA), and asthma is characteristic of EGPA. Despite recent progresses in the diagnosis and management of these conditions, several questions remain and are discussed here, including local treatments for subglottic stenosis, the uncertain efficacy of plasma exchanges for alveolar hemorrhage, the potential role of antifibrotic agents in ILD associated with MPA, and the use of novel anti-IL-5 strategies in EGPA.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Doenças Pulmonares Intersticiais/etiologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Asma/etiologia , Asma/patologia , Asma/terapia , Síndrome de Churg-Strauss/complicações , Síndrome de Churg-Strauss/patologia , Síndrome de Churg-Strauss/terapia , Granuloma/etiologia , Granuloma/patologia , Granuloma/terapia , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/patologia , Granulomatose com Poliangiite/terapia , Humanos , Inflamação/etiologia , Inflamação/patologia , Inflamação/terapia , Doenças Pulmonares Intersticiais/patologia , Doenças Pulmonares Intersticiais/terapia , Poliangiite Microscópica/complicações , Poliangiite Microscópica/patologia , Poliangiite Microscópica/terapia , Necrose/etiologia , Necrose/patologia , Necrose/terapiaRESUMO
Severe infections are common in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We aimed to describe the characteristics of patients with AAV and severe infections according to clinical phenotype. Retrospective cohort study including patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Baseline characteristics were compared between patients with and without at least one severe infection. Demographics, comorbidities, clinical characteristics, laboratory and treatment were retrieved at diagnosis and at every infectious event. One hundred and eight patients were included (57 with and 51 without infections). Patients with an infection had received more frequently methylprednisolone boluses at AAV diagnosis than patients without infections (OR 2.6, 95% CI 1.1-5.9, p = 0.01). There were a total of 108 severe infections in 57 patients (median follow-up 18 months). Thirty-two patients (56%) had an infectious complication within the first year of AAV diagnosis, 43 (75%) had pulmonary involvement during the first infection. The most frequent type of infection was pneumonia. Phenotypes were: Non-severe AAV (n = 11), severe PR3-AAV (n = 30), severe MPO-AAV (n = 9); the number of infectious events in each group was 11, 69, 18, respectively. Patients with severe MPO phenotype were older and required more frequently ICU stay compared to other phenotypes. Positive correlation was found between total of infections and pulmonary infiltrates due to vasculitis (ρ = 0.40, p = 0.003), endobronchial involvement (ρ = 0.40, p = 0.003), and alveolar hemorrhage (ρ = 0.34, p = 0.015). Severe infections, most commonly pneumonia, were frequent in this cohort, especially during the first year after diagnosis, in patients with pulmonary involvement and severe PR3 phenotype who received methylprednisolone boluses.
Assuntos
Glucocorticoides/efeitos adversos , Granulomatose com Poliangiite/complicações , Poliangiite Microscópica/complicações , Sepse/etiologia , Adulto , Anti-Inflamatórios , Anticorpos Anticitoplasma de Neutrófilos/sangue , Estudos de Casos e Controles , Feminino , Glucocorticoides/administração & dosagem , Granulomatose com Poliangiite/imunologia , Humanos , Terapia de Imunossupressão/efeitos adversos , Terapia de Imunossupressão/métodos , Masculino , México , Poliangiite Microscópica/imunologia , Pessoa de Meia-Idade , Fenótipo , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
CASE DESCRIPTION: A 16 year-old female who presented with initial ear, nose and throat manifestations who later progressed to severe renal disease, requiring hemodialysis after 11 months of unique laryngeal involvement. CLINICAL FINDINGS: Unilateral vocal cord paralysis without other symptoms or signs, but with positive perinuclear anti-neutrophil cytoplasmic antibodies (ANCA) and anti-myeloperoxidase autoantibodies, followed an unfavorable course months later with rapidly progressive glomerulonephritis. Renal biopsy confirmed an ANCA-associated vasculitis. She was diagnosed with microscopic polyangiitis. TREATMENT AND OUTCOME: High-dose glucocorticoids, intravenous cyclophosphamide, plasma exchange and finally, hemodialysis and renal transplantation. CLINICAL RELEVANCE: In contrast to granulomatosis with polyangiitis (Wegener), ear, nose and throat manifestations in microscopic polyangiitis are uncommon, while involvement of the lungs and kidneys are usual. We present a case with an isolated rare involvement, which progressed to severe disease. This atypical case warns about laryngeal symptoms as initial manifestation of an anti-myeloperoxidase positive systemic vasculitides, and emphasizes the relevance of close observation when unexplained isolated conditions with accompanying evidence of autoimmunity, in this case high levels of specific autoantibodies, are present.
