The systemic vasculitides are a group of uncommon conditions characterized by inflammation and necrosis of blood vessel walls. Some of these syndromes are also characterized by the presence of antineutrophil cytoplasmic antibodies (ANCA).

Epidemiology

• Incidence - 100/1,000,000
• Age - peak onset 65-74 years; unusual in children
• Sex - slight male preponderance

Classification

• Based on affected vessel size (small, medium or large)
• Small - Wegener granulomatosis microscopic polyangiitis, renal vasculitis, Henoch Schönlein purpura
• Medium - polyarteritis nodosa, Churg Strauss syndrome, Kawasaki disease
• Large - Cogan syndrome, Takayasu arteritis, giant cell (temporal) arteritis

Refer to Vasculitis topic at www.arupconsult.com for Chapel Hill Consensus Conference Nomenclature of Systemic Vasculitis

Pathophysiology

• Anti-neutrophil cytoplasmic antibodies (ANCA) are directed against certain proteins in the cytoplasmic granules of neutrophils and monocytes
• ANCA are specific for enzymes in the lysosome-proteinase 3-specific (PR-3) and myeloperoxidase-specific (MPO) antibodies. ANCA have been subdivided into pANCA (perinuclear) and cANCA (cytoplasmic)
  • The pANCA pattern mimics anti-nuclear antibodies (ANA)
  • cANCA has specificity for PR-3 and p-ANCA for MPO for 80% of cases
• Binding of ANCA may induce activation of neutrophils with resultant endothelial cell damage

Clinical Presentation

• Nonspecific signs and symptoms early in the disease - fever, arthralgias, fatigue, weight loss, myalgias
• Multisystem involvement later in the course of the disease - dermatologic, ophthalmologic, renal, pulmonary

Diagnosis

• Indications for testing - multisystem disease presentation (including upper airway disease, renal disease, pulmonary disease, palpable purpura, urticaria or mononeuritis multiplex)

Refer to Vasculitis topic at www.arupconsult.com for a chart of ANCA Presence in Vasculitis Syndromes

• Laboratory testing
  • ESR - usually elevated
  • UA - evaluate for presence of hematuria suggesting renal involvement
  • ANCA
    • Indirect immunofluorescence assay (IFA) is a sensitive marker for ANCA-associated systemic vasculitisTo confirm specificity , PR3 or MPO specific assays ( ELISA, Western blot or mutianalyte fluorescence detection (MAFD) are required
  • Histology
    • Will determine which size artery is involved
    • In conjunction with clinical presentation, ANCA and UA can usually diagnose specific vasculitis (see the Vasculitis Testing Algorithms)

Disease Monitoring

• ANCA - titers may decrease after induction of remission and rise secondary to relapse
  • Rising titers to not reliably predict relapse
  • Cannot use titers to guide treatment

Differential Diagnosis

• Autoimmune disease (eg, SLE)
• Neoplasm
• Infection (eg, HIV, HCV)
• Glomerulonephritis
• Antiphospholipid syndrome
• Sarcoidosis