Clinical meaning
Microscopic polyangiitis (MPA) is an ANCA-associated small-vessel vasculitis characterized by necrotizing inflammation of capillaries, venules, and arterioles without granulomatous inflammation — this absence of granuloma formation is the key histopathological distinction from granulomatosis with polyangiitis (GPA/Wegener). MPA is strongly associated with perinuclear ANCA (p-ANCA) directed against myeloperoxidase (MPO-ANCA, positive in 80-90% of cases). The pathogenesis begins with neutrophil priming by pro-inflammatory cytokines (TNF-alpha, complement factor C5a) that cause MPO to translocate from azurophilic granules to the neutrophil cell surface. Circulating MPO-ANCA antibodies then bind surface-expressed MPO, activating neutrophils through Fc-gamma receptor crosslinking and direct F(ab')2-mediated signaling, triggering degranulation and release of reactive oxygen species, proteolytic enzymes (elastase, proteinase 3), and neutrophil extracellular traps (NETs) that directly damage the endothelium of small vessels. Activated neutrophils also adhere firmly to endothelial cells via beta-2 integrin interactions, concentrating their destructive cargo at the vessel wall and producing fibrinoid necrosis. The hallmark clinical presentation is the pulmonary-renal syndrome: rapidly progressive glomerulonephritis (RPGN) presenting as hematuria with red blood cell casts, proteinuria, and rapidly rising serum creatinine — the renal biopsy shows pauci-immune crescentic glomerulonephritis (minimal immunoglobulin or complement deposition on immunofluorescence, distinguishing it from immune complex-mediated glomerulonephritis such as lupus nephritis or anti-GBM disease). Pulmonary involvement manifests as diffuse alveolar hemorrhage (DAH) from capillaritis — necrotizing inflammation of alveolar capillaries causes red blood cells to flood the alveolar space, producing hemoptysis, bilateral ground-glass infiltrates on imaging, and a progressively dropping hemoglobin; importantly, hemoptysis may be absent in up to one-third of DAH cases. The complement alternative pathway amplification loop plays an important role in MPA pathogenesis, and the C5a receptor inhibitor avacopan represents a targeted complement-blocking therapy. Treatment follows a remission-induction protocol (rituximab or cyclophosphamide plus corticosteroids) followed by maintenance therapy (rituximab or azathioprine). The clinician differentiates MPA from GPA (p-ANCA/MPO versus c-ANCA/PR3, absence versus presence of granulomas and upper airway involvement), evaluates for dual-positive disease (concurrent anti-GBM and ANCA antibodies), and coordinates nephrology, pulmonology, and rheumatology care.