Organizing Pneumonia in A Patient Double-Positive for ANCA and Anti-GBM Antibodies: A Case Report / 中国医学科学杂志(英文版)

Both anti-glomerular basement membrane (GBM) disease and the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are common causes of pulmonary-renal syndrome. Organizing pneumonia (OP), a special pattern of interstitial lung disease, is extremely rare either in AAV or anti-GBM disease. We report an old woman presented with OP on a background of co-presentation with both ANCA and anti-GBM antibodies.

Anti-neutrophil cytoplasmic antibody-associated vasculitis with gastrointestinal bleeding as the main symptom: a case report and literature review / 中华危重病急救医学

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) has a wide range of symptoms, and it is difficult for clinicians to make a quick and correct diagnosis. On November 11, 2021, a 36-year-old male patient with AAV was admitted to the emergency and critical care department of Yichang Central People's Hospital. He was admitted to the emergency intensive care unit (EICU) with gastrointestinal symptoms (abdominal pain, black stool) as the main physical signs, and was initially diagnosed as AAV with gastrointestinal hemorrhage (GIH). No bleeding point was found after repeated gastroscopy and colonoscopy. Abdominal emission CT (ECT) showed diffuse hemorrhage in the ileum, ascending colon and transverse colon. Multi-disciplinary consultation in the whole hospital considered the diffuse hemorrhage caused by small vascular lesions in the digestive tract caused by AAV. Pulse therapy with methylprednisolone 1 000 mg/d and immunosuppressive therapy with cyclophosphamide (CTX) 0.2 g/d were administered. The patient's symptoms quickly relieved and transferred out of the EICU. After 17 days of treatment, the patient finally died of massive gastrointestinal bleeding. A systematic review of relevant literatures combined with the case diagnosis and treatment process found that only a minority of AAV patients present with gastrointestinal symptoms as their first symptoms, and patients with GIH were very rare. Such patients had a poor prognosis. This patient delayed the use of induced remission and immunosuppressive agents due to the treatment of gastrointestinal bleeding, which may be the main cause of life-threatening GIH secondary to AAV. Gastrointestinal bleeding is a rare and fatal complication of vasculitis. Timely and effective induction and remission treatment is the key to survival. Whether patients should receive maintenance therapy, the duration of maintenance therapy, and the search for markers of disease diagnosis and treatment response are directions and challenges for further research.

Granulomatosis with polyangiitis: A case report of early systemic fulminant presentation

Granulomatosis with polyangiitis is a systemic vasculitis that affects medium and small vessels, with high expression of anti-neutrophil cytoplasmic autoantibody. A case is pre sented on a patient with an initial compromise of the lower airway, who did not respond to management, required intensive care unit management, and died due to severe diffuse alveolar hemorrhage. His definitive diagnosis was established with a clinical autopsy. Gran-ulomatosis with polyangiitis is a disease with different ways of presentation, and can have fatal outcomes if it is not diagnosed early.

La granulomatosis con poliangeítis es un tipo de vasculitis que afecta a vasos de mediano y pequeño calibre de manera sistémica, con una alta expresión de anticuerpos contra el citoplasma del neutrófilo. Se presenta el caso de un paciente con un compromiso inicial de la vía área inferior, que no respondió al tratamiento y requirió manejo en unidad de cuidados intensivos. Finalmente, falleció por una hemorragia alveolar difusa severa. Su diagnóstico definitivo se estableció con una autopsia clínica. La granulomatosis con poliangeítis tiene diferentes formas de presentación y puede tener desenlaces fatales si no se diagnostica a tiempo.

Compromiso pulmonar en vasculitis asociadas a anticuerpos anticitoplasma de neutrófilos / Pulmonary manifestations of anti-neutrophil cytoplasmic antibody associated vasculitis

This article reviews the pulmonary manifestations of anti-neutrophil cytoplasmic antibody associated vasculitis (AAV). Its frequency in the different phenotypes of the disease, clinical manifestations and updated therapeutic recommendations are reviewed, aiming to alert the medical community about the existence of these diseases. We pretend to stimulate a timely suspicion, diagnostic precision, and the implementation of effective therapies, to reduce the eventual sequelae derived from a diagnostic omission or an inappropriate treatment for the different clinical scenarios in which these diseases appear.

Manifestaciones pulmonares al diagnóstico de 170 pacientes con vasculitis asociadas a anticuerpos anticitoplasma de neutrófilos: cohorte retrospectiva de un centro universitario / Pulmonary manifestations at the diagnosis of 170 patients with vasculitis associated with anticytoplasmic neutrophil antibodies: retrospective cohort of a university center

