Systemic vasculitides overview

Last updated 28 Mar 2026

Systemic Vasculitides — Overview

Systemic vasculitides are a heterogeneous group of disorders characterised by inflammation and necrosis of blood vessel walls, leading to ischaemia and organ damage. They are classified according to the size of the predominant vessel involved: large-vessel, medium-vessel, and small-vessel vasculitis. The Chapel Hill Consensus Conference (CHCC) 2012 nomenclature provides the current classification framework. Early recognition is critical as delay in diagnosis and treatment leads to irreversible organ damage and significant mortality.

Australian Context

Vasculitides are rare but clinically significant conditions encountered across general practice, emergency medicine, rheumatology, nephrology, and respiratory medicine. Giant cell arteritis (GCA) is the most common vasculitis in Australia, predominantly affecting those over 50 years. ANCA-associated vasculitides (AAV) affect approximately 2–3 per 100,000 Australians annually. Awareness of presenting features by primary care clinicians is essential for timely referral.

Classification and Pathophysiology

CHCC 2012 Classification by Vessel Size

Large-vessel vasculitis: Giant cell arteritis (GCA), Takayasu arteritis (TAK) — aorta and major branches
Medium-vessel vasculitis: Polyarteritis nodosa (PAN), Kawasaki disease (KD) — main visceral arteries and branches
Small-vessel vasculitis — ANCA-associated: Granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA)
Small-vessel vasculitis — immune complex: IgA vasculitis (Henoch-Schönlein purpura), cryoglobulinaemic vasculitis, anti-GBM disease
Variable-vessel vasculitis: Behçet syndrome, Cogan syndrome

Shared Pathogenic Mechanisms

Depending on the vasculitis type, pathogenesis involves ANCA-mediated neutrophil activation (AAV), T-cell granulomatous inflammation (GCA, GPA), immune complex deposition (IgA vasculitis, cryoglobulinaemia), or direct endothelial injury. All converge on vessel wall inflammation, leading to stenosis, occlusion, aneurysm formation, or rupture.

Clinical Presentation

Constitutional Features (All Vasculitides)

Fever, fatigue, weight loss, malaise, and night sweats are common to most systemic vasculitides. These non-specific features often lead to initial misdiagnosis as infection or malignancy. A high index of suspicion is required, particularly with multi-system involvement.

Organ-Specific Presentations by Type

Vasculitis	Key Clinical Features	Red Flag Signs
Giant Cell Arteritis	Headache, jaw claudication, scalp tenderness, elevated ESR/CRP	Sudden visual loss — ophthalmic emergency
Takayasu Arteritis	Arm claudication, pulse asymmetry, hypertension, bruits	Aortic regurgitation, stroke
GPA / MPA	Sinusitis, haemoptysis, haematuria, renal impairment	Pulmonary haemorrhage, RPGN
Kawasaki Disease	Prolonged fever, rash, conjunctivitis, lip changes, lymphadenopathy	Coronary artery aneurysms
IgA Vasculitis	Palpable purpura (buttocks/legs), arthritis, abdominal pain, haematuria	Intussusception, nephritis

Investigations

Essential
ESR and CRP
Markedly elevated in most active vasculitides, particularly GCA (ESR often >50 mm/hr). Serial measurement guides treatment response.
Essential
ANCA (c-ANCA/PR3 and p-ANCA/MPO)
Highly specific for AAV. PR3-ANCA (c-ANCA) associated with GPA; MPO-ANCA (p-ANCA) with MPA and EGPA. Both by immunofluorescence and ELISA.
Essential
Urinalysis and Renal Function
Haematuria and proteinuria suggest glomerulonephritis. Rapidly progressive renal failure warrants urgent biopsy. eGFR monitoring essential on treatment.
Essential
Full Blood Count, LFTs, Coagulation
Anaemia of chronic disease common. Eosinophilia in EGPA. Thrombocytosis in active inflammation. Baseline for immunosuppression monitoring.
Available
CT / MRI / PET-CT Angiography
Large-vessel vasculitis assessment. PET-CT detects active aortic and branch vessel inflammation. CTA/MRA for vascular anatomy and aneurysm detection.
Referral
Tissue Biopsy
Temporal artery biopsy for GCA. Renal, lung, or skin biopsy for small-vessel vasculitis. Essential for histological confirmation in most cases.

