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1.
BMJ Case Rep ; 14(2)2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33526532

RESUMO

Polyangiitis overlap syndrome (POS) is a diagnostic term coined by Leavitt and Fauci that characterises patients with overlapping features of more than one vasculitis. Prior case studies of antineutrophil cytoplasmic antibodies (ANCA)-associated POS have only been published in patients with eosinophilic granulomatosis with polyangiitis (EGPA) and granulomatosis with polyangiitis alongside proteinase-3/cytoplasmic (C)-ANCA positivity. We present a case of a 60-year-old woman with dyspnoea, hemoptysis, positive perinuclear-ANCA and renal biopsy demonstrating evidence of microscopic polyangiitis. In addition, our patient also had asthma, mononeuritis multiplex, eosinophilia and migratory pulmonary infiltrates, thus fulfilling the criteria for EGPA. This novel case report suggests that POS is not limited to C-ANCA positivity and has variable presentations.


Assuntos
Síndrome de Churg-Strauss/diagnóstico , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Poliangiite Microscópica/diagnóstico , Mononeuropatias/fisiopatologia , Insuficiência Renal Crônica/fisiopatologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Azatioprina/uso terapêutico , Síndrome de Churg-Strauss/tratamento farmacológico , Síndrome de Churg-Strauss/imunologia , Síndrome de Churg-Strauss/fisiopatologia , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Poliangiite Microscópica/tratamento farmacológico , Poliangiite Microscópica/imunologia , Poliangiite Microscópica/fisiopatologia , Pessoa de Meia-Idade , Peroxidase/imunologia , Prednisona/uso terapêutico , Insuficiência Renal Crônica/patologia , Tomografia Computadorizada por Raios X
2.
Artigo em Inglês | MEDLINE | ID: mdl-33093767

RESUMO

Objective: To describe the clinical and serological patients characteristics with Microscopic Polyangiitis (MPA) and Interstitial lung disease (ILD). Methods: Of all the patients with AAV diagnosed between 2007-2017 at the Hospital Clinico Universidad de Chile, those with MPA and ILD were selected and studied retrospectively. Results: All patients were Hispanic; median age at diagnosis 65 years (32-84). 59% were female. All were positive for p-ANCA, 16 patients for MPO. Most common manifestations were constitutional symptoms, weight loss and fever. CT-Scans patterns were Usual Interstitial Pneumonia (UIP) in 10 patients, Nonspecific Interstitial Pneumonia (NSIP) in 6 and fibrosis not UIP or NSIP pattern in 1. In 6 cases, ILD was diagnosed 0.5-14 years before MPA and concomitantly in 11. Conclusions: Although infrequent, Microscopic Polyangiitis should be suspected in patients with ILD particularly if extra-pulmonary manifestations that rise the possibility of a systemic illness are present, regardless of the time elapsed between the latter and the diagnosis of this type of lung involvement. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (1): 37-42).


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/sangue , Doenças Pulmonares Intersticiais/sangue , Poliangiite Microscópica/sangue , Peroxidase/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Chile , Feminino , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/imunologia , Masculino , Poliangiite Microscópica/diagnóstico , Poliangiite Microscópica/imunologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Testes Sorológicos , Tomografia Computadorizada por Raios X
4.
Am J Kidney Dis ; 75(1): 124-137, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31358311

RESUMO

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of disorders characterized by inflammation and destruction of small- and medium-sized blood vessels and the presence of circulating ANCA. Clinical disease phenotypes include granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, and renal-limited vasculitis. Serologic classification of AAV into proteinase 3-ANCA disease and myeloperoxidase-ANCA disease correlates with a number of disease characteristics. AAV has a predilection for the kidney, with >75% of patients having renal involvement characterized by rapidly progressive glomerulonephritis. The cause and pathogenesis of AAV are multifactorial and influenced by genetics, environmental factors, and responses of the innate and adaptive immune system. Randomized controlled trials in the past 2 decades have refined the therapy of AAV and transformed AAV from a fatal disease to a chronic illness with relapsing course and associated morbidity. This article in AJKD's Core Curriculum in Nephrology series provides a detailed review of the epidemiology, pathogenesis, diagnosis, and advances in the management of AAV.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Glomerulonefrite/terapia , Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Síndrome de Churg-Strauss/genética , Síndrome de Churg-Strauss/imunologia , Síndrome de Churg-Strauss/patologia , Síndrome de Churg-Strauss/terapia , Ciclofosfamida/uso terapêutico , Progressão da Doença , Glomerulonefrite/genética , Glomerulonefrite/imunologia , Glomerulonefrite/patologia , Granulomatose com Poliangiite/genética , Granulomatose com Poliangiite/imunologia , Granulomatose com Poliangiite/patologia , Granulomatose com Poliangiite/terapia , Humanos , Transplante de Rim , Poliangiite Microscópica/genética , Poliangiite Microscópica/imunologia , Poliangiite Microscópica/patologia , Poliangiite Microscópica/terapia , Ácido Micofenólico/uso terapêutico , Mieloblastina/imunologia , Peroxidase/imunologia , Indução de Remissão , Diálise Renal , Rituximab/uso terapêutico
5.
Mod Rheumatol ; 30(2): 338-344, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30929541