INTRODUCCIÓN: Las Vasculitis Asociadas a Anticuerpos Anticitoplasma de Neutrófilos (VAA) son infrecuentes, pero de amplio espectro de presentación. Si bien el consenso de clasificación de Chapel Hill del año 2012, sigue vigente, la tendencia actual es clasificarlas de acuerdo al marcador inmunológico: anti-Proteinasa 3 (PR3) o anti-mieloperoxidasa (MPO). Las manifestaciones pulmonares clásicas son la hemorragia alveolar y los nódulos pulmonares. En los últimos 10 años se ha descrito la enfermedad pulmonar difusa (EPD). Los estudios epidemiológicos son escasos, y suelen representar en su mayoría poblaciones norteamericanas o europeas. El objetivo es describir las características del compromiso pulmonar al debut en VAA en un centro universitario. PACIENTES Y MÉTODO: De un total de 190 pacientes con diagnóstico de VAA se incluyeron 170 en seguimiento en nuestro centro. Se revisaron aspectos clínicos, demográficos, laboratorio e imagenológicos de los pacientes incluidos. RESULTADOS: De los 170 pacientes, 112 (65,88%) presentaron compromiso pulmonar. 106 (94,64%) de los pacientes fueron anticuerpos anti citoplasma de neutrófilos (ANCA) positivos; de estos, 56 (53,27%) MPO (+) y 39 (36,45%) PR-3 (+). Un tercio de los pacientes de ambos grupos presentó hemorragia alveolar. En los pacientes MPO (+) predomina la EPD (53,5%) y en PR-3 (+) los nódulos pulmonares (69,23%). Destaca la baja frecuencia de patología obstructiva asociada. CONCLUSIONES: El compromiso pulmonar en las VAA es prevalente y heterogéneo. En nuestra serie, destaca la frecuencia de EPD en VAA MPO (+), lo que releva la importancia del estudio con ANCA en paciente con diagnóstico y seguimiento por EPD.

INTRODUCTION: Antineutrophil Cytoplasmic Antibodies (ANCA) associated vasculitis (AAV) are uncommon, but of broad spectrum of presentation. Although the 2012 Chapel Hill classification consensus remains valid, the current trend is to classify them according to the immunological marker: anti-Proteinase 3 antibody (PR-3) or anti-Myeloperoxidase antibody (MPO). The classic pulmonary manifestations are alveolar hemorrhage and pulmonary nodules. Interstitial lung disease (ILD) has been described in the last 10 years. Epidemiological studies are scarce, and they usually represent mostly North American or European populations. The objective is to describe the characteristics of lung involvement upon debut in AAV in a university center. PATIENTS AND METHODS: Of a total of 190 patients diagnosed with AAV, 170 were included in follow-up at our center. Clinical, demographic, laboratory and imaging aspects of the included patients were reviewed. RESULTS: Of the 170 patients, 112 (65.88%) had lung involvement. 106 (94.64%) of the patients were ANCA (+); of these, 56 (53.27%) MPO (+) and 39 (36.45%) PR-3 (+). One third of the patients in both groups had alveolar hemorrhage. In MPO (+) patients, ILD predominates (53.5%) and in PR-3 (+) pulmonary nodules (69.23%). The low frequency of associated obstructive pathology stands out. CONCLUSIONS: Pulmonary manifestations in AAVs are frequent and heterogeneous. Locally, the association of ILD and AAV MPO (+) stands out, which highlights the importance of ANCA study in patients with diagnosis and follow-up by ILD.

High levels of platelet-to-lymphocyte ratio may predict reduced risk of end stage of renal disease in Chinese patients with MPO-ANCA associated vasculitis / 中南大学学报(医学版)

OBJECTIVES@#Platelet-to-lymphocyte ratio (PLR) has recently been investigated as a new inflammatory marker in many inflammatory diseases, including systemic lupus erythematosus and immunoglobulin A vasculitis. However, there were very few reports regarding the clinical role of PLR in patients with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis. This study was thus undertaken to investigate the relationship between inflammatory response and disease activity in Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis. Furthermore, we evaluated whether PLR predicts the progression of end stage of renal disease (ESRD) and all-cause mortality.@*METHODS@#The clinical, laboratory and pathological data, and the outcomes of MPO-ANCA associated vasculitis patients were collected. The Spearman correlation coefficient was computed to examine the association between 2 continuous variables. Cox regression analysis was used to estimate the association between PLR and ESRD or all-cause mortality.@*RESULTS@#A total of 190 consecutive patients with MPO-ANCA associated vasculitis were included in this study. Baseline PLR was positively correlated with CRP (r=0.333, P<0.001) and ESR (r=0.218, P=0.003). PLR had no obvious correlation with Birmingham Vasculitis Activity Score (BVAS). Patients having PLR≥330 exhibited better cumulative renal survival rates than those having PLR<330 (P=0.017). However, there was no significant difference in the cumulative patient survival rates between patients with PLR≥330 and those with PLR<330 at diagnosis (P>0.05). In multivariate analysis, PLR is associated with the decreased risk of ESRD (P=0.038, HR=0.518, 95% CI 0.278 to 0.963). We did not find an association between PLR with all-cause mortality using multivariate analysis (HR=1.081, 95% CI 0.591 to 1.976, P=0.801).@*CONCLUSIONS@#PLR is positively correlated with CRP and ESR. Furthermore, PLR may independently predict the risk of ESRD.

