Key Facts

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly Churg-Strauss syndrome, is an ANCA-associated small-vessel vasculitis characterised by asthma, peripheral blood eosinophilia, and eosinophilic granulomatous inflammation affecting multiple organs.

Epidemiology

EGPA is rare — annual incidence 0.5-4 per million. Mean age at diagnosis is 40-50 years. Slight male predominance. It is the rarest of the three ANCA-associated vasculitides (GPA, MPA, EGPA). Nearly all patients have a history of asthma, typically adult-onset and often initially categorised as severe eosinophilic asthma.

Aetiology

The exact cause is unknown. Genetic susceptibility involving HLA-DRB4 and IL-10 polymorphisms has been identified. Triggers may include leukotriene receptor antagonists (e.g. montelukast — likely unmasking rather than causation as oral steroids are weaned), vaccinations (rare reports), and infections. The relationship between ANCA status and disease phenotype is increasingly recognised.

Pathophysiology

Th2-driven immune dysregulation leads to eosinophil activation and tissue infiltration. IL-5 is the key cytokine driving eosinophil production, activation, and survival. Eosinophil degranulation releases toxic granule proteins causing tissue damage. In ANCA-positive patients, anti-MPO antibodies activate neutrophils and cause small-vessel necrotising vasculitis. The disease thus has two overlapping pathological processes: eosinophilic tissue infiltration (especially heart and lungs) and small-vessel vasculitis (especially kidneys, nerves, skin).

Allergic Phase

• Adult-onset asthma (often severe, steroid-dependent)
• Allergic rhinitis with nasal polyposis
• Sinusitis
• May precede vasculitic phase by years

Eosinophilic Phase

• Peripheral eosinophilia (often >1.5 × 10⁹/L, may be >10)
• Eosinophilic infiltration of lungs (fleeting infiltrates), GI tract (abdominal pain, diarrhoea)

Vasculitic Phase

• Peripheral neuropathy: mononeuritis multiplex (most common neurological feature — 70%); sensorimotor polyneuropathy
• Cardiac: myocarditis, pericarditis, heart failure, coronary vasculitis — the leading cause of EGPA mortality
• Skin: purpura, nodules, urticarial lesions (40-70%)
• Renal: focal segmental glomerulonephritis (less severe than GPA/MPA)
• GI: abdominal pain, eosinophilic gastroenteritis, bowel perforation (rare)
• Constitutional: fever, weight loss, malaise, myalgia

Red Flags

• New cardiac symptoms in known severe eosinophilic asthma (chest pain, heart failure)
• Mononeuritis multiplex (foot/wrist drop)
• Rapidly worsening renal function
• GI perforation
• Any combination of asthma + eosinophilia + systemic features

Bedside

• ECG: ST changes, heart block, arrhythmias (cardiac involvement)
• Urinalysis: haematuria, proteinuria (glomerulonephritis)
• Neurological examination: mononeuritis multiplex assessment

Bloods

• FBC: marked eosinophilia (>1.5 × 10⁹/L, often >5)
• ANCA: pANCA/anti-MPO positive in ~40%; cANCA/PR3 positive in <5%
• CRP/ESR: raised (active vasculitis)
• U&Es: renal function assessment
• IgE: often elevated
• Troponin, BNP/NT-proBNP: cardiac involvement
• CK: if myositis

Imaging

• CXR/HRCT: transient migratory infiltrates, ground-glass opacities, consolidation (no cavitation — unlike GPA)
• Cardiac MRI: gold standard for myocardial involvement — oedema, late gadolinium enhancement, reduced EF
• Echocardiography: LV function, pericardial effusion, wall motion abnormalities
• CT sinuses: mucosal thickening, polyps

Special Tests

• Tissue biopsy: eosinophilic infiltration, necrotising vasculitis, extravascular granulomata; skin, sural nerve, or lung biopsy
• NCS/EMG: peripheral neuropathy characterisation
• BAL: eosinophilia (>33% suggests EGPA)
• PFTs: obstructive pattern (asthma component)

Non-pharmacological

• MDT approach: respiratory, rheumatology, cardiology, neurology as needed
• Smoking cessation
• Monitoring: regular echocardiography, NCS, renal function, eosinophil count

Pharmacological

• Induction (FFS = 0, no organ-threatening disease): prednisolone 1 mg/kg/day (max 60 mg) for 3-4 weeks, taper over 9-12 months
• Induction (FFS ≥1 or organ-threatening): prednisolone 1 mg/kg/day PLUS cyclophosphamide IV 15 mg/kg (max 1.2 g) every 2 weeks × 3 then every 3 weeks × 3 (CYCLOPS protocol); OR rituximab 375 mg/m² weekly × 4
• Maintenance: azathioprine 2-3 mg/kg/day (check TPMT) or methotrexate 15-25 mg/week for ≥24 months
• Mepolizumab (anti-IL5): 300 mg SC monthly — licensed for relapsing/refractory EGPA (MIRRA trial) — NICE TA946
• Benralizumab (anti-IL5R): emerging evidence (MANDARA trial)
• Continue asthma therapy: ICS/LABA, consider biologic therapies

Surgical/Interventional

• Plasma exchange: if rapidly progressive glomerulonephritis or pulmonary haemorrhage
• Nasal polypectomy: for symptomatic nasal polyps

Referral Criteria

• Urgent rheumatology/vasculitis service referral for all suspected EGPA
• Cardiology referral for cardiac involvement
• Neurology for mononeuritis multiplex
• Nephrology for renal involvement

With treatment, 5-year survival is >80%. The Five-Factor Score (FFS) predicts mortality: FFS 0 = good prognosis; FFS ≥2 = poorer prognosis (5-year mortality ~25%). Cardiac involvement is the leading cause of death (~50% of EGPA deaths). Relapse rate is approximately 25-35% within 5 years. ANCA-positive patients have higher relapse rates. Peripheral neuropathy may cause significant long-term disability despite otherwise well-controlled disease. Mepolizumab has improved outcomes in refractory disease.

Five-Factor Score (FFS) for EGPA Prognosis

ANCA Status and Disease Phenotype