ANCA-Associated and ANCA-Negative Vasculitis: Diagnosis and Management
Yes, both ANCA-associated and ANCA-negative vasculitis can occur, with approximately 10% of patients with clinical features of small-vessel vasculitis being ANCA-negative. 1
Diagnostic Approach for Suspected Vasculitis
ANCA Testing and Interpretation
- High-quality antigen-specific immunoassays for both MPO-ANCA and PR3-ANCA are the preferred screening method 2
- ANCA positivity strongly supports the diagnosis when clinical presentation is compatible
- However, ANCA negativity does not exclude the diagnosis, particularly in:
- Eosinophilic granulomatosis with polyangiitis (EGPA) - up to 60% are ANCA negative 3
- Some cases of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA)
Diagnostic Algorithm
Clinical assessment for compatible features:
- Kidney involvement (hematuria, proteinuria, declining GFR)
- Pulmonary manifestations (hemoptysis, infiltrates)
- Upper respiratory tract involvement
- Skin lesions
- Constitutional symptoms
Laboratory workup:
- MPO and PR3-ANCA testing
- Complete blood count with differential
- Renal function tests
- Urinalysis with microscopic examination
- Inflammatory markers (ESR, CRP)
- Hepatitis B and C serology
- Cryoglobulins when indicated 2
Biopsy decision:
For ANCA-positive cases with compatible clinical presentation:
- Treatment can be initiated without waiting for biopsy results if rapidly deteriorating 1
- Biopsy can be performed soon after starting treatment
For ANCA-negative cases with compatible clinical presentation:
- Biopsy is essential for diagnosis when feasible 1
- Should not delay treatment if clinical suspicion is high and patient is deteriorating
Management Principles
Induction Therapy
- First-line treatment: Glucocorticoids combined with either rituximab or cyclophosphamide 1
- For severe disease (serum creatinine >4 mg/dl [>354 μmol/l]):
- Cyclophosphamide with glucocorticoids OR
- Combination of rituximab and cyclophosphamide 1
Factors Influencing Treatment Choice
Cyclophosphamide preferred for:
- Severe glomerulonephritis with markedly reduced GFR
- Rapidly progressive disease
Rituximab preferred for:
- Younger patients
- Fertility concerns
- Relapsing disease
Disease Monitoring
- Regular assessment of disease activity using Birmingham Vasculitis Activity Score (BVAS)
- Monitor ANCA levels - persistence or increase may predict relapse 1
- Regular urinalysis and renal function tests to detect kidney involvement
- Monitor for treatment complications, especially infections
Important Considerations
ANCA-Negative Vasculitis
- Requires high clinical suspicion as laboratory confirmation is challenging
- Biopsy is crucial for diagnosis
- Several non-vasculitic diseases may mimic small-vessel vasculitis, including:
- Systemic lupus erythematosus
- Infections
- Malignancies 1
Referral Recommendation
- Patients with suspected or confirmed ANCA-associated vasculitis should be treated at centers with experience in AAV management 1
- This ensures access to appropriate diagnostic testing, treatment options, and management of complications
Prognosis
- Without appropriate immunosuppressive therapy, AAV has poor outcomes
- Even with treatment, mortality remains higher than age/sex-matched population 4
- Main causes of early mortality (first year) are infection (48%) and active vasculitis (19%)
- Later mortality is due to cardiovascular disease (26%), malignancy (22%), and infection (20%) 4
Common Pitfalls
- Delaying treatment in rapidly deteriorating patients while waiting for biopsy results
- Misdiagnosing pseudovasculitis (thrombotic disorders, embolic phenomena) 2
- Underestimating systemic involvement in seemingly limited disease
- Failing to recognize ANCA-negative vasculitis due to overreliance on ANCA testing
Remember that early diagnosis and prompt initiation of appropriate immunosuppressive therapy are critical for improving outcomes in both ANCA-positive and ANCA-negative vasculitis.