Anti-Myeloperoxidase (MPO) associated Vasculitis in a young Filipino Male with Bronchiectasis: A case report

Background@#ANCA-associated vasculitis and its subtypes have been associated with pulmonary manifestations, with bronchiectasis being a unique clinical presentation.@*Case Summary@# We report the case of a 26-year-old Filipino male who presented with progressive dyspnea, neuropathic pain, and purpuric rash. Diagnostic evaluation revealed upper lobe bronchiectasis and lower lobe pneumonia, as well as hematuria and proteinuria. ANCA-associated vasculitis (AAV) and tuberculosis were considered. There was improvement of dyspnea, cough and rashes with antibiotics, glucocorticoids (GC), and anti-TB coverage. However, neuropathic pain progressed to the upper and lower extremities with development of weakness. Anti-myeloperoxidase (MPO) Anti-Neutrophil Cytoplasmic Antibody (ANCA) was positive, Electromyography-Nerve Conduction Velocity (EMG-NCV) revealed diffuse sensorimotor axonal polyradiculopathy of both upper and lower extremities. Cyclophosphamide was then given. The patient gradually regained his motor strength while sensory deficits persisted. He was referred to rehabilitation medicine for physical therapy and eventually discharged. This case highlights vasculitis as an associated extrapulmonary manifestation of bronchiectasis, and the possible role of bronchiectasis in the immune-mediated pathogenesis of ANCA- associated vasculitides.

Renal Amyloidosis Secondary to ANCA-Associated Vasculitis: A Case Report / 中国医学科学杂志(英文版)

Renal amyloidosis secondary to anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is extremely rare. Here, we reported a 77-year-old woman with ANCA-associated vasculitis. Renal biopsy with Masson trichrome staining showed pauci-immune crescentic glomerulonephritis, and electron microscopy showed amyloid deposition in the mesangial area. Immunofluorescence revealed kappa light chain and lambda light chain negative. Bone marrow biopsy revealed no clonal plasma cell. Finally, she was diagnosed as ANCA-associated vasculitis with secondary renal amyloid A amyloidosis.

Clinical characteristics and prognostic factors in an argentinian cohort with ANCA-associated vasculitis / Características clínicas y factores pronósticos en una cohorte argentina de vasculitis asociada a ANCA

Abstract ANCA-associated vasculitis is a heterogeneous group of rare autoimmune conditions of unknown cause. Clinical characteristics and prognostic factors were analyzed in 47 patients: 20 (42.5%) with granulomatosis with polyangiitis, 17 (36.2%) with microscopic polyangiitis, 6 (12.8%) with renal-limited vasculitis, and 4 (8.5%) with eosinophilic granulomatosis with polyangiitis. Mean age at diagnosis was 53.5 ± 16.5 years and the median of BVAS (Birmingham Vasculitis Activity Score) was 14 (4-42). The most frequent clinical manifesta tions were: general in 44 (93.6%), renal in 30 (63.8%) and respiratory in 28 (59.6%). All received corticosteroids at the beginning of treatment. Intravenous cyclophosphamide was associated in 20 (42.5%) and oral route in 14 (29.8%); azathioprine in 3 (6.4%) and rituximab in 2 (4.2%). At a median follow-up of 35.5 months (range 0.14- 234), 21 relapses were recorded in 14 patients. Overall mortality was 3.5 deaths per 100 patient-year in the whole group. Those over 55 years old, the presence of alveolar hemorrhage, those with FFS (Five Factor Score) of 2, and patients with MPA had poor prognosis. Renal involvement, ANCA pattern and BVAS were not associated to a poorer prognosis.

Resumen Las vasculitis asociadas a ANCA son un grupo heterogéneo de entidades autoinmunes, poco frecuentes, de etiología desconocida. Analizamos las características clínicas y factores pronóstico en 47 pacientes: 20 (42.5%) granulomatosis con poliangeítis, 17 (36.2%) poliangeítis microscópica, 6 (12.8%) vasculitis limitada al riñón y 4 (8.5%) granulomatosis eosinofílica con poliangeítis. La edad promedio al diagnóstico fue 53.5 ± 16.5 años y la mediana de BVAS (Birmingham Vasculitis Activity Score) 14 (4-42). Las manifestaciones clínicas más frecuentes fueron: generales en 44 (93.6%), renales 30 (63.8%) y respiratorias en 28 (59.6%). Todos recibieron corticoides al inicio del tratamiento. Se asoció ciclofosfamida endovenosa en 20 (42.5%) y oral en 14 (29.8%); azatioprina en 3 (6.4%) y rituximab en 2 (4.2%). En una mediana de seguimiento de 35.5 meses (rango 0.14-234), se registraron 21 recaídas en 14 pacientes. La mortalidad fue 3.5 por cien pacientes-año en todo el grupo. Los mayores de 55 años, con presencia de hemorragia alveolar, FFS (Five Factor Score) de 2, y los casos con poliangeítis microscópica tuvieron peor pronóstico. El compromiso renal, el patrón de ANCA y el BVAS no se asociaron a peor pronóstico.

