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ANCA-Associated Vasculitis (AAV)

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Testing

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of rare, autoimmune, multisystemic disorders characterized by the destruction of smaller blood vessels throughout the body. The immune system produces autoantibodies that attack specific proteins normally found within neutrophils. These proteins include myeloperoxidase (MPO) and proteinase 3 (PR3). These neutrophil-autoantibody complexes then target the blood vessels, resulting in necrosis.1 

The 3 primary diseases in this group include granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA).2 Each disease subtype requires the identification of specific features for diagnosis, involving a variety of tests including laboratory studies, imaging, organ function tests, and tissue biopsies from affected organs.

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Laboratory Testing for AAV

Complete Blood Count With Differential

A complete blood count with differential is useful in detecting eosinophilia, which may indicate EGPA. Patients with EGPA usually exhibit anemia and eosinophilia with at least 10% eosinophils (5000 to 9000 eosinophils/µL). They also frequently display elevated C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR).3 

Around 50% of patients with GPA present with mild normochromic normocytic anemia. ESR and CRP levels are elevated in around 90% of patients with GPA.4 Hypergammaglobulinemia may also occur in patients with EGPA or GPA.3,4 Similarly, patients with MPA typically demonstrate elevated ESR, normocytic anemia, and leukocytosis.5

A comprehensive metabolic panel can identify elevated serum creatinine and blood urea nitrogen (BUN) levels in patients with renal involvement.3,4 Patients with GPA may present with hypoalbuminemia and normal to elevated levels of serum complement.4 Approximately 70% of patients with MPA demonstrate elevated BUN and serum creatinine levels.5 

Clinicians can rule out bacterial endocarditis by performing blood cultures.5 

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Urinalysis 

Urinalysis detects abnormalities in the urine indicative of renal involvement, particularly underlying glomerulonephritis. These abnormal tests may show proteinuria, red blood cell casts, microscopic hematuria, and abnormal sediments.3,4 Urinalysis may also reveal leukocyturia in around 44% of patients with MPA.5

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ANCA Autoantibody Testing

Specific blood tests identify the presence of ANCAs, which cause inflammation, swelling, and necrosis of the blood vessels in AAV. These blood tests differentiate between 2 types of ANCAs: perinuclear ANCAs (pANCAs), which target MPO within neutrophils, and cytoplasmic ANCAs (cANCAs), which target PR3 within neutrophils.6

ANCA blood tests are conducted using 2 methods, indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA) testing. IIF detects ANCAs via staining patterns within neutrophils. cANCA staining occurs throughout the neutrophil’s cytoplasm, while pANCA staining occurs around the nucleus. ELISA testing measures the amount of PR3 or MPO ANCAs present in a blood sample.2

Test results for both MPO and PR3 ANCAs are negative when ≤19 AU/mL, equivocal when between 20 and 25 AU/mL, and positive when ≥26 AU/mL. ANCA immunoglobulin G (IgG) levels below 1:20 are not significant.7 

Around 40% of patients with EGPA demonstrate ANCAs, mainly consisting of pANCA-positive patterns.3 Up to 90% of patients with GPA demonstrate cANCA patterns against the PR3 protein. Rarely, patients with GPA test negative for ANCAs. Patients with MPA more often test positive for pANCA patterns than for cANCA patterns (60% vs 40%, respectively).3,8

Around two-thirds of patients with GPA demonstrate positive rheumatoid factor in a low titer, while 10% to 20% of patients with GPA exhibit antinuclear antibodies (ANAs).4 This may also occur in patients with EGPA.3

Read more about AAV histology

Imaging Studies for AAV

Radiography can be performed to assess pulmonary involvement. Pulmonary opacities occur in 26% to 77% of patients with EGPA, while around one-quarter of patients with EGPA present with normal chest radiographs. When present, opacities are typically bilateral, more peripheral, and patchy in appearance in patients with AAV.9-11

Patients with GPA and pulmonary involvement present with diffuse nodules, 50% of which are cavitated.11 Patients with EGPA and MPA present with pulmonary cavitary lesions less frequently than those with GPA.9,10

Chest radiography may also demonstrate pulmonary infiltrates similar to patients with chronic eosinophilic pneumonia; however, they may also be nodular in appearance.9 In GPA, high-resolution computed tomography (CT) scans may reveal diffuse or patchy ground-glass opacities, consolidations, or both.11

Intra-alveolar hemorrhage due to pulmonary alveolar capillaritis, hilar nodal enlargement, pleural effusions, atelectasis, and obstructive pneumonia secondary to bronchial stenosis may also present on imaging studies.9-11

CT scans of the chest and abdomen can detect pancreatitis, bronchial dilatation, bronchial wall thickening, peripheral regions of parenchymal consolidation, and pulmonary arterial enlargement in patients with EGPA.9

