ANCA-associated vasculitis: recognising GPA, MPA and EGPA in general practice

ANCA-associated vasculitis (AAV) is a group of rare autoimmune diseases that cause necrotising inflammation of small and medium blood vessels throughout the body. Three distinct but related conditions sit under this umbrella: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). All are defined by anti-neutrophil cytoplasmic antibodies (ANCA), though EGPA is ANCA-positive in only around 40% of cases.

Australian and New Zealand data estimate prevalence at approximately 150–200 per million, with an annual incidence of 20–40 per million. Peak age of onset is 50–70; there is no strong sex predominance. Without treatment, one-year mortality approaches 80%. With modern therapy — rituximab-based induction, steroid-sparing approaches, and long-term maintenance — remission is achievable for most patients.

The GP’s role is not to manage immunosuppression but to recognise AAV early, refer urgently, and then carry the long-term shared-care burden alongside rheumatology and nephrology. A pattern of refractory sinusitis, bloody nasal crusts, haematuria, rising creatinine, haemoptysis, or palpable purpura should prompt immediate investigation rather than another antibiotic course.

A. Core clinical — the AU general-practice framework

Recognising the three subtypes

Therapeutic Guidelines — rheumatology and the RACGP describe the characteristic clinical patterns that a GP is most likely to encounter:

GPA (c-ANCA/PR3-positive in ~60%) targets the upper respiratory tract, lower respiratory tract, and kidneys. The hallmark is chronic sinusitis that fails repeated antibiotic courses, with persistent bloody nasal crusts, septal perforation, and — in more advanced disease — a saddle-nose deformity from cartilage destruction. Subglottic stenosis presents as progressive stridor. Lung cavities, nodules, or diffuse alveolar haemorrhage may develop.

MPA (p-ANCA/MPO-positive in ~60%) predominantly attacks the kidneys — causing rapidly progressive glomerulonephritis — and the lungs via pulmonary capillaritis and alveolar haemorrhage. Unlike GPA, there are no granulomata and significant ENT disease is typically absent. MPA-associated interstitial lung disease, particularly the usual interstitial pneumonia (UIP) pattern, is increasingly recognised in older MPO-ANCA patients and overlaps with idiopathic pulmonary fibrosis (KDIGO 2024 Glomerular Diseases guideline).

EGPA (ANCA-positive in ~40%, usually MPO) has a distinctive triad: late-onset or severe asthma, peripheral blood eosinophilia above 10%, and systemic vasculitis. The vasculitic phase is often preceded by years of refractory asthma; when mononeuritis multiplex, myocarditis, palpable purpura, or GI ischaemia appear, the diagnosis must be actively considered. Cardiac involvement is the leading cause of EGPA mortality and may be clinically silent on routine examination (MIRRA — Wechsler, NEJM 2017).

The GP assessment

History — multi-system review:

• Constitutional: fever, weight loss, night sweats, profound fatigue, myalgia — present in over 70% of active AAV
• ENT: bloody nasal crusts, epistaxis, anosmia, hearing loss, stridor (GPA-dominant)
• Respiratory: dry cough, any-volume haemoptysis — haemoptysis combined with haematuria or rising creatinine is a same-day emergency
• Renal: frothy urine (proteinuria), frank haematuria, oedema, new hypertension
• Skin: palpable non-blanching purpura on the lower limbs, livedo, digital ischaemia
• Neurological: asymmetric sensorimotor deficits, foot drop, wrist drop — mononeuritis multiplex is the hallmark peripheral sign
• Ocular: deep painful red eye with tenderness (scleritis), proptosis (retro-orbital pseudotumour in GPA), visual change
• Cardiac (especially EGPA): chest pain, palpitations, unexplained dyspnoea or heart failure
• Drug and exposure history: hydralazine, propylthiouracil, levamisole-cocaine — all cause drug-induced ANCA; silica dust and engineered-stone bench fabrication are recognised AU occupational triggers (Safe Work Australia — engineered-stone ban effective 1 July 2024)

Examination: Bilateral blood pressure, oxygen saturation on air, temperature. Anterior rhinoscopy — crusts, septal perforation, saddle-nose. Chest auscultation for crackles (haemorrhage) or wheeze (EGPA). Skin inspection for palpable purpura on the lower limbs. Full peripheral neurological assessment for an asymmetric sensorimotor pattern. Urine dipstick at the bedside is the single most informative GP test — blood plus protein demands microscopy that day.

