Laboratory Evaluation for Suspected Vasculitis in Leg Pain
For a middle-aged to older adult with leg pain and suspected vasculitis, obtain ANCA testing (both PR3-ANCA and MPO-ANCA by antigen-specific immunoassay), complete blood count, comprehensive metabolic panel with creatinine, ESR, CRP, and urinalysis with microscopy at the initial evaluation. 1
Essential Initial Laboratory Panel
The core laboratory workup should include:
- Complete blood count with differential to identify anemia, leukocytosis, thrombocytosis, or cytopenias indicating active inflammation or bone marrow suppression 1, 2
- Comprehensive metabolic panel including serum creatinine to assess renal function, as acute kidney injury commonly occurs in vasculitis 1
- Urinalysis with microscopy looking specifically for hematuria, proteinuria, dysmorphic red blood cells, and red cell casts that suggest glomerulonephritis 1, 3
- ESR and CRP as inflammatory markers, though these are nonspecific and cannot distinguish vasculitis from infection 1, 2
ANCA Testing: The Diagnostic Cornerstone
High-quality antigen-specific immunoassays (MPO-ANCA and PR3-ANCA ELISA) are the preferred screening methodology for ANCA-associated vasculitis, not indirect immunofluorescence alone 1, 2. Both tests should be performed together for optimal diagnostic accuracy 3.
Key Points About ANCA Testing:
- Approximately 90% of patients with small-vessel vasculitis have ANCA directed against MPO or PR3 3
- About 10% of true ANCA-associated vasculitis patients are persistently ANCA-negative, requiring tissue biopsy for definitive diagnosis 1, 3
- ANCA testing should be performed in the appropriate clinical context—not as a screening test in all patients with leg pain 4
Additional Autoimmune Serologies
- Anti-nuclear antibodies (ANA) should be evaluated to assess for connective tissue diseases that can present with secondary vasculitis 1
- A positive ANA with negative MPO-ANCA and PR3-ANCA does not confirm vasculitis and suggests alternative diagnoses like lupus or Sjögren's syndrome 3
Organ-Specific Testing When Renal Involvement Suspected
If urinalysis shows abnormalities:
- 24-hour urine collection for protein and creatinine clearance 1
- Consider kidney biopsy, which has diagnostic yield over 70% and up to 91.5% in granulomatosis with polyangiitis with renal involvement 1, 3
Critical Clinical Caveats
When to Act Without Waiting for Complete Workup:
If clinical presentation is compatible with ANCA-associated vasculitis and PR3-ANCA or MPO-ANCA is positive, do not delay immunosuppressive therapy while waiting for biopsy results, especially in rapidly deteriorating patients 1, 3. This is particularly crucial when serum creatinine is rapidly rising or exceeds 4 mg/dL (354 μmol/L) 3.
Important Limitations:
- ESR and CRP are nonspecific and cannot distinguish between vasculitis disease activity and concomitant infection 1, 2
- A negative biopsy does not exclude vasculitis due to the focal and patchy nature of vascular inflammation, with diagnostic yield approximately 70% even under optimal conditions 5
- About 10% of ANCA-associated vasculitis patients can have normal inflammatory markers 3
Monitoring Laboratory Tests During Follow-Up
Once vasculitis is diagnosed or treatment initiated:
- Urinalysis at every clinic visit to screen for infection, renal relapse, or bladder complications from cyclophosphamide 1
- Complete blood count and liver function tests every 1-3 months to monitor for drug toxicity, with acute fall in white cell count requiring dose reduction or discontinuation of immunosuppressives 1
- Inflammatory markers and renal function every 1-3 months to monitor disease status 1
- Serum immunoglobulin levels prior to each course of rituximab if used 4
Referral Recommendation
All patients with suspected vasculitis should be managed in close collaboration with, or at, centers of expertise 4, 1. These centers provide access to specialized diagnostic services including rapid biopsy interpretation and advanced imaging, which improves outcomes 1.