Eosinophilic Granulomatosis with Polyangiitis
ANCA-associated small-vessel vasculitis (formerly Churg-Strauss syndrome) characterised by asthma, eosinophilia, and granulomatous vasculitis. ANCA (p-ANCA/MPO) positive in only 40% of cases. Distinguished from other AAV by prominent eosinophilia and asthma.
Key Facts
EGPA (formerly Churg-Strauss) is characterised by asthma (>95%), peripheral eosinophilia, and vasculitis affecting small-medium vessels p-ANCA (anti-MPO) positive in only ~40%; ANCA-positive patients have more renal and neurological involvement Three phases: prodromal (allergic rhinitis, asthma), eosinophilic (tissue infiltration), vasculitic (systemic vasculitis) Cardiac involvement (cardiomyopathy, pericarditis) is the leading cause of death (~50% of EGPA mortality); often ANCA-negative Five-Factor Score (FFS): predicts prognosis; cardiac, GI, renal involvement = worse outcome Treatment: prednisolone ± cyclophosphamide (if FFS ≥1); mepolizumab (anti-IL-5) is NICE approved for relapsing/refractory EGPA Incidence: ~2 per million/year; rarest of the three AAV types
Overview
Key Facts
EGPA is unique among AAV due to its association with asthma and eosinophilia. The distinction between ANCA-positive and ANCA-negative disease has important implications for organ involvement and treatment.
Epidemiology
- Incidence: ~2 per million/year
- Peak age: 40-60; M=F
- Rarest of the three AAV
Pathophysiology
- Eosinophilic tissue infiltration + granulomatous inflammation + small-vessel vasculitis
- IL-5-driven eosinophil activation and survival
- ANCA-positive: more GN and neuropathy (similar to other AAV)
- ANCA-negative: more cardiac and pulmonary infiltrates (eosinophil-driven)
Clinical Presentation
Prodromal Phase
- Allergic rhinitis, nasal polyps
- Adult-onset asthma (usually severe, steroid-dependent)
- May last years before vasculitic phase
Eosinophilic Phase
- Peripheral eosinophilia (often >1.5 × 10⁹/L, sometimes >10 × 10⁹/L)
- Eosinophilic pulmonary infiltrates: migratory, transient
- Eosinophilic gastroenteritis: abdominal pain, diarrhoea
Vasculitic Phase
- Cardiac (leading cause of death): myocarditis, pericarditis, cardiomyopathy, heart failure
- Nervous system: mononeuritis multiplex (most common neuropathy; 70%), cranial neuropathy
- Skin: palpable purpura (50%), nodules
- Renal: crescentic GN (less common than GPA/MPA; ~25%)
- GI: mesenteric vasculitis, perforation
- Constitutional: fever, weight loss, fatigue
Red Flags
- Cardiac involvement → echocardiogram, troponin, cardiac MRI
- Mononeuritis multiplex → nerve conduction studies
- GI vasculitis → surgical emergency if perforation
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| GPA | No asthma, granulomata in upper airway, PR3-ANCA | ANCA, CT |
| MPA | No asthma/eosinophilia, MPO-ANCA | ANCA, biopsy |
| Hypereosinophilic syndrome | Eosinophilia, organ damage, no vasculitis | FIP1L1-PDGFRA |
| Allergic bronchopulmonary aspergillosis | Asthma, eosinophilia, Aspergillus sensitisation | IgE, Aspergillus IgE |
| Parasitic infection | Travel history, eosinophilia | Stool OCP, serology |
Diagnosis / Investigation
Bloods
- FBC: eosinophilia (usually >1.5 × 10⁹/L; often >10)
- p-ANCA (anti-MPO): positive in ~40%
- IgE: elevated
- CRP/ESR: elevated
- Troponin: cardiac involvement
- U&Es: renal function
Imaging
- CT chest: patchy migratory infiltrates, ground-glass opacities
- Cardiac MRI: myocarditis, fibrosis (most sensitive for cardiac EGPA)
- Echocardiogram: pericardial effusion, LV dysfunction
Biopsy
- Tissue biopsy (skin, nerve, lung): eosinophilic infiltration, granulomata, vasculitis
- Nerve biopsy: vasculitic neuropathy
Neurophysiology
- Nerve conduction studies/EMG: mononeuritis multiplex pattern
Management
Induction
FFS = 0 (no poor prognosis factors):
- Prednisolone 1mg/kg/day alone; taper over months
FFS ≥1 (cardiac, GI, renal, CNS):
- Prednisolone + IV cyclophosphamide (CYCLOPS protocol) OR rituximab
Maintenance
- Azathioprine 2mg/kg/day or methotrexate
- Continue low-dose prednisolone (many patients require long-term due to asthma)
Mepolizumab (Anti-IL-5)
- NICE TA845: approved for relapsing/refractory EGPA
- MIRRA trial: 300mg SC monthly; reduced relapse by 50%, reduced steroid dose
- Particularly effective for eosinophil-driven disease
Asthma Management
- Optimise asthma therapy (inhalers, biologics)
- Often severe, steroid-dependent asthma
- Mepolizumab also treats severe eosinophilic asthma
Referral
- All EGPA → rheumatology
- Cardiac involvement → cardiology (cardiac MRI)
- Neuropathy → neurology
Prognosis
- 5-year survival: 80-90% with treatment
- Cardiac involvement: major determinant of mortality (~50% of deaths)
- Five-Factor Score (FFS): higher score = worse prognosis
- Relapse rate: 25-35% within 5 years
- Mepolizumab: significantly reduces relapse and steroid requirements
- ANCA-positive: more renal/neurological; ANCA-negative: more cardiac
Other Relevant Information
Five-Factor Score (FFS) for EGPA
| Factor | Points |
|---|---|
| Cardiac involvement | 1 |
| GI involvement | 1 |
| Renal insufficiency (creatinine >141 µmol/L) | 1 |
| Proteinuria (>1g/day) | 1 |
| CNS involvement | 1 |
FFS 0: good prognosis; FFS ≥1: poor prognosis → immunosuppression required