Urgent GP investigations:

• Urine dipstick and microscopy — specifically request dysmorphic red blood cells and red cell casts (MBS 66536); these confirm glomerulonephritis and are the most time-sensitive finding
• Urine albumin-to-creatinine ratio (ACR) — quantify proteinuria
• ANCA panel (MBS 73529): indirect immunofluorescence plus PR3 ELISA and MPO ELISA — combined specificity exceeds 98% in a clinically relevant pre-test setting (Bossuyt, Nat Rev Rheumatol 2017)
• FBC with differential (MBS 65070) — eosinophil count above 10% strongly points to EGPA; anaemia of chronic inflammation is common
• UEC (MBS 66500) — baseline eGFR and trend; a rising creatinine changes urgency from “refer this week” to “refer today”
• CRP and ESR — non-specific but track disease activity
• Anti-GBM antibody — mandatory if any pulmonary-renal syndrome; approximately 25% of AAV patients are double-positive with anti-GBM disease
• Hepatitis B (surface antigen, surface antibody, core antibody) and hepatitis C antibody plus RNA, HIV — exclude mimic vasculitides and mandatory pre-immunosuppression screening
• ANA, ENA, anti-dsDNA, complement C3/C4 — to exclude lupus
• Quantiferon-TB Gold — mandatory before any immunosuppression commences

Do not wait for a specialist appointment before ordering these. If ANCA is positive or creatinine is rising, phone or fax results to nephrology or rheumatology the same day.

B. Modern treatment — induction and maintenance

The EULAR 2022 recommendations for AAV and ACR/Vasculitis Foundation 2021 guideline converge on the framework below. All immunosuppression is specialist-initiated; GPs administer prophylaxis, monitor shared-care parameters, and act on relapse signals.

Induction — severe or organ-threatening disease

Rituximab 375 mg/m² weekly for four weeks (or 1 g twice, two weeks apart) is the preferred induction agent for most patients with severe AAV and is listed on the PBS Section 100 Highly Specialised Drugs programme under Authority Required criteria. The RAVE trial (Stone, NEJM 2010) and RITUXVAS trial (Jones, NEJM 2010) demonstrated non-inferiority to cyclophosphamide for induction, with superiority in relapsing disease. Rituximab is particularly preferred for women of childbearing age and those wishing to avoid bladder and gonadal toxicity.

Cyclophosphamide pulse IV — 15 mg/kg every two weeks for three pulses, then every three weeks for three to six cycles — is a valid alternative when rituximab is contraindicated (CYCLOPS — de Groot, Lancet 2009). It requires pre-treatment hydration, mesna bladder protection, and fertility counselling before starting.

Glucocorticoids accompany induction as pulse intravenous methylprednisolone 500–1000 mg for three days, followed by a reduced-dose oral prednisolone taper beginning at around 30 mg/day and weaning to 5 mg by month five. The PEXIVAS trial (Walsh, NEJM 2020) demonstrated that this reduced-dose regimen is non-inferior to standard dosing for death and end-stage kidney disease, with significantly fewer serious infections at one year — it is now the standard of care.

Avacopan (Tavneos) 30 mg twice daily for 12 months — a complement C5a receptor antagonist — has been PBS-listed under Section 100 Authority Required (Streamlined) since December 2022 (PBS listing). The ADVOCATE trial (Jayne, NEJM 2021) showed superiority over placebo for sustained remission at week 52 and improved eGFR recovery, with reduced cumulative steroid exposure. Liver function monitoring is required.

Plasma exchange is no longer routinely recommended following the PEXIVAS 2020 results and their seven-year extension, which showed no reduction in death or end-stage kidney disease. It is reserved for refractory alveolar haemorrhage with respiratory failure, co-positive anti-GBM disease, or selected severe dialysis-dependent cases — always a specialist decision.

Maintenance

Rituximab 500 mg every six months for two to four years is the preferred maintenance strategy. The MAINRITSAN trial (Guillevin, NEJM 2014) and its successors demonstrated superiority over azathioprine for relapse-free survival. The specialist prescribes and oversees each infusion; the GP coordinates pre-infusion bloods (FBC, LFT, immunoglobulins) and monitors for infection between doses.

Azathioprine 2 mg/kg/day — check TPMT enzyme activity before commencing to avoid severe myelosuppression (Australian Medicines Handbook 2025). An appropriate alternative when rituximab is not tolerated.

