A rapid diagnosis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is critical because life-threatening injury to organs often develops quickly.1
Additionally, as ANCA-associated vasculitis is mitigated dramatically by immunosuppressive therapy such as cyclophosphamide, corticosteroids, and methotrexate it is vital to start these treatments as early as possible. Laboratory and imaging studies are essential in helping to confirm a clinical diagnosis but are of limited value in the absence of clinical signs when considering a diagnosis of systemic vasculitis.1
Symptoms that should prompt consideration of a diagnosis of vasculitis are: unexplained systemic disturbance, arthritis or arthralgia, polymyalgia, episcleritis (inflammation of the episclera in the eye), neuropathy, microscopic hematuria (blood in urine), pulmonary infiltrates or nodules, and late-onset asthma.1 Due to this wide array of symptoms patients will often be identified and managed by an interdisciplinary team. This team may include:
Investigations are aimed at confirming the diagnosis, excluding secondary causes of vasculitis, assessing organ involvement and disease severity1
The ANCA-associated vasculitides are a group of uncommon diseases, with a prevalence of 255 per million, characterised by inflammatory cell infiltration and necrosis of blood vessel walls2
ANCA-associated vasculitides often involve small and sometimes medium-sized arteries, and are associated with a high risk of glomerulonephritis2
ANCA-associated vasculitis includes three conditions: granulomatosis with polyangiitis (formally known as Wegener's granulomatosis), which affects the nose, lungs, and kidneys; microscopic polyangiitis, which primarily affects the kidneys; and eosinophilic granulomatosis with polyangiitis (formally known Churg-Strauss syndrome), which affects the lungs, kidneys, heart and skin2
What are the benefits of early diagnosis?
Clinical and laboratory assessments are very important to provide a full picture of the disease and assist in identifying the specific type of vasculitis. Using PR3-ANCA and MPO-ANCA can help:3
Identify patients that are at risk of life-threatening ANCA-associated vasculitis and other renal diseases
Differentiate between PR3-ANCA-associated vasculitis and MPO-ANCA-associated vasculitis, enabling the tailoring of care
Provide patients with appropriate targeted treatment earlier in their journey, potentially improving their quality of life and halting disease progression
How can tests be used to personalise care?
PR3-ANCA and MPO-ANCA are diagnostic tests with high specificity for ANCA-associated vasculitis and should be used to help identify patients with ANCA-associated vasculitis.* However, it is important to recognise that a negative ANCA does not exclude vasculitis and a positive ANCA does not necessarily prove vasculitis.1
The presence of PR3-ANCA is strongly suggestive of a diagnosis of granulomatosis with polyangiitis. Studies have shown that:3
Irrespective of the specific diagnosis, extra-renal organ manifestations and respiratory tract granulomas are more frequent in patients with PR3-ANCA-associated vasculitis than in patients with MPO-ANCA-associated vasculitis
Patients with necrotising crescentic glomerulonephritis and PR3-ANCA-associated vasculitis have more dramatic deterioration of renal function and relapse more frequently than patients who have MPO-ANCA-associated vasculitis
The presence of MPO-ANCA is most frequently associated with microscopic polyangiitis, but is also associated with eosinophilic granulomatosis with polyangiitis.1 Studies have shown that:
Renal survival is significantly worse in patients with MPO-ANCA-associated vasculitis, suggesting that MPO-ANCA-associated vasculitis associated glomerulonephritis is less responsive to treatment3
*Note that up to 30% of cases with eosinophilic granulomatosis with polyangiitis or localised granulomatosis with polyangiitis may be ANCA negative and other investigations (C-reactive protein and erythrocyte sedimentation rate, which are typically elevated in the acute phases of most vasculitides; urinalysis, which should be performed as soon as a diagnosis of vasculitis is suspected because renal involvement can progress silently; full blood count for eosinophilia; tests of critical organ function; connective tissue disease tests to exclude systemic lupus erythematosus; tests for rheumatoid arthritis; complement levels, which may be raised as part of an acute phase response but lowered in immune complex mediated essential mixed cryoglobulinemia, bacterial infections, and systemic lupus erythematosus; cardiolipin antibodies and lupus anticoagulant for anti-phospholipid syndrome; and cryoglobulins) should be used to aid in your diagnosis.1
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