MR imaging findings of musculoskeletal involvement in microscopic polyangiitis: a comparison with inflammatory myopathy.

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.

Polyangiitis overlap syndrome: a novel presentation of microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis.

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.

Evaluation of poor prognostic factors of respiratory related death in microscopic polyangiitis complicated by interstitial lung disease.

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.

Pulmonary manifestations and outcomes in paediatric ANCA-associated vasculitis: a single-centre experience.

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.

The complexity of classifying ANCA-associated small-vessel vasculitis in actual clinical practice: data from a multicenter retrospective survey.

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.

Rituximab prescription patterns and efficacy in the induction treatment of ANCA-Associated Vasculitis in a Belgian multicenter cohort.

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..

Microscopic polyangiitis masquerading as a pancreatic neoplasm with multiple lung metastases.

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.

Poliangitis microscópica y enfermedad pulmonar intersticial / Microscopic polyangiitis and interstitial lung disease

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An 80-Year-Old Man With Hemoptysis and Unilateral Patchy Opacities.

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.

Microscopic Polyangiitis: New Insights into Pathogenesis, Clinical Features and Therapy.

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.

Hypocomplementemia is associated with worse renal survival in ANCA-positive granulomatosis with polyangiitis and microscopic polyangiitis.

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.

Remission Induction Therapy with Rituximab for Microscopic Polyangiitis: A Feasibility Study.

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.

Assessment of autonomic function in a cohort of patients with ANCA-associated vasculitis.

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.

Comparing Presenting Clinical Features in 48 Children With Microscopic Polyangiitis to 183 Children Who Have Granulomatosis With Polyangiitis (Wegener's): An ARChiVe Cohort Study.

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.

[Microscopic polyangiitis associated with antineutrophil cytoplasmic antibodies: clinical features].

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.

ANCA-associated vasculitis in Hispanic Americans: an unrecognized severity.

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.

Manifestaciones pulmonares de la granulomatosis con poliangitis / Pulmonary manifestations of granulomatosis with polyangiitis

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)

Tissue-specific microvascular endothelial cells show distinct capacity to activate NK cells: implications for the pathophysiology of granulomatosis with polyangiitis.

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.