What is ANCA vasculitis?
ANCA = Anti-Neutrophil Cytoplasmic Antibody. These antibodies activate the body's own neutrophils to attack small blood vessels (arterioles, capillaries, venules) — particularly in kidneys, lungs, nose/sinuses, skin and nerves.
Three Main Types
1. GRANULOMATOSIS WITH POLYANGIITIS (GPA) — formerly Wegener's:
- PR3-ANCA antibody (cytoplasmic = c-ANCA)
- Upper airway (sinuses, nose), lower airway (lungs), kidneys
- Saddle nose deformity, bloody nasal crusts
- ~50% relapse rate
2. Microscopic Polyangiitis (Mpa)
- MPO-ANCA antibody (perinuclear = p-ANCA)
- Kidneys, lungs (pulmonary haemorrhage)
- Less upper airway involvement
- ~30% relapse rate
3. EOSINOPHILIC GPA (EGPA) — Churg-Strauss:
- Asthma, nasal polyps, raised eosinophils
- Heart and nerves often more affected than kidneys
- MPO-ANCA in ~40%
- Treated similarly + sometimes mepolizumab
UK incidence: ~20 per million per year. Peaks age 60-70. Slight male predominance (except EGPA).
Symptoms — every doctor should suspect this
ANCA vasculitis is a 'great mimicker' and easy to miss. ANY combination of these should prompt ANCA testing:
Upper Airway
- Persistent sinusitis, bloody nasal crusts
- Hearing loss, ear pain
- Mouth ulcers, saddle nose collapse
Lower Airway
- Cough, breathlessness, coughing blood (haemoptysis)
- Lung nodules or infiltrates on CT
Kidney
- Microscopic blood in urine (look for red cell casts)
- Proteinuria
- Rising creatinine over days to weeks (rapidly progressive GN)
General
- Fever, night sweats, weight loss
- Fatigue, malaise
Skin
- Palpable purpura (raised purple spots, usually legs)
- Skin ulcers
Nerve
- Mononeuritis multiplex — sudden weakness/numbness in a specific nerve distribution (foot drop, wrist drop)
Eye
- Painful red eye (scleritis, episcleritis)
- Orbital pseudotumour
Kidney Vitality is a daily multivitamin developed by a UK Consultant Nephrologist using renal nutrition principles. It contains no added potassium, magnesium, phosphorus or iron, and no herbal blends. See the formulation.
Diagnosis
Tests
- ANCA blood test (PR3 and MPO, plus indirect immunofluorescence)
- Urinalysis with microscopy (red cells, red cell casts = active glomerulonephritis)
- Creatinine, eGFR (often rising)
- CRP, ESR (raised)
- FBC (anaemia, raised neutrophils, raised eosinophils in EGPA)
- Chest CT (nodules, ground-glass, haemorrhage)
- ENT review
Kidney Biopsy
- Definitive diagnosis
- Classic finding: pauci-immune crescentic and necrotising glomerulonephritis
- 'Crescents' = aggressive inflammation in the kidney filter
- Pauci-immune = little or no immune complex staining (unlike lupus or IgAN)
- Berden classification predicts outcome: focal > crescentic > mixed > sclerotic
This Is A Medical Emergency
- If creatinine is rising fast, suspicion alone is enough to start steroids while waiting biopsy
- Delay = irreversible kidney damage and dialysis dependence
Treatment — induction and beyond
INDUCTION (3-6 MONTHS) — get inflammation under control:
Steroids
- IV methylprednisolone 500-1000 mg ×3 days if severe
- Then oral prednisolone, tapering using PEXIVAS reduced-dose schedule (starts 60 mg, halves by 8 weeks)
Plus Either
- RITUXIMAB — 4 weekly infusions of 375 mg/m² OR 2 doses of 1 g (RAVE/RITUXVAS trials)
- CYCLOPHOSPHAMIDE — IV every 2 weeks for 6 doses, then 3-weekly
Rituximab often preferred:
- Relapsing disease
- PR3-ANCA / GPA
- Young patients (fertility preservation)
- Previous cyclophosphamide
Add Avacopan (NICE Ta825, 2022)
- Oral C5a receptor antagonist
- Allows much faster steroid taper
- Significantly reduces steroid side effects
- Now standard for new severe AAV
Plasma Exchange (Plex)
- Reserved for: creatinine > 300 µmol/L, dialysis-dependent AKI, OR pulmonary haemorrhage
- PEXIVAS trial showed limited mortality benefit but useful for selected cases
Adjuncts
- Co-trimoxazole prophylaxis (PCP pneumonia)
- Bone protection
- PPI for gastric protection
- Vaccines BEFORE rituximab where possible
MAINTENANCE (2-4+ YEARS):
- Rituximab every 4-6 months (MAINRITSAN, RITAZAREM trials) — now standard
- OR azathioprine 2 mg/kg/day
- Slowly weaning steroid
- Long-term in relapsing disease
Living with vasculitis
Monitoring
- Monthly clinic during induction
- 3-monthly when stable
- ANCA titre, urinalysis, creatinine, FBC at every visit
- Rising ANCA may precede clinical relapse
RELAPSE — watch for:
- Sinus crusts returning
- Cough or breathlessness
- Blood or protein returning in urine
- Fevers, weight loss
- REPORT IMMEDIATELY — early treatment prevents kidney loss
Infection Risk On Immunosuppression
- Take co-trimoxazole prophylaxis as prescribed
- Annual flu, COVID, 5-yearly pneumococcal vaccines (BEFORE rituximab ideally)
- Avoid live vaccines (yellow fever, MMR) on immunosuppression
- Tell every doctor about your immunosuppression
- Low threshold for seeking help with fever, breathlessness
Long-term Health
- Cardiovascular risk is high — statins, BP control
- Cancer surveillance — long cyclophosphamide raises bladder cancer risk
- Mental health support — vasculitis is a major life event
- Fertility preservation discussed before cyclophosphamide
Outcomes
- 5-year survival now ~80-85% (was < 20% in 1960s)
- Relapse rate 30-50% over 5 years — lifelong vigilance
- Patient organisations: Vasculitis UK (vasculitis.org.uk)
