Microscopic Polyangiitis

ArticleinRheumatic diseases clinics of North America 36(3):545-58 · August 2010with10 Reads
DOI: 10.1016/j.rdc.2010.04.003 · Source: PubMed
In 1923, Friedrich Wohlwill described two patients with a "microscopic form of periarteritis nodosa," which was distinct from the classical form. This disease, now known as microscopic polyangiitis (MPA), is a primary systemic vasculitis characterized by inflammation of the small-caliber blood vessels and the presence of circulating antineutrophil cytoplasmic antibodies. Typically, microscopic polyangiitis presents with glomerulonephritis and pulmonary capillaritis, although involvement of the skin, nerves, and gastrointestinal tract is not uncommon. Treatment of MPA generally requires use of a cytotoxic agent (such as cyclophosphamide) in addition to high-dose glucocorticoids. Recent research has focused on identifying alternate treatment strategies that minimize or eliminate exposure to cytotoxic agents. This article reviews the history, pathogenesis, clinical manifestations, and treatment of MPA.
    • "Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome), also an AAV, is characterized by allergic and vasculitic features and is usually studied separately from GPA and MPA [3]. Renal and pulmonary involvement is common in AAV, with an incidence of glomerulonephritis of 38– 70% in GPA and 80-100% in MPA, and pulmonary involvement of 60-85% and 25-55%, respectively [4,5]. Rapidly progressive glomerulonephritis (RPGN) and diffuse alveolar hemorrhage (DAH) are considered severe disease manifestations that compromise organic function and may be life-threatening [2]. "
    [Show abstract] [Hide abstract] ABSTRACT: The evidence of the benefit of plasmapheresis in renal and survival outcomes in patients with severe manifestations of ANCA-associated vasculitides is inconsistent. To address whether plasmapheresis is associated with improvement in renal function and survival at 12 months in patients with severe manifestations of ANCA-associated vasculitides. Single-center retrospective comparative cohort of 24 patients with granulomatosis with polyangiitis or microscopic polyangiitis that received plasmapheresis adjunctive to conventional therapy (steroids and immunosuppressants), matched 1:1 according to age, estimated glomerular filtration rate (eGFR) and disease activity with 24 patients treated with standard treatment only. Comorbidities, demographic, clinical, treatment and laboratory characteristics were recorded. After 12 months both groups showed improvement in eGFR (19.0 ± 14.34 to 41.61 ± 37.77 ml/min, p = 0.003 in plasmapheresis group; 23.16 ± 14.71 to 39.86 ± 25.67 ml/min, p = 0.001 in conventional therapy group). No differences were found between groups (p = 0.68). Patients free of dialysis at 12 months after intervention increased in the plasmapheresis group from 9/24 (38%) to 12/24 (50%), p = 0.5; and in the conventional therapy group from 19/24 (79%) to 22/24 (92%), p = 0.25. Difference between groups was significant at 12 months (p = 0.001). Survival at 12 months after intervention was 79% in the plasmapheresis group and 96% in the conventional therapy group (p = 0.08). The main cause of death was infectious and a tendency for a higher prevalence of severe infections was observed in patients that received plasmapheresis (p = 0.07). Both plasmapheresis and conventional therapy improved eGFR at 12 months after intervention. Dialysis independence and survival were similar between groups. J. Clin. Apheresis, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Full-text · Article · Jul 2015
    • "In diagnosing MPA, histological confirmation of vasculitis is still the gold-standard and should be sought in every patient. Renal and surgical lung biopsies have a high yield and are extremely valuable in the diagnosis of glomerulonephritis and pulmonary vasculitis, respectively [11,19]. Currently, there is no laboratory test that has diagnostic specificity for MPA. "
    [Show abstract] [Hide abstract] ABSTRACT: Microscopic polyangiitis (MPA) is an idiopathic autoimmune disease characterized by systemic vasculitis. The disease predominantly affects small-calibre blood vessels and is associated with the presence of antineutrophil cytoplasmic autoantibodies (ANCA). Microscopic polyangiitis was considered to be a disease entity by Savage et al. in 1985. Microscopic polyangiitis has a reported low incidence and a slight male predominance. The aetiology of MPA remains unknown. There is, however, increased evidence that MPA is an autoimmune disease in which ANCAs, particularly those reacting with MPO, are pathogenic. MPA belongs to the systemic vasculitides, indicating that multiple organs can be affected. The major organs involved in MPA are the kidneys and the lungs. As expected for an illness that affects multiple organ systems, patients with MPA can present with a myriad of different symptoms. Ear, nose and throat (ENT) manifestations are not considered to be clinical symptoms of MPA, but in the majority of populations described, ENT involvement was found in surprisingly high percentages. MPA is part of the ANCA-associated vasculitides, which are characterized by necrotizing vasculitis of small vessels. Diagnosis is mainly established by clinical manifestations, computed tomography (TC), ANCA antibody detection and renal and pulmonary biopsy. The introduction of aggressive immunosuppressive treatment has substantially improved the prognosis. The standardized therapeutic regimen is based on cyclophosphamide and corticosteroids. Using this regimen, remission can be achieved in most of the patients. Rituximab may represent an important alternative to cyclophosphamide for patients who may not respond adequately to antimetabolite therapies. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · May 2015
    • "The skin, peripheral nerves, and gastrointestinal tract are also frequently involved [3]. Rapidly progressive glomerulonephritis and hemorrhagic alveolitis are among the main causes of morbidity and mortality [2,3]. "
    [Show abstract] [Hide abstract] ABSTRACT: Microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are systemic, necrotizing, small-vessel vasculitis associated with circulating anti-neutrophil cytoplasmic autoantibodies (ANCA), and thus called ANCA-associated vasculitides (AAV). The aim of the present study is to evaluate a potential role of interleukin (IL)-6 and its pathway in the pathogenesis of AAV and to review previous evidence of IL-6 in MPA and GPA. Blood and histological samples from 10 untreated myeloperoxidase (MPO)-ANCA/proteinase 3 (PR3)-ANCA-positive patients with active AAV were studied. Serum levels of cytokines/chemokines were evaluated by means of a Bio-Plex Multiple Cytokine Assay. IL-6 production at sites of active vasculitis was assessed by means of both immunohistochemistry and in situ hybridization techniques. We also treated a patient with MPA who was resistant or allergic to conventional treatments with a 12-month course of the IL-6 inhibitor tocilizumab and followed him up for 24 additional months. We also reviewed all the published cases in the English literature of histologically confirmed MPA or GPA, in which elevated IL-6 serum levels or intralesional IL-6 expression were reported. IL-6 serum levels were significantly increased in patients with AAV as compared to controls (median = 51.96pg/mL; range: 34.11-84.30; versus 0.68pg/mL; range: 0.01-1.81; P < 0.005). Also, IL-6 was expressed and produced at sites of active vasculitis. Treatment with tocilizumab was able to induce a complete and sustained disease remission in a patient with severe multisystemic MPA, as well as normalization of circulating levels of IL-6-associated pro-inflammatory cytokines and chemokines. Previous evidence of IL-6 pathway activation in AAV is scarce. Increased serum levels of IL-6 were reported in seven clinical studies for a total of approximately 120 patients, mainly affected by GPA. The finding of an activated IL-6 pathway in patients with AAV, together with the observed effects of tocilizumab monotherapy, provides evidence for a possible central role of IL-6 in the pathogenesis of AAV and suggests its targeting as a potential treatment. Copyright © 2015 Elsevier Inc. All rights reserved.
    Full-text · Article · Feb 2015
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