What are the investigations for Wegener's (Granulomatosis with Polyangiitis)?

From the Guidelines

The investigation of Wegener's granulomatosis (GPA) should prioritize blood tests for c-ANCA/PR3 and imaging studies like HRCT chest and CT sinuses, as outlined in the European position paper on rhinosinusitis and nasal polyps 2020 1. When investigating GPA, it is crucial to consider both laboratory and imaging studies to assess the extent of disease and guide treatment.

• Key laboratory tests include:
  • c-ANCA/PR3, which is positive in 95% of patients with systemic disease and 50% with limited disease 1
  • p-ANCA, although less specific, can be positive in a smaller percentage of patients 1
  • Raised erythrocyte sedimentation rate (ESR) and C-reactive protein, indicating inflammation 1
• Imaging studies are also vital and should include:
  • HRCT chest to evaluate pulmonary involvement 1
  • CT sinuses to assess upper respiratory tract involvement 1 These investigations are essential for diagnosing GPA and differentiating it from other conditions like eosinophilic granulomatosis with polyangiitis (EGPA) and sarcoidosis, which may present with similar symptoms but have distinct laboratory and imaging findings 1.
• For instance, EGPA is characterized by blood eosinophilia, elevated IgE, and p-ANCA/MPO positivity, whereas sarcoidosis may show hypercalcaemia, hypercalciuria, and raised angiotensin-converting enzyme levels 1. Early and accurate diagnosis of GPA is critical for initiating appropriate treatment and improving patient outcomes, given the potential for significant morbidity and mortality associated with this condition.

From the Research

Investigation of Wegner's

• Wegner's granulomatosis, now known as Granulomatosis with Polyangiitis (GPA), is an anti-neutrophilic cytoplasmic autoantibody (ANCA)-associated small-vessel vasculitis 2, 3.
• GPA can affect several organ systems, predominantly the respiratory and renal systems, and its pathogenesis is initiated by the activation of the immune system to produce ANCA, leading to widespread necrosis and granulomatous inflammation 2, 4.
• The diagnosis of GPA is made through clinical symptoms, positive antibody testing, imaging, and kidney biopsy 3, and early diagnosis and management are vital to alter the prognosis of the disease 2.
• Treatment of GPA typically involves the combination of immunosuppressant drugs and corticosteroids, which has converted this typically fatal illness into one in which 80% of patients achieve remission 5.
• However, despite considerable therapeutic progress, relapses remain frequent (50% at 5 years), and maintenance treatment is now the main therapeutic challenge 5.
• Studies have shown that the major cause of renal functional impairment in GPA is relapse of the disease, usually within 2 years after clinical remission, and that prolonged treatment with cyclophosphamide for at least 2 years after clinical remission is recommended 6.
• The pathogenesis of GPA is complex and involves gene-environment interactions, with ANCA, cellular immunity, neutrophils extracellular traps, fibroblasts, vascular endothelial cells, and inflammatory mediators playing a major role 4.