What is ANCA-associated vasculitis?

ANCA-associated vasculitis (AAV) is a group of autoimmune conditions in which antibodies (ANCAs — anti-neutrophil cytoplasmic antibodies) attack and activate neutrophils, causing them to damage small and medium blood vessels. This produces inflammation and necrosis of vessel walls — leading to organ damage wherever the affected vessels are located. The three main forms: GPA (granulomatosis with polyangiitis — formerly Wegener's): upper airway, lungs and kidneys. MPA (microscopic polyangiitis): predominantly kidneys and lungs. EGPA (eosinophilic GPA — formerly Churg-Strauss): asthma + eosinophilia + vasculitis of peripheral nerves, heart and skin.

What are the symptoms of GPA?

GPA (Wegener's granulomatosis) classically involves: Upper airway: persistent nasal congestion, nosebleeds, crusting, nasal septal perforation → saddle-nose deformity (cartilage destruction); sinusitis; otitis media; subglottic tracheal stenosis (a devastating late complication causing stridor and respiratory failure). Lower respiratory tract: pulmonary infiltrates; cavitating nodules; pulmonary haemorrhage (haemoptysis — life-threatening). Kidneys: rapidly progressive glomerulonephritis (AKI with haematuria, proteinuria, red cell casts) — the main cause of permanent organ damage. Eyes: orbital pseudotumour (painful proptosis); scleritis; uveitis. Systemic: fever, weight loss, fatigue, arthralgia.

How is ANCA vasculitis treated?

Two phases: Induction of remission (first 3-6 months): the goal is rapid suppression of active vasculitis. Standard: rituximab 375mg/m² IV weekly × 4 (preferred) OR cyclophosphamide IV monthly × 6-9 — combined with high-dose corticosteroids (prednisolone 1mg/kg/day tapering). Avacopan (Tavneos) is added as a steroid-sparing agent in severe disease. Maintenance of remission (ongoing): rituximab 500mg IV every 6 months (MAINRITSAN 2 — superior to azathioprine). Alternatively: azathioprine or mycophenolate. Monitor for relapse: ANCA titres + clinical symptoms + urinalysis + CRP. Relapse rate: approximately 50% at 5 years — vigilance is essential.

What is EGPA and how does it differ from GPA?

Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome) is the third ANCA vasculitis — distinguished by: asthma (often severe, preceding vasculitis by years); peripheral blood eosinophilia (>10% or >1.5×10⁹/L); ANCA-negative in approximately 60% (unlike GPA where >90% are c-ANCA positive). Unique organ involvement: cardiac (EGPA-specific — eosinophilic myocarditis/pericarditis is the main cause of death; requires cardiac MRI screening); mononeuritis multiplex (peripheral nerve infarction — foot drop, wrist drop); skin (purpura); relatively less renal involvement than GPA. The asthma that precedes EGPA may be severe and steroid-dependent before vasculitis develops.

Can ANCA vasculitis be cured?

ANCA vasculitis is not yet curable — it is a chronic relapsing-remitting condition for most patients. Modern therapy achieves initial remission in approximately 70-80% of patients. However: approximately 50% relapse within 5 years (PR3-positive GPA has higher relapse rate than MPO-positive MPA); each relapse requires re-induction with further immunosuppression and cumulative treatment toxicity; permanent organ damage accumulates with disease activity and treatment (renal impairment, hearing loss, subglottic stenosis, chronic sinusitis, medication side effects). Rituximab maintenance (every 6 months for 5 years) has reduced relapse rates significantly — the most important advance in maintenance therapy.

How does GMJ News cover ANCA vasculitis?

GMJ News covers GPA/MPA/EGPA clinical features, c-ANCA/p-ANCA testing, pulmonary-renal syndrome emergency, RAVE trial (rituximab equals cyclophosphamide), avacopan 2021 approval, PEXIVAS plasma exchange trial, EGPA cardiac involvement, benralizumab 2024 for EGPA, MAINRITSAN maintenance rituximab, and relapse monitoring. ANCA vasculitis — the most common serious vasculitis — is directly relevant to PHIG's rare disease programme and nephrology/rheumatology clinical priorities.

