Microscopic Polyangiitis



Microscopic Polyangiitis


Surya V. Seshan, MD





Key Facts


Terminology



  • Necrotizing vasculitis, with few or no immune deposits, affecting small arteries (capillaries, venules, or arterioles)


  • Necrotizing glomerulonephritis is common


Etiology/Pathogenesis



  • ANCA-mediated small vessel vasculitis


  • Cell-mediated immune mechanism


Clinical Issues



  • Rapidly progressive or oliguric acute renal failure


  • Pulmonary hemorrhage


  • p-ANCA/anti-myeloperoxidase positive (60%)


  • c-ANCA/anti-PR3 positive (15%)


  • Renal (90-100%), lung (25-55%)


Microscopic Pathology



  • Crescentic glomerulonephritis with fibrinoid necrosis


  • Vasculitis



    • Not always present, even in multiple levels


  • Rarely, isolated tubulointerstitial inflammation


  • No significant granulomatous inflammation


  • IF: Fibrin in crescents but little or no IgG, IgA, or IgM


  • Linear IgG in GBM indicates concurrent anti-GBM disease


  • EM: Rare deposits, breaks in GBM


Top Differential Diagnoses



  • Granulomatosis with polyangiitis (Wegener) and Churg-Strauss syndrome


  • Immune complex-mediated glomerulonephritis


  • Anti-GBM disease







MPO-ANCA-mediated crescentic glomerulonephritis shows segmental transmural necrotizing small vessel vasculitis image adjacent to a glomerulus with circumferential crescent image.






Two glomeruli show segmental pauci-immune type glomerulonephritis with small cellular crescents image in the Bowman space. The remaining portions of the glomeruli are unremarkable.


TERMINOLOGY


Abbreviations



  • Microscopic polyangiitis (MPA)


Synonyms



  • Microscopic polyarteritis


  • p-ANCA mediated small vessel vasculitis


  • Systemic or renal limited crescentic glomerulonephritis


  • “Pauci-immune” glomerulonephritis


Definitions



  • Chapel Hill Consensus Conference



    • Necrotizing vasculitis, with few or no immune deposits, affecting small vessels (i.e., capillaries, venules, or arterioles)


    • Necrotizing arteritis involving small and medium-sized arteries may be present


    • Necrotizing glomerulonephritis is very common


    • Pulmonary capillaritis often occurs


ETIOLOGY/PATHOGENESIS


Environmental Exposure



  • Higher rate of onset in winter than summer



    • Similar to granulomatosis with polyangiitis (Wegener)


Pathogenesis



  • Anti-neutrophil cytoplasmic antibody (ANCA)-mediated small vessel vasculitis



    • Mainly autoantibodies to antigen myeloperoxidase (p-ANCA)


    • Minority have autoantibodies to antigen proteinase 3 (c-ANCA)


    • Subset of MPO-ANCA small vessel vasculitis is renal-limited necrotizing crescentic glomerulonephritis


    • Subset are ANCA(-) renal-limited necrotizing crescentic glomerulonephritis


  • Cell-mediated immune mechanism with T-lymphocytes, neutrophils, and histiocytes are necessary for development of crescentic glomerulonephritis



    • ANCA-activated neutrophils tend to adhere to activated microvascular endothelium to initiate injury


    • Alternate pathway of complement has been shown to initiate and enhance endothelial injury and vasculitis


CLINICAL ISSUES


Epidemiology



  • Incidence



    • Varies with geographic locations



      • 1-8/1,000,000 in Europe and United States


      • 10-24/1,000,000 in Asian and Arab countries


  • Age



    • All ages affected


    • Average age at onset is 50 years


  • Ethnicity



    • Geographic variations may be related to ethnic background


Presentation



  • General



    • Pulmonary renal syndrome


    • Constitutional symptoms (up to 75%)



      • Fever, weakness, weight loss


      • Arthralgias, myalgias (25-50%)


      • Hypertension


  • Renal (90-100%)