EGPA-specific — mepolizumab: Mepolizumab 300 mg subcutaneously every four weeks — note this is a higher dose than the severe-asthma indication (100 mg) — is PBS Authority Required for relapsing or refractory EGPA on prednisolone ≥7.5 mg/day (MIRRA — Wechsler, NEJM 2017). It doubles accrued weeks of remission and enables meaningful steroid tapering.

C. Infection prophylaxis, bone health, and vaccination

These three domains are GP-managed adjuncts to immunosuppression and are not optional (eTG rheumatology; AMH 2025).

PJP prophylaxis: TMP-SMX 160/800 mg (one Bactrim Forte tablet) three times per week is prescribed during high-dose immunosuppression, while on cyclophosphamide, and for six to twelve months after rituximab while B-cell counts remain suppressed. The Stegeman NEJM 1996 trial established this standard for GPA — it reduced respiratory infections and may reduce relapse via anti-staphylococcal action. For sulfa allergy: dapsone 100 mg daily (check G6PD status first) or atovaquone 1500 mg daily.

Bone protection bundle: All patients starting long-term corticosteroids need calcium and vitamin D supplementation, a baseline DXA scan repeated at 12 months, and a bisphosphonate (PBS Authority Streamlined once T-score ≤ −1.5 on prednisolone ≥7.5 mg/day for ≥3 months) — per RACGP Osteoporosis guidelines 2024. Gastric protection with a PPI is warranted if high-dose pulse steroids or NSAIDs are used. Blood pressure, lipids, and HbA1c warrant aggressive management given the accelerated cardiovascular risk of chronic inflammation combined with steroid exposure.

Vaccinations: Per the Australian Immunisation Handbook — immunocompromised chapter, the following non-live vaccines are NIP-funded for immunocompromised patients: annual influenza, COVID-19 boosters per schedule, PCV20 followed by PPV23 eight weeks later, Shingrix (recombinant zoster vaccine — safe on immunosuppression; preferred over the live Zostavax), and hepatitis B with post-vaccine titre at one month. Live vaccines are strictly contraindicated during immunosuppression: MMR, VZV/Zostavax, BCG, yellow fever, and oral typhoid. Schedule any indicated live vaccines at least four weeks before immunosuppression starts, or confirm B-cell reconstitution at least six to twelve months after rituximab first.

D. Australian operations

MBS billing for shared care:

• Standard GP consultations: Level B 23, C 36, D 44
• GPCCMP preparation 965 and review 967 — AAV qualifies as a complex chronic condition; the multi-disciplinary team plan should include rheumatology, nephrology, physiotherapy (steroid myopathy, deconditioning), psychology (adjustment disorder, body image), and dietitian (steroid weight gain, bone health); target three-monthly review
• Case conference 132/133 — appropriate for MDT coordination
• Mental Health Care Plan 2715/review 2717 — low threshold at diagnosis, body-image change (saddle-nose, alopecia), or peripheral neuropathy

Key pathology MBS items: ANCA panel + PR3 + MPO ELISA 73529; UEC 66500; urine microscopy + dysmorphic RBCs 66536.

PBS authority highlights:

• Rituximab: Section 100 Highly Specialised Drugs, Authority Required — rheumatology or nephrology-initiated
• Avacopan: Section 100 Authority Required (Streamlined) for AAV since 1 December 2022
• Mepolizumab: Authority Required for relapsing/refractory EGPA (300 mg dose — distinct from severe-asthma 100 mg indication)
• Azathioprine, methotrexate, mycophenolate: Authority Required
• Bisphosphonates: Authority Required Streamlined for steroid-induced osteoporosis

Occupational exposure and workers’ compensation: The nationwide ban on engineered-stone bench-top fabrication (effective 1 July 2024 under Safe Work Australia regulations) recognised the silica–AAV and silicosis link. Any patient with a history of stonemasonry, sandblasting, or engineered-stone fabrication warrants workers’ compensation notification, occupational hygiene assessment, and notification of the relevant state authority. This is a medico-legal obligation alongside the clinical one.

E. Special populations

Older adults (≥70 years): Frailty and comorbidity amplify infection risk on immunosuppression. Reduced-dose steroid regimens per PEXIVAS are particularly important in this group. Monitor closely for rituximab-induced hypogammaglobulinaemia; check IgG before each rituximab cycle and consider immunoglobulin replacement if recurrent serious infections occur. Document baseline cognition — both pachymeningitis (GPA) and high-dose corticosteroids affect neuropsychological function.