Home › Topics › ANCA-Associated Vasculitis

ANCA-Associated Vasculitis

GMJ News knowledge hub · last reviewed September 2026 · Georgian Medical Journal

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ANCA-associated vasculitis (AAV) — encompassing granulomatosis with polyangiitis (GPA, formerly Wegener’s), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss) — is the most common form of primary systemic vasculitis affecting small and medium vessels, causing the devastating combination of rapidly progressive glomerulonephritis and diffuse alveolar haemorrhage (pulmonary-renal syndrome) that, untreated, carried approximately 90% 2-year mortality in GPA before the introduction of cyclophosphamide (ECDC/WHO). The 2010 RAVE trial (NEJM) established rituximab as non-inferior to cyclophosphamide for remission induction — sparing patients from cyclophosphamide’s severe toxicity — while avacopan (Tavneos), a C5a receptor inhibitor FDA-approved in 2021, has added a steroid-sparing strategy that reduces the cumulative glucocorticoid burden responsible for much of the long-term morbidity.

Key messages

Untreated GPA: ~90% 2-year mortality — now highly treatable

Before cyclophosphamide, generalised granulomatosis with polyangiitis (GPA) carried approximately 90% 2-year mortality. Cyclophosphamide + corticosteroids transformed survival. Rituximab (2010 RAVE trial) is now the preferred induction agent — equally effective with less toxicity. Avacopan (2021) reduces the corticosteroid burden.

c-ANCA/anti-PR3 vs p-ANCA/anti-MPO — the diagnostic test

ANCA testing: c-ANCA (cytoplasmic pattern) + anti-PR3 antibodies: predominantly GPA (~90% of generalised GPA); p-ANCA (perinuclear pattern) + anti-MPO antibodies: predominantly MPA (~60-70%) and EGPA (~40%). Important: in EGPA, approximately 60% are ANCA-negative — diagnosis is clinical. ANCA testing should always include both IF pattern AND specific antigen (anti-PR3 and anti-MPO) by ELISA — IF pattern alone is insufficient.

RAVE trial 2010 — rituximab equals cyclophosphamide

The RAVE trial (NEJM 2010): rituximab vs cyclophosphamide for induction in GPA and MPA — rituximab was non-inferior for remission induction (64% vs 53% complete remission) and superior for PR3-positive relapsing disease. Rituximab avoids cyclophosphamide's severe toxicities (haemorrhagic cystitis, infertility, bladder cancer, secondary malignancy, severe infections).

Pulmonary-renal syndrome — the most life-threatening presentation

Combination of rapidly progressive glomerulonephritis (RPGN — acute kidney injury with red cell casts in urine) and diffuse alveolar haemorrhage (DAH — haemoptysis, bilateral infiltrates, falling haemoglobin) is called pulmonary-renal syndrome. ANCA vasculitis (GPA or MPA) is the most common cause. This is a medical emergency requiring immediate treatment (rituximab or cyclophosphamide + high-dose corticosteroids ± plasma exchange).

Avacopan — steroid-sparing C5a receptor inhibitor (FDA 2021)

Avacopan (Tavneos, InflaRx) — a selective C5aR1 inhibitor blocking C5a-induced neutrophil activation — was FDA-approved October 2021 for ANCA vasculitis (GPA/MPA). ADVOCATE trial (NEJM 2021): avacopan non-inferior to prednisolone taper for remission induction but superior at 52 weeks (65.7% vs 54.9% sustained remission) — with dramatically less corticosteroid exposure. This reduces the profound morbidity from prolonged high-dose steroids.

EGPA — asthma + eosinophilia + vasculitis

Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss) is the vasculitis associated with asthma and eosinophilia (>10% eosinophils or >1.5×10⁹/L). The three phases: prodromal (asthma, rhinitis — years before vasculitis); eosinophilic (peripheral eosinophilia, eosinophilic organ infiltration); vasculitic (mononeuritis multiplex, cardiac involvement, glomerulonephritis). Cardiac involvement (myocarditis, pericarditis) is the major cause of mortality. Benralizumab (anti-IL-5Rα, already approved for severe asthma) was approved for EGPA in 2024 by FDA — a steroid-sparing agent.

Key statistics

~90%

2-year mortality in untreated GPA (pre-cyclophosphamide era)

NEJM/ESC

RAVE 2010

rituximab non-inferior to cyclophosphamide for GPA/MPA induction (NEJM)

NEJM 2010

Oct 2021

avacopan (Tavneos) FDA approval for AAV — steroid-sparing C5a blocker

FDA 2021

c-ANCA/PR3

predominantly GPA; p-ANCA/MPO predominantly MPA (both by IF + ELISA)

EULAR

~50%

relapse rate at 5 years with standard therapy — monitoring essential

ESC/EULAR

2024

year benralizumab FDA-approved for EGPA (Churg-Strauss) — steroid-sparing

FDA 2024

ANCA vasculitis — organ involvement by type (GPA, MPA, EGPA)

Source: EULAR. GPA: upper+lower respiratory+renal. MPA: predominantly renal. EGPA: lungs+heart+peripheral nerves.

