Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) refers to a group of autoimmune diseases characterized by inflammation and damage to small blood vessels.
ANCA associated vasculitis, a type of small vessel vasculitis can affect any organ including the skin, eyes, lungs, kidneys, joints, ears, nose, throat and nervous system, and cause constitutional symptoms such as fatigue and weight loss.
The inflammation is caused by ANCAs, self-reactive antibodies that bind to neutrophils, and overly activate them.
ANCA vasculitis immune system malfunction is caused by a combination of genetics and environmental factors.
Worldwide incidence of ANCA associated vasculitis ranges from 13 to 20 cases per million per year and peaks at a 60 to 70 years.
Depending on the constellation of symptoms and microscopic findings of ANCA vasculitis patients can be grouped into three major disease subtypes: Granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis.
The disease affects about 1 in 50,000 people.
It is more prevalent in middle-aged white men and women.
In ANCA vasculitis the autoantibodies called ANCAs are found at elevated levels and bind to neutrophils.
The activated neutrophils 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 ANCA associated vasculitis, each resulting in distinct disease manifestations.
The mechanisms for ANCA associated autoimmune vasculitis disease are not entirely known, but suggests acombination of genetics and environmental factors, such as exposure to pollutants, drugs, and microbial infections.
The strongest associated relationship is observed for the major histocompatibility complex (MHC), a family of genes containing information to produce proteins with a key role in immune response.
The two ANCAs are associated with a perinuclear pattern.
Inhalation of silica, (pesticides) or industry alcohols and glues may increase the risk for ANCA associated vasculitis.
Prolonged use of cocaine, and infections with certain viruses and bacteria also have been associated with the development of ANCA associated vasculitis.
ANCA associated vasculitis symptoms reflect the underlying organ involvement.
Vascular damage in the kidneys and lungs are among the most common manifestations of ANCA vasculitis.
Kidney damage includes proteinuria, and hypertension.
ANCA vasculitis symptoms include fatigue, respiratory problems, inflammation in the trachea that may lead to a hoarse voice and cough.
ANCA vasculitis nerve problems include: numbness, tingling, burning sensation, muscle weakness, headaches, cognitive impairment and seizures also are frequent.
Symptoms of vasculitis in the ears, sinuses, nose, and throat include inflammation in the sinus, or sinusitis, eye irritation or pain, bloody discharge from the nose, ear pain and infection.
Patients may experience pain in the muscles and joints.
Gastrointestinal problems such as blood in stools, diarrhea, nausea, vomiting, and abdominal pain may occur.
Non-specific symptoms as weight loss, fevers, flu-like symptoms, and malaise are frequent.
Cutaneous manifestations, including palpable purpura, petechiae, painful skin lesions, maculopapular rash, and splinter hemorrhages are the presenting feature in 35% of patients.
Patients with severe cutaneous manifestations are more likely to have systemic vasculitis than those without skin involvement.
There are three main types of ANCA vasculitis:
Microscopic polyangiitis (MPA):
Microscopic polyangiitis (MPA) signs and symptoms include: kidney inflammation, skin lesions, and nerve damage, weight loss and fevers.
MPO-ANCAs are the most common autoantibodies in MPA.
Granulomatosis with polyangiitis (GPA) patients can experience blood vessel damage in various tissues, typically in the lungs, kidneys, and upper respiratory tract which can involve the nose, trachea, and ears.
In granulomatosis with polyangiitis (GPA) the inflammation is specifically caused by granulomas.
Granulomas are masses of immune cells that form in the vasculature.
Granulomatosis with polyangiitis (GPA) vasculitis is frequently associated with PR3-ANCAs.
Eosinophilic granulomatosis with polyangiitis (EGPA) is typically limited to the lungs and gastrointestinal tract, although other organs, like the heart and kidneys, may be affected. It is the least common of the ANCA associated vascular disease.
Its granulomas are primarily made up of eosinophils.
Eosinophilic granulomatosis with polyangiitis (EGPA) patients may experience asthma-like symptoms for many years before other symptoms of vasculitis appear.
It is a multi system inflammatory disorder characterized by chronic rhinosinusitis, asthma, and eosinophilia.
The mean onset of age is 50 years and the prevalence is roughly equal among men and women.
Organs affected by eosinophilic granulomatosis with polyangiitis include the long, with the asthma present and 90% of cases, upper airway come in skin typically with tender subcutaneous nodules, classically on extensive surfaces.
anti–MPO is positive and 30-40 % of cases and positive cases are more likely to have peripheral neuropathy and renal and dermatologic involvement whereas those that are ANCA negative disease more likely to have cardiac manifestations.
There are two major ANCA indirect immunofluorescence patterns: c-ANCA in which antibodies are typically directed against PR3. and p-ANCA, in which antibodies are typically directed against myeloperoxidase.
Eosinophilic granulomatosis with polyangiitis typically develops in phases.
A prodromal phase coming occurs in the third of fourth decade and includes atopic asthma, eczema and allergies, but peripheral eosinophilia is not typically seen.
There may be an eosinophilic phase in which eosinophilia and eosinophilic infiltration of tissues develop, and finally the vascularitic phase involves the development of vascular and extravascular granulomatosis.
Cardiac involvement is identified in about 1/3 of patients with eosinophilic granulomatosis with polyangiitis and accounts for approximately half the deaths.
Patients most commonly manifest with pericardial effusion, myocardial involvement, and heart failure.
Blood and urine can be collected to test for autoantibodies, inflammatory markers, and kidney disease.
Tissue samples, or biopsies, also are needed to confirm the diagnosis.
Diagnosis is based on clinical features, pathology, the presence of ANCA antiantibodies against specific proteins in neutrophils that help delineate disease subtype.
Imaging scans, X-rays and computed tomography, may be recommended to examine the lungs or head and neck regions.
Bronchoscopy, nasal endoscopy, to examine the airways and sinuses, respectively, may be helpful.
ANCA vasculitis is not curative, but a number of treatments are available.
The kind of treatments used depends on disease severity and subtype, but most are designed to lower immune system responses: corticosteroids, cyclophosphamide, rituximab, azathioprine, and methotrexate.
The severity of the disease must be determined: life-threatening disease involves alveolar hemorrhage, rapidly progressive glomerulonephritis, and severe cardiac, CNS, gastrointestinal, or ocular involvement.
Therapy in severe disease includes pulse glucocorticoids combined with rituximab of cyclophosphamide.
Prednisone maintenance includes oral prednisone for up to three months.
For milder disease low-dose oral steroids along with methotrexate or mycophenolate mofetil or maintenance with rituximab.