RESUMO

Objectives: To identify the factors associated with the risk of diffuse alveolar hemorrhage (DAH) in patients with microscopic polyangiitis (MPA), focusing on other preexisting lung involvements such as interstitial lung disease (ILD) and airway disease.Methods: In this retrospective cohort study, we analyzed consecutive patients with myeloperoxidase-antineutrophil cytoplasmic antibody-positive MPA who had undergone chest computed tomography (CT) before starting treatment between 2006 and 2016. Patients who already had DAH at initial CT imaging were excluded. CT images were evaluated for the presence of ILD and airway disease. The association between preexisting lung involvements and the development of DAH was assessed using logistic regression models adjusted for various clinical characteristics.Results: We identified 113 patients (median age 72 years; median follow-up duration 39 months), and 27 (24%) of them developed DAH during the follow-up. Airway disease was identified in 41 (36%) patients and was independently associated with the development of DAH (adjusted odds ratio 6.86, 95% confidence interval 1.85-25.4). However, ILD identified in 45 (40%) patients was not associated with DAH.Conclusion: Our findings suggest that DAH in MPA occurs frequently in patients with airway disease. Attention to preexisting airway disease may help predict the development of DAH.


Assuntos
Hemorragia/epidemiologia , Doenças Pulmonares Intersticiais/epidemiologia , Poliangiite Microscópica/complicações , Adulto , Idoso , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Feminino , Hemorragia/complicações , Humanos , Doenças Pulmonares Intersticiais/complicações , Masculino , Poliangiite Microscópica/imunologia , Pessoa de Meia-Idade , Peroxidase/imunologia
6.
Expert Rev Clin Immunol ; 15(12): 1273-1286, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31762340

RESUMO

Introduction: The majority of the patients with anti-neutrophil cytoplasmic autoantibody (ANCA) associated vasculitis (AAV) achieve remission with effective induction therapy. Therefore, prevention of relapses and avoiding long-term damage and treatment-related toxicity are major challenges.Areas covered: This review provides an update on maintenance therapy in AAV, emphasizing the available treatment options for granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Among the spectrum of all patients with AAV, those at higher risk of relapse have recently been identified. Clinical trials have yielded robust results about various options for maintenance of remission including common disease-modifying anti-rheumatic drugs (DMARDs, i.e. azathioprine, methotrexate, and mycophenolate mofetil) and rituximab (RTX). However, outcomes of these studies are not easy to compare.Expert opinion: Regardless of the treatment used, patients presenting with an anti-proteinase-3 ANCA, relapsing GPA have a substantially higher risk of relapse compared to patients with newly diagnosed MPA or positive anti-myeloperoxidase ANCA. While the efficacy of common DMARDs for remission maintenance is heterogeneous, the role of RTX seems particularly promising for the high-risk patients, although the most appropriate dose and timing of retreatment with RTX remain under controversial. Low-dose glucocorticoid use for remission maintenance versus complete discontinuation also remains under investigation.


Assuntos
Antirreumáticos/uso terapêutico , Granulomatose com Poliangiite/tratamento farmacológico , Quimioterapia de Manutenção , Poliangiite Microscópica/tratamento farmacológico , Ensaios Clínicos como Assunto , Granulomatose com Poliangiite/imunologia , Granulomatose com Poliangiite/patologia , Humanos , Poliangiite Microscópica/imunologia , Poliangiite Microscópica/patologia , Indução de Remissão
7.
Arthritis Rheumatol ; 71(11): 1888-1893, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31216123