Severe Pulmonary Embolism, Thrombosis of Lower Extremity, Unexpected Mild Renal Disorder in MPO-ANCA Associated Vasculitis: A Case Report / 中国医学科学杂志(英文版)

Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis is an autoimmune disease usually with severe multiple dysfunction syndrome, especially prominent acute renal failure. A 65-year-old woman was admitted with progressive dyspnoea for six months and fever, sputum with blood, pain of the lower extremities and intermittent claudication for two days, indicating multiple organ involvement (respiratory system, blood vessels). The renal involvement was relatively mild, presenting with microscopic haematuria. The chest computed tomography demonstrated multiple pulmonary embolisms. Ultrasound and computed tomography angiography for the lower extremity vessels showed venous and arterial thrombosis. Exclusion of other diseases that can cause multiple organ damage and thrombosis, the positive perinuclear ANCA and MPO-ANCA strongly support the diagnosis of MPO-ANAC-associated vasculitis. The patient's physical condition has been greatly improved by treatment with corticosteroids and anticoagulation.

Association between follistatin-related protein 1 and the functional status of patients with anti-neutrophil cytoplasmic antibody-associated vasculitis / 中华医学杂志(英文版)

BACKGROUND@#Follistatin-like 1 (FSTL1) plays both pro-inflammatory and anti-inflammatory roles in the inflammatory processes. We investigated whether serum FSTL1 could predict the current anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV)-specific indices.@*METHODS@#We randomly selected 74 patients with AAV from a prospective and observational cohort of Korean patients with AAV. Clinical and laboratory data and AAV-specific indices were recorded. FSTL1 concentration was determined using the stored sera. The lowest tertile of the short-form 36-item health survey (SF-36) was defined as the current low SF-36. The cutoffs of serum FSTL1 for the current low SF-36 physical component summary (PCS) and SF-36 mental component summary (MCS) were extrapolated by the receiver operator characteristic curve.@*RESULTS@#The median age was 62.5 years (55.4% were women). Serum FSTL1 was significantly correlated with SF-36 PCS (r =  - 0.374), SF-36 MCS (r = -0.377), and C-reactive protein (CRP) (r = 0.307), but not with Birmingham vasculitis activity score (BVAS). In the multivariable linear regression analyses, BVAS, CRP, and serum FSTL1 were independently associated with the current SF-36 PCS (β = -0.255, β = -0.430, and β = -0.266, respectively) and the current SF-36 MCS (β = -0.234, β =-0.229, and β = -0.296, respectively). Patients with serum FSTL1 ≥779.8 pg/mL and those with serum FSTL1 ≥841.6 pg/mL exhibited a significantly higher risk of having the current low SF-36 PCS and SF-36 MCS than those without (relative risk 7.583 and 6.200, respectively).@*CONCLUSION@#Serum FSTL1 could predict the current functional status in AAV patients.

Eficácia e segurança de Rituximabe comparado a outras drogas no tratamento de vasculites sistêmicas: revisão rápida de evidências / Efficacy and safety of Rituximab compared to other drugs in the treatment of systemic vasculitides: rapid response review of evidence

Objetivo: descrever as evidências disponíveis na literatura científica sobre eficácia e segurança do rituximabe comparado a diferentes tratamentos. Materiais e métodos: é uma revisão rápida de evidências científicas para tomada de decisão informada por evidências em políticas e práticas de saúde. Conclusão: o Rituximabe tem eficácia e segurança similares à da Ciclofosfamida, para terapia de indução de remissão e para manutenção da remissão e, para pacientes com doença recidivante, o Rituximabe é mais eficaz que a Ciclofosfamida para manter a remissão. Para terapia de manutenção, Rituximabe é mais eficaz que Azatioprina, com perfil de segurança similar. Diferentes regimes de dosagem do Rituximabe tem eficácia e segurança similar para terapia de manutenção. O Infliximabe parece ser superior ao Rituximabe nos desfechos de eficácia (indução e manutenção da remissão).

Objective: to describe the evidence available in the scientific literature on the efficacy and safety of rituximab compared to different treatments. Materials and Methods: is a rapid review of scientific evidence for evidence-informed decision making in health policy and practice. Conclusion: Rituximab has similar efficacy and safety to Cyclophosphamide, for remission induction therapy and for maintenance of remission, and for patients with relapsing disease, Rituximab is more effective than Cyclophosphamide in maintaining remission. For maintenance therapy, Rituximab is more effective than Azathioprine, with a similar safety profile. Different dosing regimens of Rituximab have similar efficacy and safety for maintenance therapy. Infliximab appears to be superior to Rituximab in efficacy outcomes (induction and maintenance of remission).

