What is the recommended workup and treatment for a patient with suspected vasculitis?

Workup and Treatment for Suspected Vasculitis

For suspected vasculitis, immediately obtain ANCA testing (MPO-ANCA and PR3-ANCA by ELISA), inflammatory markers (ESR/CRP), complete blood count, comprehensive metabolic panel, and urinalysis with microscopy, then initiate high-dose glucocorticoids (40-60 mg/day prednisone-equivalent for large vessel vasculitis or 1 mg/kg/day for ANCA-associated vasculitis) without waiting for biopsy confirmation if clinical presentation is compatible and disease is rapidly progressive. 1, 2

Initial Diagnostic Workup

Essential Laboratory Tests

• ANCA testing using antigen-specific immunoassays (MPO-ANCA and PR3-ANCA ELISA) is the gold standard for diagnosing ANCA-associated vasculitis, with approximately 90% of small-vessel vasculitis patients testing positive. 2, 3

• Complete blood count with differential detects anemia, leukocytosis, thrombocytosis, or cytopenias indicating active inflammation or bone marrow suppression. 2

• Comprehensive metabolic panel including serum creatinine evaluates renal function, as acute kidney injury is common in vasculitis. 2

• ESR and CRP serve as inflammatory markers, though they are nonspecific and cannot distinguish vasculitis activity from infection—approximately 10% of ANCA-associated vasculitis patients have normal values. 1, 2

• Urinalysis with microscopy at every visit is crucial to detect hematuria (especially dysmorphic red blood cells), proteinuria, and red cell casts suggesting glomerulonephritis. 2, 3

Vessel Size-Specific Imaging

• For suspected large vessel vasculitis (giant cell arteritis/Takayasu arteritis), temporal artery ultrasound shows 88% sensitivity and 97% specificity for diagnosing giant cell arteritis. 1, 2

• MRI/MRA of head, neck, and affected arterial territories identifies extracranial large artery involvement with high accuracy. 2

• For suspected CNS vasculitis, MRI brain is the preferred initial imaging modality with abnormal findings in >90% of cases. 2

Tissue Biopsy Strategy

• Temporal artery biopsy should be performed whenever giant cell arteritis is suspected (at least 1 cm length), but this should not delay treatment—biopsy can be performed up to 1-2 weeks after starting glucocorticoids without affecting results. 1

• Kidney biopsy provides diagnostic confirmation in approximately 91.5% of cases and offers prognostic information through assessment of glomerular, tubulointerstitial, and vascular histopathology. 2, 3

• Biopsy of affected organs (lung, skin, nerve) reveals typical vasculitic lesions when clinical suspicion is high despite negative serology. 3

Disease Severity Classification

Use the European Vasculitis Study (EUVAS) classification to stratify ANCA-associated vasculitis and guide treatment decisions: 2

• Localized disease: Upper/lower respiratory tract disease without systemic involvement or constitutional symptoms 2

• Early systemic disease: Any manifestation without organ-threatening or life-threatening disease 2

• Generalized disease: Renal or other organ-threatening disease with serum creatinine <500 μmol/L (5.6 mg/dL) 2

• Severe disease: Renal or vital organ failure with serum creatinine >500 μmol/L (5.6 mg/dL) 2

• Refractory disease: Progressive disease unresponsive to glucocorticoids and cyclophosphamide 2

Treatment Approach by Vasculitis Type

Large Vessel Vasculitis (Giant Cell Arteritis/Takayasu Arteritis)

• Initiate high-dose glucocorticoids (40-60 mg/day prednisone-equivalent) immediately upon clinical suspicion to prevent complications such as blindness in giant cell arteritis or aortic aneurysm/vascular stenosis. 1, 2

• For giant cell arteritis with visual loss, pulsed intravenous methylprednisolone may benefit patients who present early following onset of visual symptoms. 1

• Add tocilizumab for patients with refractory or relapsing giant cell arteritis, or those at increased risk for glucocorticoid-related adverse events—methotrexate may be used as an alternative. 1, 2