RESUMO

OBJECTIVE: To assess the frequency of venous thromboembolism (VTE) events in the Rituximab in Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis (RAVE) trial and identify novel potential risk factors. METHODS: VTE events in 197 patients enrolled in the RAVE trial were analyzed. Baseline demographic and clinical characteristics were recorded, and univariate and multivariate analyses were performed to identify factors associated with VTE in ANCA-associated vasculitis (AAV). RESULTS: VTE occurred in 16 patients (8.1%) with an overall average time to event of 1.5 months (range 1.0-2.75). In univariate analyses with calculation of hazard ratios (HRs) and 95% confidence intervals (95% CIs), heart involvement (HR 17.408 [95% CI 2.247-134.842]; P = 0.006), positive proteinase 3 (PR3)-ANCA (HR 7.731 [95% CI 1.021-58.545]; P = 0.048), pulmonary hemorrhage (HR 3.889 [95% CI 1.448-10.448]; P = 0.008), and the presence of red blood cell casts (HR 15.617 [95% CI 3.491-69.854]; P < 0.001) were associated with the onset of VTE. In multivariate models adjusted for age and sex, the significant associations between VTE events and heart involvement (HR 21.836 [95% CI 2.566-185.805]; P = 0.005), PR3-ANCA (HR 9.12 [95% CI 1.158-71.839]; P = 0.036), pulmonary hemorrhage (HR 3.91 [95% CI 1.453-10.522]; P = 0.007), and urinary red blood cell casts (HR 16.455 [95% CI 3.607-75.075]; P < 0.001) remained. CONCLUSION: Patients diagnosed as having AAV with pulmonary hemorrhage, positive PR3-ANCA, heart involvement, and the presence of red blood cell casts are at an increased risk to develop VTE. Further studies are needed to confirm and expand these findings and to explore the mechanisms of hypercoagulability in these patients with the aim of informing potential targets for therapeutic intervention.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/epidemiologia , Eritrócitos , Hemorragia/epidemiologia , Pneumopatias/epidemiologia , Embolia Pulmonar/epidemiologia , Urina/citologia , Trombose Venosa/epidemiologia , Adulto , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Feminino , Granulomatose com Poliangiite/tratamento farmacológico , Granulomatose com Poliangiite/epidemiologia , Granulomatose com Poliangiite/imunologia , Humanos , Masculino , Poliangiite Microscópica/tratamento farmacológico , Poliangiite Microscópica/epidemiologia , Poliangiite Microscópica/imunologia , Pessoa de Meia-Idade , Mieloblastina/imunologia , Peroxidase/imunologia , Modelos de Riscos Proporcionais , Fatores de Risco , Tromboembolia Venosa/epidemiologia
8.
PLoS One ; 14(6): e0218272, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31216309

RESUMO

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), are autoimmune conditions associated with small vessel inflammation. Earlier studies indicate that complement activation via the alternative pathway plays a major role in the pathogenesis. In this study we have investigated if ANCA-activation of neutrophils from AAV patients leads to activation of the alternative complement pathway. C5a-primed neutrophils (PMN) from 10 AAV patients and 10 healthy controls (HC) were stimulated with PMA or IgG purified from PR3-ANCA positive patients (ANCA IgG). The supernatants were analyzed for release of complement proteins and markers of different granules by ELISA, and release of microparticles (MP) by flow cytometry. The ability of the supernatants to activate the alternative complement pathway was determined by incubation with normal serum and C3bBbP and C5a were measured by ELISA. MP were analyzed by flow cytometry and removed by centrifugation. The supernatants from the AAV patients' neutrophils produced significantly more C3bBbP compared with HCs (p = 0.0001). C3bBbP levels correlated with the number of MP. After removal of MP from the supernatants, alternative pathway activation was significantly lower. This study shows that primed and ANCA-stimulated neutrophils from AAV patients have a greater ability to activate the alternative complement pathway compared to primed neutrophils from healthy controls. This finding emphasizes the role of complement in the pathogenesis of AAV - underlining the therapeutic potential of C5a and other complement blockade.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Inflamação/imunologia , Neutrófilos/imunologia , Idoso , Animais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Ativação do Complemento/efeitos dos fármacos , Ativação do Complemento/imunologia , Complemento C5a/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Granulomatose com Poliangiite/sangue , Granulomatose com Poliangiite/imunologia , Granulomatose com Poliangiite/patologia , Humanos , Imunoglobulina G/administração & dosagem , Imunoglobulina G/imunologia , Inflamação/sangue , Inflamação/patologia , Masculino , Poliangiite Microscópica/sangue , Poliangiite Microscópica/imunologia , Poliangiite Microscópica/patologia , Neutrófilos/patologia
9.
BMC Nephrol ; 20(1): 123, 2019 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-30961527

