What is the recommended approach for a vasculitis workup and treatment?

Vasculitis Workup and Treatment

For suspected vasculitis, immediately obtain ANCA testing (both indirect immunofluorescence and ELISA), inflammatory markers (ESR/CRP), comprehensive metabolic panel with creatinine, urinalysis with microscopy, and pursue tissue biopsy of the affected organ to confirm diagnosis before initiating high-dose glucocorticoids combined with either cyclophosphamide or rituximab for organ-threatening disease. 1

Initial Diagnostic Workup

Essential Laboratory Testing

• ANCA testing is mandatory when small or medium vessel vasculitis is suspected, using both indirect immunofluorescence and antigen-specific ELISA for proteinase-3 (PR3) and myeloperoxidase (MPO) antibodies 1, 2
• Measure inflammatory markers including ESR and CRP, which are highly sensitive for giant cell arteritis and other forms of vasculitis 1
• Obtain complete blood count, comprehensive metabolic panel with serum creatinine, and liver function tests 3
• Perform urinalysis with microscopic examination and quantify proteinuria to detect glomerulonephritis 3
• Check serum immunoglobulin levels (IgA, IgG, IgM), complement levels, cryoglobulins, and hepatitis B/C serology 1, 2

Tissue Biopsy

• Biopsy of affected tissue is strongly recommended and remains the gold standard for diagnosis 1
• For suspected giant cell arteritis, perform temporal artery biopsy with at least 1 cm length to examine multiple sections, but do not delay treatment while awaiting biopsy 1
• The biopsy should be performed within 1-2 weeks of starting glucocorticoids, as treatment prior to biopsy is unlikely to affect results 1
• For cutaneous vasculitis, obtain biopsy extending to the subcutis from the most tender, erythematous or purpuric lesion, with consideration for direct immunofluorescence 4

Imaging Studies

• For suspected Takayasu arteritis or large vessel vasculitis, perform thorough imaging assessment of the arterial tree using magnetic resonance angiography, positron emission tomography, or conventional angiography 1
• Ultrasonography of the temporal artery demonstrates 88% sensitivity and 97% specificity for giant cell arteritis, showing vessel wall edema 1

Disease Activity Assessment

• Use structured clinical assessment tools including the Birmingham Vasculitis Activity Score (BVAS) and Disease Extent Index at each visit 3, 5
• Clinical assessment rather than serial ANCA testing should guide treatment decisions, as ANCA levels do not reliably correlate with disease activity 1

Disease Categorization

ANCA-Associated Vasculitis Severity Classification

Categorize patients by disease severity to guide treatment intensity 1:

• Non-organ threatening: Constitutional symptoms without organ dysfunction
• Generalized: Renal or other organ involvement without immediate life threat (creatinine <500 μmol/L or 5.7 mg/dL)
• Severe/life-threatening: Renal failure with creatinine ≥500 μmol/L (5.7 mg/dL), pulmonary hemorrhage, or other immediately life-threatening manifestations
• Refractory: Progressive disease despite optimal therapy

Treatment Approach

Organ-Threatening or Life-Threatening ANCA-Associated Vasculitis

For remission induction, use glucocorticoids (1 mg/kg/day oral prednisone, maximum 80 mg/day) combined with EITHER cyclophosphamide (2 mg/kg/day oral or IV pulse) OR rituximab (375 mg/m² weekly for 4 weeks). 1, 6, 7

• Administer 1,000 mg IV methylprednisolone daily for 1-3 days before initial treatment in severe cases 7
• Rituximab and cyclophosphamide demonstrate equivalent efficacy, with 64% vs 53% complete remission rates at 6 months respectively 7
• Consider plasma exchange for patients with serum creatinine ≥500 μmol/L (5.7 mg/dL) due to rapidly progressive glomerulonephritis (Level 1B evidence, Grade B recommendation) 1
• Plasma exchange can also be considered for severe diffuse alveolar hemorrhage 1

Non-Organ Threatening ANCA-Associated Vasculitis

• Use glucocorticoids combined with methotrexate (oral or parenteral) as a less toxic alternative to cyclophosphamide (Level 1B evidence, Grade B recommendation) 1
• Mycophenolate mofetil with glucocorticoids is an alternative option (Level 1B evidence, Grade C recommendation) 1

Giant Cell Arteritis and Large Vessel Vasculitis

• Initiate high-dose glucocorticoids immediately upon strong clinical suspicion, prior to biopsy, due to risk of irreversible ocular involvement 1
• Normal ESR or CRP should raise suspicion for an alternative diagnosis in suspected giant cell arteritis 1

Remission Maintenance Therapy

After achieving remission, continue low-dose glucocorticoids combined with azathioprine (first-line), rituximab, methotrexate, or mycophenolate mofetil for at least 24 months. 1, 6

• Azathioprine has Level 1B evidence with Grade A recommendation for GPA/MPA maintenance 1
• Leflunomide and methotrexate are alternatives with Level 1B-2B evidence 1

Refractory Disease

• For patients failing initial therapy, switch from cyclophosphamide to rituximab or vice versa 1
• Refer refractory patients to expert centers for further evaluation and potential enrollment in clinical trials 1

Mandatory Supportive Measures

• Provide Pneumocystis jirovecii prophylaxis with trimethoprim-sulfamethoxazole for all patients receiving immunosuppression 6
• Administer mesna with cyclophosphamide to prevent hemorrhagic cystitis 6
• Pre-medicate with antihistamine and acetaminophen prior to rituximab infusions 7

Monitoring During Treatment

Regular Laboratory Monitoring

• Complete blood count, renal function, and liver function tests at each visit 3, 6
• Monitor blood glucose while on glucocorticoid therapy 3
• Urinalysis at each visit to detect early relapse or cyclophosphamide-related bladder toxicity 3
• Test serum immunoglobulin levels prior to each rituximab course and in patients with recurrent infections, as hypogammaglobulinemia occurs in 27-58% of patients 1, 7

Long-Term Surveillance

• Investigate persistent unexplained hematuria in patients with prior cyclophosphamide exposure due to bladder cancer risk (Level 2B evidence, Grade C recommendation) 1
• Perform periodic cardiovascular risk assessment (Level 2B evidence, Grade B recommendation) 1
• Monitor for long-term complications including cardiovascular disease, malignancy, cerebrovascular events, and metabolic abnormalities 1, 6

Critical Management Principles

• All vasculitis patients should be managed in close collaboration with or at centers of expertise due to disease complexity and need for specialized imaging and treatment 1
• Infusion-related reactions with rituximab occur most commonly with the first infusion (9-32% in pediatric patients, 12% in adults) and decrease with subsequent doses 7
• Infection rates are high (47-62%) during induction therapy, with serious infections occurring in approximately 10-11% of patients 7