What is ANCA Positive Vasculitis?
Antineutrophilic cytoplasmic antibody (ANCA) associated vasculitides are a type of rare autoimmune conditions. “Autoimmune” means that the body is attacking itself, and “vasculitides” is inflammation of the blood vessels. This category of conditions has various symptoms depending on individuals. It includes three main diseases: Granulomatosis with polyangiitis (GPA), previously known as Wegener granulomatosis; Eosinophilic granulomatosis with polyangiitis (EGPA), earlier known as Churg-Strauss syndrome; and Microscopic polyangiitis (MPA). Other conditions associated with these antibodies include drug-induced vasculitis and renal limited vasculitis, where the inflammation is limited only to the vessels in the kidneys.
What Causes ANCA Positive Vasculitis?
The connection between certain medical conditions (GPA, EGPA, and MPA) and a specific type of antibody known as an antineutrophilic cytoplasmic antibody (ANCA) was first established in 1988. This connection was discovered when the blood samples of patients suffering from a kidney disease called crescentic glomerulonephritis, were found to stick to a type of white blood cell called neutrophils in two distinct ways: either near the nucleus or spread evenly throughout the cell’s interior.
Further study revealed that these distinct patterns represented two different types of antibodies. The P-ANCA antibody fights against a substance found in neutrophils known as myeloperoxidase (MPO), while C-ANCA battles against another substance in neutrophils called proteinase 3 (PR3).
Usually, patients suffering from these clinical syndromes test positive for either P-ANCA or C-ANCA, but not both.
Risk Factors and Frequency for ANCA Positive Vasculitis
Antineutrophilic cytoplasmic antibody (ANCA) associated vasculitides are uncommon conditions. They typically have about 10 to 20 reported cases per million people. The most common type, GPA, typically affects 5 to 10 people per million, usually around the age of 55. MPA is less common than GPA and is more frequent in males than in females with a 2:1 ratio. EGPA is the least common of all.
- ANCA associated vasculitides are rare conditions, with 10 to 20 cases per million people.
- The most common type is GPA, which affects 5 to 10 people per million, usually around age 55.
- MPA is less common, and it more commonly affects males than females, with a 2:1 ratio.
- EGPA is the least common of all the types.
Signs and Symptoms of ANCA Positive Vasculitis
Patients with antineutrophilic cytoplasmic antibody (ANCA) vasculitides often complain about feeling tired, having a fever, and losing weight. This condition can present in several different ways:
- GPA:
- This typically affects the upper and lower respiratory tracts and the kidneys.
- Symptoms include a bloody nasal discharge, sores in the nose, sinusitis, and a recurring ear infection. The nasal cartilage can also become damaged, leading to a notable change in the shape of the nose.
- If the lower respiratory tract is affected, this can lead to lung nodules and bleeding in the lungs, which can be severe and even fatal. Rarely, it can cause narrowing of the windpipe.
- If the kidneys are affected, this can lead to rapidly worsening kidney failure, high blood pressure, new-onset protein in the urine, and signs of infection in the urinary tract. About 90% of patients with active GPA affecting multiple systems test positive for ANCA, but a negative ANCA test does not automatically rule out the diagnosis.
- MPA:
- MPA causes inflammation and necrosis of small blood vessels, often resulting in kidney inflammation and acute kidney failure. Almost all patients with MPA have kidney involvement.
- Lung involvement is less common than in GPA. It can lead to severe bleeding in the lungs (capillaritis) and lung scarring (fibrosis). About 90% of patients test positive for ANCA. Sometimes, the disease only manifests in the kidneys, and this manifestation is sometimes called renal-limited MPA.
- EGPA:
- This condition can cause inflammation and granuloma formation in several areas, including the skin, heart, and digestive tract. The peripheral nervous system is also commonly affected.
- Both types of ANCA, PR3 and MPO, have frequently been found in these patients.
