What is Granulomatosis with Polyangiitis (GPA), formerly known as Wegener's granulomatosis?

From the Guidelines

Granulomatosis with Polyangiitis (GPA) is a rare autoimmune disorder that causes inflammation of blood vessels, primarily affecting the respiratory tract and kidneys, and is characterized by the presence of anti-neutrophil cytoplasmic antibodies (ANCA) that attack neutrophils, triggering inflammation in small and medium-sized blood vessels. The condition is also known as Wegener's granulomatosis. According to the 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis 1, GPA can be classified into different disease statuses, including active severe disease, active non-severe disease, remission, refractory disease, and relapse. Key characteristics of GPA include:

• Active disease: new, persistent, or worsening clinical signs and/or symptoms attributed to GPA and not related to prior damage
• Severe disease: vasculitis with life- or organ-threatening manifestations, such as alveolar hemorrhage, glomerulonephritis, or central nervous system vasculitis
• Non-severe disease: vasculitis without life- or organ-threatening manifestations, such as rhinosinusitis, asthma, or mild systemic symptoms
• Remission: absence of clinical signs or symptoms attributed to GPA, on or off immunosuppressive therapy Treatment of GPA typically involves a combination of corticosteroids and immunosuppressants, with the goal of inducing remission and preventing relapse. Some of the key recommendations for the treatment of GPA include:
• Initial therapy with prednisone (1 mg/kg/day, maximum 80 mg daily) combined with cyclophosphamide (either oral at 2 mg/kg/day or intravenous at 15 mg/kg every 2-3 weeks) for severe disease 1
• Alternatively, rituximab (375 mg/m² weekly for 4 weeks) may be used instead of cyclophosphamide 1
• Maintenance therapy with less toxic agents like azathioprine (2 mg/kg/day), methotrexate (20-25 mg weekly), or mycophenolate mofetil (2 g/day) is recommended for at least 18-24 months 1
• Patients should receive Pneumocystis pneumonia prophylaxis with trimethoprim-sulfamethoxazole during treatment 1
• Regular monitoring of kidney function, complete blood counts, and urinalysis is essential 1 It is essential to note that the treatment of GPA should be individualized based on the patient's clinical condition, values, and preferences, and that the optimal duration of anticoagulation is unknown for patients with GPA who experience venous thrombotic events 1. In patients with GPA and active glomerulonephritis, plasma exchange may be considered for those at higher risk of progression to end-stage renal disease, although the benefit of plasma exchange must be weighed against the increased risk of serious infection 1. Overall, GPA is a complex and potentially life-threatening condition that requires prompt and effective treatment to induce remission and prevent long-term damage.

From the Research

Definition and Characteristics of Granulomatosis with Polyangiitis (GPA)

• Granulomatosis with Polyangiitis (GPA), formerly known as Wegener's granulomatosis, is a systemic vasculitis characterized by involvement of the upper airways, lungs, and kidneys 2.
• It is a granulomatous disorder associated with systemic necrotizing vasculitis, predominantly involving the upper airways, lung, and kidneys 3.
• GPA is associated with the presence of circulating antineutrophil cytoplasm antibodies (c-ANCAs) 4.

Clinical Manifestations and Diagnosis

• The disease often begins with symptoms limited to the upper and/or lower respiratory tracts and may transform into a generalized phase, characterized by systemic necrotizing vasculitis 3.
• The diagnosis of GPA is based on clinical manifestations, histological findings, and the presence of ANCA in serum 5.
• The American College of Rheumatology criteria for diagnosis include oral and nasal inflammation, abnormal chest radiography, urinary sediment, and granulomatous inflammation on biopsy 5.

Treatment and Management

• The current treatment of GPA is stratified based on severity, with options including glucocorticoids combined with either cyclophosphamide or rituximab for severe disease 2.
• For patients with active but non-severe GPA, methotrexate and glucocorticoids can induce and maintain remission 2.
• Rituximab has been found to be as effective as cyclophosphamide in inducing remission of severe active GPA, but there are still questions regarding relapse rate, use of repeat courses, long-term toxicity, and combination with maintenance agents 2.