Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Inhibidores de las Cinasas Janus/uso terapéutico , Piperidinas/uso terapéutico , Pirimidinas/uso terapéutico , Adulto , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/metabolismo , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/fisiopatología , Sedimentación Sanguínea , Proteína C-Reactiva/metabolismo , Síndrome de Churg-Strauss/tratamiento farmacológico , Síndrome de Churg-Strauss/metabolismo , Síndrome de Churg-Strauss/fisiopatología , Femenino , Granulomatosis con Poliangitis/tratamiento farmacológico , Granulomatosis con Poliangitis/metabolismo , Granulomatosis con Poliangitis/fisiopatología , Humanos , Masculino , Poliangitis Microscópica/tratamiento farmacológico , Poliangitis Microscópica/metabolismo , Poliangitis Microscópica/fisiopatología , Persona de Mediana Edad , Proyectos Piloto , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: The purpose of this study was to evaluate the importance of MR imaging findings of musculoskeletal involvement of the lower limbs in diagnosing microscopic polyangiitis (MPA) vs polymyositis (PM) or dermatomyositis (DM). MATERIALS AND METHODS: This study included 13 patients diagnosed with MPA clinically and through histologically, and 38 diagnosed with PM/DM, who underwent MR imaging of the lower limbs prior to treatment. Axial and coronal short tau inversion recovery (STIR) images were reviewed retrospectively. RESULTS: The sites affected by MPA were the lower legs in six (46%) patients and the thighs in seven (54%). Intramuscular hyperintensity and fascial hyperintensity were observed in all cases of MPA (100%). Fascial hyperintensity was more frequently encountered in MPA than in PM/DM (100% vs. 45%, p < 0.01). As the predominantly involved sites, the fascial regions were more frequently affected by MPA than by PM/DM (77% vs. 18%, p < 0.01). Diffuse subcutaneous fat hyperintensity was more frequently observed in MPA than in PM/DM (100% vs. 16%, p < 0.01). However, no significant differences in intramuscular hyperintensity (100% vs. 97%, p = 0.745) and subcutaneous fat hyperintensity (54% vs. 50%, p = 0.533) were found between MPA and PM/DM. CONCLUSION: Intramuscular hyperintensity and fascial hyperintensity have always been observed in MPA, and the predominantly affected sites were usually the fascial regions. Compared with PM/DM, fascial hyperintensity and diffuse subcutaneous fat hyperintensity were more frequent in MPA.
Asunto(s)
Imagen por Resonancia Magnética/métodos , Poliangitis Microscópica/diagnóstico por imagen , Músculo Esquelético/diagnóstico por imagen , Miositis/diagnóstico por imagen , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Humanos , Extremidad Inferior/diagnóstico por imagen , Masculino , Poliangitis Microscópica/fisiopatología , Persona de Mediana Edad , Músculo Esquelético/fisiopatología , Miositis/fisiopatología , Estudios Retrospectivos , Adulto JovenRESUMEN
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.
Asunto(s)
Síndrome de Churg-Strauss/diagnóstico , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Poliangitis Microscópica/diagnóstico , Mononeuropatías/fisiopatología , Insuficiencia Renal Crónica/fisiopatología , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Azatioprina/uso terapéutico , Síndrome de Churg-Strauss/tratamiento farmacológico , Síndrome de Churg-Strauss/inmunología , Síndrome de Churg-Strauss/fisiopatología , Ciclofosfamida/uso terapéutico , Femenino , Humanos , Inmunosupresores/uso terapéutico , Poliangitis Microscópica/tratamiento farmacológico , Poliangitis Microscópica/inmunología , Poliangitis Microscópica/fisiopatología , Persona de Mediana Edad , Peroxidasa/inmunología , Prednisona/uso terapéutico , Insuficiencia Renal Crónica/patología , Tomografía Computarizada por Rayos XRESUMEN
The prognosis of microscopic polyangiitis (MPA) with interstitial lung disease (ILD) is significantly worse than that of MPA without ILD. However, the clinical characteristics in MPA-ILD, especially poor prognostic factors, are not elucidated. We evaluated demographic, clinical, laboratory, and radiological findings, treatments, and outcomes of 80 patients with MPA, and investigated prognostic factors of respiratory-related death in patients with myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) positive MPA-ILD. Ground-glass opacity and fibrosis were evaluated as scores on high-resolution computed tomography (HRCT). The presence of ILD was consistent with a high risk of respiratory-related death (hazard ratio, 4.8; P = 0.04). Multivariable logistic regression analyses using propensity scoring showed right or left lower lobe fibrosis score to be significantly associated with respiratory-related death (P = 0.0005 and 0.0045, respectively). A right or left lower lobe fibrosis score ≥ 2, indicating the presence of honeycombing at 1 cm above the diaphragm, was determined to be the best cut-off value indicating a poor prognosis. The 5-year survival rate was significantly lower in patients with right or left lower lobe fibrosis score ≥ 2 (survival rates: 37% and 19%, respectively) than those with a score < 2 (71% and 68%, respectively) (P = 0.002 and 0.0007, respectively). These findings suggest that the presence of honeycomb lesions in bilateral lower lobes on chest HRCT was associated with respiratory-related death in patients with MPO-ANCA positive MPA-ILD.