RESUMO

BACKGROUND: Thymic hyperplasia and thymic epithelial tumor (thymoma) have been associated with a variety of autoimmune diseases. Renal involvement has been reported in patients with thymoma. Minimal change disease and membranous nephropathy are frequently observed in glomerular lesions of thymoma patients, but ANCA-associated renal vasculitis is rare. We present a case of thymoma-associated microscopic polyangiitis with positivity for three ANCAs: MPO-ANCA, PR3-ANCA and azurocidin-ANCA. CASE PRESENTATION: An 89-year-old Japanese woman was admitted to our hospital following an episode of general fatigue, nausea, muscle weakness of the lower limbs, and ophthalmoplegia. On urinalysis, proteinuria, hematuria, and cellular casts were observed. Elevated levels of serum creatinine and C-reactive protein were also demonstrated, and MPO-, PR3- and azurocidin-ANCA were detected on serological examination. Renal biopsy showed pauci-immune crescentic glomerulonephritis. We therefore diagnosed rapidly progressive glomerulonephritis due to microscopic polyangiitis. Acetylcholine-receptor antibody was also detected. Chest computed tomography and MRI revealed a lobulated tumor in the anterior mediastinum. We thus also diagnosed myasthenia gravis with thymoma. CONCLUSION: Considering the patient's triple-ANCA positivity, thymic diseases may be associated with the pathogenesis of ANCA-associated vasculitis due to central T-cell tolerance. A further accumulation of cases is needed, because thymectomy does not always induce the remission of thymoma-associated autoimmune diseases.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Anticorpos Anticitoplasma de Neutrófilos , Mediastino/diagnóstico por imagem , Poliangiite Microscópica , Timoma , Neoplasias do Timo , Idoso de 80 Anos ou mais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Anticorpos Anticitoplasma de Neutrófilos/sangue , Anticorpos Anticitoplasma de Neutrófilos/classificação , Biópsia/métodos , Diagnóstico Diferencial , Progressão da Doença , Feminino , Humanos , Glomérulos Renais/patologia , Imagem por Ressonância Magnética/métodos , Poliangiite Microscópica/complicações , Poliangiite Microscópica/imunologia , Poliangiite Microscópica/patologia , Poliangiite Microscópica/urina , Administração dos Cuidados ao Paciente , Timoma/complicações , Timoma/diagnóstico , Timoma/imunologia , Timoma/patologia , Neoplasias do Timo/complicações , Neoplasias do Timo/diagnóstico , Neoplasias do Timo/imunologia , Neoplasias do Timo/patologia , Tomografia Computadorizada por Raios X/métodos , Urinálise/métodos
10.
Z Rheumatol ; 78(6): 518-528, 2019 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-31028473

RESUMO

Granulomatosis with polyangiitis (GPA, formerly Wegener's granulomatosis) and microscopic polyangiitis (MPA) are associated with the detection of antibodies against neutrophilic cytoplasmic antigens (ANCA) and are referred to as ANCA-associated vasculitides (AAV). In the event of the clinical suspicion of AAV the ANCA should first be determined by means of an antigen-specific immunoassay for proteinase 3­ANCA and myeloperoxidase-ANCA, according to current consensus recommendations. The diagnosis of AAV should also be confirmed by biopsy if possible. The classification criteria for AAV are currently being revised. Diagnostic criteria do not exist. The standard induction therapy consists of rituximab or cyclophosphamide, each in combination with glucocorticoids (GC). In the absence of severe organ involvement, methotrexate can alternatively be used. Recent study data suggest that additive plasmapheresis does not improve the long-term outcome. After remission, remission-preserving treatment with azathioprine, methotrexate or rituximab should be given for at least 48 months. The risk of severe infections is markedly increased, especially during the remission induction phase but can also be reduced during treatment with rituximab by the prophylactic administration of trimethoprim-sulfamethoxazole. In view of the increased risk of infection, GC-reduced or GC-free treatment regimens are currently the focus of clinical development.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Granulomatose com Poliangiite , Poliangiite Microscópica , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Azatioprina , Produtos Biológicos/uso terapêutico , Ciclofosfamida/uso terapêutico , Quimioterapia Combinada , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/imunologia , Humanos , Poliangiite Microscópica/diagnóstico , Poliangiite Microscópica/imunologia , Mieloblastina , Indução de Remissão , Resultado do Tratamento
11.
Rheumatology (Oxford) ; 58(7): 1293-1298, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30897615

