What is eosinophilic granulomatosis with polyangitis?

What is Eosinophilic Granulomatosis with Polyangiitis?

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is a rare small-vessel vasculitis that occurs in patients with asthma and eosinophilia, histologically characterized by tissue eosinophilia, necrotizing vasculitis, and eosinophil-rich granulomatous inflammation. 1

Epidemiology and Demographics

• Incidence ranges between 0.5 and 4.2 cases per million people per year, with prevalence between 10 and 14 cases per million inhabitants globally 1
• Equal frequency in men and women, with mean age at diagnosis around 50 years 1
• Pediatric cases are extremely rare 1

Clinical Phases and Presentation

EGPA typically evolves through three distinct but often overlapping phases 1:

1. Prodromic "Allergic" Phase

• Marked by asthma and chronic rhinosinusitis 1
• Can last for several years 1
• Includes allergic rhinitis and nasal polyposis 1

2. Eosinophilic Phase

• Peripheral blood eosinophilia develops 1
• Eosinophil infiltration into tissues occurs 1
• End-organ involvement appears 1

3. Vasculitic Phase

• Necrotizing vasculitis leads to multi-organ dysfunction 1
• Mononeuritis multiplex and glomerulonephritis are characteristic 1

Important caveat: These phases often overlap, do not necessarily develop in this sequence, and some patients never manifest vasculitic complications 1

ANCA Status and Clinical Phenotypes

ANCA (usually anti-myeloperoxidase) is detectable in only 30-40% of cases, creating two distinct clinical phenotypes 1:

ANCA-Positive Phenotype

• More frequent vasculitic features: glomerulonephritis, peripheral neuropathy, and purpura 1
• Histopathological evidence of vasculitis is more common 1

ANCA-Negative Phenotype

• More frequent eosinophilic features: cardiac involvement and gastroenteritis 1
• Associated with genetic variants in mucosal responses and eosinophil biology (GPA33, IL5) 1

Features Common to Both Phenotypes

• Asthma occurs in >90% of all patients 1
• ENT disease occurs in 60-80% of all patients 1

Organ System Involvement

Respiratory System

• Asthma is present in >90% of patients 1
• Lung infiltrates can occur 1

Cardiovascular System

• Cardiomyopathy is more common in ANCA-negative patients 1
• Heart involvement is the most common cause of death in EGPA 2

Neurological System

• Peripheral neuropathy, particularly mononeuritis multiplex 1
• Polyneuropathies are common and may be severe 2

Renal System

• Glomerulonephritis occurs more frequently in ANCA-positive patients 1

Gastrointestinal System

• Gastroenteritis is more frequent in ANCA-negative patients 1

Dermatological

• Purpura occurs more often in ANCA-positive patients 1

Pathogenesis

The disease is driven by both genetic and environmental factors 1:

Genetic Factors

• HLA-DQ association with MPO-ANCA-positive EGPA 1
• GPA33 and IL5 variants associated with ANCA-negative EGPA 1

Environmental Risk Factors

• Exposure to silica, organic solvents, and farming increases risk 1
• Cigarette smoking is associated with lower risk 1

Immunopathogenesis

• Eosinophils are central to tissue damage 1
• CD4+ T cells are polarized toward TH2 phenotype 1
• B cell dysregulation with ANCA production and enhanced IgG4 production 1
• IL-5 is a critical survival factor for eosinophils, making it an effective therapeutic target 1

Histopathology

Three characteristic histological features 1:

• Tissue eosinophilia
• Necrotizing vasculitis
• Eosinophil-rich granulomatous inflammation

EGPA lesions usually include eosinophilic infiltrates (with or without granulomas) along with necrotizing vasculitis, making categorization as purely vasculitic or eosinophilic difficult 1

Distinguishing EGPA from Other Conditions

Versus Hypereosinophilic Syndrome (HES)

• EGPA can be distinguished by the presence of vasculitic features and asthma 1
• HES has peripheral eosinophilia (AEC >1500 cells/μL) but lacks vasculitis 1
• When esophageal symptoms occur with hypereosinophilia, screen for multi-organ involvement to differentiate EGPA from HES 1

Versus Allergic Bronchopulmonary Aspergillosis (ABPA)

• EGPA has ANCA positivity in 30-40% of cases; ABPA is always ANCA-negative 3
• ABPA has markedly elevated Aspergillus-specific IgE and IgG; EGPA may have elevated IgE but not Aspergillus-specific 3
• Presence of peripheral neuropathy, renal involvement, purpura, or cardiac involvement strongly suggests EGPA over ABPA 3
• Central bronchiectasis with mucoid impaction is characteristic of ABPA, not EGPA 3

Prognosis and Outcomes

• Overall survival has improved markedly with glucocorticoids and immunosuppressants 4
• Relapse rates remain high 4
• Cardiac involvement is the most common cause of death 2
• Prolonged corticosteroid treatment is often necessary for asthma management 2