Severity Assessment

MILD

Limited Disease

Single organ involvement, no vital organ threatened, stable function

Oral corticosteroids ± conventional immunosuppression

MODERATE

Generalised Disease

Multi-organ involvement, renal impairment, constitutional symptoms

High-dose corticosteroids + rituximab or cyclophosphamide

SEVERE

Organ/Life-Threatening

RPGN, pulmonary haemorrhage, vision loss, stroke, cardiac involvement

IV methylprednisolone pulses + urgent immunosuppression ± plasma exchange

Use the Birmingham Vasculitis Activity Score (BVAS) or Five Factor Score (FFS) for standardised severity assessment and treatment guidance in systemic vasculitis.

Treatment Strategy

Induction Therapy

High-dose corticosteroids are the cornerstone of induction therapy for most vasculitides. Prednisolone 1 mg/kg/day (max 60–80 mg/day) or IV methylprednisolone 500–1000 mg daily for 3 days for severe/life-threatening disease. Rituximab (anti-CD20) has replaced cyclophosphamide as preferred induction agent for AAV in many centres due to equivalent efficacy and superior safety profile. Cyclophosphamide remains appropriate for severe disease or rituximab-intolerant patients.

Maintenance Therapy

After remission induction (typically 3–6 months), transition to maintenance therapy to prevent relapse. Options include azathioprine (2 mg/kg/day), mycophenolate mofetil (2–3 g/day), methotrexate (20–25 mg weekly), or rituximab maintenance (500 mg every 6 months for AAV). Duration typically 2–4 years minimum; individualise based on relapse risk and disease type.

Steroid Tapering

Slow corticosteroid taper essential to prevent relapse. Reduce by 10 mg/day every 2 weeks to 20 mg, then by 2.5 mg every 2–4 weeks to 10 mg, then by 1 mg/month. Do not taper faster than tolerated — relapse requires re-escalation. Bone protection (calcium, vitamin D, bisphosphonate) mandatory for prolonged steroid use.

Directed Therapy

💉

Rituximab

MabThera®, Riximyo® · Anti-CD20 Biologic

Adult Dose375 mg/m² IV weekly × 4 doses OR 1000 mg IV × 2 doses (2 weeks apart)

Paediatric375 mg/m² per dose; specialist dosing

RouteIntravenous infusion

FrequencyInduction; then maintenance every 6 months (AAV)

DurationIndividualised; typically 2–4 years

Renal Adj.No formal adjustment required

Hepatic Adj.Caution; monitor LFTs

PBS StatusPBS Authority Required

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Cyclophosphamide

Endoxan® · Alkylating Agent

Adult DoseIV: 15 mg/kg (max 1.2 g) every 2–3 weeks × 6 pulses; Oral: 2 mg/kg/day

Paediatric500–750 mg/m² IV per pulse; specialist dosing

RouteIV pulse or oral

FrequencyEvery 2–3 weeks (IV); daily (oral)

Duration3–6 months induction; switch to maintenance agent

Renal Adj.Reduce dose if eGFR <30; avoid if eGFR <10

Hepatic Adj.Caution in hepatic impairment

PBS Status✓ PBS Listed

💊

Azathioprine

Imuran® · Antimetabolite · Maintenance

Adult Dose2 mg/kg/day (max 200 mg/day)

Paediatric1–3 mg/kg/day

RouteOral

FrequencyOnce or twice daily

Duration2–4 years minimum

Renal Adj.Reduce dose with renal impairment; check TPMT before starting

Hepatic Adj.Caution; monitor LFTs

PBS Status✓ PBS Listed

Acute Management

Organ-Threatening Vasculitis — Emergency Management

Start high-dose corticosteroids immediately on clinical suspicion — do not wait for biopsy result in GCA with visual symptoms. IV methylprednisolone 500–1000 mg/day for 3 days for imminent vision loss. For pulmonary haemorrhage or RPGN in AAV: IV methylprednisolone pulses, then initiate rituximab or cyclophosphamide urgently. Plasma exchange (PLEX) considered for RPGN with severe renal impairment (creatinine >500 µmol/L) or simultaneous pulmonary haemorrhage.

Urgent Referral

All suspected systemic vasculitis should be urgently referred to rheumatology, nephrology, or relevant specialty depending on organ involvement. GCA with visual symptoms — ophthalmology same day. Pulmonary haemorrhage — ICU admission. RPGN — nephrology same day with consideration of urgent biopsy and dialysis if required.

Infection Exclusion

Always exclude infectious mimics before initiating immunosuppression. Blood cultures, hepatitis B/C serology (HBV can cause PAN), HIV, IGRA for TB, ANCA testing, and tissue biopsy where feasible. Delay in starting treatment risks organ loss; early expert opinion is essential.