Asunto(s)
Enfermedades Pulmonares Intersticiales/mortalidad , Poliangitis Microscópica/mortalidad , Anciano , Anciano de 80 o más Años , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/inmunología , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Femenino , Humanos , Japón , Pulmón/patología , Enfermedades Pulmonares Intersticiales/fisiopatología , Masculino , Poliangitis Microscópica/complicaciones , Poliangitis Microscópica/fisiopatología , Peroxidasa/inmunología , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de Supervivencia , Tomografía Computarizada por Rayos X/métodosRESUMEN
OBJECTIVES: ANCA-associated vasculitis (AAV) usually involves the renal and respiratory systems, but the paediatric literature on pulmonary manifestations and outcomes is limited. We aimed to describe pulmonary manifestations and outcomes after therapy in a cohort of paediatric AAV (pAAV) patients. METHODS: A retrospective chart review of all patients <19 years presenting to our institution with AAV between 1/2008 and 2/2018 was conducted. Patient demographics, clinical presentation, diagnostic testing, therapy and pulmonary outcomes over the first 3 years after presentation were evaluated. RESULTS: A total of 38 patients were included; all had ANCA positivity by immunofluorescence. A total of 23 had microscopic polyangiitis (MPA), 13 had granulomatosis with polyangiitis and 2 had eosinophilic granulomatosis with polyangiitis. A total of 30 (79%) had pulmonary manifestations, with cough (73%) and pulmonary haemorrhage (67%) being the most common. Abnormalities were noted in 82% of chest CT scans reviewed, with nodules and ground-glass opacities being the most common. At 6, 12 and 36 months follow-up, respectively, 61.8%, 39.4% and 29% of patients continued to show pulmonary manifestations. Five MPA patients with re-haemorrhage are described in detail. CONCLUSION: MPA was more common than granulomatosis with polyangiitis, with pulmonary involvement being common in both. MPA patients had more severe pulmonary manifestations. Chest CT revealed abnormal findings in a majority of cases. A subgroup of young MPA patients experienced repeat pulmonary haemorrhage. Treatment modality and response were comparable in different subtypes of AAV, except for this young MPA group. Additional prospective studies are needed to better understand the different phenotypes of pAAV.
Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/fisiopatología , Tos/fisiopatología , Hemoptisis/fisiopatología , Hemorragia/fisiopatología , Enfermedades Pulmonares/fisiopatología , Nódulos Pulmonares Múltiples/fisiopatología , Adolescente , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/inmunología , Autoanticuerpos/inmunología , Niño , Preescolar , Síndrome de Churg-Strauss/inmunología , Síndrome de Churg-Strauss/fisiopatología , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Granulomatosis con Poliangitis/inmunología , Granulomatosis con Poliangitis/fisiopatología , Hemoptisis/inmunología , Hemorragia/inmunología , Humanos , Lactante , Enfermedades Pulmonares/diagnóstico por imagen , Enfermedades Pulmonares/inmunología , Masculino , Poliangitis Microscópica/inmunología , Poliangitis Microscópica/fisiopatología , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Mieloblastina/inmunología , Peroxidasa/inmunología , Recurrencia , Estudios Retrospectivos , Tomografía Computarizada por Rayos XAsunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Antirreumáticos/uso terapéutico , Rituximab/uso terapéutico , Agammaglobulinemia/inducido químicamente , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/fisiopatología , Síndrome de Churg-Strauss/tratamiento farmacológico , Síndrome de Churg-Strauss/fisiopatología , Técnica Delphi , Duración de la Terapia , Granulomatosis con Poliangitis/tratamiento farmacológico , Granulomatosis con Poliangitis/fisiopatología , Humanos , Huésped Inmunocomprometido , Vacunas contra la Influenza/uso terapéutico , Gripe Humana/inmunología , Gripe Humana/prevención & control , Quimioterapia de Mantención , Poliangitis Microscópica/tratamiento farmacológico , Poliangitis Microscópica/fisiopatología , Neutropenia/inducido químicamente , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/uso terapéutico , Neumonía por Pneumocystis/inmunología , Neumonía por Pneumocystis/prevención & control , Guías de Práctica Clínica como Asunto , Recurrencia , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Reino UnidoRESUMEN
Introduction: The RAVE trial has revolutionized induction treatment of anti-neutrophil cytoplasmic antibodies (ANCA)-Associated Vasculitis (AAV)by demonstrating the non-inferiority of rituximab (RTX) compared with cyclophosphamide.Objectives: We studied AAV patients' characteristics, RTX prescription practices and efficacy in AAV induction treatment in four Belgian university hospitals. The patient population, selected according to the Belgian reimbursement criteria, was relatively homogeneous and comparable to the one of RAVE trial.Methods: 57 patients, receiving RTX as AAV induction therapyfrom May 2014 to June 2017 were enrolled in an observational retrospective multicenter trial involving four Belgian university hospitals. We focused on the type of AAV, ANCA specificity, prescriber's specialty, used reimbursement criteria, organ involvements, severity of the flares and finally RTX efficacy in AAV induction treatment by considering the RAVE primary (complete remission without prednisone) and secondary (complete remission with prednisone <10 mg) outcomes at 6, 12, 18 and 24 months.Results: 66.7% of the patients reached complete remission with prednisone <10 mg at 6 months, 55.3% at 12 months, 40% at 18 months and 25% at 24 months. The rates of complete remission without steroids were very low at 6, 12, 18 and 24 months. The rates of relapses were high between 18 and 24 months. Conclusions: Our results confirm those of RAVE regarding complete remission rates with prednisone <10 mg/day, in a 'real-life' cohort of patients selected according to data of RAVE trial. The high prevalence of relapses - especially after 18 months - underlines the need to optimize maintenance treatment after an induction treatment with RTX..
