Vasculitis refers to a group of diseases characterized by inflammation of the blood vessels, which can restrict blood flow and lead to organ damage. Anti-Neutrophil Cytoplasmic Antibody (ANCA) vasculitis is a specific and severe form of this condition, where the immune system mistakenly creates autoantibodies that target the body’s own tissues. This systemic disease affects small-to-medium-sized blood vessels throughout the body, most commonly in the kidneys, lungs, and upper respiratory tract.
Understanding the ANCA Mechanism
ANCA stands for Anti-Neutrophil Cytoplasmic Antibodies, which are proteins produced by the immune system that target components within neutrophils, a type of white blood cell. These autoantibodies mistakenly recognize and bind to two primary proteins found inside the neutrophil’s cytoplasm: Proteinase 3 (PR3) and Myeloperoxidase (MPO). Due to triggers like infection, neutrophils become “primed,” causing PR3 and MPO to move to the cell surface.
When autoantibodies bind to these surface-exposed proteins, the neutrophils become hyper-activated. These activated neutrophils release toxic substances and destructive enzymes that damage the walls of small blood vessels, such as capillaries and arterioles. This process causes inflammation (vasculitis), compromising the vessel integrity and leading to tissue injury in various organs.
The Major Forms of ANCA Vasculitis
ANCA vasculitis includes three clinical syndromes defined by unique pathological features and organ involvement. Granulomatosis with Polyangiitis (GPA), formerly known as Wegener’s, is characterized by inflammation that forms granulomas. GPA typically involves the upper and lower respiratory tracts, causing chronic sinusitis, nasal crusting, or lung nodules, and is most commonly associated with PR3-ANCA.
Microscopic Polyangiitis (MPA) is distinguished from GPA by the absence of granuloma formation. This form frequently presents with severe kidney involvement, known as rapidly progressive glomerulonephritis, and often affects the lungs. MPA is most frequently associated with MPO-ANCA.
The third type is Eosinophilic Granulomatosis with Polyangiitis (EGPA), previously called Churg-Strauss syndrome. EGPA is unique due to its strong association with asthma and high levels of eosinophils. Patients often experience severe asthma for years before vasculitis symptoms appear. Only about 40% of EGPA patients test positive for ANCA, typically the MPO subtype.
Common Symptoms and Organ Involvement
The onset of ANCA vasculitis often includes general, non-specific symptoms that can be mistaken for other illnesses, making early identification difficult. These systemic manifestations include persistent fever, profound fatigue, and unexplained weight loss.
As the disease progresses, organ-specific symptoms develop based on where the small blood vessels are damaged. The kidneys are affected in a majority of cases, leading to glomerulonephritis, which may result in blood and protein in the urine. Lung involvement can cause coughing, shortness of breath, or pulmonary hemorrhage. Damage to the upper respiratory tract is common, particularly in GPA, manifesting as chronic sinus infections, nosebleeds, or the characteristic saddle nose deformity.
How ANCA Vasculitis is Diagnosed
Diagnosing ANCA vasculitis requires clinical evaluation, specialized blood tests, and often tissue confirmation. Blood testing for ANCA uses two main methods. Indirect immunofluorescence (IIF) identifies a staining pattern, categorizing them as cytoplasmic ANCA (c-ANCA) or perinuclear ANCA (p-ANCA).
The Enzyme-Linked Immunosorbent Assay (ELISA) is a more specific test that directly measures antibodies targeting the autoantigens, PR3 and MPO. C-ANCA staining typically correlates with PR3-ANCA, while p-ANCA staining usually corresponds to MPO-ANCA. The presence of ANCA strongly supports the diagnosis when clinical signs of vasculitis are present.
Tissue biopsy remains the definitive method to confirm the diagnosis and assess organ damage. A biopsy, often taken from the kidney, lung, or skin, allows pathologists to visualize the inflammation and destruction of the small blood vessel walls.
Current Treatment Strategies
The management of ANCA vasculitis is divided into two phases: induction and maintenance, both relying on potent immunosuppressive therapy. The Induction phase aims to achieve rapid disease remission, typically involving high-dose corticosteroids combined with either cyclophosphamide or the biological therapy rituximab.
Rituximab, which targets B-cells, is increasingly preferred for induction therapy, as B-cells produce the pathogenic ANCA autoantibodies. Cyclophosphamide remains a viable option, though its use is limited by potential long-term side effects.
Once remission is achieved, the patient transitions to the Maintenance phase, focused on preventing disease relapse over several years. Rituximab has been shown to be superior to traditional immunosuppressants like azathioprine for maintaining long-term remission. Managing potential side effects, such as infections and drug-related toxicities, is a continuous part of specialized care.