- Drug-induced ANCA vasculitis:
- Certain medications may cause vasculitis, such as Propylthiouracil, Methimazole, Carbimazole, Hydralazine, and Minocycline. Common symptoms include joint pains, fatigue, and a skin rash. However, patients can also experience a wide range of other symptoms, including rapidly progressing kidney failure and bleeding in the lungs.
Testing for ANCA Positive Vasculitis
If your doctor suspects that you might have vasculitis, which is an inflammation of the blood vessels, arriving at an accurate diagnosis can be quite challenging. This is because vasculitis is a rare disease that can affect multiple parts of your body. Therefore, the first important steps involve a detailed history-taking and physical examination process.
To confirm the diagnosis, doctors usually combine findings from the clinical assessment with blood tests for certain antibodies. In some cases, they may even need to take a small tissue sample, or biopsy, for further examination. It’s important to rule out other potential conditions and determine how severe the vasculitis is and which organs might be involved.
Patients with a specific type of vasculitis condition, known as Granulomatosis with polyangiitis (GPA), often show a specific pattern in blood tests, with the presence of certain antibodies along with common vasculitis symptoms. Although the results from blood tests could be enough for diagnosis, your doctor may still require a tissue biopsy to ensure accuracy given the complexity of the treatment. When the tissue biopsy is examined, it typically shows signs of vasculitis along with specific structures called granulomas, except when the biopsy is taken from the kidney.
In another type of vasculitis known as Microscopic polyangiitis (MPA), blood tests generally show a different type of antibody pattern. In a third type of vasculitis, Eosinophilic granulomatosis with polyangiitis (EGPA), blood tests may detect one of two types of antibodies, but it’s important to note that about 40% of the patients may not show these specific antibodies. One particular characteristic of EGPA is the presence of a high number of a type of white blood cells, eosinophils, in blood and other tissues.
Occasionally, certain medications can cause a type of vasculitis. If you show the symptoms and have been taking these specific medications, your doctor may suspect that the medication is causing your condition. A few examples of these medications are propylthiouracil, methimazole, carbimazole, hydralazine, minocycline, and allopurinol, among others.
Your doctor may also carry out other tests to rule out conditions that are similar to vasculitis, such as lupus and Goodpasture syndrome, a rare autoimmune disease. In addition, conditions like infective endocarditis and chronic hepatitis can also replicate symptoms of vasculitis and must be ruled out.
Once vasculitis has been diagnosed, it is important to monitor if and how the disease is progressing, and whether the chosen treatment is working. Regular tests measuring inflammation markers, antibodies, and kidney function can be carried out. Your doctor may also use a clinical tool like the Birmingham Vasculitis Activity Score (BVAS), that helps monitor the progression and activity of the illness over time.
Treatment Options for ANCA Positive Vasculitis
Treatment for a type of blood vessel inflammation, called antineutrophilic cytoplasmic antibody (ANCA) vasculitides, usually starts with trying to get the disease into remission. Remission means stopping the disease from flaring up; this is done to protect the organs or slow down their involvement. The specific definition of remission is agreed upon internationally by groups of specialists, such as the European Vasculitis Society and the European League against Rheumatism.
To achieve remission, a drug called cyclophosphamide is often used alongside high-dose steroids. In severe cases, such as when a person’s life is threatened or their kidneys are severely involved, doctors may also carry out a plasma exchange – a procedure where the liquid part of the blood, or plasma, is removed and replaced.
Moreover, a drug called rituximab is becoming increasingly popular for inducing remission because it has fewer side effects than cyclophosphamide yet it’s just as effective. So much so that a study found rituximab to be even better than cyclophosphamide in patients who had a relapse of their disease. In this study, 67% of patients returned to remission after 6 months with rituximab treatment compared to 42% who used cyclophosphamide.
There are other ways to induce remission, like methotrexate or mycophenolate mofetil, but these are less commonly used. These options are typically reserved for patients who don’t have evidence of severe disease or threat to their organ function.
