What are the key findings and diagnostic approach for granulomatosis with polyangitis (GPA)?

Key Findings and Diagnostic Approach for Granulomatosis with Polyangiitis (GPA)

A multidisciplinary diagnostic evaluation is essential for diagnosing granulomatosis with polyangiitis (GPA), focusing on clinical features, laboratory findings, and histological evidence of vasculitis. 1

Clinical Manifestations

ENT and Respiratory Findings

• Nasal crusting, stuffiness, epistaxis (nosebleeds), and chronic rhinosinusitis with possible nasal polyps are common presenting symptoms 1
• Otitis media and hearing loss may occur in patients with GPA 1
• Nasal septal perforation can develop in advanced cases 1
• Pulmonary infiltrates and nodules are common; these are often multiple and migratory, responding to treatment with systemic glucocorticoids 1, 2
• Alveolar hemorrhage can occur in severe cases 1

Renal Manifestations

• Glomerulonephritis is a hallmark feature, though not always present at initial presentation 1, 2
• Manifests as proteinuria, hematuria, and varying degrees of kidney failure 1
• Kidney biopsy typically shows crescentic necrotizing glomerulonephritis 3

Systemic Manifestations

• Peripheral neuropathy with mononeuritis multiplex pattern, often sensory but may cause motor deficits 1
• Skin lesions including palpable purpura (most vasculitis-specific lesion) 1
• Arthralgia and myalgia are common systemic manifestations 1
• Systemic symptoms such as fatigue, weight loss, and fever may be present 2

Laboratory Findings

ANCA Testing

• Anti-neutrophil cytoplasmic antibodies (ANCA) testing should be performed in all suspected cases of GPA 1
• PR3-ANCA (c-ANCA) is highly specific to GPA and present in 80-90% of cases 1, 2
• ANCA positivity is not essential for diagnosis but has high diagnostic value when present 2

Other Laboratory Tests

• Complete blood count with differential diagnosis 3
• Urinalysis showing hematuria and proteinuria in cases with renal involvement 1
• Inflammatory markers (ESR, CRP) are typically elevated 3
• Renal function tests (creatinine, BUN) to assess kidney involvement 3

Diagnostic Evaluation

Baseline Investigations

• Routine laboratory investigations including complete blood count, renal function, and inflammatory markers 3
• Urinalysis, 24-h proteinuria or urinary protein-to-creatinine ratio 3
• Chest radiograph and/or high-resolution CT (HRCT) 3
• ENT consultation with nasal endoscopy 3
• Echocardiography to evaluate cardiac involvement 3

Specialized Investigations

• Biopsy of affected organs is recommended when feasible to confirm diagnosis 3
• Common biopsy sites include kidney, skin, ENT region, and lung 3
• Pulmonary function tests to assess respiratory involvement 3
• Electromyography and nerve conduction studies for peripheral neuropathy 3
• Brain and/or spinal cord MRI for CNS manifestations 3

Disease Assessment Tools

• Birmingham Vasculitis Activity Score (BVAS) is the primary validated tool for assessing disease activity 1, 4
• BVAS/WG evaluates manifestations across multiple systems including systemic, cutaneous, mucous/ocular, ENT, pulmonary, cardiovascular, gastrointestinal, and renal 4
• Five-Factor Score (FFS) predicts mortality risk in patients with established diagnosis 4

Differential Diagnosis

• Other small-vessel vasculitides (microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis) 3
• IgA vasculitis and cryoglobulinaemia (typically show immune deposits, which are absent in GPA) 3
• Infectious processes (tuberculosis, fungal infections) 5
• Malignancies (lymphoma, lung cancer) 5
• Sarcoidosis 5

Treatment Approach

• Initial therapy includes glucocorticoids combined with either rituximab or cyclophosphamide 1, 6
• Rituximab 375 mg/m² once weekly for 4 weeks plus glucocorticoids is effective for remission induction 6
• Plasma exchange may be considered in cases with pulmonary hemorrhage or severe renal involvement 1
• Options for maintenance therapy include azathioprine, methotrexate, rituximab, or co-trimoxazole 1

Monitoring and Prognosis

• Regular monitoring of ANCA levels is recommended, though decisions should not be based solely on ANCA titers 4
• Routine monitoring of organ-specific manifestations, particularly lung function, cardiovascular events, and neurological complications 4
• Long-term monitoring for treatment-related complications (infections, malignancy, osteoporosis) is essential 4

Common Pitfalls and Caveats

• Diagnosis may be delayed due to nonspecific initial symptoms 5
• Early mortality during the first year of treatment is often due to infections under immunosuppressive therapy 7
• Refractory disease activity, particularly granulomatous manifestations, can be challenging to treat 7
• ANCA may be negative in some cases, particularly in limited forms of the disease 2
• Treatment decisions should be modified for special populations (children, elderly, pregnant women) 3