What is the next best step for a patient with a positive anti-neutrophil cytoplasmic antibody (ANCA) test?

Next Steps After Positive ANCA Test

The next best step after a positive anti-neutrophil cytoplasmic antibody (ANCA) test is to perform specific antigen testing for proteinase 3 (PR3) and myeloperoxidase (MPO) to determine the exact ANCA specificity, followed by a comprehensive clinical evaluation for signs of ANCA-associated vasculitis (AAV). 1

Immediate Follow-up Testing

1. Antigen-specific immunoassays:

   • Order PR3-ANCA and MPO-ANCA tests (ELISA)
   • These are the preferred screening methods according to the 2017 revised international consensus 1
   • About 90% of patients with small-vessel vasculitis have ANCA directed primarily to MPO or PR3 1

2. Clinical evaluation for vasculitis manifestations:

   • Assess for kidney involvement:
     • Urinalysis (look for hematuria with dysmorphic red cells, red cell casts)
     • Urine protein quantification (typically 1-3 g/day in AAV)
     • Serum creatinine and estimated GFR
   • Evaluate for respiratory tract involvement:
     • Upper respiratory symptoms (nasal crusting, bleeding, sinusitis)
     • Lower respiratory symptoms (cough, hemoptysis, dyspnea)
   • Check for other systemic manifestations:
     • Skin lesions
     • Neurological symptoms
     • Eye involvement
     • Constitutional symptoms (fever, weight loss, fatigue)

3. Laboratory workup:

   • Complete blood count
   • C-reactive protein and ESR (inflammatory markers)
   • Anti-GBM antibodies (to rule out anti-GBM disease or dual-positive disease)
   • Complement levels
   • Urinalysis with microscopy

Diagnostic Algorithm

Positive ANCA test
    │
    ├─ Order PR3-ANCA and MPO-ANCA specific tests
    │   │
    │   ├─ PR3-ANCA positive → Suggests GPA (Wegener's)
    │   │
    │   └─ MPO-ANCA positive → Suggests MPA or EGPA
    │
    ├─ Evaluate for organ involvement
    │   │
    │   ├─ Kidney: Urinalysis, proteinuria, creatinine
    │   │
    │   ├─ Pulmonary: Chest imaging, PFTs if indicated
    │   │
    │   └─ Other systems: Based on symptoms
    │
    └─ Consider kidney biopsy if:
        │
        ├─ Evidence of kidney involvement
        │
        └─ Diagnosis remains uncertain

Important Considerations

• Clinical correlation is essential: A positive ANCA test alone is not diagnostic of vasculitis and must be interpreted in the clinical context 1

• Kidney biopsy: Should always be considered in patients with suspected active kidney involvement, but treatment should not be delayed in rapidly deteriorating patients with positive ANCA and compatible clinical picture 1

• Referral to specialists: Patients with suspected AAV should be treated at centers with experience in AAV management, equipped with adequate facilities for rapid diagnosis and management 1

• Timing is critical: Without immunosuppressive therapy, AAV is associated with poor outcomes; early diagnosis and treatment are essential for improving survival 1

Common Pitfalls to Avoid

• Delaying treatment: In the case of a clinical presentation compatible with small-vessel vasculitis and positive MPO or PR3-ANCA, waiting for a kidney biopsy should not delay starting immunosuppressive therapy, especially in rapidly deteriorating patients 1

• Overlooking mimics: Several non-vasculitic diseases may mimic small-vessel vasculitis, including systemic lupus erythematosus, infections, and malignancies 1

• Ignoring ANCA-negative vasculitis: About 10% of patients presenting with signs and symptoms of MPA, GPA, or NCGN are persistently ANCA-negative 1

• Failing to test for anti-GBM antibodies: Some patients can be positive for both ANCA and anti-GBM antibodies, which may require different treatment approaches 1, 2

By following this systematic approach after identifying a positive ANCA test, you can efficiently diagnose ANCA-associated vasculitis and initiate appropriate treatment to improve patient outcomes.