What is the appropriate workup for a vasculitis (inflammation of blood vessels) autoimmune profile?

From the Guidelines

A vasculitis autoimmune profile workup should include both general inflammatory markers and specific autoantibody tests, starting with complete blood count, comprehensive metabolic panel, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), followed by specific autoantibody testing including antineutrophil cytoplasmic antibodies (ANCA) with both immunofluorescence patterns (c-ANCA and p-ANCA) and specific antigen testing for proteinase-3 (PR3) and myeloperoxidase (MPO) as recommended by the most recent guidelines 1.

Initial Assessment

The initial assessment of a patient suspected of having vasculitis should include a thorough clinical evaluation, laboratory tests, and imaging studies to determine the extent and severity of the disease.

• Complete blood count (CBC) to assess for anemia, leukocytosis, or thrombocytosis
• Comprehensive metabolic panel (CMP) to evaluate renal and liver function
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to assess overall inflammation
• Urinalysis with microscopy to detect renal involvement

Autoantibody Testing

Specific autoantibody testing is crucial in diagnosing and differentiating between various types of vasculitis.

• Antineutrophil cytoplasmic antibodies (ANCA) with both immunofluorescence patterns (c-ANCA and p-ANCA) and specific antigen testing for proteinase-3 (PR3) and myeloperoxidase (MPO) 1
• Antinuclear antibodies (ANA), rheumatoid factor (RF), anti-double stranded DNA, complement levels (C3, C4), cryoglobulins, and anti-glomerular basement membrane antibodies

Additional Tests

Depending on the clinical presentation, additional tests may be necessary to rule out other conditions or to assess the extent of organ involvement.

• Testing for hepatitis B and C, as they can trigger vasculitis
• Anti-phospholipid antibodies, serum immunoglobulins, and HLA-B51 for Behçet's disease
• Imaging studies such as chest X-ray, CT scan, or MRI to assess organ involvement

Diagnosis and Treatment

The diagnosis of vasculitis is based on a combination of clinical findings, laboratory tests, and imaging studies.

• The 2024 EULAR recommendations for the management of ANCA-associated vasculitis suggest that a positive biopsy is strongly supportive of a diagnosis of vasculitis and recommend biopsies to assist in establishing a new diagnosis and for further evaluation for patients suspected of having relapsing vasculitis 1
• Treatment decisions should be guided by the severity and extent of the disease, as well as the presence of organ-threatening or life-threatening manifestations.
• The use of cyclophosphamide is strongly associated with the risk of bladder cancer, and patients should be monitored closely for this complication 1.

Management

The management of vasculitis requires a multidisciplinary approach, with close collaboration between rheumatologists, nephrologists, and other specialists.

• Patients with vasculitis should be managed in close collaboration with, or at, centers of expertise 1
• Structured clinical assessment, rather than ANCA testing alone, should inform decisions on changes in treatment for AAV 1

From the Research

Laboratory Tests for Vasculitis

• Routine laboratory tests for vasculitis include erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), blood count, serum creatinine, urinalysis, specific autoantibodies, complement, immunoglobulin, cryoglobulin, and Hepatitis B and C serology 2
• Autoantibodies such as anti-neutrophil cytoplasmic antibodies (ANCAs), anti-glomerular basement membrane (GBM) antibodies, and anti-C1q antibodies are helpful for diagnosis 2, 3
• ANCA subtypes (proteinase-3-ANCA and myeloperoxidase-ANCA) are associated with different epidemiological, genetic, and clinical features 2, 3

Diagnostic Approach

• Diagnosis is based on clinical manifestation, ANCA-testing, and histology 4
• A tissue biopsy can provide a definite diagnosis, especially when there is access to clinically affected tissue 5
• Angiographic studies may confirm the diagnosis, particularly if there is laboratory and clinical evidence of specific organ involvement 5
• Serial measurements of acute phase reactants, complete blood cell count with differential, biochemistry profiles, urinalysis, and C3 and C4 levels should be obtained in all patients 5

Autoantibody Testing

• ANCA-directed proteinase 3 (PR3-) or myeloperoxidase (MPO-) are sensitive and specific serologic markers for ANCA-associated vasculitides (AAV) 3
• Anti-GBM antibodies are highly specific for the patients with anti-GBM antibody disease (formerly Goodpasture's syndrome) 3
• Autoantibodies to C1q are characteristic of hypocomplementemic urticarial vasculitis syndrome (HUVS; anti-C1q vasculitis) 3

Clinical Utility

• The presence of PR3- and MPO-ANCA have led to the differentiation of distinct disease phenotype of AAV: PR3-ANCA-associated vasculitis (PR3-AAV), MPO-ANCA-associated vasculitis (MPO-AAV), and ANCA-negative vasculitis 3
• Clinical examination of other systems and organs involved in the pathological process, including the skin and kidneys, as well as the detection of autoantibodies can improve approaches to early diagnosis and treatment of vasculitis 6