Now, once remission is achieved, the next goal is to maintain it. This is often done using drugs such as methotrexate or azathioprine. The exact duration of this maintenance phase isn’t set in stone but it’s typically given for 18 to 24 months to prevent the disease from flaring up again.
What else can ANCA Positive Vasculitis be?
There are two types of small vessel vasculitis: ANCA-associated vasculitis and immune complex vasculitis. Both can cause similar signs and symptoms, which can make distinguishing between them a challenge.
Immune complex vasculitis is characterized by a large amount of immune complex deposition in the affected tissues. This type of vasculitis can be caused by various infections like hepatitis B and C viruses, the Human Immune deficiency virus (HIV), or endocarditis. It could also result from autoimmune conditions such as lupus (SLE), rheumatoid arthritis, and Sjögren syndrome. One specific type of immune complex vasculitis, known as cryoglobulinemia, can be caused by chronic hepatitis C infection.
Another disease, known as anti-glomerular basement membrane disease (Goodpasture syndrome), can mimic ANCA vasculitis. This disease typically involves the kidneys and lungs. Interestingly, between 10 and 40 percent of patients with this disease also test positive for ANCA, a condition known as “dual-positivity”. Such patients are at a higher risk of recurring disease.
Atrial myxoma, a type of heart tumor, can also appear with symptoms similar to vasculitis including fatigue, fever, weight loss, skin rashes, neurological problems, and lung injury due to embolization.
Finally, some forms of cancer, such as lymphoma, that involve blood vessels can mimic vasculitis. In other cases, the symptoms of vasculitis might appear as a secondary effect of the cancer, a phenomenon known as paraneoplastic disease.
What to expect with ANCA Positive Vasculitis
The outlook for ANCA vasculitis, a type of blood vessel inflammation, has significantly improved. Previously, 80% of patients did not survive beyond the first year. Now, many patients can achieve long-lasting remission and the death rate has fallen to 10%.
However, it’s common for the disease to come back, particularly in patients with a type known as GPA. In fact, more than half of these patients experience a recurrence of the disease within five years.
Possible Complications When Diagnosed with ANCA Positive Vasculitis
Complications can arise either from the disease or the treatment.
The disease can affect various organs like the lungs, kidneys, and peripheral nerves, leading to a range of complications. Additionally, patients could be at a higher risk of developing high blood pressure, heart disease, heart attacks, mouth ulcers, and diseases related to the brain and blood vessels.
Treatment can also lead to complications such as cancer, bladder irritation caused by chemicals, bone marrow failure, failure of reproductive organs, diabetes, and brittle bones.
Common complications:
- Impacted organs: lungs, kidneys, peripheral nerves
- Increased risk of high blood pressure
- Increased risk of heart disease and heart attacks
- Mouth ulcers
- Increased risk of brain and blood vessel diseases
- Possibility of developing cancer from treatment
- Bladder irritation caused by chemicals from treatment
- Bone marrow failure due to treatment
- Failure of reproductive organs due to treatment
- Possibility of developing diabetes and brittle bones due to treatment
Preventing ANCA Positive Vasculitis
Patients should be fully informed about the disease they are dealing with, the prescribed treatment, and the potential side effects they may experience.
Vasculitis is a condition that causes inflammation or swelling of your blood vessels. These are crucial vessels our bodies rely upon to transport oxygen and vital nutrients to our tissues. When they get damaged due to Vasculitis, it can ultimately lead to damage to the tissues they supply.
There are various types of Vasculitis. Some can be caused by certain medications whilst others occur without any known cause.
The symptoms of Vasculitis can vary, but common ones include feeling tired, muscle pain, fever, cough, coughing up blood, abdominal pain, presence of blood in urine or feeling weak and numbness in your hands or feet.
To treat Vasculitis, doctors often use steroids alongside other medications designed to suppress the immune system. These can include medications like cyclophosphamide or rituximab.