DESCRIPCIÓN DEL CASO: Una mujer de 16 años se presentó inicialmente con manifestaciones otorrinolaringológicas y posteriormente progresó hacia enfermedad renal grave, requiriendo hemodiálisis después de 11 meses de tener exclusivamente afección laríngea. HALLAZGOS CLÍNICOS: parálisis de cuerda vocal unilateral sin otros síntomas ni signos, pero con autoanticuerpos anticitoplasma de neutrófilo (ANCA) con patrón perinuclear y especificidad contra mieloperoxidasa, siguiendo un curso desfavorable meses después con desarrollo de glomerulonefritis rápidamente progresiva. La biopsia renal confirmó una vasculitis asociada con ANCA (VAA). Se diagnosticó entonces como poliangitis microscópica. TRATAMIENTO Y DESENLACE: Glucocorticoides a dosis altas, ciclofosfamida endovenosa, recambio plasmático y finalmente, hemodiálisis y transplante renal. RELEVANCIA CLÍNICA: en contraste con la granulomatosis con poliangitis (Wegener), las manifestaciones otorrinolaringológicas en poliangitis microscópica son poco comunes, mientras que la afección pulmonar y renal es común. Presentamos un caso con afección inusual aislaea, que progresó a enfermedad grave. Este caso atípico enfatiza sobre los síntomas laríngeos como manifestación inicial de una vasculitis antimieloperoxidasa positiva, y subraya la relevancia de una estrecha observación cuando condiciones aisladas inexplicables, que como en este caso se acompañan de evidencia de autoinmunidad manifestado por presencia de niveles altos de autoanticuerpos, se presentan para su atención.
Assuntos
Nefropatias/etiologia , Poliangiite Microscópica/diagnóstico , Paralisia das Pregas Vocais/etiologia , Adolescente , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Autoanticorpos/imunologia , Ciclofosfamida/uso terapêutico , Progressão da Doença , Feminino , Glucocorticoides/uso terapêutico , Humanos , Nefropatias/terapia , Transplante de Rim/métodos , Poliangiite Microscópica/complicações , Poliangiite Microscópica/terapia , Troca Plasmática/métodos , Diálise Renal , Índice de Gravidade de DoençaRESUMO
Abstract Case Description: A 16 year-old female who presented with initial ear, nose and throat manifestations who later progressed to severe renal disease, requiring hemodialysis after 11 months of unique laryngeal involvement. Clinical Findings: Unilateral vocal cord paralysis without other symptoms or signs, but with positive perinuclear anti-neutrophil cytoplasmic antibodies (ANCA) and anti-myeloperoxidase autoantibodies, followed an unfavorable course months later with rapidly progressive glomerulonephritis. Renal biopsy confirmed an ANCA-associated vasculitis. She was diagnosed with microscopic polyangiitis. Treatment and Outcome: High-dose glucocorticoids, intravenous cyclophosphamide, plasma exchange and finally, hemodialysis and renal transplantation. Clinical Relevance: In contrast to granulomatosis with polyangiitis (Wegener), ear, nose and throat manifestations in microscopic polyangiitis are uncommon, while involvement of the lungs and kidneys are usual. We present a case with an isolated rare involvement, which progressed to severe disease. This atypical case warns about laryngeal symptoms as initial manifestation of an anti-myeloperoxidase positive systemic vasculitides, and emphasizes the relevance of close observation when unexplained isolated conditions with accompanying evidence of autoimmunity, in this case high levels of specific autoantibodies, are present.