• For Takayasu arteritis, give non-biological glucocorticoid-sparing agents in combination with glucocorticoids to all patients, and use biological agents for refractory or relapsing disease. 1, 2

• Maintain initial high-dose glucocorticoids for one month, then taper gradually (not alternate-day therapy, as this increases relapse risk)—at 3 months, the dose should be 10-15 mg/day. 1

ANCA-Associated Vasculitis (Small Vessel)

• For generalized or severe disease, initiate combination therapy with glucocorticoids (1 mg/kg/day, maximum 60 mg/day) plus either rituximab or cyclophosphamide without waiting for biopsy results if ANCA is positive and clinical presentation is compatible. 2, 4

• Prefer cyclophosphamide when there is severe glomerulonephritis with serum creatinine >4 mg/dL (>354 μmol/L). 2

• Prefer rituximab for younger patients with fertility concerns, relapsing disease, or PR3-ANCA positive disease. 2

• Add plasma exchange for patients requiring dialysis, with rapidly rising creatinine, or with diffuse alveolar hemorrhage causing hypoxemia. 4

• For maintenance of remission, use azathioprine in most patients after successful induction with cyclophosphamide. 1, 5, 6

Critical Management Principles

When to Start Treatment Without Biopsy

• If ANCA testing is positive (MPO or PR3) and clinical picture aligns with ANCA-associated vasculitis, start immunosuppressive therapy immediately without awaiting biopsy results, especially in rapidly deteriorating patients. 2, 3

• In life- or organ-threatening presentations (rapidly progressive glomerulonephritis, pulmonary hemorrhage, severe constitutional symptoms), start high-dose glucocorticoids combined with rituximab or cyclophosphamide immediately. 3, 4

ANCA-Negative Vasculitis

• Approximately 10% of patients with true ANCA-associated vasculitis remain persistently ANCA-negative—these patients require tissue biopsy for definitive diagnosis but receive the same therapeutic regimen as ANCA-positive patients. 2, 3, 4

• In ANCA-negative cases, rigorously exclude infections and malignancies before confirming vasculitis. 3

Monitoring and Prophylaxis

• Urinalysis at every clinic visit screens for infection, renal relapse, or bladder complications from cyclophosphamide. 2

• Monitor inflammatory markers and renal function every 1-3 months to assess disease status. 2

• Complete blood count and liver function tests at similar intervals screen for drug toxicity—an acute fall in white cell count requires dose reduction or discontinuation of immunosuppressives. 2, 4

• Trimethoprim-sulfamethoxazole (800/160 mg on alternate days or 400/80 mg daily) for Pneumocystis jirovecii prophylaxis throughout immunosuppressive therapy. 4

• All patients should receive bone protection therapy in the absence of contraindications. 1

Referral to Specialized Centers

• All patients with suspected vasculitis should be managed at centers with vasculitis expertise because of the rarity of disease, limited availability of specialist imaging and vascular surgery, and difficulty treating these conditions. 1, 2, 3

• Experienced centers provide access to rapid ANCA testing, expert histopathology interpretation, rituximab/plasma-exchange protocols, and intensive-care/hemodialysis capabilities. 4

Common Pitfalls to Avoid

• Do not delay treatment while awaiting biopsy results if the patient shows clinical deterioration or organ-threatening disease. 2, 3

• Do not assume a negative ANA excludes autoimmune disease—ANCA-associated vasculitis is typically ANA-negative, and a negative ANA should shift diagnostic focus toward ANCA-associated vasculitis. 3

• Do not use antiplatelet or anticoagulant therapy routinely for treatment of large vessel vasculitis unless indicated for other reasons. 1

• Recognize that ESR and CRP cannot distinguish between vasculitis disease activity and concomitant infection—clinical correlation is essential. 2

• Remember that approximately 10% of ANCA-associated vasculitis is ANCA-negative—in these patients, tissue biopsy becomes essential for diagnosis. 2, 3