Symptoms of Granulomatosis with Polyangiitis (GPA)
Granulomatosis with polyangiitis presents with a characteristic triad of upper respiratory tract, lower respiratory tract, and renal involvement, though the clinical spectrum ranges from localized disease to fulminant multisystem vasculitis. 1, 2
Upper Respiratory Tract Manifestations (Most Common Initial Presentation)
The upper respiratory tract is involved in 70-100% of cases and often represents the first clinical manifestation 3:
- Nasal symptoms: Chronic nasal crusting, stuffiness, and epistaxis (nosebleeds) are hallmark presenting features 2
- Chronic rhinosinusitis with possible nasal polyps that commonly recur after surgical excision 2
- Nasal septal perforation can develop in advanced cases 2
- Otologic disease: Otitis media and hearing loss occur in approximately 35% of cases (range 19-61%) 3
Lower Respiratory Tract Manifestations
Pulmonary involvement is a cardinal feature of GPA 4, 5:
- Pulmonary infiltrates and nodules are common findings 2
- Alveolar hemorrhage can occur in severe cases and represents a life-threatening complication 2
- Necrotizing granulomatous inflammation of the bronchi and lung parenchyma 4
Renal Manifestations
Kidney involvement is a defining feature that significantly impacts prognosis 1:
- Glomerulonephritis manifesting as proteinuria, hematuria, and varying degrees of kidney failure 2
- Pauci-immune necrotizing crescentic glomerulonephritis is the pathologic hallmark 1
- Elevated serum creatinine indicating renal dysfunction 1
- The 10-year survival rate is approximately 40% when kidneys are involved versus 60-70% without renal involvement 3
Ocular Manifestations
Eye involvement occurs frequently 2:
- Scleritis is a common ocular manifestation 2
- Retro-orbital tumors can develop as part of granulomatous disease 5
Neurological Manifestations
Peripheral nervous system involvement is frequent 2:
- Peripheral neuropathy with a mononeuritis multiplex pattern 2
- Pachymeningitis (inflammation of the dura mater) can occur 5
Cutaneous Manifestations
Skin lesions are common but heterogeneous 2:
- Palpable purpura is the most vasculitis-specific skin lesion 2
- Various other skin manifestations may occur 2
Systemic Manifestations
Constitutional symptoms are frequently present 2:
Cardiac Manifestations (Less Common)
Cardiac involvement is infrequent but can occur 6:
- Cardiac complications represent one of the less common but serious manifestations 6
Important Clinical Pearls
PR3-ANCA (c-ANCA) positivity is present in 80-90% of GPA cases and is highly specific for this diagnosis, though ANCA negativity does not exclude the disease 1, 2. The disease spectrum is heterogeneous, ranging from indolent single-site involvement to fulminant multiorgan vasculitis 4. Without treatment, mean survival is only 5 months, but with modern immunosuppressive therapy, mean survival has improved to 21.7 years from diagnosis 1.