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Organ-Specific Testing

Electrocardiography (ECG) is performed to check for possible myocardial infarction, pericarditis, or heart failure. Gastrointestinal endoscopy reveals gastrointestinal bleeding. Electromyography (EMG) and other nerve conduction tests are warranted in cases of suspected peripheral neuropathy.12,13

Pulmonary tests to determine the extent of lung involvement may include spirometry, pulmonary function testing for forced expiratory volume in 1 second and forced vital capacity, and bronchoscopy to assess for hemorrhaging, infection, disease, and endobronchial lesions. Single-breath diffusing capacity may be increased in patients with GPA with alveolar hemorrhage.14

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Biopsy

Although vasculitis is often not observed, renal biopsy may detect segmental crescentic necrotizing glomerulonephritis with little to no immunoglobulin or complement accumulation. Renal biopsies do not differentiate between GPA and MPA.15,16 Renal biopsies in patients with GPA often do not show granulomas.15

Open or thoracoscopic lung biopsy may show granulomatous inflammation and vasculitis in patients with GPA and MPA.15,16 Lung biopsies must be considered with caution in individuals with known alveolar hemorrhage.15

Upper respiratory tract biopsies from the nose, sinuses, and subglottal region often do not aid in diagnosis but can reveal granulomatosis, vasculitis, and necrosis in around 15% of patients with GPA.15

If EMG studies indicate peripheral nerve involvement, sural or peripheral nerve biopsies may help diagnose conditions such as mononeuritis multiplex.15,16

Muscle biopsy can detect either necrotizing or non-necrotizing systemic vasculitis, despite the absence of elevated serum creatine phosphokinase (CPK) levels or myalgia.15,16 Muscle biopsy may be a relatively safe and effective method to assess and diagnose small or medium blood vessel vasculitis.15,17

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References

  1. Xiao H, Hu P, Falk RJ, Jennette JC. Overview of the pathogenesis of ANCA-associated vasculitis. Kidney Dis (Basel). 2016;1(4):205-215. doi:10.1159/000442323
  2. What is ANCA? Vasculitis UK. Accessed March 3, 2023.
  3. Lowe ST. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) workup: laboratory studies. Medscape. Updated August 6, 2022. Accessed March 3, 2023.
  4. Tracy CL. Granulomatosis with polyangiitis (GPA, formerly Wegener granulomatosis) workup: approach considerations. Medscape. Updated August 31, 2021. Accessed March 3, 2023.
  5. Farid-Moayer M. Microscopic polyangiitis workup: laboratory studies. Medscape. Updated September 24, 2021. Accessed March 3, 2023.
  6. Antineutrophil cytoplasmic antibodies (ANCA) test. MedlinePlus. Updated March 2, 2021. Accessed March 3, 2023.
  7. Bronfenbrener R. Antineutrophil cytoplasmic autoantibody, cytoplasmic (c-ANCA). Medscape. Updated November 27, 2019. Accessed March 3, 2023.
  8. Tracy CL. Granulomatosis with polyangiitis (GPA, formerly Wegener granulomatosis) workup: ANCA detection. Medscape. Updated August 31, 2021. Accessed March 3, 2023.
  9. Lowe ST. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) workup: imaging studies. Medscape. Updated August 6, 2022. Accessed March 3, 2023.
  10. Farid-Moayer M. Microscopic polyangiitis workup: imaging studies. Medscape. Updated September 24, 2021. Accessed March 3, 2023.
  11. Tracy CL. Granulomatosis with polyangiitis (GPA, formerly Wegener granulomatosis) workup: radiography and CT scanning. Medscape. Updated August 31, 2021. Accessed March 3, 2023.
  12. Lowe ST. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) workup: other tests. Medscape. Updated August 6, 2022. Accessed March 3, 2023.
  13. Farid-Moayer M. Microscopic polyangiitis workup: other tests. Medscape. Updated September 24, 2021. Accessed March 3, 2023.
  14. Tracy CL. Granulomatosis with polyangiitis (GPA, formerly Wegener granulomatosis) workup: pulmonary testing. Medscape. Updated August 31, 2021. Accessed March 3, 2023.
  15. Tracy CL. Granulomatosis with polyangiitis (GPA, formerly Wegener granulomatosis) workup: biopsy. Medscape. Updated August 31, 2021. Accessed March 3, 2023.
  16. Farid-Moayer M. Microscopic polyangiitis workup: procedures. Medscape. Updated September 24, 2021. Accessed March 3, 2023.
  17. Nunokawa T, Yokogawa N, Shimada K, Enatsu K, Sugii S. The use of muscle biopsy in the diagnosis of systemic vasculitis affecting small to medium-sized vessels: a prospective evaluation in Japan. Scand J Rheumatol. 2016;45(3):210-214. doi:10.3109/03009742.2015.1086431

Reviewed by Kyle Habet, MD, on 3/21/2023.

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