Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) refers to a group of systemic autoimmune conditions where there is inflammation of small vessels in the body (vasculitis), leading to tissue and organ damage. It comprises three diseases which are linked by the presence of the ANCA antibodies:
1) Granulomatous polyangiitis (GPA),
2) Microscopic polyangiitis (MPA), and
3) Eosinophilic granulomatous polyangiitis (EPGA)
There are two main ANCA antibodies, Proteinase-3 (PR3) and Myeloperoxidase (MPO) which are associated with different types of AAV. ANCA-associated vasculitis is more common in middle-aged adults aged 45-60 years but it can affect people of all ages. Small vessel inflammation in AAV can affect different organ systems, particularly the lungs, kidneys and nerves. The disease can range from mild to severe life-threatening complications such as bleeding in the lungs, or kidney failure. Hence, prompt diagnosis and treatment is key.
ANCA-associated vasculitis comprises three different conditions: Granulomatous polyangiitis (GPA), Microscopic polyangiitis (MPA), and Eosinophilic granulomatous polyangiitis (EPGA). All three conditions can present with similar symptoms but have certain distinct features. Symptoms vary depending on which organ system is affected and the severity of involvement. Common symptoms that patients may have in any of the three conditions include:
• Persistent fever
• Fatigue
• Loss of appetite, loss of weight
• Painful, purplish rashes
• Lung involvement
o Shortness of breath
o Cough, coughing out blood
• Nerve involvement:
o Numbness/tingling in the hands or feet
o Weakness in the hands or feet
• Kidney involvement:
o Frothy, bubbly urine (suggesting protein in the urine)
o Persistent red blood cells in the urine which may not always be visible to the naked eye (also known as microscopic haematuria)
o Leg swelling due to fluid retention
• Body aches (myalgia), joint pain / swelling / stiffness
Not everyone will experience all of these symptoms. These symptoms may improve with treatment and recur during disease flares.
The three types of ANCA-associated vasculitis have distinct characteristics:
1) Granulomatous polyangiitis (GPA)
- Previously known as Wegener’s granulomatosis
- In addition to the above symptoms, GPA commonly affects the ears (causing blocked ears, hearing loss, fluid in the ears, hearing a high-pitched sound i.e. tinnitus) and nose (causing sinusitis, crusting of the nose and nose bleeding)
- It is associated with the PR3 antibody
2) Microscopic polyangiitis (MPA)
- Patients with MPA usually have lung and kidney involvement which can be severe
- It is associated with the MPO antibody
3) Eosinophilic granulomatous polyangiitis (EPGA)
- Previously known as Churg-Strauss syndrome
- Patients with EGPA usually have asthma which develops in adulthood and is difficult to treat
- It is associated with very high eosinophils, a type of white blood cell commonly raised in asthma and allergies
- In severe cases, the heart, nerves and kidneys can be affected
- About 50% of patients with EGPA do not have ANCA antibodies detectable in the blood, the remainder may have either PR3 or MPO antibody
AAV is a systemic condition that can be managed effectively with medications, which are given based on degree and severity of organ involvement. With treatment, many patients can attain good disease control and lead normal active lives.
• Corticosteroids are fast-acting medications that effectively suppress the immune system. These are usually started at high doses (intravenous injections through the veins or oral), then reduced over time.
• Immunosuppressive agents are used in addition to steroids to reduce the need for long-term steroids and for control of disease activity.
o In severe or life-threatening disease (e.g. lung, kidney, heart, nerve involvement), infusion (intravenous) medications administered through the veins are required (induction treatment). Examples include cyclophosphamide and rituximab. Following induction treatment, patients are usually switched to oral maintenance treatment (e.g. azathioprine, methotrexate, mycophenolate mofetil) or are continued on infusion rituximab after a few months
o In milder disease, oral immunosuppressants are usually started alongside corticosteroids (e.g. azathioprine, methotrexate, mycophenolate mofetil) and continued long-term.
• Biologic agents are newer targeted medications given intravenously or subcutaneously into the abdomen or thighs. These may be given as part of induction treatment during disease flares or as maintenance treatment to prevent flares. Rituximab is an example of a biologic agent. Other biologics used in EGPA include benralizumab and mepolizumab.
Blood tests monitoring are usually required while on immunosuppressive medications.
In severe disease,
• Patients may require plasma exchange – a form of treatment where the harmful antibodies in the plasma (a component of the blood) are removed from the body and replaced with fluids
• Supportive care such as dialysis and mechanical ventilation (breathing with the aid of a machine known as the ventilator) may be required in patients with kidney failure and respiratory failure respectively. Such patients may need to be managed in the intensive care unit until their condition has stabilised.
As multiple organ systems may be affected in AAV, patients are often cared for by a multidisciplinary team of medical professionals, including a primary rheumatologist and other relevant subspecialty teams and allied health professionals. Your treatment plan will be carefully tailored to your symptoms, preferences, and goals of care.
To prevent infections when on high doses of immune suppression medications, prophylactic antibiotics and certain vaccinations are encouraged (e.g. influenza, pneumococcal, COVID-19, shingles and respiratory syncytial virus). Patients are also advised to avoid crowded areas or sick contacts, or wear a mask if these are unavoidable.
Patients with ANCA-associated vasculitis are able to live active lives with the right treatment and support. Some recommended lifestyle changes include:
• Eat a balanced diet. Avoid raw and partially cooked food to reduce risks of infections, especially if you are on medications that suppress the immune system (e.g. steroids).
• Avoid smoking.
• Stay active and exercise in moderation. Ensure sufficient rest and sleep well.
• Attend regular medical check-ups to monitor your health. Participate actively in your care and ask questions during your clinic consultations.
• Take your medications as prescribed, even when you feel well, to avoid disease flares.
• Seek medical attention early if you are unwell or suspect that your disease may be flaring up.