The novel fibrosis index at diagnosis may predict all-cause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis without substantial liver diseases

OBJECTIVES: Antineutrophil cyto plasmic antibody-associated vasculitis (AAV) is a fatal disease. Currently, predictors of mortality due to AAV are based on the distribution of organ involvement. The novel fibrosis index (NFI) is an index composed of laboratory results that reflect the degree of liver fibrosis. This study aimed to evaluate whether NFI can predict poor outcomes in patients with AAV without substantial liver disease. METHODS: A total of 210 patients with immunosuppressive drug-naïve AAV were retrospectively reviewed. NFI was calculated as follows: NFI=(serum bilirubin × (alkaline phosphatase)2)/(platelet count×(serum albumin)2). NFI cut-off was set at 1.24 (the highest quartile). Poor outcomes were defined as all-cause mortality, relapse, and end-stage renal disease (ESRD). RESULTS: During the median 34.5 months of follow-up, 21 patients (10%) died, 72 patients (34.3%) relapsed, and 38 patients (18.1%) had ESRD due to AAV progression. The median calculated NFI was 0.61, and it was higher in AAV patients with all-cause mortality than in those without mortality, but the difference was not statistically significant (1.26 vs. 0.59). AAV patients with NFI at diagnosis ≥1.24 exhibited a significantly lower cumulative patient survival rate than those with NFI at diagnosis <1.24 (p=0.002). Multivariate Cox hazard model analysis showed that NFI at diagnosis ≥1.24 was an independent predictor of all-cause mortality in AAV (hazard ratios [HR] 2.850, 95% confidence interval [CI] 1.026, 7.910). CONCLUSIONS: NFI ≥1.24, which may be an independent predictive marker for all-cause mortality in AAV patients without substantial liver disease.

Comportamiento clínico y factores asociados a mortalidad temprana en una cohorte de pacientes chilenos con vasculitis asociadas a anticuerpos anti citoplasma de neutrófilos (VAA) / Variables associated with mortality in 103 patients with anti-neutrophil cytoplasmic antibodies associated vasculitis

Background: Cumulative survival in patients with anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (VAA) is 88 and 78% at 1 and 5 years, respectively. Despite this, mortality continues to be 2.7 times higher than the general population. Differences in the clinical profile of VAA in different ethnicities have been observed. Aim: To identify factors at the time of diagnosis, associated with mortality at one year of follow-up and to describe the clinical characteristics of these patients. Material and Methods: We identified in local databases and reviewed clinical records of patients with VAA with at least one year of follow up in a clinical hospital. Demographic and laboratory parameters and clinical activity scores were analyzed. Results: Of 103 patients with VAA identified, 65 met the inclusion criteria and were analyzed. Their age ranged from 45 to 63 years and 56% were women. Thirty-five patients (54%) were diagnosed as granulomatosis with Polyangiitis (GPA) and 30 patients (46%) with Microscopic Polyangiitis (MPA). The frequency of renal disease was 53% and pulmonary involvement occurred in 72%. At one year of follow-up 11 patients died resulting in a mortality of 17%. Seven patients died within three months after diagnosis. MPO ANCA were more common than PR3 ANCA. In the multivariate analysis, the presence of ophthalmological involvement, lung kidney syndrome and a Five Factor Score (FFS) of 1 or more were independent factors associated with mortality at one year. Conclusions: In these patients, pulmonary manifestations predominate. Lung kidney syndrome, ophthalmological involvement and a FFS score ≥ 1 were associated with mortality.

Rituximab use in adult glomerulopathies and its rationale / Uso do rituximabe em glomerulopatias em adultos e justificativas

Abstract Glomerulopathies are one of the leading causes of end-stage renal disease. In the last years, clinical research has made significant contributions to the understanding of such conditions. Recently, rituximab (RTX) has appeared as a reasonably safe treatment. The Kidney Disease: Improving Global Outcomes guidelines (KDIGO) recommended RTX only as initial treatment in antineutrophil cytoplasm antibody associated vasculitis (AAV) and in non-responders patients with lupus nephritis (LN), but these guidelines have not been updated since 2012. Nowadays, RTX seems to be at least as effective as other immunosuppressive regimens in idiopathic membranous nephropathy (IMN). In minimal-change disease, (MCD) this drug might allow a long-lasting remission period in steroid-dependent or frequently relapsing patients. Preliminary results support the use of RTX in patients with pure membranous LN and immunoglobulin-mediated membranoproliferative glomerulonephritis (MPGN), but not in patients with class III/IV LN or complement-mediated MPGN. No conclusion can be drawn in idiopathic focal segmental glomerulosclerosis (FSGS) and anti-glomerular basement membrane antibody glomerulonephritis (anti-GBM GN) because studies are small, heterogeneous, and scarce. Lastly, immunosuppression including RTX is not particularly useful in IgA nephropathy. This review presents the general background, outcomes, and safety for RTX treatment in different glomerulopathies. In this regard, we describe randomized controlled trials (RCTs) performed in adults, whenever possible. A literature search was performed using clinicaltrials.gov and PubMed.

