What is the pathophysiology and clinical presentation of vasculitis (inflammation of blood vessels)?

From the Guidelines

Vasculitis treatment should prioritize reduced dose glucocorticoid regimens, as they have been shown to reduce serious infections without compromising efficacy, as demonstrated in the PEXIVAS trial 1.

Overview of Vasculitis

Vasculitis is a group of disorders characterized by inflammation of blood vessel walls, affecting vessels of any size throughout the body. This inflammation causes vessel walls to thicken, narrow, and potentially close off, leading to tissue and organ damage due to restricted blood flow. Vasculitis can be primary (occurring on its own) or secondary (resulting from another condition). Common types include giant cell arteritis, Takayasu's arteritis, polyarteritis nodosa, Kawasaki disease, and ANCA-associated vasculitides like granulomatosis with polyangiitis.

Classification and Clinical Presentation

ANCA-associated vasculitis (AAV) includes granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), with classification also possible based on ANCA serology (myeloperoxidase ANCA or proteinase 3 ANCA) 1. Typical features of GPA include nasal crusting, stuffiness, and epistaxis, while patients with MPA are typically older and present with more severe kidney disease. All forms of AAV can involve pulmonary hemorrhage.

Treatment Approach

Initial therapy for AAV includes induction of remission with immunosuppressive therapy, with options including glucocorticoids, rituximab, cyclophosphamide, and others 1. Maintenance of remission involves immunosuppressive therapy for a variable period to prevent relapse. The PEXIVAS trial showed that a reduced dose regimen of glucocorticoid reduced serious infections at 1 year compared to the standard dose regimen group 1.

Key Considerations

• Reduced dose glucocorticoid regimens are recommended to minimize serious infections without compromising efficacy.
• Treatment should be tailored to the specific type and severity of vasculitis.
• Regular monitoring of disease activity, medication side effects, and organ function is essential.
• The choice of immunosuppressive therapy should be based on the latest evidence and guidelines, such as those from the American College of Rheumatology/Vasculitis Foundation 1.

Pathophysiology and Disease Management

The pathophysiology of vasculitis involves immune system dysregulation, with both cellular and humoral immunity contributing to vessel damage through various inflammatory mediators and autoantibodies. Defective neutrophil apoptosis or impaired clearance of apoptotic cell fragments may lead to prolonged exposure of the immune system to these antigens, and infection may also play a role through molecular mimicry 1. Effective management of vasculitis requires a comprehensive approach, including diagnosis, treatment, and regular monitoring to prevent complications and improve patient outcomes.

From the Research

Definition and Classification of Vasculitis

• Vasculitis refers to a pathologic condition defined by inflammatory cell infiltration and destruction of blood vessels 2
• Systemic vasculitis is classified as primary (eg, polyarteritis nodosa, Churg-Strauss syndrome) or secondary, the latter associated with connective tissue disorders, infections, medications, and rarely, as a paraneoplastic phenomenon 2

Treatment of Vasculitis

• The efficacy of cyclophosphamide (CY) in the treatment of severe systemic vasculitis has been demonstrated, but its optimal administration regimen remains to be defined 3
• Combination treatment with rituximab, low-dose cyclophosphamide, and plasma exchange has been shown to be effective in treating severe antineutrophil cytoplasmic antibody-associated vasculitis 4
• High-dose prednisone is the standard platform therapy for patients with systemic and nonsystemic vasculitic neuropathy (NSVN); for those with systemic vasculitis, at least 3 to 12 months of treatment with cyclophosphamide is also necessary to sustain remission and allow successful prednisone tapering 2
• Azathioprine can be safely substituted for cyclophosphamide after 3 months without an increased relapse rate 2

Advances in Treatment

• There have been great advances in the management of ANCA-associated vasculitis over the past decades, with the ability to use pulse cyclophosphamide or rituximab as alternates to oral cyclophosphamide for induction of remission 5
• New approaches have drastically changed the approach to maintenance, with much longer durations of maintenance therapy being more successful in preventing relapse 5
• Steroids have long been the bane of treatment, but new data is being published showing lower doses of steroids being equally effective, and several ongoing seminal trials are looking at agents that could completely replace steroids very early on 5

Diagnosis and Support

• The diagnosis of vasculitis should be established by tissue (preferably nerve) biopsy 2
• Living with vasculitis can be challenging for patients, and improved understanding of the disease process and new treatments can improve quality of life for patients 6
• The role of the nurse specialist is important in providing support and advice to patients and their families 6