Women of childbearing age: Rituximab is preferred over cyclophosphamide to preserve ovarian reserve. Methotrexate, mycophenolate, and cyclophosphamide are teratogenic — stop at least three to six months before planned conception. Per EULAR pregnancy recommendations (Götestam Skorpen, ARD 2017), azathioprine is the maintenance agent of choice in pregnancy; refer to a fertility specialist before starting cyclophosphamide when the patient may wish to conceive. Contraception counselling is essential while on teratogenic agents.

Aboriginal and Torres Strait Islander patients: Barriers of geographic remoteness, under-representation in specialist services, and compounded renal risk from comorbid hypertension and type 2 diabetes mean that AAV can present later and behave more aggressively. Integrate care with an Aboriginal health worker and coordinate with the 715 Health Assessment pathway (NACCHO) for comprehensive chronic-disease management. Culturally safe communication about diagnosis and treatment is essential.

Silica-exposed workers: Stonemasons, sandblasters, engineered-stone kitchen fabricators, tunnel workers. AAV in this occupational group may be more aggressive — early specialist input and prompt workers’ compensation notification are warranted alongside clinical management.

EGPA with severe asthma: Co-manage with a respiratory specialist. Ensure ICS-LABA optimisation; monotherapy LABA is contraindicated. Arrange cardiac MRI for myocarditis surveillance in all EGPA patients at diagnosis — even when asymptomatic from a cardiac standpoint.

When to escalate

Same-day emergency — call 000 or send directly to ED:

• Any haemoptysis combined with haematuria, rising creatinine, or dyspnoea — pulmonary-renal syndrome
• Oliguria, anuria, or serum potassium above 6.0 mmol/L
• New foot drop, wrist drop, or rapidly progressive peripheral neurology — mononeuritis multiplex
• Stridor — subglottic stenosis
• Suspected cardiac involvement (chest pain, palpitations, or new heart failure in an EGPA context)

Same-day phone call to rheumatology or nephrology:

• Any new ANCA-positive result, even if the patient currently looks well
• RPGN pattern — 2+ blood and protein on dipstick with rising creatinine
• New sensorineural hearing loss combined with chronic sinusitis
• Scleritis

Routine referral:

• Stable maintenance monitoring and surveillance scope (ENT for nasal disease, ophthalmology, audiology)
• Fertility planning discussion before any teratogenic agent

What this article is and is not

This article contains general health information based on current Australian and international rheumatology guidelines — eTG, EULAR 2022 AAV recommendations, ACR/VF 2021 guideline, and KDIGO 2024 — interpreted for the Australian general practice context. It does not constitute personal medical advice and does not create a doctor–patient relationship. Specific treatment decisions — including initiation, dosing, and monitoring of immunosuppression — are made in partnership with the patient’s rheumatologist, nephrologist, and GP as part of a shared-care plan.

For patient resources: HealthDirect — vasculitis, Vasculitis Foundation Australia, Kidney Health Australia, Better Health Channel.

For urgent help: call 000. For mental-health support: Lifeline 13 11 14, Beyond Blue 1300 22 4636.

---

Sources cited

1. EULAR 2022 recommendations — Hellmich et al, Ann Rheum Dis 2024
2. ACR/Vasculitis Foundation 2021 Guideline — Chung et al
3. KDIGO 2024 Glomerular Diseases guideline
4. Therapeutic Guidelines (eTG complete) — rheumatology
5. Australian Rheumatology Association
6. RACGP — vasculitis
7. Australian Medicines Handbook (AMH 2025)
8. RAVE — Stone et al, NEJM 2010
9. RITUXVAS — Jones et al, NEJM 2010
10. CYCLOPS — de Groot et al, Lancet 2009
11. PEXIVAS — Walsh et al, NEJM 2020
12. ADVOCATE — Jayne et al, NEJM 2021
13. MAINRITSAN — Guillevin et al, NEJM 2014
14. MIRRA — Wechsler et al, NEJM 2017
15. Stegeman et al, NEJM 1996
16. Bossuyt et al — ANCA testing consensus, Nat Rev Rheumatol 2017
17. Australian Immunisation Handbook — immunocompromised
18. Safe Work Australia — engineered-stone prohibition
19. PBS — rituximab, avacopan, mepolizumab
20. HealthDirect — vasculitis
21. Vasculitis Foundation Australia
22. Kidney Health Australia
23. RACGP osteoporosis 2024
24. EULAR pregnancy recommendations — Götestam Skorpen et al, ARD 2017