RESUMO

OBJECTIVE: Although ANCA is the major autoantibody in patients with ANCA-associated vasculitis, previous studies have suggested the presence of anti-neutrophil extracellular trap (NET) antibody in patients with microscopic polyangiitis (MPA), one type of ANCA-associated vasculitis. In this study, we aimed to determine the prevalence and pathogenic role of anti-NET antibody (ANETA) in MPA. METHODS: We examined the presence or absence of ANETA in sera obtained from 19 MPA patients by indirect immunofluorescence. We compared the clinical parameters, including age, sex, MPO-ANCA, creatinine, CRP, MPO-DNA complexes and vasculitis activity, in ANETA-positive and ANETA-negative MPA patients. We investigated the serum NET induction and degradation abilities of ANETA-positive and ANETA-negative MPA patients with reference to healthy controls (n = 8). Furthermore, we assessed the relationship between ANETA and the effect of IgG depletion on the serum NET degradation ability. RESULTS: ANETA was present in 10 of the 19 MPA patients. There was no significant difference in the clinical parameters in ANCA-positive and ANCA-negative MPA patients. Although the NET induction ability was higher and the NET degradation ability was lower in MPA sera than those in healthy controls, these abilities were not different between ANETA-positive and ANETA-negative MPA sera. Interestingly, the NET degradation ability in some sera with ANETA was markedly increased by IgG depletion. CONCLUSION: Some MPA patients produce ANETA and some ANETA possess an inhibitory function against the serum NET degradation ability. Although further studies are needed, ANETA is worthy of attention in order to understand the pathophysiology of MPA.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/sangue , Armadilhas Extracelulares/imunologia , Poliangiite Microscópica/imunologia , Neutrófilos/imunologia , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Estudos de Casos e Controles , Feminino , Técnica Indireta de Fluorescência para Anticorpo/métodos , Humanos , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade
12.
Rheumatology (Oxford) ; 58(10): 1731-1739, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30805643

RESUMO

OBJECTIVES: In ANCA-associated vasculitis (AAV), classifications have emerged to individualize homogeneous clinical and outcomes patterns, including the recently defined anti-MPO granulomatosis with polyangiitis (GPA) subgroup. This study aimed to retrospectively evaluate the impacts of re-classification based on clinicopathological criteria and/or ANCA specificity. METHODS: A retrospective monocentric study conducted at Caen University Hospital led to the identification of PR3 or MPO-ANCA AAV patients from January 2000 or September 2011, respectively, to June 2016. Eosinophilic GPA patients were excluded. AAVs were thereby also classified either as GPA or microscopic polyangiitis (MPA) according to the European Medicines Agency vasculitis algorithm. RESULTS: A total of 150 AAV patients were included (94 GPA, 56 MPA; 87 anti-PR3 and 63 anti-MPO patients). GPA patients exhibited a worse relapse-free survival but a better renal survival (P < 0.001 and P = 0.021, respectively) than MPA patients. Overall, relapse-free and renal survival rates were similar between anti-PR3 and anti-MPO patients (P = 0.35, 0.17 and 0.15, respectively). Similarly, the prognosis was identical between anti-MPO MPA patients and anti-PR3 MPA patients (P = 0.33, 0.19 and 0.65, respectively), and between anti-MPO GPA patients and anti-PR3 GPA patients (P = 0.06, 0.99 and 0.64, respectively). Moreover, anti-PR3 GPA and anti-MPO GPA patients exhibited no differences in clinical manifestations or BVAS score. CONCLUSION: Clinicopathological classification appeared to be the strongest criterion for distinguishing among homogeneous prognoses of AAV. Individualizing the anti-MPO GPA subgroup does not appear to bring additional value to clinical practice, but multicentre studies are required to confirm this trend.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/classificação , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Especificidade de Anticorpos/imunologia , Granulomatose com Poliangiite/classificação , Poliangiite Microscópica/classificação , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/mortalidade , Feminino , Granulomatose com Poliangiite/imunologia , Granulomatose com Poliangiite/mortalidade , Humanos , Rim/imunologia , Masculino , Poliangiite Microscópica/imunologia , Poliangiite Microscópica/mortalidade , Pessoa de Meia-Idade , Peroxidase/imunologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
13.
Eur Cytokine Netw ; 30(4): 151-159, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32096477

