What are the guidelines for diagnosing Anti-Neutrophil Cytoplasmic Antibodies (ANCA) vasculitis?

Guidelines for Diagnosing ANCA Vasculitis

For diagnosing ANCA-associated vasculitis (AAV), testing for both PR3-ANCA and MPO-ANCA using high-quality antigen-specific assays is recommended as the primary diagnostic method, combined with clinical evaluation and tissue biopsy when possible. 1

Diagnostic Approach

Laboratory Testing

1. ANCA Testing:

   • Test for both PR3-ANCA and MPO-ANCA using high-quality antigen-specific immunoassays 1
   • If immunoassay is negative but clinical suspicion remains high, perform a second test (another immunoassay and/or immunofluorescence) 1
   • Note: A negative ANCA does not exclude AAV diagnosis, especially in disease limited to respiratory tract or renal-limited vasculitis 1, 2

2. Initial Laboratory Workup:

   • Complete blood count with differential
   • Comprehensive metabolic panel
   • Inflammatory markers (ESR, CRP)
   • Urinalysis with microscopic examination (look for red cell casts, dysmorphic erythrocytes, proteinuria)
   • Complement levels
   • Hepatitis B and C serology 2

Tissue Biopsy

• Gold standard for diagnosis with diagnostic yield >70% 2
• Target clinically affected tissue for highest diagnostic yield 2
• Important: Treatment should not be delayed while waiting for biopsy results in rapidly deteriorating patients with positive ANCA and compatible clinical presentation 2

Imaging Studies

• Select imaging based on suspected vessel size:
  • Large vessels: CT/CTA, MRI/MRA, or FDG-PET/CT
  • Medium vessels: CTA of affected regions (renal, mesenteric, coronary)
  • Small vessels: MRI/MRA or FDG-PET/CT 2

Disease Classification and Diagnosis

Diagnostic Criteria

• Diagnosis should be based on:

  1. Compatible clinical picture
  2. Histopathology OR surrogate parameters 1
  3. ANCA serology (PR3-ANCA or MPO-ANCA) 1

• Disease should be classified according to:

  • Chapel Hill Consensus Conference (CHCC) definitions
  • American College of Rheumatology (ACR) classification criteria 1
  • ANCA serotype (PR3-ANCA, MPO-ANCA, or ANCA-negative) 1, 3

Clinical Variants

• Specify the clinical-pathologic variant:

  • Granulomatosis with polyangiitis (GPA, formerly Wegener's)
  • Microscopic polyangiitis (MPA)
  • Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss)
  • Renal-limited vasculitis 3

• Define disease stage and activity state:

  • Localized vs. generalized
  • Remission, response, refractory disease, or relapse 1

Disease Assessment and Monitoring

• Comprehensive disease assessment requires:

  • Disease activity measurement (Birmingham Vasculitis Activity Score)
  • Disease Extent Index
  • Vasculitis Damage Index
  • Functional assessment (Short Form 36) 1

• Regular monitoring should include:

  • Renal function tests (serum creatinine, eGFR)
  • Urinalysis with microscopic examination
  • Inflammatory markers (ESR, CRP)
  • ANCA levels
  • Complete blood count with differential 2

Important Caveats and Pitfalls

• Do not rely solely on ANCA serology for diagnosis as ANCA can be found in other inflammatory diseases, infections, or may be drug-induced 1

• Do not delay treatment in rapidly deteriorating patients while waiting for biopsy results if ANCA is positive with compatible clinical presentation 2

• Do not exclude vasculitis diagnosis based solely on negative ANCA as some patients with limited disease may be ANCA-negative 1, 2

• Do not rely only on ESR and CRP as they are nonspecific markers 2

• Consider additional testing for anti-GBM antibodies in pulmonary-renal syndrome 1

• Recognize that ANCA status alone should not determine treatment choice but may have prognostic implications 2

• Consider that ANCA-positive and ANCA-negative EGPA may represent genetically different syndromes with different clinical manifestations 1