Asunto(s)
Granulomatosis con Poliangitis/tratamiento farmacológico , Factores Inmunológicos/uso terapéutico , Poliangitis Microscópica/tratamiento farmacológico , Rituximab/uso terapéutico , Adulto , Anciano , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/inmunología , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Bélgica , Estudios de Cohortes , Femenino , Glucocorticoides/uso terapéutico , Granulomatosis con Poliangitis/inmunología , Granulomatosis con Poliangitis/fisiopatología , Hospitales Universitarios , Humanos , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/inmunología , Enfermedades Renales/fisiopatología , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/inmunología , Enfermedades Pulmonares/fisiopatología , Masculino , Poliangitis Microscópica/inmunología , Poliangitis Microscópica/fisiopatología , Persona de Mediana Edad , Mieloblastina/inmunología , Enfermedades Otorrinolaringológicas/tratamiento farmacológico , Enfermedades Otorrinolaringológicas/inmunología , Enfermedades Otorrinolaringológicas/fisiopatología , Peroxidasa/inmunología , Pautas de la Práctica en Medicina , Prednisona/uso terapéutico , Inducción de Remisión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The different sets of criteria for diagnosis or classification of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) lead to numerous overlapping and reclassified diagnoses in clinical practice. We designed this study to assess the difficulties in classifying patients with AAV. As a secondary objective, different variables were tested to predict prognosis. We conducted a retrospective chart review in a Western Spain multicentre survey. A total of 115 adult patients diagnosed with AAV from 2002 to 2013 and followed for at least 3 years were included. They were classified according to (1) Chapel Hill Consensus Conference (CHCC), (2) European Medicines Agency algorithm and (3) French Vasculitis Study Group/European Vasculitis Society phenotypes. Fifty-three patients (46%) had neither distinctive histopathological data of a single AAV definition nor any surrogate markers for granulomatous inflammation and thus did not fulfill any diagnostic criteria. Ocular, ear, nose, throat, skin, and lung involvement were more frequent with proteinase 3 (PR3) antibodies, whereas peripheral neuropathy was more frequent with myeloperoxidase (MPO) antibodies. When the disease was severe at diagnosis, the HR for mortality was 10.44. When induction treatment was not given in accordance with the guidelines, the HR for mortality was 4.00. For maintenance treatment, the HR was 5.49 for mortality and 2.48 for relapse. AAV classification is difficult because many patients had neither specific clinical data nor distinctive histological features of a single CHCC definition. A structured clinical assessment of patient severity is the best tool to guide the management of AAV.
Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/clasificación , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/patología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/fisiopatología , Mortalidad , Anciano , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/inmunología , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Síndrome de Churg-Strauss/clasificación , Síndrome de Churg-Strauss/inmunología , Síndrome de Churg-Strauss/patología , Síndrome de Churg-Strauss/fisiopatología , Epistaxis/inmunología , Epistaxis/patología , Epistaxis/fisiopatología , Oftalmopatías/inmunología , Oftalmopatías/patología , Oftalmopatías/fisiopatología , Femenino , Enfermedades Gastrointestinales/inmunología , Enfermedades Gastrointestinales/patología , Enfermedades Gastrointestinales/fisiopatología , Granulomatosis con Poliangitis/clasificación , Granulomatosis con Poliangitis/inmunología , Granulomatosis con Poliangitis/patología , Granulomatosis con Poliangitis/fisiopatología , Humanos , Hipertensión/inmunología , Hipertensión/patología , Hipertensión/fisiopatología , Enfermedades Renales/inmunología , Enfermedades Renales/patología , Enfermedades Renales/fisiopatología , Fallo Renal Crónico/fisiopatología , Enfermedades Pulmonares/inmunología , Enfermedades Pulmonares/patología , Enfermedades Pulmonares/fisiopatología , Masculino , Poliangitis Microscópica/clasificación , Poliangitis Microscópica/inmunología , Poliangitis Microscópica/patología , Poliangitis Microscópica/fisiopatología , Persona de Mediana Edad , Mieloblastina/inmunología , Enfermedades del Sistema Nervioso Periférico/inmunología , Enfermedades del Sistema Nervioso Periférico/patología , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Peroxidasa/inmunología , Prevención Primaria , Pronóstico , Modelos de Riesgos Proporcionales , Recurrencia , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Sinusitis/inmunologíaRESUMEN
A 71-year-old man was admitted to our hospital with right lower abdominal pain. Blood analysis indicated severe inflammation, and abdominal CT revealed a pancreatic head tumour and multiple lung nodules. The level of a tumour marker was high. Pancreatic cancer with multiple lung metastases was suspected; however, because the mass was not detected via endoscopic ultrasonography, it was not biopsied. The serum creatinine level increased rapidly with a urine disorder, and myeloperoxidase-antineutrophil cytoplasmic antibody staining was positive. Severe rapidly progressive glomerulonephritis (RPGN) and microscopic polyangiitis were diagnosed, and high-dose glucocorticoid treatment was started. The patient's high fever returned to normal, and the serum creatinine level declined. Because the RPGN was severe, cyclophosphamide was administrated, and the glucocorticoid was tapered. The pancreatic tumour regressed, the lung nodules disappeared, and the tumour marker level normalised during the treatment. Renal function improved, and maintenance haemodialysis was avoided.