Resumo As glomerulopatias figuram entre as principais causas de doença renal terminal. Nos últimos anos, a pesquisa clínica efetuou contribuições significativas para a compreensão desse grupo de patologias. Recentemente, o rituximabe (RTX) surgiu como um tratamento razoavelmente seguro. As diretrizes do Kidney Disease: Improving Global Outcomes (KDIGO) recomendam o RTX apenas como tratamento inicial na vasculite associada ao ANCA (VAA) e em pacientes não respondedores com nefrite lúpica (NL), embora não sejam atualizadas desde 2012. Atualmente, o RTX parece ser pelo menos tão eficaz quanto outros esquemas imunossupressores na nefropatia membranosa idiopática (NMI). Na doença por lesão mínima (DLM), o medicamento pode proporcionar um período de remissão duradouro em pacientes córtico-dependentes ou com recidivas frequentes. Resultados preliminares corroboram o uso de RTX em pacientes com NL membranosa pura e glomerulonefrite membranoproliferativa (GNMP) mediada por imunoglobulina, mas não em pacientes com NL classe III/IV ou GNMP mediada por complemento. Os achados a respeito de glomeruloesclerose segmentar e focal (GESF) idiopática e doença por anticorpo antimembrana basal glomerular (anti-MBG) não são conclusivos em função do pequeno número, porte e heterogeneidade dos estudos publicados até o presente momento. Por fim, a imunossupressão com RTX não é particularmente útil na nefropatia por IgA. A presente revisão apresenta o racional da prescrição de RTX nas diferentes glomerulopatias, desfechos e segurança. Nesse sentido, foram incluídos ensaios clínicos randomizados (ECRs) realizados em adultos, sempre que possível. Pesquisas bibliográficas foram realizadas nas bases de dados do clinictrials.gov e no PubMed.

Antineutrophil cytoplasmic antibodies in patients treated with methimazole: a prospective Brazilian study / Anticorpos anticitoplasma de neutrófilos em pacientes tratados com metimazol: um estudo prospectivo brasileiro

Abstract Introduction: The side effects of antithyroid drugs are well known. Antineutrophil cytoplasmic antibody-associated vasculitis is a severe adverse reaction. Most studies evaluating antineutrophil cytoplasmic antibodies related to antithyroid drugs have been carried out with patients treated with propylthiouracil, but less information is available for methimazole. Furthermore, most studies that investigated antineutrophil cytoplasmic antibodies related to antithyroid drugs were conducted on Asian populations. Objective: To evaluate the frequency of antineutrophil cytoplasmic antibodies and antineutrophil cytoplasmic antibodies-positive vasculitis in an adult population of Brazilian patients treated with methimazole. Methods: This was a prospective study. We evaluated patients ≥18 years with Graves' disease who have been using methimazole for at least 6 months (Group A, n = 36); with Grave's disease who had been previously treated with methimazole but no longer used this medication for at least 6 months (Group B, n = 33), and with nodular disease who have been using methimazole for at least 6 months (Group C, n = 13). Results: ANCA were detected in 17 patients (20.7%). Four patients (4.9%) had a strong antineutrophil cytoplasmic antibodies-positive test. The frequency of antineutrophil cytoplasmic antibodies was similar in the groups. When Groups A and B were pooled and compared to Group C to evaluate the influence of Grave's disease, and when Groups A and C were pooled and compared to Group B to evaluate the influence of methimazole discontinuation, no difference was found in the frequency of antineutrophil cytoplasmic antibodies. No difference was observed in sex, age, etiology of hyperthyroidism, anti-TSH receptor antibodies, dose or time of methimazole use between patients with versus without antineutrophil cytoplasmic antibodies. The titers of these antibodies were not correlated with the dose or time of methimazole use. None of the antineutrophil cytoplasmic antibodies-positive patient had clinical event that could potentially result from vasculitis. Conclusion: This clinical study of a Brazilian population shows a considerable frequency of antineutrophil cytoplasmic antibodies in patients treated with methimazole but the clinical repercussion of these findings remains undefined.

Resumo Introdução: Os efeitos adversos de drogas antitireoidianas são conhecidos. Vasculite associada a anticorpos anticitoplasma de neutrófilos é uma reação adversa grave. A maioria dos estudos que avaliam anticorpos anticitoplasma de neutrófilos relacionado a drogas antitireoidianas envolveu pacientes tratados com propiltiouracil, entretanto menos informação se encontra disponível para o metimazol. Além disso, a maioria dos estudos que investigaram anticorpos anticitoplasma de neutrófilos relacionado a drogas antitireoidianas foi conduzida em populações asiáticas. Objetivo: Avaliar a frequência de anticorpos anticitoplasma de neutrófilos e vasculite anticorpos anticitoplasma de neutrófilos-positivo em uma população adulta de pacientes brasileiros tratados com metimazol. Método: Este foi um estudo prospectivo. Avaliamos pacientes ≥ 18 anos com doença de Graves com o uso de metimazol há pelo menos seis meses (Grupo A, n = 36); com doença de Graves previamente tratados com metimazol, mas que não usaram esse medicamento por pelo menos seis meses (Grupo B, n = 33) e com doença nodular em uso de metimazol há pelo menos seis meses (Grupo C, n = 13). Resultado: Anticorpos anticitoplasma de neutrófilos foram detectados em 17 pacientes (20,7%). Quatro pacientes (4,9%) tinham anticorpos anticitoplasma de neutrófilos fortemente positivos. A frequência de anticorpos anticitoplasma de neutrófilos foi semelhante nos grupos. Quando os Grupos A e B foram somados e comparados ao Grupo C para avaliar a influência da doença de Graves, e quando os Grupos A e C foram somados e comparados ao Grupo B para avaliar a influência da interrupção do metimazol, não foi encontrada diferença na frequência de anticorpos anticitoplasma de neutrófilos. Não houve diferença em relação a sexo, idade, etiologia do hipertireoidismo, anticorpos antirreceptor de TSH, dose ou tempo de uso de metimazol entre pacientes com e sem anticorpos anticitoplasma de neutrófilos. Os títulos desses anticorpos não se correlacionaram com dose ou tempo de uso de metimazol. Nenhum paciente anticorpos anticitoplasma de neutrófilos-positivo apresentou evento clínico resultante de vasculite. Conclusão: Este estudo clínico de uma população brasileira apresenta frequência considerável de anticorpos anticitoplasma de neutrófilos em pacientes tratados com metimazol, mas a repercussão clínica desse achado permanece indefinida.