RESUMO

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disorder of unknown etiology with dysregulated cytokines levels. OBJECTIVES: The main aim of this study was to assess the clinical correlation between antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, granulomatosis with polyangiitis (GPA) serum levels of the microscopic polyangiitis (MPA), serum levels of the proinflammatory cytokines, interleukin (IL)-32 and interleukin-6. METHODS: Study included 71 patients, 47 with GPA and 24 with MPA. Serum IL-32 and IL-6 concentrations were analyzed in all patients, and compared with levels observed in 10 controls. IL-32 and IL-6 were evaluated using DuoSet and Quantikine HS ELISA, respectively. IL-32 and IL-6 concentrations were correlated with disease-related clinical and laboratory findings. RESULTS: IL-32 and IL-6 levels were significantly higher in GPA and MPA than in controls, especially IL-32 levels in GPA were elevated. IL-32 concentrations correlated positively with anti-proteinase 3 - ANCA (PR3-ANCA) levels in GPA (P < 0.0001), and with anti-myeloperoxidase ANCA (MPO-ANCA) in MPA (P = 0.049). IL-32 levels correlated positively with disease activity in GPA and MPA (P < 0.0001). GPA patients with pulmonary, cutaneous, and musculoskeletal involvement presented the highest IL-6 serum levels. Cutaneous manifestations correlated positively with IL-6 levels in MPA patients (P = 0.05). ANCA-positive patients with GPA expressed significantly high IL-6 levels (P = 0.036). No significant difference in IL-32 values was observed between ANCA-positive and ANCA-negative patients. CONCLUSIONS: Patients with GPA and MPA present higher serum IL-32 and IL-6 levels than controls. IL-32 levels correlate positively with disease activity.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/sangue , Granulomatose com Poliangiite/diagnóstico , Interleucina-6/sangue , Interleucinas/sangue , Poliangiite Microscópica/diagnóstico , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Diagnóstico Diferencial , Feminino , Expressão Gênica , Granulomatose com Poliangiite/sangue , Granulomatose com Poliangiite/genética , Granulomatose com Poliangiite/imunologia , Humanos , Interleucina-6/genética , Interleucina-6/imunologia , Interleucinas/genética , Interleucinas/imunologia , Masculino , Poliangiite Microscópica/sangue , Poliangiite Microscópica/genética , Poliangiite Microscópica/imunologia , Pessoa de Meia-Idade , Mieloblastina/sangue , Mieloblastina/genética , Mieloblastina/imunologia , Peroxidase/sangue , Peroxidase/genética , Peroxidase/imunologia , Índice de Gravidade de Doença
14.
Chest ; 154(5): e135-e138, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30409367

RESUMO

CASE PRESENTATION: An 80-year-old man presented with a 5-day history of hemoptysis, mild shortness of breath on exertion, fatigue, and malaise. He denied chest pain or fever. He had a history of hypertension, congestive heart failure, and left nephrectomy for renal cancer 10 years earlier; he was a former cigarette smoker with a 50 pack-year history, having quit 5 years prior to presentation. The patient did not report any recent travel history or occupational or animal exposures, and he did not have gastroesophageal reflux. Medications included diltiazem hydrochloride, irbesartan, hydrochlorothiazide, and ranitidine.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/sangue , Ciclofosfamida/administração & dosagem , Dispneia/diagnóstico , Hemoptise , Metilprednisolona/administração & dosagem , Poliangiite Microscópica , Insuficiência Renal , Idoso de 80 Anos ou mais , Broncoscopia/métodos , Diagnóstico Diferencial , Dispneia/etiologia , Imunofluorescência , Hemoglobinas/análise , Hemoptise/diagnóstico , Hemoptise/etiologia , Hemoptise/fisiopatologia , Humanos , Imunossupressores/administração & dosagem , Testes de Função Renal/métodos , Pulmão/diagnóstico por imagem , Masculino , Poliangiite Microscópica/diagnóstico , Poliangiite Microscópica/imunologia , Poliangiite Microscópica/fisiopatologia , Alvéolos Pulmonares/patologia , Insuficiência Renal/diagnóstico , Insuficiência Renal/etiologia , Insuficiência Renal/imunologia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
15.
Yonsei Med J ; 59(7): 865-871, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30091320

RESUMO

PURPOSE: We investigated whether C-reactive protein (CRP) to serum albumin ratio (CAR) could be an independent predictor of all-cause mortality in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). MATERIALS AND METHODS: We retrospectively reviewed the medical records of 170 patients with AAV. We collected clinical and laboratory data. We also examined AAV-related and traditional risk factors of all-cause mortality. To assess the hazard ratios of variables, we performed univariable and multivariable Cox hazard model analyses. RESULTS: The mean age was 55.0 years and 53 patients (31.2%) were male among 170 patients with AAV (88 microscopic polyangiitis, 43 granulomatosis with polyangiitis, and 39 eosinophilic granulomatosis with polyangiitis). ANCA was detected in 129 patients (75.9%). The initial mean CRP and serum albumin were 41.1 (mg/L) and 3.6 (g/dL), and the mean CAR at diagnosis was 14.8. The most common risk factor of mortality was hypertension (42.4%), followed by chronic kidney disease ≥stage 3 (25.9%). Fourteen patients (8.2%) died during the mean follow-up of 56.7 months. In both multivariable Cox hazard model analyses, CAR at diagnosis was identified as an independent predictor of all-cause of mortality comparable to diabetes mellitus (DM). Moreover, patients with CAR ≥10.35 and having DM exhibited a higher frequency of all-cause mortality than those without. CONCLUSION: CAR at diagnosis can be an independent predictor of all-cause mortality, comparable to DM, the conventional risk factor of mortality.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/mortalidade , Proteína C-Reativa/metabolismo , Poliangiite Microscópica/mortalidade , Mortalidade , Albumina Sérica/metabolismo , Adulto , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Feminino , Humanos , Hipertensão/complicações , Masculino , Poliangiite Microscópica/imunologia , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
16.
Clin Exp Rheumatol ; 36 Suppl 111(2): 12-32, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29799395
17.
Arthritis Rheumatol ; 70(10): 1626-1633, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29790303