    • Kidney is common organ involved in MPA


    • Hematuria


    • Proteinuria


    • Renal insufficiency


    • Rapidly progressive or oliguric acute renal failure


  • Skin




    • Purpuric rash, palpable (45%)


  • Lung (25-55%)



    • Hemoptysis


    • Dyspnea


    • Pulmonary hemorrhage


    • Lung infiltrates


  • Gastrointestinal (50%)



    • Abdominal pain



      • Severe form with bowel perforation


    • Hepatomegaly


  • Neurologic (30%)



    • Peripheral neuropathy less frequent than PAN


    • Central nervous system


  • Ear, nose, throat (30-35%)



    • Mouth ulcers


    • Epistaxis


    • Sinusitis


Laboratory Tests



  • Anemia (normochromic normocytic)


  • Elevation of acute phase proteins



    • Erythrocyte sedimentation rate


    • C-reactive protein


  • Leukocytosis and thrombocytosis


  • Rheumatoid factor (39-50%)


  • Antinuclear antibodies (21-33%)


  • p-ANCA/anti-myeloperoxidase positive (60%)


  • c-ANCA/anti-PR3 positive (15%)


  • Renal



    • Urinalysis shows red cells and RBC casts


    • Varying degrees of proteinuria


    • Elevated serum BUN and creatinine levels


Treatment



  • Remission induction, remission maintenance, and relapse treatment are 3 phases of therapy


  • Corticosteroids combined with cyclophosphamide is most common induction protocol


  • Other forms of immunosuppressive therapy in refractory cases (10%)


  • Oral cyclophosphamide, mycophenolate mofetil, or azathioprine used for remission maintenance


Prognosis



  • Severe form of glomerular disease with aggressive course


  • 1-year mortality rate of untreated cases is 80%


  • Early deaths are usually due to fulminant renal disease and lung hemorrhage in MPA


  • Frequent relapses occur (25-35%)



    • Different or new organs may be involved during relapses


    • Often associated with rash and arthralgias


    • Generally less severe


  • Induction protocol



    • Improvement in > 90% of patients


    • Complete remission in > 75%


  • Independent factors that correlate with worse prognosis are older age, higher initial serum creatinine, and pulmonary hemorrhage


  • Pathologic parameters representative of recovery of renal function include percent of normal glomeruli at initial biopsy, tubular injury, glomerular crescents, and interstitial inflammation


MACROSCOPIC FEATURES


General Features



  • Normal or mildly increased kidney size


  • Infarcts when present are small


  • Petechial hemorrhages



    • Focal or diffuse


    • Represent glomerular necrosis; hemorrhage in Bowman space or within tubular lumina


MICROSCOPIC PATHOLOGY


Histologic Features



  • Glomeruli



    • Pauci-immune crescentic glomerulonephritis



      • Segmental or, rarely, global glomerular necrosis (80-100%)



      • Disruption of glomerular basement membranes with accumulation of eosinophilic/fuchsinophilic fibrinoid material


      • Majority of glomeruli have crescents (average 45-55%), which frequently accompany necrosis


      • Segmental to extensive lysis of Bowman capsule in severe necrotizing glomerular lesions


      • Sometimes mild to moderate endocapillary hypercellularity with neutrophils and macrophages


    • Active periglomerular inflammation of varying intensity composed of lymphocytes, neutrophils, eosinophils, and histiocytes



      • Periglomerular granulomatous reaction is unlike that seen in granulomatosis with polyangiitis (Wegener)


    • Subacute or chronic glomerular lesions display fibrocellular or fibrous crescents



      • Segmental and global glomerular necrosis heals by sclerosis


      • Sclerosing glomerular changes are accompanied by tubular atrophy and interstitial fibrosis


  • Tubules and interstitium



    • Active disease often associated with acute tubulointerstitial inflammation


    • Rare isolated tubulointerstitial inflammation is noted without glomerular lesions in kidney biopsy


    • No significant granulomatous inflammation is noted


  • Renal and extrarenal vessels

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Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Microscopic Polyangiitis

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