Vasculitis, ANCA-Related

Vasculitis, ANCA-Related

Monica P. Revelo, MD, PhD



  • Pauci-immune glomerulonephritis (PIGN)

  • Pauci-immune crescentic glomerulonephritis

  • Rapidly progressive glomerulonephritis (RPGN)



  • Autoantibodies made to neutrophil lysosomal components (PR3 or MPO)

  • Antigens expressed on surface of activated neutrophils

  • ANCA augments neutrophil-mediated cytotoxicity

  • ANCA initiates signal transduction pathways for cell activation, FcR participation

  • Neutrophils activate alternative complement pathway

  • Leukocyte activation and adhesion to primed endothelial cells, resulting in cell damage

  • Trigger for ANCA production unknown

    • Presumed immune dysregulation

    • Evidence of molecular mimicry

    • Can be precipitated by drugs (propylthiouracil, hydralazine, penicillamine, minocycline)

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



  • Incidence

    • Overall, AAV is rare in children

      • GPA: 3.2:100,000 children/year

      • GPA > MPA in some studies

      • CSS very rare in children

  • Gender

    • F > M

  • Ethnicity

    • Whites more commonly involved

    • MPA most common small vessel vasculitis in Japan, China, Spain, and Kuwait


  • Systemic manifestations

    • Malaise, fever, weight loss (89%)

  • Lung symptoms

    • Shortness of breath, chronic cough, hemoptysis/alveolar hemorrhage, nodules, abnormal pulmonary function, fixed pulmonary infiltrates (80%)

  • Ear, nose, and throat symptoms

    • Nasal involvement, sinusitis, otitis/mastoiditis, subglottic involvement, hearing loss, oral ulcers (80%)

  • Renal symptoms

    • Abnormal urinalysis (hematuria, proteinuria), biopsy-proven pauci-immune crescentic glomerulonephritis, elevated serum creatinine (75.4%)

  • Other symptoms

    • Conjunctivitis, scleritis, palpable purpura, abdominal pain, arthralgias/myalgia, arthritis, severe headache, dizziness

Laboratory Tests

  • Positive ANCA test by indirect immunofluorescence and ELISA

    • Myeloperoxidase (MPO) ANCA (p-ANCA) is most common in PIGN, MPA, and CSS

    • Proteinase 3 (PR3) ANCA (c-ANCA) is most common in GPA

Natural History

  • With treatment, clinical remission is possible, but relapses are common

  • Progression to end-stage renal disease may occur (˜ 10%)


  • Remission of kidney and systemic manifestations can be accomplished with current therapy

    • Reported remission rate: 80-84%

    • Low mortality

  • Relapses are common after discontinuation of therapy

  • Prognostic factors of poor outcome include

    • Decreased glomerular filtration rate at presentation

    • Chronic lesions in renal biopsy

    • Nephrotic range proteinuria

  • Serum creatinine has been inversely correlated with kidney survival

Diagnostic Criteria for GPA (EULAR/PRINTO/PRES)

  • At least 3 criteria are necessary for diagnosis of GPA in childhood

    • Upper airway involvement

    • Laryngeo-tracheal-bronchial stenoses

    • Pulmonary involvement

    • Renal involvement

    • Granulomatous inflammation within arterial wall or perivascular/extravascular area

    • ANCA positivity


Histologic Features

  • Glomerular lesions are similar in all PIGN

    • Fibrinoid necrosis and capillary basement membrane disruption

    • Crescents: Cellular/fibrocellular (in active phase) and fibrous (chronic phase) involving most of glomeruli present, usually > 50%

    • Neutrophils can be seen within capillary loops

    • Minimal cellular proliferation (endocapillary/mesangial) may be seen

    • Bowman capsule rupture and periglomerular inflammation in severe cases

    • Segmental scars in healing/chronic phase

  • Tubules and interstitium

    • Significant mixed interstitial inflammatory infiltrate (neutrophils, mononuclear cells, and eosinophils) in acute phase

      • In GPA, interstitial inflammation may show granulomatous features

      • True granulomas are unusual in kidney biopsies, but their presence favors GPA

      • Eosinophils are more prominent in CSS and less prominent in MPA

    • Interstitial hemorrhage

    • Tubular necrosis with tubulitis may be seen

  • Vessels

    • Type of vessel involved

      • Interlobular/small arteries, arterioles, capillaries, and venules are affected in GPA

      • Arteries, arterioles, and capillaries in MPA

      • Arteries, arterioles, and, rarely, capillaries in CCS

    • Segmental/circumferential fibrinoid necrosis and perivascular inflammation

      • Eosinophils are more prominent in CSS

    • Progressive vascular sclerosis with loss of elastic in healing phase

    • Renal medullary capillaritis can be seen in GPA and MPA

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Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Vasculitis, ANCA-Related
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