Hemorragia alveolar difusa secundaria a vasculitis asociada a ANCA. Recaída durante hemodiálisis / Diffuse alveolar hemorrhage secondary to ANCA-associated vasculitis. Relapse during hemodialysis

Resumen La hemorragia alveolar difusa (HAD) masiva es una complicación inusual de los pacientes con vasculitis ANCA, frecuentemente amenaza la vida y está asociada con una mortalidad de hasta el 100%. La información en la literatura acerca del tratamiento en casos refractarios y cuando el paciente se encuentra en diálisis es escasa. Se presenta el caso de un paciente con vasculitis p-ANCA con compromiso renal y pulmonar en el escenario de síndrome pulmón-riñón, con múltiples recaídas de hemorragia alveolar a pesar de tratamiento con corticoide, azatioprina, ciclofosfamida y terapia de recambio plasmático. Se instauró manejo con anticuerpo monoclonal anti CD20 e inmunoglobulina, logrando resolución del episodio de hemorragia alveolar y permaneciendo sin actividad. Se resalta la utilidad del rituximab como estrategia terapéutica en casos refractarios. (Acta Med Colomb 2019; 44: 111-114).

Abstract Massive diffuse alveolar hemorrhage (DAH) is an unusual complication of patients with ANCA vasculitis that frequently threatens life and is associated with mortality up to 100%. In formation in the literature about treatment in refractory cases and when the patient is on dialysis is scarce. The case of a patient with p-ANCA vasculitis with renal and pulmonary involvement in the lung-kidney syndrome scenario, with multiple relapses of alveolar hemorrhage despite treatment with corticosteroid, azathioprine, cyclophosphamide and plasma exchange therapy is presented. Management with anti-CD20 monoclonal antibody and immunoglobulin was estab lished, achieving resolution of the episode of alveolar hemorrhage and remaining without activity. The usefulness of rituximab as a therapeutic strategy in refractory cases is highlighted. (Acta Med Colomb 2019; 44: 111-114).

Síndrome pulmón-riñón: serie de 12 casos / Pulmonary renal syndrome: series of 12 cases

El síndrome pulmón-riñón es una entidad infrecuente, que comprende un gran espectro de patologías, como las vasculitis asociadas a ANCA y la enfermedad por anticuerpos antimembrana basal glomerular entre otras. Se describen en esta serie 12 casos donde las entidades más prevalentes fueron las antes mencionadas, observándose además un caso de lupus y uno de granulomatosis con poliangeítis, que se encuentran dentro de las causas menos frecuentes. La forma de presentación clínica inicial fue simultánea renal y pulmonar en 5/12 pacientes y renal en 7/12 de los mismos. El diagnóstico temprano de dichas patologías basándose en criterios clínicos, radiológicos, de laboratorio e histológicos, permite instaurar terapéuticas tempranas como la inmunosupresión y plasmaféresis, pudiendo prevenir complicaciones tales como las infecciones y la insuficiencia renal crónica terminal, siendo las primeras la principal causa de muerte (AU)

Pulmonary-renal syndrome is an infrequent condition. It includes a wide variety of conditions such as ANCA (antineutro-phil cytoplasmic autoantibody) associated with systemic vasculitis and anti-GBM (anti-glomerular basement membrane) disease among others. In this series we describe twelve cases, in which the most prevalent diseases were the above mentioned as well as one case of lupus and one of granulomatosis with polyangiitis (these being less frequent causes). The clinical presentation was both renal and pulmonary simultaneously in five of twelve patients and renal in seven of twelve patients. Early diagnosis of this condition on the basis of clinical, radiological, histological and analytic criteria allows early treatments such as immunosuppression and plasma exchange, thus avoiding complications such as infections (the main cause of death) and terminal chronic renal failure (AU)

ANCA associated vasculitis: experience of a tertiary care referral center / Vasculite associada a ANCA: experiência de um centro de referência de atendimento terciário