Asunto(s)
Glomerulonefritis/diagnóstico , Glucocorticoides/uso terapéutico , Neoplasias Pulmonares/diagnóstico , Poliangitis Microscópica/diagnóstico , Páncreas/patología , Neoplasias Pancreáticas/diagnóstico , Dolor Abdominal/diagnóstico por imagen , Anciano , Diagnóstico Diferencial , Glomerulonefritis/tratamiento farmacológico , Glomerulonefritis/fisiopatología , Humanos , Masculino , Poliangitis Microscópica/tratamiento farmacológico , Poliangitis Microscópica/fisiopatología , Páncreas/diagnóstico por imagen , Radiografía Abdominal , Resultado del TratamientoRESUMEN
No disponible
Asunto(s)
Humanos , Femenino , Anciano de 80 o más Años , Poliangitis Microscópica/diagnóstico , Poliangitis Microscópica/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Poliangitis Microscópica/fisiopatología , Enfermedades Pulmonares Intersticiales/patología , Anticuerpos Anticitoplasma de Neutrófilos , Reacción en Cadena de la PolimerasaRESUMEN
Microscopic polyangiitis (MPA) is one of the main clinical presentations of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides. Although the disease is defined by clinical and pathological criteria, the anti-myeloperoxidase (MPO) specificity of ANCAs is observed in almost 80% of MPA patients. The direct pathogenic role of anti-MPO antibodies has been proven in animal models, in which the disease was transmitted by transfer of anti-MPO antibodies or anti-MPO-specific splenocytes. The most frequently affected organs in this disease are the kidneys and the lungs. Necrotizing and crescentic glomerulonephritis can be revealed by rapidly progressive renal failure, but kidney injury can be more slowly progressive and lead to end-stage renal disease without major extrarenal manifestations. The most frequent pulmonary manifestation is diffuse alveolar hemorrhage, but some patients may present with chronic interstitial fibrosis leading to respiratory failure. General signs such as fever and weight loss, muscular and articular symptoms, peripheral neuropathy, and cutaneous involvement may also reveal the disease. Although the relapse rate is quite low after induction of remission, 5-year mortality is 25%, with even higher mortality rates in older patients (> 65 years old), or those with significant kidney dysfunction. Iatrogenic causes (particularly infections) are an important cause of deaths in these vulnerable patients. Future studies are warranted to determine the optimal maintenance immunosuppressive regimen to minimize side effects of immunosuppression.
Asunto(s)
Ciclofosfamida/administración & dosificación , Inmunosupresores/administración & dosificación , Poliangitis Microscópica/tratamiento farmacológico , Poliangitis Microscópica/fisiopatología , Animales , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Antimetabolitos/uso terapéutico , Modelos Animales de Enfermedad , Esquema de Medicación , Hemorragia/etiología , Humanos , Riñón/fisiopatología , Pulmón/fisiopatología , Poliangitis Microscópica/diagnóstico , Recurrencia , Inducción de RemisiónRESUMEN
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.
Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/sangre , Ciclofosfamida/administración & dosificación , Disnea/diagnóstico , Hemoptisis , Metilprednisolona/administración & dosificación , Poliangitis Microscópica , Insuficiencia Renal , Anciano de 80 o más Años , Broncoscopía/métodos , Diagnóstico Diferencial , Disnea/etiología , Técnica del Anticuerpo Fluorescente , Hemoglobinas/análisis , Hemoptisis/diagnóstico , Hemoptisis/etiología , Hemoptisis/fisiopatología , Humanos , Inmunosupresores/administración & dosificación , Pruebas de Función Renal/métodos , Pulmón/diagnóstico por imagen , Masculino , Poliangitis Microscópica/diagnóstico , Poliangitis Microscópica/inmunología , Poliangitis Microscópica/fisiopatología , Alveolos Pulmonares/patología , Insuficiencia Renal/diagnóstico , Insuficiencia Renal/etiología , Insuficiencia Renal/inmunología , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoRESUMEN
Recent data suggest the existence of a complement alternative pathway activation in the pathogenesis of antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a condition that remains poorly understood. This study aims to assess the clinical characteristics and outcomes of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) patients with regard to their plasma complement levels at diagnosis. A retrospective monocentric study carried out at Caen University Hospital led to the identification of proteinase-3- or myeloperoxidase-ANCA-positive GPA and MPA patients from January 2000 to June 2016 and from September 2011 to June 2016, respectively. All patients with available C3 and C4 levels at diagnosis were included. Patients were categorized in the hypocomplementemia group if their C3 and/or C4 levels at diagnosis were below the lower limit of the normal range. Among the 76 AAV patients (43 GPA, 33 MPA), 4 (5%) had hypocomplementemia, and the 72 remaining patients exhibited normal plasma complement levels. All 4 hypocomplementemia patients had renal involvement. Hypocomplementemia was followed in 1 patient whose post-treatment complement level normalized within 1 month. Among all clinical and ANCA specificity, including relapse-free survival (p = 0.093), only overall and renal survival rates were significantly lower in the hypocomplementemia group (p = 0.0011 and p<0.001, respectively). Hypocomplementemia with low C3 and/or C4 levels at GPA or MPA diagnosis may be responsible for worse survival and renal prognosis. These results argue for larger and prospective studies to better determine the epidemiology of the disease and to assess complement-targeting therapy in these patients.
Asunto(s)
Complemento C3/metabolismo , Complemento C4/metabolismo , Granulomatosis con Poliangitis/fisiopatología , Enfermedades Renales/fisiopatología , Riñón/fisiopatología , Poliangitis Microscópica/fisiopatología , Anciano , Autoanticuerpos/metabolismo , Biomarcadores/sangre , Femenino , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/terapia , Humanos , Terapia de Inmunosupresión , Enfermedades Renales/complicaciones , Enfermedades Renales/terapia , Masculino , Poliangitis Microscópica/complicaciones , Poliangitis Microscópica/terapia , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is systemic vascular inflammation. Microscopic polyangiitis (MPA) is a major type of AAV in Japan. MPA often affects the kidneys and lungs, leading to death if untreated. Induction therapy (i.e., initial treatment) for MPA has not been optimized, although methylprednisolone and cyclophosphamide are commonly used. Recently, rituximab (RTX) (a monoclonal antibody against the protein CD20) has also been used to treat refractory AAV. RTX at 375 mg/m2/week for 4 weeks (i.e., the conventional lymphoma dosing schedule) is used, but the optimal dosing schedule is controversial. Indeed, a single-dose of RTX successfully controlled nephrotic syndrome. However, to date, the effectiveness of a single RTX dose in treating MPA has not been fully investigated in Japan. This was a retrospective observational study. Six newly diagnosed patients with MPA were initially treated with methylprednisolone and a single dose of RTX (375 mg/m2). We investigated the patients' clinical features, as well as the efficacy and safety of RTX treatment. All patients attained remission on a tapered prednisolone dose of < 10 mg/day during the first 12 months. One patient relapsed after 12 months whereas another required hospitalization owing to infective spondyloarthritis. Adverse reactions to RTX infusion and late-onset neutropenia were not observed. Therefore, a single-dose treatment with RTX induced remission with few complications, and allowed tapering the prednisolone treatment. We conclude that a single dose of RTX is a promising induction therapy for MPA, reducing the cost associated with multiple doses.
Asunto(s)
Poliangitis Microscópica/tratamiento farmacológico , Rituximab/uso terapéutico , Anciano , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Linfocitos B/metabolismo , Relación Dosis-Respuesta a Droga , Estudios de Factibilidad , Femenino , Tasa de Filtración Glomerular , Humanos , Recuento de Linfocitos , Masculino , Poliangitis Microscópica/sangre , Poliangitis Microscópica/diagnóstico , Poliangitis Microscópica/fisiopatología , Persona de Mediana Edad , Prednisolona/administración & dosificación , Prednisolona/uso terapéutico , Inducción de Remisión , Rituximab/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: To assess symptoms and objective parameters of autonomic dysfunction (AD) in patients with ANCA-associated vasculitides. METHODS: Symptoms and objective parameters of AD were assessed in patients with ANCA-associated vasculitis and in age-matched healthy controls. Autonomic symptoms were explored by COMPASS31, a validated questionnaire addressing symptoms of six autonomic domains (orthostatic, vasomotor, secretomotor, gastrointestinal, pupillomotor, and bladder dysfunction). Objective autonomic parameters consisted of expiratory/inspiratory (E/I) ratio during the deep breathing test (DBT), blood pressure response to cold pressor test (CPT), and skin conductance changes during mental arithmetic. RESULTS: 27 patients and 27 healthy controls have been enrolled. 27 patients and 27 controls completed COMPASS31. 21 patients and 18 controls underwent objective autonomic testing. Vasculitis patients had significantly higher COMPASS31 total scores than controls (median 10.4 vs 3.0; p = 0.005). In the sub-domain analysis, significant differences were seen in the vasomotor and the bladder domain (p = 0.004; p < 0.001, respectively). No correlation was found between COMPASS31 score and disease duration, number of affected organs, or Birmingham vasculitis activity score (BVAS). There was no significant difference in any of the objective autonomic parameters between patients and controls. In a subgroup analysis, no difference in objective autonomic parameters was found between patients with active disease (n = 12) and patients in remission (n = 7). CONCLUSION: Patients with ANCA-associated vasculitides commonly have symptoms of autonomic dysfunction that are independent of disease duration and disease severity. However, at least in this single-centre observation, there was no evidence of impaired autonomic regulation in three autonomic function tests in vasculitis patients.
Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/fisiopatología , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Sistema Nervioso Autónomo/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Presión Sanguínea , Síndrome de Churg-Strauss/fisiopatología , Estudios de Cohortes , Frío , Femenino , Respuesta Galvánica de la Piel , Humanos , Masculino , Poliangitis Microscópica/fisiopatología , Persona de Mediana Edad , Respiración , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVE: To uniquely classify children with microscopic polyangiitis (MPA), to describe their demographic characteristics, presenting clinical features, and initial treatments in comparison to patients with granulomatosis with polyangiitis (Wegener's) (GPA). METHODS: The European Medicines Agency (EMA) classification algorithm was applied by computation to categorical data from patients recruited to the ARChiVe (A Registry for Childhood Vasculitis: e-entry) cohort, with the data censored to November 2015. The EMA algorithm was used to uniquely distinguish children with MPA from children with GPA, whose diagnoses had been classified according to both adult- and pediatric-specific criteria. Descriptive statistics were used for comparisons. RESULTS: In total, 231 of 440 patients (64% female) fulfilled the classification criteria for either MPA (n = 48) or GPA (n = 183). The median time to diagnosis was 1.6 months in the MPA group and 2.1 months in the GPA group (ranging to 39 and 73 months, respectively). Patients with MPA were significantly younger than those with GPA (median age 11 years versus 14 years). Constitutional features were equally common between the groups. In patients with MPA compared to those with GPA, pulmonary manifestations were less frequent (44% versus 74%) and less severe (primarily, hemorrhage, requirement for supplemental oxygen, and pulmonary failure). Renal pathologic features were frequently found in both groups (75% of patients with MPA versus 83% of patients with GPA) but tended toward greater severity in those with MPA (primarily, nephrotic-range proteinuria, requirement for dialysis, and end-stage renal disease). Airway/eye involvement was absent among patients with MPA, because these GPA-defining features preclude a diagnosis of MPA within the EMA algorithm. Similar proportions of patients with MPA and those with GPA received combination therapy with corticosteroids plus cyclophosphamide (69% and 78%, respectively) or both drugs in combination with plasmapheresis (19% and 22%, respectively). Other treatments administered, ranging in decreasing frequency from 13% to 3%, were rituximab, methotrexate, azathioprine, and mycophenolate mofetil. CONCLUSION: Younger age at disease onset and, perhaps, both gastrointestinal manifestations and more severe kidney disease seem to characterize the clinical profile in children with MPA compared to those with GPA. Delay in diagnosis suggests that recognition of these systemic vasculitides is suboptimal. Compared with adults, initial treatment regimens in children were comparable, but the complete reversal of female-to-male disease prevalence ratios is a provocative finding.
Asunto(s)
Granulomatosis con Poliangitis/fisiopatología , Hemorragia/fisiopatología , Fallo Renal Crónico/fisiopatología , Enfermedades Pulmonares/fisiopatología , Poliangitis Microscópica/fisiopatología , Síndrome Nefrótico/fisiopatología , Insuficiencia Respiratoria/fisiopatología , Adolescente , Corticoesteroides/uso terapéutico , Distribución por Edad , Anticuerpos Anticitoplasma de Neutrófilos , Asia/epidemiología , Azatioprina/uso terapéutico , Canadá/epidemiología , Niño , Preescolar , Estudios de Cohortes , Ciclofosfamida/uso terapéutico , Quimioterapia Combinada , Europa (Continente)/epidemiología , Femenino , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/epidemiología , Granulomatosis con Poliangitis/terapia , Hemorragia/etiología , Humanos , Inmunosupresores/uso terapéutico , Lactante , Fallo Renal Crónico/etiología , Fallo Renal Crónico/terapia , Enfermedades Pulmonares/etiología , Masculino , Metotrexato/uso terapéutico , Poliangitis Microscópica/complicaciones , Poliangitis Microscópica/epidemiología , Poliangitis Microscópica/terapia , Ácido Micofenólico/uso terapéutico , Síndrome Nefrótico/etiología , Terapia por Inhalación de Oxígeno , Plasmaféresis , Proteinuria/etiología , Diálisis Renal , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/terapia , Rituximab/uso terapéutico , Estados Unidos/epidemiologíaRESUMEN
