What is Churg-Strauss Syndrome?

Eosinophilic Granulomatosis with Polyangiitis (EGPA)

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is a rare systemic vasculitis characterized by asthma, eosinophilia, and small-to-medium vessel vasculitis with eosinophilic tissue infiltration and granulomatous inflammation. 1

Clinical Features and Pathophysiology

EGPA typically evolves through three distinct phases:

1. Prodromal (allergic) phase:

   • Asthma (occurs in >90% of patients)
   • Allergic rhinitis
   • Nasal polyposis
   • This phase can last for several years

2. Eosinophilic phase:

   • Peripheral blood eosinophilia (>1500 cells/μL)
   • Eosinophilic infiltration into tissues
   • Organ involvement begins

3. Vasculitic phase:

   • Necrotizing vasculitis
   • Multi-organ dysfunction

The pathophysiology involves genetic and environmental factors, with an exaggerated Th2 immune response playing a central role. Eosinophilic infiltration and endothelial damage are key mechanisms, with evidence of involvement of Th1 and Th17 cells in later disease stages 1.

Diagnostic Criteria

According to the American College of Rheumatology, at least four of these six criteria must be present for diagnosis 1:

1. Asthma
2. Eosinophilia >10%
3. Mono- or polyneuropathy
4. Non-fixed pulmonary infiltrates
5. Paranasal sinus abnormalities
6. Biopsy showing accumulated eosinophils in extravascular tissue

Clinical Manifestations

EGPA can affect multiple organ systems:

• Respiratory: Asthma (>90%), pulmonary infiltrates, pleural effusions
• ENT: Rhinosinusitis, nasal polyps (60-80%)
• Neurological: Peripheral neuropathy, mononeuritis multiplex
• Skin: Purpura, nodules, urticaria
• Cardiac: Myocarditis, pericarditis, heart failure
• Gastrointestinal: Abdominal pain, diarrhea, bleeding
• Renal: Glomerulonephritis (less common than in other ANCA-associated vasculitides)

Laboratory Findings

• Elevated eosinophil count (>1500 cells/μL)
• ANCA positivity in 30-40% of cases (primarily MPO-ANCA)
• Elevated IgE levels
• Elevated inflammatory markers (ESR, CRP)
• Increased IgG4 and IgG4/IgG ratios in some cases 1

Disease Subtypes

EGPA presents with two distinct phenotypes based on ANCA status 1:

1. ANCA-positive (30-40% of cases):

   • More vasculitic features
   • Higher rates of glomerulonephritis, peripheral neuropathy, and purpura
   • Better response to immunosuppressive therapy

2. ANCA-negative (60-70% of cases):

   • More eosinophilic tissue infiltration
   • Higher rates of cardiac involvement and eosinophilic gastroenteritis
   • May respond better to targeted therapies against eosinophils

Prognosis

Prognosis is determined by the Five-Factor Score (FFS), which includes 2:

• Cardiac involvement
• Gastrointestinal involvement
• Renal insufficiency
• Proteinuria >1g/24h
• Central nervous system involvement

Patients with FFS=0 have better survival rates than those with FFS≥1 3.

Treatment

Treatment should be tailored according to disease severity and FFS:

1. For all patients:

   • High-dose corticosteroids: Prednisone 1 mg/kg/day or methylprednisolone with tapering over 6 months 4
   • For severe or rapidly progressing disease: IV methylprednisolone pulse (1g/day for 3 days)

2. For patients with poor prognostic factors (FFS≥1) or refractory disease:

   • Cyclophosphamide for induction therapy (15 mg/kg IV every 2-3 weeks) 5, 2
   • Rituximab as an alternative to cyclophosphamide 5
   • Maintenance therapy with azathioprine (1.5-2 mg/kg/day) for 18-24 months 5, 2

3. For refractory cases:

   • Intravenous immunoglobulin (IVIG) may be beneficial, particularly for neuropathy and cardiomyopathy 4
   • Mepolizumab (anti-IL-5) shows promise for steroid-sparing and maintaining remission 6

Monitoring and Follow-up

• Regular monitoring of eosinophil counts, inflammatory markers, and organ function
• Vigilance for disease relapse, which can occur even after years of remission
• Screening for treatment-related complications
• Long-term follow-up is essential as relapses are not uncommon, though overall survival is excellent with appropriate treatment 2, 7

Differential Diagnosis

EGPA must be distinguished from:

• Hypereosinophilic syndromes
• Other ANCA-associated vasculitides (GPA, MPA)
• Parasitic infections
• Drug reactions
• Other eosinophilic lung diseases

When EGPA affects the esophagus, symptoms can mimic eosinophilic esophagitis but can be distinguished by peripheral eosinophilia and multi-organ involvement 1.

EGPA represents a distinct entity within the spectrum of vasculitides, with unique clinical features and treatment considerations. Early recognition and appropriate management significantly improve outcomes and reduce mortality.