What is the clinical approach to diagnosing and treating vasculitis?

Clinical Approach to Diagnosing and Treating Vasculitis

The diagnosis and management of vasculitis requires a structured approach based on vessel size classification, comprehensive laboratory testing, appropriate imaging, and often tissue biopsy for definitive diagnosis, with treatment tailored to the specific type and severity of vasculitis. 1

Diagnostic Approach

Classification and Initial Assessment

• Vasculitis is categorized based on vessel size involvement: large vessel vasculitis (e.g., Giant Cell Arteritis, Takayasu Arteritis), medium vessel vasculitis (e.g., Polyarteritis Nodosa), and small vessel vasculitis (e.g., ANCA-associated vasculitis) 1
• Patients with suspected vasculitis should be managed at centers with experience in vasculitis management to ensure optimal outcomes 2, 3
• Initial laboratory evaluation should include complete blood count, comprehensive metabolic panel, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and urinalysis 4

Laboratory Testing

• ANCA testing using both indirect immunofluorescence and ELISA is essential when small vessel vasculitis is suspected 2, 4
• The 2017 revised international consensus recommends high-quality antigen-specific immunoassays as the preferred screening method for MPO- and PR3-ANCA 2
• Additional laboratory tests should include autoimmune serologies, renal function tests, and evaluation for hepatitis B and C, particularly with liver involvement 4, 5
• Urinalysis is crucial to detect hematuria, proteinuria, and red cell casts that suggest renal involvement 2, 4

Imaging Studies

• Imaging selection should be guided by the suspected vessel size involved and affected organ systems 1
• For large vessel vasculitis (e.g., Takayasu Arteritis), thorough assessment of the arterial tree using MRI/MRA or PET is recommended 2, 1
• For Giant Cell Arteritis, ultrasound of the temporal artery shows 88% sensitivity and 97% specificity 2, 1
• FDG-PET/CT is valuable for diagnosis of large vessel vasculitis, showing inflammatory cell accumulation in vessel walls 1

Tissue Biopsy

• Biopsy of affected tissue remains the gold standard for diagnosis of vasculitis 2, 3
• In ANCA-associated vasculitis, kidney biopsy provides both diagnostic and prognostic information through assessment of glomerular, tubulointerstitial, and vascular histopathology 2
• The diagnostic yield of biopsies demonstrating either granuloma or vasculitis is over 70%, varying according to the organ sampled 2
• In the case of a clinical presentation compatible with small-vessel vasculitis with positive MPO- or PR3-ANCA serology, treatment should not be delayed while waiting for biopsy results, especially in rapidly deteriorating patients 2

Treatment Approach

Disease Categorization and Activity Assessment

• Patients with ANCA-associated vasculitis should be categorized according to disease severity: non-organ threatening, generalized, severe, and refractory disease 3
• Structured clinical assessment tools such as the Birmingham Vasculitis Activity Score (BVAS) should be used at each visit to evaluate disease activity 3
• Disease activity states should be clearly defined as remission, response, refractory disease, or relapse 3

Remission Induction

• For generalized organ or life-threatening ANCA-associated vasculitis, a combination of cyclophosphamide and glucocorticoids is recommended 3
• Rituximab with glucocorticoids is an effective alternative for remission induction, with 64% of patients achieving complete remission at 6 months compared to 53% with cyclophosphamide 6
• For non-organ threatening disease, methotrexate with glucocorticoids is recommended as a less toxic alternative to cyclophosphamide 3

Remission Maintenance

• Remission maintenance therapy should consist of low-dose glucocorticoids combined with either azathioprine, leflunomide, methotrexate, or rituximab 3
• In GPA/MPA patients, rituximab maintenance therapy has shown lower relapse rates compared to azathioprine (5% vs 29% at 28 months) 6

Monitoring and Follow-up

• Regular monitoring should include structured clinical assessment, urinalysis, periodic assessment of inflammatory markers and renal function 3
• Serial ANCA measurements may be useful for monitoring disease activity in ANCA-associated vasculitis 3
• Patients with prior exposure to cyclophosphamide require investigation of persistent unexplained hematuria due to increased risk of bladder cancer 3

Special Considerations

Refractory Disease

• Patients with refractory disease should be referred to expert centers for further management 3
• For refractory vasculitis, plasmapheresis and intravenous immunoglobulin are viable considerations 7
• Biologic therapies such as rituximab have shown benefit in certain settings, particularly ANCA-associated vasculitis 6, 7

Pulmonary-Renal Syndrome

• Acute kidney injury presenting with alveolar hemorrhage (pulmonary-renal syndrome) should raise concern for vasculitis 2
• In this situation, serologic testing is of great diagnostic importance - a positive test for anti-GBM antibodies suggests anti-GBM disease, while positive MPO or PR3-ANCA supports a diagnosis of ANCA-associated vasculitis 2
• Pulmonary hemorrhage affects 10% of patients with ANCA-associated vasculitis and is associated with increased mortality risk 2

ANCA-Negative Vasculitis

• About 10% of patients with clinical features of ANCA-associated vasculitis may be ANCA-negative, requiring tissue biopsy for definitive diagnosis 2, 4
• These patients are generally treated similarly to ANCA-positive patients, although no study has focused specifically on this population 2
• When considering ANCA-negative patients, it's important to rule out non-vasculitic diseases that may mimic small-vessel vasculitis, including systemic lupus erythematosus, infections, and malignancies 2