AIM: To study the clinical features of early- and extended-stage microscopic polyangiitis (MPA) and its outcomes on the basis of a long-term follow-up in a rheumatologist's practice. SUBJECTS AND METHODS: The clinical features of early- and extended-stage MPA were studied in detail and the premorbid background and possible precipitating factors were analyzed in 70 patients with MPA and the proven hyperproduction of antineutrophil cytoplasmic antibodies (anti-proteinase-3 (anti-PR3) antibodies in 55% and anti-myeloperoxidase (anti-MPO) antibodies in 45%) who had been followed up for more than a year. RESULTS: There is evidence for the nosological unity of the two immunological types of MPA associated with anti-PR-3 or anti-MPO antibodies. MPA has been demonstrated to be an aggressive, polysyndromic disease prone to recurrences (52%), the typical manifestation of which is glomerulonephritis (94%) that is rapidly progressive in every four cases and accompanied by hemorrhagic alveolitis (69%) and involvement of other organs. ENT organs and lungs have been noted to be commonly involved in early-stage MPA, which was observed in 61% of the patients in the premorbid period, and to become the first manifestation of MPA (63%) concurrent with body temperature rises (64%), arthralgia or arthritis (41%). Respiratory tract involvement in MPA may be asymptomatic. Anti-PR-3-associated MPA may manifest itself more aggressively and in the first 2 years it is characterized by a poorer prognosis than of anti-MPO-associated MPA (survival rates, 82 and 94%, respectively; p = 0.04). With time, the differences were levelled off; recurrences in the patients with anti-PR-3 and anti-MPO develop equally frequently and proceed showing the similar clinical picture; the survival curves converge by age 3. Anti-MPO-associated MPA is characterized by the highest rate of lung involvement in the clinical phase of the disease (61%) and by a propensity to develop hemorrhagic alveolitis, diffuse interstitial (22%) or circumscribed pulmonary fibrosis in the outcome. CONCLUSION. The findings emphasize how important to diagnose MPA early and to prescribe long-term active treatment using the entire current arsenal of medications as soon as possible until severe injury to organs and systems develops. To specify regularities in the development of MPA may be of value for the better diagnosis of the disease and the further elaboration of optimal treatment policy.
Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/sangre , Poliangitis Microscópica/fisiopatología , Adolescente , Adulto , Anciano , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Poliangitis Microscópica/sangre , Poliangitis Microscópica/patología , Persona de Mediana Edad , Recurrencia , Adulto JovenRESUMEN
This study aims to compare the severity and outcomes of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) between Hispanics and Caucasians living in the same geographical area. All patients diagnosed with AAV at two academic institutions in Chicago from January 2006 to December 2012 were retrospectively and prospectively identified. Disease activity was measured with the Birmingham Vasculitis Activity Score (BVAS), and disease damage was measured with the Vasculitis Damage Index (VDI). Student's t test and chi-square tests were employed; p ≤ 0.05 was considered significant. Seventy patients with AAV were identified; 15 patients were excluded. Fifty-five patients were included in the study: 23 Hispanics and 32 Caucasians, 35 patients with granulomatosis with polyangiitis (Wegener's), 12 with microscopic polyangiitis, 7 with eosinophilic granulomatosis with polyangiitis, and 1 with renal-limited vasculitis. Compared to Caucasians, Hispanics had a higher BVAS at presentation (16.3 ± 7.6 versus 10.7 ± 7.5, p = 0.006), a higher VDI at presentation (2.90 ± 1.50 versus 2.06 ± 1.30, p = 0.030), and a cumulative VDI (3.90 ± 1.70 versus 2.50 ± 1.90, p = 0.010). Renal involvement was more common among Hispanics (85 % of Hispanics versus 48 % of Caucasians, p = 0.01). Seventy percent of Hispanics had acute renal failure (mean creatinine = 3.37 ± 4.4 mg/dl) of whom seven (50 %) required dialysis, versus 25 % of Caucasians (mean creatinine = 1.78 ± 1.57 mg/dl, p = 0.03) and only two requiring dialysis. Compared to Caucasians, Hispanics with AAV present with more severe disease and higher damage indices. Larger studies are required to confirm these findings and delineate the respective roles of environment and genetics in the pathogenesis of the disease.
