What are the presentations of Granulomatosis with Polyangiitis (GPA), formerly known as Wegener's (Wegener's) granulomatosis?

From the Guidelines

Granulomatosis with polyangiitis (GPA) typically presents with a triad of upper airway, lung, and kidney involvement, and patients often initially experience nonspecific symptoms like fever, fatigue, weight loss, and night sweats. The clinical manifestations of GPA can be varied, but common presentations include:

• Upper respiratory manifestations: sinusitis, nasal crusting, epistaxis, nasal septal perforation, and otitis media
• Pulmonary involvement: cough, hemoptysis, dyspnea, and chest pain, with radiographic findings showing nodules, infiltrates, or cavitary lesions
• Renal disease: hematuria, proteinuria, and can progress to rapidly progressive glomerulonephritis
• Other presentations: ocular inflammation (scleritis, episcleritis), skin lesions (purpura, ulcers), neurological symptoms (mononeuritis multiplex, cranial nerve palsies), and arthralgia 1. According to the most recent evidence, the diagnosis of GPA requires clinical suspicion, positive ANCA (typically c-ANCA/PR3-ANCA) serology, and tissue biopsy showing necrotizing granulomatous inflammation 1. It is essential to recognize GPA early, as prompt treatment with immunosuppressive therapy significantly improves outcomes in this potentially life-threatening vasculitis 1. The clinical presentation of GPA can vary, and some patients may present with extrarenal manifestations, such as pulmonary hemorrhage, which affects 10% of patients with ANCA-associated vasculitis and is associated with an increased risk of death 1. In terms of treatment, the KDIGO 2024 clinical practice guideline for the management of ANCA-associated vasculitis recommends initial therapy with immunosuppressive agents, such as glucocorticoids, rituximab, or cyclophosphamide, and maintenance therapy with immunosuppressive agents to prevent relapse 1.

From the Research

Clinical Presentations of Granulomatosis with Polyangiitis (GPA)

The clinical presentations of Granulomatosis with Polyangiitis (GPA), formerly known as Wegener's granulomatosis, are diverse and can affect various organs. The key features of GPA include:

• Upper respiratory tract involvement, such as sinusitis, crusting rhinitis, saddle nose deformity, and otitis media 2, 3, 4, 5, 6
• Lower respiratory tract involvement, including excavated lung nodules and alveolar hemorrhage 2, 3, 4, 5, 6
• Kidney involvement, characterized by crescentic necrotizing glomerulonephritis 2, 3, 4, 5, 6
• Necrotizing vasculitis involving small vessels, extensive "geographic" necrosis, and granulomatous inflammation 2, 3, 4, 5, 6
• Mononeuritis multiplex and necrotic purpura are frequent symptoms in GPA 4
• The presence of anti-neutrophil cytoplasmic antibodies (ANCA) directed against proteinase 3, which is highly specific to GPA and has a high diagnostic value 5

Organ Involvement

The organs involved in GPA can vary, but the most common sites of involvement are:

• Upper respiratory tract (70-100% of cases) 6
• Lower respiratory tract (bronchi and lung) 2, 3, 4, 5, 6
• Kidney (characterized by crescentic necrotizing glomerulonephritis) 2, 3, 4, 5, 6
• Ear, nose, and throat (ENT) area, including the nasal cavity and paranasal sinuses (85-100% of cases) 6
• Otolological disease (approximately 35% of cases) 6

Disease Spectrum and Severity

The spectrum and severity of GPA can range from:

• Indolent disease involving only one site 2, 3
• Fulminant, multiorgan vasculitis 2, 3
• Limited, non-life-threatening disease 3
• Generalized, multisystemic disease 2, 3