Resumen Descripción del caso: Una mujer de 16 años se presentó inicialmente con manifestaciones otorrinolaringológicas y posteriormente progresó hacia enfermedad renal grave, requiriendo hemodiálisis después de 11 meses de tener exclusivamente afección laríngea. Hallazgos clínicos: parálisis de cuerda vocal unilateral sin otros síntomas ni signos, pero con autoanticuerpos anticitoplasma de neutrófilo (ANCA) con patrón perinuclear y especificidad contra mieloperoxidasa, siguiendo un curso desfavorable meses después con desarrollo de glomerulonefritis rápidamente progresiva. La biopsia renal confirmó una vasculitis asociada con ANCA (VAA). Se diagnosticó entonces como poliangitis microscópica. Tratamiento y desenlace: Glucocorticoides a dosis altas, ciclofosfamida endovenosa, recambio plasmático y finalmente, hemodiálisis y transplante renal. Relevancia clínica: en contraste con la granulomatosis con poliangitis (Wegener), las manifestaciones otorrinolaringológicas en poliangitis microscópica son poco comunes, mientras que la afección pulmonar y renal es común. Presentamos un caso con afección inusual aislaea, que progresó a enfermedad grave. Este caso atípico enfatiza sobre los síntomas laríngeos como manifestación inicial de una vasculitis antimieloperoxidasa positiva, y subraya la relevancia de una estrecha observación cuando condiciones aisladas inexplicables, que como en este caso se acompañan de evidencia de autoinmunidad manifestado por presencia de niveles altos de autoanticuerpos, se presentan para su atención.
Assuntos
Adolescente , Feminino , Humanos , Paralisia das Pregas Vocais/etiologia , Poliangiite Microscópica/diagnóstico , Nefropatias/etiologia , Troca Plasmática/métodos , Autoanticorpos/imunologia , Índice de Gravidade de Doença , Diálise Renal , Transplante de Rim/métodos , Progressão da Doença , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Ciclofosfamida/uso terapêutico , Poliangiite Microscópica/complicações , Poliangiite Microscópica/terapia , Glucocorticoides/uso terapêutico , Nefropatias/terapiaRESUMO
Several classification schemes have been developed for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), with actual debate focusing on their clinical and prognostic performance. Sixty-two patients with renal biopsy-proven AAV from a single center in Mexico City diagnosed between 2004 and 2013 were analyzed and classified under clinical (granulomatosis with polyangiitis [GPA], microscopic polyangiitis [MPA], renal limited vasculitis [RLV]), serological (proteinase 3 anti-neutrophil cytoplasmic antibodies [PR3-ANCA], myeloperoxidase anti-neutrophil cytoplasmic antibodies [MPO-ANCA], ANCA negative), and histopathological (focal, crescenteric, mixed-type, sclerosing) categories. Clinical presentation parameters were compared at baseline between classification groups, and the predictive value of different classification categories for disease and renal remission, relapse, renal, and patient survival was analyzed. Serological classification predicted relapse rate (PR3-ANCA hazard ratio for relapse 2.93, 1.20-7.17, p = 0.019). There were no differences in disease or renal remission, renal, or patient survival between clinical and serological categories. Histopathological classification predicted response to therapy, with a poorer renal remission rate for sclerosing group and those with less than 25 % normal glomeruli; in addition, it adequately delimited 24-month glomerular filtration rate (eGFR) evolution, but it did not predict renal nor patient survival. On multivariate models, renal replacement therapy (RRT) requirement (HR 8.07, CI 1.75-37.4, p = 0.008) and proteinuria (HR 1.49, CI 1.03-2.14, p = 0.034) at presentation predicted renal survival, while age (HR 1.10, CI 1.01-1.21, p = 0.041) and infective events during the induction phase (HR 4.72, 1.01-22.1, p = 0.049) negatively influenced patient survival. At present, ANCA-based serological classification may predict AAV relapses, but neither clinical nor serological categories predict renal or patient survival. Age, renal function and proteinuria at presentation, histopathology, and infectious complications constitute the main outcome predictors and should be considered for individualized management.