ABSTRACT Background and objectives: Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis is a small vessel vasculitis with insufficient epidemiologic estimates in the United States. We aimed to determine demographic and clinical features of ANCA associated vasculitis patients presenting to a large tertiary care referral center in Upstate New York. Design, setting, participants, and measurements: A retrospective analysis of cases with pauci-immune GN on renal biopsy and clinical diagnosis of ANCA vasculitis presenting over 11 years was conducted. Outcomes of interest were: demographics, ANCA antibody positivity, patient and renal survival, and regional trends. Results: 986 biopsies were reviewed, 41 cases met the criteria for inclusion: 18 GPA, 19 MPA, and 4 double positive (anti-GBM disease plus ANCA vasculitis). Mean age at presentation was 52.4 years (SD 23.7), 23 (56%) were male and median creatinine was 2.6 mg/dL. The median patient follow up was 77 weeks (IQR 10 - 263 weeks), with a 3-month mortality rate of 5.7% and a 1-year estimated mortality rate of 12%. Thirteen patients required hemodialysis at the time of diagnosis; 7 patients came off dialysis, with median time to renal recovery of 4.86 weeks (IQR 1.57 - 23.85 weeks). C-ANCA positivity (p < 0.001) and C-ANCA plus PR3 antibody pairing (p = 0.005) was statistically significant in GPA versus MPA. P-ANCA positivity was observed in MPA versus GPA (p = 0.02) and double positive versus GPA (p = 0.002), with P-ANCA and MPO antibody pairing in MPA versus GPA (p = 0.044). Thirty-seven of the 41 cases were referred locally, 16 cases were from within a 15-mile radius of Albany, Schenectady, and Saratoga counties. Conclusions: ANCA vasculitis is associated with end stage renal disease and increased mortality. Our study suggests the possibility of higher regional incidence of pauci-immune GN in Upstate New York. Further studies should investigate the causes of clustering of cases to specific regions.

RESUMO Introdução e objetivos: A vasculite associada a anticorpos anticitoplasma de neutrófilo (ANCA) é uma vasculite de pequenos vasos com estimativas epidemiológicas insuficientes nos Estados Unidos. Nosso objetivo foi determinar características demográficas e clínicas de pacientes com vasculite associada à ANCA, apresentando-se a um grande centro de referência de atendimento terciário em Upstate New York. Formato, cenário, participantes e medidas: Foi realizada uma análise retrospectiva dos casos de GN pauci-imune em biópsias renais e diagnóstico clínico de vasculite ANCA por mais de 11 anos. Os resultados de interesse foram: dados demográficos, positividade de anticorpos ANCA, sobrevidas renal e de pacientes e tendências regionais. Resultados: 986 biópsias foram revisadas, 41 casos preencheram os critérios de inclusão: 18 GPA, 19 PAM, e 4 duplo-positivos (doença anti-MBG com vasculite ANCA). A média de idade na apresentação foi de 52,4 anos (DP 23,7), 23 (56%) eram do sexo masculino e mediana de creatinina de 2,6 mg/dL. O acompanhamento mediano dos pacientes foi de 77 semanas (IQR 10 - 263 semanas), com uma taxa de mortalidade de 3 meses de 5,7% e uma taxa de mortalidade estimada em 1 ano de 12%. Treze pacientes necessitaram de hemodiálise no momento do diagnóstico; 7 pacientes saíram da diálise, com tempo médio para recuperação renal de 4,86 semanas (IQR 1,57 - 23,85 semanas). A positividade para C-ANCA (p < 0,001) e o pareamento de anticorpos C-ANCA mais PR3 (p = 0,005) foram estatisticamente significantes em GPA versus PAM. A positividade de P-ANCA foi observada em PAM versus GPA (p = 0,02) e duplo positivo versus GPA (p = 0,002), com pareamento de anticorpos P-ANCA e MPO em PAM versus GPA (p = 0,044). Trinta e sete dos 41 casos foram encaminhados localmente, 16 casos foram de dentro de um raio de 15 milhas dos condados de Albany, Schenectady e Saratoga. Conclusões: A vasculite por ANCA está associada à doença renal terminal e aumento da mortalidade. Nosso estudo sugere a possibilidade de maior incidência regional de GN pauci-imune no norte do estado de Nova York. Novos estudos devem investigar as causas do acúmulo de casos em regiões específicas.

A Pediatric Case of a D-Penicillamine Induced ANCA-associated Vasculitis Manifesting a Pulmonary-Renal Syndrome

D-penicillamine has been reported to cause antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis presenting as rapidly progressive glomerulonephritis or pulmonary-renal syndrome mostly in adults. We report a pediatric case of D-penicillamine induced ANCA-associated vasculitis that manifests as a pulmonary-renal syndrome with a mild renal manifestation. A 13-year-old girl who has been taking D-penicillamine for five years under the diagnosis of Wilson disease visited the emergency room because of hemoptysis and dyspnea. She had diffuse pulmonary hemorrhage, microscopic hematuria, and proteinuria. Myeloperoxidase ANCA was positive, and a renal biopsy revealed pauci-immune crescentic glomerulonephritis. Under the diagnosis of D-penicillamine-induced ANCA-associated vasculitis, D-penicillamine was switched to trientine, and the patient was treated with plasmapheresis, glucocorticoid, cyclophosphamide, and mycophenolate mofetil. Pulmonary hemorrhage improved rapidly followed by the disappearance of the hematuria and proteinuria five months later.