What are the clinical presentation and initial treatment of acute vasculitis?

From the Guidelines

Acute vasculitis should be treated with a combination of cyclophosphamide and glucocorticoids for remission induction, particularly in cases of generalized primary small and medium vessel vasculitis, as recommended by the EULAR guidelines 1. The presentation of acute vasculitis can vary widely, including systemic symptoms such as fever, fatigue, weight loss, and organ-specific manifestations depending on the vessels affected. Common presentations include palpable purpura, mononeuritis multiplex, pulmonary hemorrhage, glomerulonephritis, or unexplained multisystem disease. Key considerations in the initial treatment of acute vasculitis include:

• The severity of the disease, with severe or life-threatening vasculitis requiring more aggressive treatment
• The specific type of vasculitis, with ANCA-associated vasculitis often requiring combination therapy with high-dose corticosteroids and cyclophosphamide or rituximab
• The need for prophylaxis against Pneumocystis jirovecii pneumonia with trimethoprim-sulfamethoxazole during intensive immunosuppression
• The importance of monitoring for drug toxicity and adjusting treatment as needed, as outlined in the EULAR guidelines 1. In terms of specific treatment regimens, the EULAR guidelines recommend a combination of cyclophosphamide (intravenous or oral) and glucocorticoids for remission induction of generalized primary small and medium vessel vasculitis, with a level of evidence 1A for WG and MPA, and grade of recommendation A 1. Some key points to consider when treating acute vasculitis include:
• The use of high-dose corticosteroids, such as methylprednisolone 500-1000mg IV daily for 3 days, followed by oral prednisone 1mg/kg/day (maximum 60-80mg)
• The use of cyclophosphamide, dosed at 15mg/kg IV every 2-3 weeks or 2mg/kg/day orally
• The potential use of rituximab, given as 375mg/m² weekly for 4 weeks, as an alternative to cyclophosphamide
• The importance of monitoring for drug toxicity and adjusting treatment as needed, as outlined in the EULAR guidelines 1.

From the FDA Drug Label

In patients treated with cyclophosphamide (followed by azathioprine for maintenance of CR), 38% of patients achieved CR at 6 and 12 months, and 31% of patients achieved CR at 6,12, and 18 months The primary endpoint was the occurrence of major relapse (defined by the reappearance of clinical and/or laboratory signs of vasculitis activity that could lead to organ failure or damage, or could be life threatening) through month 28. By month 28, major relapse occurred in 3 patients (5%) in the non-U.S. -licensed rituximab group and 17 patients (29%) in the azathioprine group.

The initial treatment for acute vasculitis involves the use of immunosuppressants such as cyclophosphamide, followed by maintenance therapy with azathioprine or rituximab.

• Rituximab has been shown to be effective in achieving complete remission in patients with GPA/MPA, with 64% of patients achieving complete remission at 6 months 2.
• The presentation of acute vasculitis can vary, but it often involves the reappearance of clinical and/or laboratory signs of vasculitis activity that could lead to organ failure or damage, or could be life threatening.
• The treatment of pediatric patients with GPA/MPA involves a remission induction phase, followed by a minimum 12-month follow-up phase, and may include the use of rituximab or other immunosuppressants 2.

From the Research

Presentation of Acute Vasculitis

• Acute vasculitis can present with a range of symptoms, including renal involvement, alveolar hemorrhage, and other organ damage 3, 4, 5.
• The diagnosis of acute vasculitis is often made based on a combination of clinical findings, laboratory tests, and biopsy results 3, 4, 5.

Initial Treatment of Acute Vasculitis

• The initial treatment of acute vasculitis typically involves the use of immunosuppressive medications, such as rituximab, cyclophosphamide, and glucocorticoids 3, 4, 5, 6, 7.
• Rituximab has been shown to be effective in inducing remission in patients with ANCA-associated vasculitis, and may be preferred over cyclophosphamide in certain situations, such as relapse after cyclophosphamide treatment or in women of childbearing age 3, 4, 6, 7.
• The choice of initial treatment may depend on the severity of the disease, the presence of renal involvement or other organ damage, and the patient's overall health status 3, 4, 5, 6, 7.
• Combination therapy with rituximab and cyclophosphamide may be effective in inducing remission in patients with ANCA-associated vasculitis, and may allow for rapid tapering of high-dose glucocorticoids 5.

Comparison of Treatment Options

• A Bayesian network meta-analysis of randomized controlled trials found that rituximab and mycophenolate mofetil (MMF) demonstrated a trend toward a higher response rate than cyclophosphamide, while rituximab had the highest probability of being a better remission-induction therapy 7.
• The same analysis found that cyclophosphamide displayed a propensity for a lower relapse rate than rituximab and MMF, but rituximab was more likely to be the safest medication due to a lower incidence of serious adverse effects 7.