Monitoring and Follow-up

Disease Activity Monitoring

Serial BVAS assessment at each visit. ESR and CRP every 4–6 weeks initially, then 3-monthly when stable. Urinalysis at every visit (vasculitis may cause haematuria/proteinuria). Renal function monthly for first 6 months, then 3-monthly. Imaging (PET-CT, CT angiography) for large-vessel vasculitis disease activity and remission assessment.

Treatment Toxicity Monitoring

Cyclophosphamide: FBC weekly, then 2-weekly on oral therapy. Haemorrhagic cystitis risk — ensure adequate hydration; mesna co-administration with IV pulses. Rituximab: B-cell counts, immunoglobulin levels before each cycle. Methotrexate: FBC, LFTs, renal function monthly for 3 months, then 3-monthly. Osteoporosis prophylaxis for all on prolonged corticosteroids.

Relapse Surveillance

Educate patients on relapse symptoms. Rising ANCA titres may predict relapse in AAV but should not alone drive treatment changes. Any new organ involvement warrants urgent reassessment and possible re-induction. Lifelong follow-up recommended for most vasculitides due to relapse risk.

Special Populations

👶 Paediatric Vasculitis

IgA Vasculitis (HSP)Most common vasculitis in children. Usually self-limiting. Monitor renal involvement closely. Systemic corticosteroids for severe abdominal pain or nephritis.

Kawasaki DiseasePeak age 6 months–5 years. Treat with IVIG 2 g/kg single dose + aspirin. Echocardiography for coronary artery assessment. Specialist paediatric cardiology input essential.

Takayasu ArteritisMost common large-vessel vasculitis in children and adolescents. Corticosteroids + methotrexate first-line. TNF inhibitors (infliximab) for refractory disease.

🤰 Pregnancy

CyclophosphamideCONTRAINDICATED in pregnancy — teratogenic. Switch to azathioprine or rituximab for maintenance before conception planning.

RituximabAvoid in pregnancy if possible. If used, ensure 6-month washout before conception. Neonatal B-cell depletion reported.

CorticosteroidsPrednisolone <20 mg/day generally safe in pregnancy. Use minimum effective dose. Monitor for gestational hypertension and glucose intolerance.

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Health

Systemic vasculitides are rare conditions that can affect any population. Aboriginal and Torres Strait Islander peoples may present with diagnostic challenges due to overlapping features with infectious and chronic conditions prevalent in these communities. Access to specialist care, advanced imaging (PET-CT, MRI angiography), and tissue biopsy services is limited in many remote areas, contributing to diagnostic delay.

Diagnostic Delay

Symptoms of vasculitis (fatigue, weight loss, fever) overlap with infections and other chronic conditions. Maintain a high index of suspicion. Facilitate urgent telehealth rheumatology or nephrology review if vasculitis suspected clinically or on urinalysis.

Infection Exclusion

Higher prevalence of TB, hepatitis B/C, and other infections in some communities complicates vasculitis management. Comprehensive infection screening is mandatory before immunosuppression. IGRA/Mantoux testing and hepatitis serology essential.

Immunosuppression Monitoring

Cyclophosphamide and rituximab require intensive laboratory monitoring not always feasible remotely. Establish shared care with metropolitan rheumatology or nephrology. Use telehealth for review between local blood test monitoring visits.

Community Support

Vasculitis is a serious, potentially life-threatening diagnosis with psychological impact. Engage Aboriginal liaison officers and community health workers in care coordination, patient education, and treatment adherence support.

Antimicrobial Stewardship

Infection Prevention and Prophylaxis

Vasculitis management with high-dose corticosteroids and immunosuppression significantly increases infection risk. Key stewardship principles:

Screen for latent TB (IGRA) and hepatitis B/C before initiating rituximab or cyclophosphamide
Trimethoprim-sulfamethoxazole prophylaxis (160/800 mg three times weekly) for Pneumocystis jirovecii pneumonia (PJP) while on cyclophosphamide or high-dose steroids for >4 weeks
Antifungal prophylaxis (fluconazole) considered in highly immunosuppressed patients
Annual influenza vaccination; pneumococcal vaccination before commencing immunosuppression; live vaccines contraindicated
Withhold immunosuppression during serious infections; restart only after resolution

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Infection Mimics: Infective endocarditis, hepatitis B-associated PAN, and HIV can present identically to primary vasculitis. Always exclude infection before committing to immunosuppression — treat the underlying infection instead.

References

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Australian Rheumatology Association. Management of Vasculitis: Australian Clinical Guidelines. Sydney: ARA; 2023.
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Jayne D, Rasmussen N, Andrassy K, et al. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med. 2003;349(1):36-44.
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