Assuntos
Anticorpos Anticitoplasma de Neutrófilos/sangue , Granulomatose com Poliangiite/mortalidade , Nefropatias/patologia , Rim/patologia , Poliangiite Microscópica/mortalidade , Mieloblastina/sangue , Adulto , Feminino , Taxa de Filtração Glomerular , Granulomatose com Poliangiite/complicações , Humanos , Estimativa de Kaplan-Meier , Masculino , México , Poliangiite Microscópica/complicações , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , RecidivaRESUMO
RESUMO A poliangeíte microscópica é uma vasculite necrotizante sistêmica que acomete arteríolas, capilares e vênulas, mas também pode atingir pequenas e médias artérias. É considerada uma doença rara, idiopática e autoimune. Diversas anormalidades oculares e sistêmicas estão associadas às oclusões arteriais retinianas. Dentre as doenças vasculares do colágeno, a literatura cita como possíveis causas de obstrução das artérias retinianas o lúpus eritematoso sistêmico, a poliarterite nodosa, a arterite de células gigantes, a granulomatose de Wegener e a granulomatose linfóide de Liebow. Até o presente momento, não se encontrou na literatura relatos da associação de casos de oclusão arterial retinana associados à PAM. Os autores relatam o caso de um paciente com poliangeíte microscópica que apresentou comprometimento renal importante e oclusão da artéria central da retina unilateral. Atenta-se para a inclusão de pesquisa da PAM, através do p-ANCA, na avaliação de possível origem sistêmica em pacientes acometidos por oclusão arterial retiniana.
ABSTRACT The microscopic polyangiitis is a systemic necrotizing vasculitis that affects arterioles, capillaries and venules, but can also reach small and medium-sized arteries. It is considered a rare disease, idiopathic in nature but clearly autoimmune. Several ocular and systemic abnormalities are associated with retinal arterial occlusions. Among the collagen vascular diseases, the literature cited as possible causes of retinal artery obstruction lupus erythematosus, polyarteritis nodosa, giant cell arteritis, Wegener’s granulomatosis and lymphoid Liebow. Until now, there were no reports in the literature of the association of cases of arterial occlusion retinana associated with PAM. The authors report a case of a 53 years old patient diagnosed with microscopic polyangiitis who presented with important renal artery occlusion and associated unilateral central retinal artery occlusion. An extended systemic evaluation of patients presenting with central retinal artery occlusion should include research of PAM through analysis op p-ANCA.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Oclusão da Artéria Retiniana/diagnóstico , Oclusão da Artéria Retiniana/etiologia , Poliangiite Microscópica/complicações , Poliangiite Microscópica/diagnóstico , Poliangiite Microscópica/tratamento farmacológico , Azatioprina/uso terapêutico , Metilprednisolona/uso terapêutico , Prednisona/uso terapêutico , Angiofluoresceinografia , Técnica Indireta de Fluorescência para Anticorpo , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Pulsoterapia , Ciclofosfamida/uso terapêutico , Eletrorretinografia , Vasculite Associada a Anticorpo Anticitoplasma de NeutrófilosRESUMO
Autoimmune liver diseases (AILD) are a group of immunologically induced hepatic disorders that can lead to liver cirrhosis and end-stage liver disease. Extra-hepatic involvement and association with rheumatic diseases (such as Sjögren's syndrome, systemic sclerosis and rheumatoid arthritis) are well known, whereas the coexistence of AILD with small-vessel vasculitis in the same patients have been only occasionally reported. In the present paper we report four such cases and an extensive review of the literature. Clinical features of autoimmune-liver diseases associated with small-vessel vasculitis are discussed, as well as possible common pathogenic pathways including HLA genomics, costimulatory molecules and autoantibodies. In conclusion, knowledge about this association can help physicians in recognising and treating an aggressive disease which could otherwise result in severe and multiple organ damage, compromising the overall prognosis and the indication to liver transplantation.
Assuntos
Síndrome de Churg-Strauss/imunologia , Granulomatose com Poliangiite/imunologia , Hepatite Autoimune/imunologia , Cirrose Hepática Biliar/imunologia , Poliangiite Microscópica/imunologia , Adulto , Idoso , Síndrome de Churg-Strauss/complicações , Feminino , Granulomatose com Poliangiite/complicações , Hepatite Autoimune/complicações , Humanos , Cirrose Hepática Biliar/complicações , Masculino , Poliangiite Microscópica/complicaçõesRESUMO
The most frequently observed pulmonary complications of vasculitis (AAV) with anti-neutrophil cytoplasmic positive antibodies (ANCA) are alveolar hemorrhage, granulomas and airway stenosis. In recent years, some reports have been published that show the association of vasculitis with pulmonary fibrosis (PF), suggesting that it may be another complication of AAV. We report and describe here two cases with such association, and their clinical, tomographic and immunological characteristics. Given that in the association between PF and AAV, as reported in the last years, PF could be the first manifestation of AAV, the search for ANCA in patients with PF may be necessary, as a cause of it and for the possible subsequent development of vasculitis.