Vasculitis - ANCA

Vasculitis - ANCA

 

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 – 10-20/1,000,000
  • Age – peak onset 65-74 years; unusual in children
  • Gender – slight male preponderance

Classification

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

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 on 80% of cases

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

  • ANCA testing
Presence of ANCA in Vasculitic Syndromes
  Approximate % of patients
positive for ANCA		 Approximate % of patients
with specific pattern
(combined patterns) C Pattern P Pattern
Wegener granulomatosis:
- Active generalized
- Limited forms
- Inactive
85-92
60-67
30-35
85-90
85-90
85-90
2-5
2-5
2-5
Idiopathic crescentic
glomerulonephritis		 80 some* majority*
Polyarteritis nodosa 50 86 14
Churg-Strauss 50 80 20
Systemic lupus erythematosus <10 0 >90
Rheumatoid arthritis <5 0 >90
Sjögren's syndrome 25 0 >90
Primary sclerosing cholangitis rare rare >85
* No quantitation in the literature

 

  • Clinical value of ANCA has been studied most in patients with Wegener granulomatosis (WG) or WG variants, as well as those with microscopic polyangiitis (MPA)
    • cANCA is closely associated with generalized WG disease, but sensitivity decreases with localized or inactive disease states
    • Although specificity of cANCA for WG was originally thought to be high, cANCA and antibody to PR3 also found in patients without classic WG
    • A few patients with idiopathic necrotizing and crescentic glomerulonephritis (NCGN) have antibody to PR-3
      • NCGN generally considered to be renal-limited form of MPA, although some patients evolve into WG
    • MPA is often ANCA-positive with approximately an equal distribution of cANCA and pANCA, and no clear clinical distinction between the two
    • As with NCGN, however, some MPA patients with antibody to PR-3 evolve into WG
  • pANCA is positive in primary sclerosing cholangitis (PSC), autoimmune cholangitis and cryptogenic chronic hepatitis
    • Atypical pattern disappears on formalin-fixed slides

Differential diagnosis

  • Infection
  • Autoimmune disease
  • Neoplasia

Monitoring

  • Numerous reports indicate that effective treatment of WG is associated with falling ANCA titers.
    • The usefulness of monitoring titers in patients in remission, however, is controversial
    • Not all patients with rising titers relapse
      • In some cases, relapse does not occur until several months after ANCA determination

See Also