Asunto(s)
Lesión Renal Aguda/etnología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/etnología , Hispánicos o Latinos , Lesión Renal Aguda/sangre , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , Adulto , Anciano , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/fisiopatología , Chicago , Síndrome de Churg-Strauss/complicaciones , Síndrome de Churg-Strauss/etnología , Síndrome de Churg-Strauss/fisiopatología , Creatinina/sangre , Femenino , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/etnología , Granulomatosis con Poliangitis/fisiopatología , Humanos , Masculino , Poliangitis Microscópica/complicaciones , Poliangitis Microscópica/etnología , Poliangitis Microscópica/fisiopatología , Persona de Mediana Edad , Diálisis Renal , Índice de Severidad de la Enfermedad , Población BlancaRESUMEN
Objetivo. Describir las diversas manifestaciones clínicas, de laboratorio e imagenológicas torácicas en 14 pacientes con poliangeítis granulomatosa (Wegener) (PAG). Material y métodos. Presentamos los datos clínicos, de laboratorio e imagen de pacientes con diagnóstico de PAG. Se incluyeron pacientes con manifestaciones torácicas sugerentes de PAG evaluados en 3 hospitales entre los años 2000 y 2012. A todos los pacientes les realizamos tinciones y cultivos bacteriológicos, para micobacterias y hongos, en expectoración y lavado broncoalveolar; anticuerpos anticitoplasma de neutrófilos (ANCA), anticuerpos antinucleares, factor reumatoide y biopsia de órganos afectados. Resultados. Trece pacientes tuvieron afección de por lo menos 2 órganos. Las manifestaciones torácicas fueron nódulos pulmonares, opacidades en vidrio esmerilado y parches de consolidación; otras anormalidades fueron estenosis de tráquea, hemorragia alveolar difusa, masas pulmonares con neumonía organizada. El 78% tuvo ANCA positivos (la mayoría c-ANCA). A 10 pacientes se les realizó biopsia de tejido respiratorio (8 de pulmón, una de tráquea y una nasal). En 4 pacientes el diagnóstico se sustentó con la afección de diversos órganos, ANCA positivos, biopsia de riñón o piel y respuesta a tratamiento. A los 6-12 meses todos los pacientes mostraron mejoría clínica e imagenológica, y el 54% de 11 pacientes en seguimiento presentaron recaída. Conclusiones. En esta serie de casos presentamos la mayoría de las manifestaciones radiológicas torácicas descritas en pacientes con PAG. Enfatizamos el realizar un abordaje diagnóstico ordenado para descartar otras patologías con prevalencia más alta que se expresan con manifestaciones pulmonares similares. La frecuencia de ANCA positivos fue elevada y la recurrencia de enfermedad, frecuente (AU)
Objective: To describe the clinical and laboratory data, with special emphasis on thoracic imaging findings, in 14 patients with a definitive diagnosis of granulomatosis with polyangiitis (GPA). Methods: The clinical and tomographic data of 14 patients with a definitive diagnosis of GPA are presented. Patients with thoracic manifestations suggestive of GPA were evaluated in 3 hospitals from 2000 to 2012. All patients had a sputum analysis and bronchoalveolar lavage for bacterial, mycobacterial and fungal stains and cultures; antineutrophil cytoplasmic antibodies, antinuclear-antibodies, rheumatoid factor, and a biopsy of involved organs. Results: A total of 13 patients had at least two organs involved. The most frequent thoracic findings were pulmonary nodules, ground glass opacities and patches of consolidation; other abnormalities were tracheal stenosis, diffuse alveolar hemorrhage, lung masses with organized pneumonia. More than three- quarters (78%) of patients had positive antineutrophil cytoplasmic antibodies (ANCA). Ten patients had respiratory tissue biopsy (8 open lung, one tracheal, and one nasal). In 4 patients the diagnosis was made with the classic organ involvement in GPA, positive ANCA, and renal or skin biopsy, and response to treatment on follow-up. At 6-12 months all patients showed clinical and radiological improvement, with 54% showing a recurrence of disease. Discussion: The majority of thoracic findings described in GPA are presented in this study. A complete diagnostic approach with invasive diagnostic procedures to rule out other more prevalent respiratory diseases with similar thoracic manifestations must be performed. The positivity of ANCA in this study was high, and the recurrence of the disease was frequent (AU)
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/diagnóstico , Poliangitis Microscópica/complicaciones , Nódulos Pulmonares Múltiples/complicaciones , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Biopsia/métodos , Nódulos Pulmonares Múltiples/diagnóstico , Factores Inmunológicos/uso terapéutico , Granulomatosis con Poliangitis/fisiopatología , Granulomatosis con Poliangitis , Poliangitis Microscópica/fisiopatología , Poliangitis Microscópica , Técnica del Anticuerpo FluorescenteRESUMEN
The relevance of tissue specificity of microvascular endothelial cells (MECs) in the response to inflammatory stimuli and sensitivity to immune cell-mediated injury is not well defined. We hypothesized that such MEC characteristics might shape their interaction with NK cells through the use of different adhesion molecules and NK cell receptor ligands or the release of different soluble factors and render them more or less vulnerable to NK cell injury during autoimmune vasculitis, such as granulomatosis with polyangiitis (GPA). To generate a comprehensive expression profile of human MECs of renal, lung, and dermal tissue origin, we characterized, in detail, their response to inflammatory cytokines and to proteinase 3, a major autoantigen in GPA, and analyzed the effects on NK cell activation. In this study, we show that renal MECs were more susceptible than lung and dermal MECs to the effect of inflammatory signals, showing upregulation of ICAM-1 and VCAM-1 on their surface, as well as release of CCL2, soluble fractalkine, and soluble VCAM-1. Proteinase 3-stimulated renal and lung MECs triggered CD107a degranulation in control NK cell. Notably, NK cells from GPA patients expressed markers of recent in vivo activation (CD69, CD107a), degranulated more efficiently than did control NK cells in the presence of renal MECs, and induced direct killing of renal MECs in vitro. These results suggest that, upon inflammatory conditions in GPA, renal MECs may contribute to the recruitment and activation of NK cells in the target vessel wall, which may participate in the necrotizing vasculitis of the kidney during this disease.