Glossary of key terms

ANCA (anti-neutrophil cytoplasmic antibodies)
ImmunologyAutoantibodies targeting proteins in the cytoplasm of neutrophils. Two patterns on indirect immunofluorescence (IIF): c-ANCA (cytoplasmic, granular) — predominantly anti-PR3 (proteinase 3) — associated with GPA; p-ANCA (perinuclear) — predominantly anti-MPO (myeloperoxidase) — associated with MPA and EGPA. Pathogenic role: ANCA activate primed neutrophils → neutrophil respiratory burst + degranulation → endothelial damage → pauci-immune glomerulonephritis (few or no immune deposits on biopsy — distinguishing from immune complex GN). ANCA testing: always perform BOTH IIF AND specific ELISA (anti-PR3 and anti-MPO).

Rapidly progressive glomerulonephritis (RPGN)
NephrologyAcute kidney injury developing over days to weeks with a nephritic urine sediment (red cell casts, dysmorphic red cells — indicating glomerular inflammation). On renal biopsy: crescentic glomerulonephritis (cellular crescents — macrophages and parietal epithelial cells filling Bowman's space). Three pathological types: (1) Pauci-immune (no or minimal deposits) — ANCA vasculitis (GPA, MPA) — most common. (2) Anti-GBM (linear IgG deposits along GBM) — Goodpasture's disease. (3) Immune complex (granular IgG/C3 deposits) — lupus nephritis, post-streptococcal GN, IgA nephropathy. ANCA vasculitis RPGN: immediate rituximab or cyclophosphamide + high-dose corticosteroids; plasma exchange for anti-GBM co-positive or severe AKI.

Rituximab for AAV
FDA 2011/EULARA chimeric anti-CD20 monoclonal antibody depleting B lymphocytes (which include ANCA-producing plasma cell precursors). For AAV: 375mg/m² IV weekly × 4 doses (RAVE dosing) OR 1g IV × 2 doses 2 weeks apart (RITUXVAS dosing) for remission induction. For maintenance: 500mg IV every 6 months (MAINRITSAN 2 study — rituximab superior to azathioprine for maintenance). Rituximab is preferred over cyclophosphamide for: PR3-positive disease; reproductive-age patients (cyclophosphamide causes premature ovarian failure and azoospermia); relapsing disease.

Mononeuritis multiplex
Neurology/EGPASimultaneous or sequential involvement of multiple non-contiguous peripheral nerve trunks — the classic neurological manifestation of EGPA (and other systemic vasculitides). Occurs because vasculitis affects the vasa nervorum (blood supply of peripheral nerves) → ischaemic nerve infarction. Presents as: acute foot drop (peroneal nerve); wrist drop (radial nerve); painful weakness and numbness in a nerve trunk distribution. Multifocal, asymmetric, predominantly motor, rapidly progressive. EGPA mononeuritis multiplex: treat with high-dose corticosteroids + rituximab or cyclophosphamide depending on severity.

Granuloma formation in GPA
HistopathologyGPA is distinguished from MPA by the presence of necrotising granulomas (organised collections of activated macrophages, giant cells and lymphocytes surrounding areas of necrosis) in the respiratory tract — causing the destructive upper airway disease (saddle-nose deformity from nasal septal destruction; subglottic stenosis). GPA triad: upper respiratory tract granulomatous inflammation + lower respiratory tract granulomatous inflammation + necrotising pauci-immune glomerulonephritis. ANCA (anti-PR3) are present in approximately 90% of generalised GPA. Limited GPA (upper airway without renal involvement): ANCA positive in approximately 65%.

Plasma exchange in ANCA vasculitis
MEPEX/PEXIVASPlasma exchange removes circulating ANCA antibodies — reducing the immediate antibody burden at the start of immunosuppressive therapy. Historically used for severe ANCA vasculitis (dialysis-dependent AKI or diffuse alveolar haemorrhage). The PEXIVAS trial (NEJM 2020 — 704 patients): plasma exchange did NOT reduce risk of death or ESKD at 7 years in severe ANCA vasculitis. However, it may still have a role in anti-GBM antibody co-positive patients (who have very high risk of irreversible renal failure and life-threatening pulmonary haemorrhage).

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ANCA-Associated Vasculitis

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