What is the difference between Granulomatosis with Polyangiitis (GPA) and Eosinophilic Granulomatosis with Polyangiitis (EGPA)?

From the Guidelines

Granulomatosis with Polyangiitis (GPA) and Eosinophilic Granulomatosis with Polyangiitis (EGPA) are distinct forms of vasculitis with different clinical presentations and treatment approaches. The main difference between GPA and EGPA lies in their histological characteristics, with GPA characterized by necrotizing granulomatous inflammation and EGPA characterized by eosinophilic tissue infiltration 1.

Clinical Presentation

• GPA is commonly associated with destructive sinonasal lesions, pulmonary nodules, and pauci-immune glomerulonephritis, and is most commonly associated with cytoplasmic ANCA and antibodies to proteinase 3 (PR3) 1.
• EGPA, on the other hand, is characterized by asthma, peripheral eosinophilia, and peripheral neuropathy, and only 40% of patients produce detectable ANCA 1.
• The clinical phenotype of EGPA is heterogeneous and can evolve through different phases, including a prodromic ‘allergic’ phase, an eosinophilic phase, and a vasculitic phase 1.

Treatment Approach

• Both conditions often require immunosuppressive therapy, with a common initial treatment being a combination of glucocorticoids and cyclophosphamide or rituximab 1.
• For GPA, the goal is to induce remission, which can often be achieved within 3-6 months, whereas EGPA treatment may also involve antihistamines and asthma medications to manage eosinophilic asthma symptoms.
• The treatment duration for both conditions can vary, but typically, induction therapy lasts for 3-6 months, followed by maintenance therapy with medications like methotrexate, azathioprine, or mycophenolate mofetil for at least 12-18 months to prevent relapse 1.

Key Differences

• GPA tends to have more severe renal involvement and often requires more aggressive immunosuppression, whereas EGPA is characterized by eosinophilia and asthma-like symptoms 1.
• The pathogenesis of EGPA is driven by genetic and environmental factors, with several cell types participating in the immunopathogenesis of the disease, including eosinophils, CD4+ T cells, and type 2 innate lymphoid cells 1.

From the Research

Differences between Granulomatosis with Polyangiitis (GPA) and Eosinophilic Granulomatosis with Polyangiitis (EGPA)

• GPA is a systemic vasculitis characterized by involvement of the upper airways, lungs, and kidneys, whereas EGPA is also a systemic granulomatous vasculitis, but it is distinguished by a prodromic phase characterized by asthma and rhino-sinusitis, followed by an eosinophilic phase and a vasculitic phase 2.
• GPA is associated with anti-neutrophil cytoplasmic antibodies (ANCA) and is highly specific to proteinase 3 (PR3) ANCA, whereas EGPA is also associated with ANCA, but it is more commonly associated with eosinophilia and asthma-like symptoms 2, 3.
• The clinical manifestations of GPA and EGPA can overlap, and some patients may present with features of both diseases, as seen in a case report of a patient with overlap of GPA and EGPA 4.
• The treatment of GPA and EGPA may also overlap, with both diseases requiring immunosuppressive therapy, such as corticosteroids and cyclophosphamide or rituximab, to achieve remission 5, 3.
• However, the specific treatment approach may vary depending on the severity of the disease and the presence of specific clinical features, such as eosinophilia or ANCA positivity 5, 6.

Clinical Features of GPA and EGPA

• GPA is characterized by systemic necrotizing vasculitis, necrotizing granulomatous inflammation, and necrotizing glomerulonephritis, whereas EGPA is characterized by a prodromic phase, an eosinophilic phase, and a vasculitic phase 2, 6.
• GPA can present with a range of clinical features, including ENT signs, lung involvement, and kidney involvement, whereas EGPA is more commonly associated with asthma-like symptoms, eosinophilia, and skin lesions 2, 3.
• Both GPA and EGPA can present with polymorphic cutaneous manifestations, including palpable purpura, livedo reticularis, and necrotic-ulcerative lesions 2.

Diagnosis and Classification of GPA and EGPA

• GPA is diagnosed based on clinical manifestations of systemic vasculitis and histological evidence of necrotizing vasculitis or granulomatous inflammation, whereas EGPA is diagnosed based on a combination of clinical features, including asthma, eosinophilia, and vasculitis 2, 6.
• The classification of GPA and EGPA is based on the presence of specific clinical features and laboratory findings, including ANCA positivity and eosinophilia 2, 6.