RESUMO

OBJECTIVE: To evaluate clinical links between levels of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) and relapse in patients with ANCA-associated vasculitis (AAV) using a data set from 2 nationwide prospective cohort studies. METHODS: From the cohort studies, MPO-ANCA-positive patients who achieved remission during the 6 months after remission induction therapy were enrolled. We measured MPO-ANCA levels at months 0, 3, 6, 12, 18, 24, and at the time of relapse. The primary outcome measure was relapse. A nested case-control analysis and multivariable analysis were performed to investigate the relationship between ANCA reappearance and relapse. RESULTS: Of 271 patients, 183 were classified as having microscopic polyangiitis, 34 as having granulomatosis with polyangiitis, 15 as having eosinophilic granulomatosis with polyangiitis, and 39 were unclassifiable. The median age was 73 years, and 165 (61%) were female. In 195 patients (72%), MPO-ANCA levels decreased to normal levels within 6 months after commencement of treatment, and MPO-ANCA reappeared in 73 of 181 patients (40%) with complete follow-up data. Reappearance of MPO-ANCA was more frequent in patients with relapse than in 75 age- and sex-matched control patients without relapse (odds ratio 26.2 [95% confidence interval 8.2-101], P < 0.0001) after adjustment for confounding factors. CONCLUSION: Reappearance of MPO-ANCA could be a clinically useful biomarker for predicting relapse in patients with MPO-ANCA-positive AAV in remission. This suggests that routine MPO-ANCA monitoring should be implemented in this patient population.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Anticorpos Anticitoplasma de Neutrófilos/sangue , Anticorpos/sangue , Peroxidase/imunologia , Idoso , Idoso de 80 Anos ou mais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Granulomatose com Poliangiite/imunologia , Humanos , Masculino , Poliangiite Microscópica/imunologia , Análise Multivariada , Estudos Prospectivos , Recidiva , Fatores de Risco , Fatores de Tempo
18.
Yonsei Med J ; 59(3): 397-405, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29611402

RESUMO

PURPOSE: Delta neutrophil index (DNI) represents the immature granulocytes count associated with neutrophil-consumption. We investigated whether DNI might be associated with Birmingham vasculitis activity score (BVAS) at diagnosis and could predict relapse during the follow-up in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). MATERIALS AND METHODS: We reviewed the medical records of 97 patients having DNI results. Twenty patients had granulomatosis with polyangiitis (GPA), 58 had microscopic polyangiitis (MPA), and 19 had eosinophilic GPA (EGPA). We collected clinical and laboratory data including BVAS, five factor score (FFS), and DNI. The correlation coefficient and cumulative relapse free survival rate were obtained. The optimal cut-off of DNI was extrapolated by calculating the area under the receiver operator characteristic curve. RESULTS: DNI was significantly related to cross-sectional BVAS. Furthermore, among continuous variables, only DNI could reflect BVAS of GPA and MPA, but not EGPA. Severe AAV was defined as BVAS ≥20 (the highest quartile). At diagnosis, patients having DNI ≥0.65% had a significantly higher risk of severe GPA and MPA than those having not (relative risk 4.255) at diagnosis. During the follow-up, DNI ≥0.65% could predict the higher relapse rate. CONCLUSION: DNI could reflect BVAS at diagnosis and furthermore, DNI ≥0.65% could not only identify severe AAV at diagnosis, but also predict relapse during the follow-up in patients with GPA and MPA.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Granulomatose com Poliangiite/imunologia , Poliangiite Microscópica/imunologia , Neutrófilos , Recidiva , Adulto , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/epidemiologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos , Estudos Transversais , Feminino , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/epidemiologia , Humanos , Poliangiite Microscópica/diagnóstico , Poliangiite Microscópica/epidemiologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Qualidade de Vida , Estudos Retrospectivos , Risco , Índice de Gravidade de Doença
19.
Arthritis Rheumatol ; 70(7): 1114-1121, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29693324

