Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases characterized by inflammation and damage to small blood vessels.
This inflammation is typically caused by ANCAs, self-reactive antibodies that bind to certain cells of the immune system — called neutrophils — and overly activate them. Researchers believe that a combination of genetics and environmental factors cause this immune system malfunction.
Since small blood vessels are present all over the body, AAV can cause many different symptoms. Depending on the constellation of symptoms and microscopic findings, patients can be grouped into three major disease subtypes.
The disease affects about one in 50,000 people and is more prevalent in middle-aged white men and women.
What is an autoimmune disease?
In healthy people, the immune system identifies foreign invaders and produces antibodies that attack them before they can cause harm. Autoimmune diseases occur when the immune system produces abnormal antibodies, called autoantibodies, that target healthy cells and tissue.
In AAV, autoantibodies called ANCAs are found at elevated levels and bind to white blood cells called neutrophils. This causes an activation of neutrophils, which then bind to the cells lining blood vessels, release toxic granules, and further activate the immune system, leading to vascular damage and tissue swelling.
Antibodies targeting the proteinase 3 (PR3) or the myeloperoxidase (MPO) proteins on neutrophils are the most common ANCAs in people with AAV, each resulting in distinct disease manifestations. More rarely, ANCAs may target other proteins.
Causes of ANCA vasculitis
The biological mechanisms underpinning this autoimmune disease remain to be fully elucidated, but research points to a combination of genetics and environmental factors, such as exposure to pollutants, drugs, and microbial infections.
A number of genetic factors have been associated with AAV. The strongest association was observed for the major histocompatibility complex (MHC), a family of genes containing information to produce proteins with a key role in immune response.
Inhalation of silica (a mineral found in soil that stimulates inflammatory reactions), or chemical compounds used in farming (pesticides) or industry (alcohols and glues) also may increase the risk for AAV.
Some therapies, the prolonged use of cocaine, and infections with certain viruses and bacteria also have been associated with the development of AAV.
Symptoms of ANCA vasculitis
Depending on the organ or tissue where blood vessel damage occurs, AAV can cause many different symptoms.
Vascular damage in the kidneys and lungs are among the most common manifestations of ANCA vasculitis. Symptoms include the presence of blood and protein in urine, making it appear brownish and foamy, high blood pressure, fatigue, and respiratory problems. Inflammation in the trachea may also lead to a hoarse voice and cough.
Numbness, tingling, burning sensation, and muscle weakness are common nerve problems in AAV patients. Headaches, cognitive impairment and seizures also are frequent.
Symptoms of vasculitis in the upper respiratory tract — including the ears, sinuses, nose, and throat — can include inflammation in the sinus, or sinusitis, eye irritation or pain, and bloody discharge from the nose. Ear pain and infection (otitis) also may occur.
Patients may experience strong pain in the muscles and joints, as well as gastrointestinal problems such as blood in stools, diarrhea, nausea, vomiting, and abdominal pain. Non-specific symptoms as weight loss, fevers, flu-like symptoms, and malaise are frequent.
Types of ANCA vasculitis
There are three main types of ANCA vasculitis; they usually are diagnosed based on the symptoms and histological findings under a microscope. In addition to other disease characteristics, doctors often treat AAV patients based on their specific AAV subtype.
Microscopic polyangiitis (MPA): MPA patients usually experience a range of symptoms such as kidney inflammation, skin lesions, and nerve damage, depending on which areas are affected. Weight loss and fevers frequently occur. MPO-ANCAs are the most common autoantibodies in these patients.
Granulomatosis with polyangiitis (GPA): Patients with GPA also can experience blood vessel damage in various tissues, typically in the lungs, kidneys, and upper respiratory tract (nose, trachea, and ears). However, the inflammation is specifically caused by granulomas — masses of immune cells — that form in the vasculature. Formerly known as Wegener’s granulomatosis, this type of ANCA vasculitis is frequently associated with PR3-ANCAs.
Eosinophilic granulomatosis with polyangiitis (EGPA): EGPA is typically limited to the lungs and gastrointestinal tract, although other organs, like the heart and kidneys, may be affected. It is caused by granulomas primarily made up of eosinophils, another type of white blood cell of the immune system. Patients may experience asthma-like symptoms for many years before other symptoms of vasculitis appear.
Diagnosis of ANCA vasculitis
Physicians use a series of tests to identify vasculitis and classify a patient’s specific type of ANCA vasculitis. Blood and urine are collected to test for autoantibodies, inflammatory markers, and kidney disease. Tissue samples, or biopsies, also are needed to confirm the diagnosis.
Imaging scans, such as X-rays and computed tomography, may be recommended to examine the lungs or head and neck regions. Patients may need to undergo bronchoscopy and nasal endoscopy, which use a flexible tube with a light and camera to look at the airways and sinuses, respectively.
While there is currently no cure for AAV, a number of treatments are available to manage the condition. These reduce, and in some cases resolve, the vascular inflammation and swelling that trigger uncomfortable symptoms in patients.
Patients normally undergo two phases of treatment, one designed to induce the remission of symptoms (induction treatment), and a second phase meant to keep patients in remission for as long as possible (maintenance treatment).
The kind of treatments used largely depend on disease severity and subtype, but most are designed to lower immune system responses. These include corticosteroids (prednisolone), cyclophosphamide, rituximab, azathioprine, and methotrexate.
Last updated: May 20, 2021
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