Diagnostic evaluation of the patient with suspected GPA, MPA, or renal-limited AAV

GPA: granulomatosis with polyangiitis; MPA: microscopic polyangiitis; AAV: antineutrophil cytoplasmic autoantibody-associated vasculitis; ANCA: antineutrophil cytoplasmic autoantibody; CBC: complete blood count; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; GBM: glomerular basement membrane; HBV: hepatitis B virus; HCV: hepatitis C virus; CT: computed tomography.
* The diagnosis of GPA or MPA should be suspected in any patient who presents with constitutional symptoms along with clinical evidence of glomerulonephritis, upper or lower respiratory tract involvement, or multiple mononeuropathy (refer to inset). Some patients may present with manifestations limited to a single organ, such as the kidneys or the upper respiratory tract, and then may later evolve to include other organ involvement. In a subset of patients, the disease will be limited to a single organ (eg, renal-limited vasculitis).
¶ In clinical practice, ANCA can be detected using an indirect immunofluorescence (IIF) assay or antigen-specific enzyme-linked immunosorbent assays (ELISAs) for proteinase 3 (PR3) and myeloperoxidase (MPO). These 2 techniques work well as a combined testing system. The IIF assay is more sensitive but more subject to misinterpretation. ELISA testing is more specific and is considered an essential component of testing for ANCA.
Δ Positive testing for anti-GBM antibody does not exclude the diagnosis of GPA or MPA. Some patients may have double-positive anti-GBM and ANCA-associated disease. Refer to UpToDate content on double-positive anti-GBM and ANCA-associated disease for additional information.
◊ Some clinicians obtain a chest radiograph in all patients and then obtain a chest CT if the results are abnormal. Selective use of CT scanning of the head and/or neck may be appropriate in patients with suspected involvement of sinuses, orbits, mastoids, or subglottic region.
§ Histologic examination of tissue obtained by biopsy of an affected organ (generally, kidney, skin, or lung) remains the most definitive method to establish a diagnosis of GPA or MPA. Some clinicians undertake treatment without tissue biopsy in selected cases in which the clinical presentation is highly consistent with pauci-immune vasculitis (eg, a systemic illness consistent with GPA or MPA with an active urinary sediment, a rising serum creatinine, and a strongly positive anti-PR3 or anti-MPO antibody). Unless the clinical setting indicates an extremely high probability of vasculitis, then all reasonable attempts to confirm clinical suspicion of GPA/MPA/renal-limited AAV with histopathologic evidence should be undertaken before committing patients to long-term treatment with potentially toxic medications. If a tissue biopsy cannot be performed, therapy should not be delayed, but a biopsy should be obtained as soon as possible after initiation of therapy. Refer to UpToDate content on the choice of biopsy site in patients suspected of having GPA, MPA, or renal-limited AAV.
¥ Positive testing for ANCA may occur in the absence of ANCA-associated vasculitis. Some examples include patients with a concurrent positive antinuclear antibody test, patients with bacteremia, and patients exposed to certain medications (eg, hydralazine). In patients with positive ELISA testing for anti-MPO in the setting of a positive test for antinuclear antibody, testing for anti-double-stranded DNA (anti-dsDNA) may be helpful in distinguishing between ANCA-associated vasculitis versus an alternative diagnosis (eg, systemic lupus erythematosus). A negative test for ANCA does not exclude the diagnosis of GPA or MPA. In addition, some patients with renal-limited disease may have ANCA-negative pauci-immune crescentic glomerulonephritis.
‡ If clinical suspicion for GPA, MPA, or renal-limited AAV is still high, a diagnosis is sometimes made on the basis of clinical features and laboratory testing alone.