Microscopic Polyangiitis: New Insights Into Pathogenesis, Clinical Features and Therapy

Alexandre Karras, MD, PhD

Disclosures

Semin Respir Crit Care Med. 2018;39(4):459-464. 

In This Article

Abstract and Introduction

Abstract

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.

Introduction

Microscopic polyangiitis (MPA) is a systemic autoimmune necrotizing vasculitis belonging to the group of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). Although characterized by the nearly constant positivity of circulating ANCAs, this disease is exclusively defined by histopathological and clinical criteria, according to the 2012 revised Chapel Hill Consensus Conference (CHCC) nomenclature system.[1] Like all AAVs, MPA predominantly affects small-sized vessels such as capillaries, venules, or arterioles, but medium-sized arteries are involved in some cases. Immunofluorescence studies reveal no or few immune complex deposits, in contrast to other small-vessel vasculitides such as antiglomerular membrane disease, cryoglobulinemic vasculitis, or immunoglobulin A (IgA) vasculitis (formerly known as Henoch–Schönlein's purpura). In addition, MPA is characterized by the absence of granulomatous inflammation, a feature that is frequently met in granulomatosis with polyangiitis (GPA) or in eosinophilic granulomatosis with polyangiitis (EGPA). The main clinical presentations include necrotizing glomerulonephritis, which is particularly frequent in this setting, and pulmonary capillaritis. Fever, arthralgia/myalgia, purpuric skin lesions, and mononeuritis multiplex are frequent findings, but in contrast to GPA, ENT (ear, nose, throat) abnormalities are not characteristic for MPA. Of note, the CHCC nomenclature is neither a classification nor a diagnostic system. In fact, no diagnostic criteria for MPA have been formally validated with respect to sensitivity and specificity, although an algorithm has been proposed by Watts et al to classify patients with AAV,[2] recently adapted by the European Medicines Agency[3] and validated in some cohorts.

Interestingly, the specificity of ANCA has not been included in the definition of MPA in the CHCC nomenclature. A majority of MPA patients have ANCAs of anti-myeloperoxidase (MPO) specificity, with a positivity rate ranging from 60% to more than 80% in some series, according to the definition used for MPA diagnosis and the geographical origin of the study population. However, up to 25% of MPA patients may present ANCAs recognizing proteinase 3 (PR3)[4] and 5 to 10% of them will have neither anti-MPO nor anti-PR3 antibodies. Conversely, anti-MPO antibodies can also be present in patients with GPA,[5,6] but also in 30 to 50% of patients with EGPA.[7,8]

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