RESUMO

OBJECTIVE: To evaluate circulating cytokine profiles in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), classified by antineutrophil cytoplasmic antibody (ANCA) specificity (proteinase 3 ANCA [PR3-ANCA] versus myeloperoxidase ANCA [MPO-ANCA]) or by clinical diagnosis (granulomatosis with polyangiitis [GPA] versus microscopic polyangiitis [MPA]). METHODS: A panel of 29 cytokines was tested in 186 patients with active AAV at inclusion into the Rituximab in AAV trial. Cytokine concentrations were compared between groups within each classification system. Multivariable analyses adjusted for age, sex, and renal insufficiency were performed, with each biomarker as a dependent variable and ANCA specificity and clinical diagnosis as explanatory variables of interest. RESULTS: Levels of 9 circulating cytokines (interleukin-6 [IL-6], granulocyte-macrophage colony-stimulating factor [GM-CSF], IL-15, IL-18, CXCL8/IL-8, CCL-17/thymus and activation-regulated chemokine [TARC], IL-18 binding protein [IL-18 BP], soluble IL-2 receptor α [sIL-2Rα], and nerve growth factor ß [NGFß]) were significantly higher in PR3-AAV than MPO-AAV, 4 cytokines (sIL6R, soluble tumor necrosis factor receptor type II [sTNFRII], neutrophil gelatinase-associated lipocalin [NGAL], and soluble intercellular adhesion molecule 1 [sICAM-1]) were higher in MPO-AAV than in PR3-AAV, 6 cytokines (IL-6, GM-CSF, IL-15, IL-18, sIL-2Rα, and NGFß) were higher in GPA than in MPA, and 3 cytokines (osteopontin, sTNFRII, and NGAL) were higher in MPA than in GPA (all P < 0.05). For nearly all cytokines, the difference between PR3-AAV and MPO-AAV was larger than that between GPA and MPA. The multivariate analysis showed that 8 cytokines (IL-15, IL-8, IL-18 BP, NGF-ß, sICAM-1, TARC, osteopontin, and kidney injury molecule 1 (P < 0.05) distinguished patients with AAV better (lower P values and larger effect sizes) when grouped by ANCA specificity than by clinical diagnosis. CONCLUSION: Distinct cytokine profiles were identified for PR3-AAV versus MPO-AAV and for GPA versus MPA. Differences in these circulating immune mediators are more strongly associated with ANCA specificity than with clinical diagnosis, suggesting that heterogeneity in the AAV subtypes extends beyond clinical phenotypes.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Anticorpos Anticitoplasma de Neutrófilos/sangue , Citocinas/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Biomarcadores/sangue , Citocinas/imunologia , Método Duplo-Cego , Feminino , Granulomatose com Poliangiite/sangue , Granulomatose com Poliangiite/imunologia , Humanos , Masculino , Poliangiite Microscópica/sangue , Poliangiite Microscópica/imunologia , Pessoa de Meia-Idade , Mieloblastina/imunologia , Peroxidase/imunologia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sensibilidade e Especificidade , Adulto Jovem
20.
J Neurovirol ; 24(3): 323-331, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29508305

RESUMO

This report assesses the observed risk of PML in patients treated with the anti-CD20 monoclonal antibody rituximab in the regulatory authority-approved autoimmune indications rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA). This was a cumulative analysis of confirmed PML cases in patients receiving rituximab for RA or GPA/MPA from both spontaneous reports and clinical trial sources, as captured in the manufacturer global company safety and clinical databases. Overall reporting rates were calculated and patient case details were summarized. As of 17 November 2015, there were nine confirmed PML cases among patients who had received rituximab for RA and two for GPA. Corresponding estimated reporting rates were 2.56 per 100,000 patients with RA (estimated exposure ≈ 351,396 patients) and < 1 per 10,000 patients with GPA/MPA (estimated exposure 40,000-50,000 patients). In all cases, patients had ≥ 1 potential risk factor for PML independent of rituximab treatment. In the RA population, the estimated reporting rate of PML generally remained stable and low since 2009 despite increasing rituximab exposure. There was no pattern of latency from time of rituximab initiation to PML development and no association of PML with the number of rituximab courses. Global post-marketing safety and clinical trial data demonstrated that the occurrence of PML is very rare among rituximab-treated patients with RA or GPA/MPA and has remained stable over time.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Granulomatose com Poliangiite/tratamento farmacológico , Fatores Imunológicos/efeitos adversos , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Poliangiite Microscópica/tratamento farmacológico , Rituximab/efeitos adversos , Idoso , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Bases de Dados Factuais , Feminino , Granulomatose com Poliangiite/imunologia , Granulomatose com Poliangiite/patologia , Humanos , Fatores Imunológicos/administração & dosagem , Vírus JC/isolamento & purificação , Vírus JC/patogenicidade , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Leucoencefalopatia Multifocal Progressiva/epidemiologia , Leucoencefalopatia Multifocal Progressiva/virologia , Masculino , Poliangiite Microscópica/imunologia , Poliangiite Microscópica/patologia , Pessoa de Meia-Idade , Rituximab/administração & dosagem , Suíça , Reino Unido , Estados Unidos , Ativação Viral/efeitos dos fármacos
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