Microscopic Polyangiitis

What is Microscopic Polyangiitis?

Microscopic polyangiitis is a kind of disease where small blood vessels get damaged. It is part of a larger group of diseases known as anti-neutrophil-cytoplasmic-antibody (ANCA)-associated vasculitides (AAV). This big category includes other diseases like granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis (also known as Churg-Strauss disease), and renal limited vasculitis (RLV). There is a system for classifying these diseases based on the kind of blood vessels affected, and what causes the disease. This way of classification was first established by the International Chapel Hill Convention Conference in 2012.

The name “microscopic polyarteritis” was first used in 1948 by a researcher named Davson. He used it to describe the type of kidney disease seen in patients with polyarteritis nodosa. Later on, it was used to describe a disease where the small blood vessels (like capillaries, venules, and arterioles) get damaged, without immune complex deposition. The disease often causes kidney disease, lung capillaritis, and can affect other systemic capillary beds. It has many similarities with granulomatosis with polyangiitis. The lack of inflammation in the upper respiratory tract and the inflammation in the lung capillaries are what primarily distinguishes microscopic polyangiitis from granulomatosis with polyangiitis. This disease is also a part of a group of disorders known as pulmonary-renal syndrome, which includes itself, GPA, Goodpasture disease, and systemic lupus erythematosus.

To treat microscopic polyangiitis, doctors use drugs that suppress the immune system. The best drug to use depends on how fast the disease is progressing, how far it has spread and how bad the inflammation is.

What Causes Microscopic Polyangiitis?

The development of a disease called microscopic polyangiitis (MPA), along with similar conditions, is largely thought to be due to something called anti-neutrophil-cytoplasmic antibodies, or ANCA for short. These are antibodies, which are proteins that our bodies make to fight off foreign materials like viruses or bacteria. However, in this case, these antibodies are working against our own cells, specifically the cell components in a type of white blood cell called neutrophils and a similar cell called monocytes.

Scientists believe that the creation of these antibodies is a two-step process. First, neutrophils are exposed to inflammatory proteins which lead to the production of something called myeloperoxidase (MPO). Then, due to a combination of genetic, environmental, and other factors, our bodies make MPO-ANCA. In the second step, these MPO-ANCA cause damage to our blood vessels by causing reactions between neutrophils and the cells that line our blood vessels.

However, only 70% of people with MPA have ANCA at the time of their diagnosis and many people with a less severe form of MPA don’t have ANCA at all. This has led scientists to believe that other factors also contribute to the development of MPA. For example, the disease often looks like various infections, and studies have suggested a role of a bacteria called Staphylococcus aureus in some cases.

Certain medications, including hydralazine, thionamides, sulfasalazine, and minocycline, among others, have been associated with the development of vasculitis, a condition related to MPA.

Genes have also been linked to the disease. A recent study in Europe found that genes called HLA-DP, HLA-DR3, and alpha-1 antitrypsin could contribute to the development of ANCA-associated vasculitis.

Exposure to a substance called silica has also been linked with MPA; it seems to trigger an autoimmune response in people who are genetically predisposed to the disease. An autoimmune disease is a condition in which the immune system mistakenly attacks the body.

Risk Factors and Frequency for Microscopic Polyangiitis

Microscopic polyangiitis (MPA) is a recently identified condition, so we don’t have much information about how frequently it occurs in the United States. A 20-year study in Rochester, Minnesota, found an annual rate of 3.3 cases per 100,000 people for this and related conditions, which was about 42.1 cases per 100,000 people. MPA and a similar condition called GPA had a rate of about 1.5 cases per 100,000 people.

Studies in European countries have found these conditions more often, especially in Spain and the United Kingdom, with 11.6 and 5.8 cases per million people, respectively. In the past 20 years, the rate of MPA seems to have increased, which might be partly because we now have the ability to test for it.

Generally, these conditions are more common in southern Europe than northern Europe. For example, Norway sees 2.7 cases per million people but Spain has 11.6 cases per million. Some other studies suggest that the rate of these conditions doesn’t depend on geographical location.

MPA occurs more frequently in white populations than black ones.
The average age when people get MPA is 50.
The disease is more often found in males.

Signs and Symptoms of Microscopic Polyangiitis

Patients with microscopic polyangiitis (MPA) can display a wide variety of symptoms. These can include fever, joint and muscle pain, weight loss, issues related to urination, coughing (sometimes with blood), rashes on the skin, nerve damage causing weakness or numbness, seizures, abdominal pain, digestive system bleeding, chest pain, eye pain, sinus problems, and sometimes even testicular pain. In some cases, patients may rapidly develop severe symptoms like bloody cough or urine, or even complete kidney failure.

When it comes to kidney problems associated with MPA, the main symptom is rapidly worsening kidney inflammation. Up to 100% of MPA patients show kidney-related symptoms. This can range from microscopic signs that only lab tests can detect, to complete kidney failure that needs dialysis. Common features of kidney problems include bloody urine, protein in the urine, and urinary casts (particles that form in the kidney and then get passed through the urine).

Lung problems due to MPA affect about a third to half of patients. A large-scale study found that up to 80% of patients showed at least some symptoms related to the lungs, and 92% showed abnormalities on lung imaging. The most common finding is damage to the air sacs of the lungs, leading to bleeding. However, some patients also develop long-term lung scarring that can cause breathing problems. The usual signs of this lung damage include coughing up blood, coughing, trouble breathing, and chest pain.

Coughing up blood
Coughing
Trouble breathing
Intense chest pain

Skin problems in MPA are seen in about a third to half of patients and may be the first indication of the disease in some. Common skin symptoms include reddish-purple spots (purpura), net-like patterns on the skin (livedo reticularis), hives, skin nodules, and painful skin ulcers with tissue death. Skin symptoms often come with joint pain.

The most common digestive system problem related to MPA is abdominal pain. Digestive system bleeding sometimes occurs, but severe, life-threatening bleeding is rare.

Neurological issues related to MPA often involve the peripheral nerves rather than the central nervous system (brain and spine). The most common nerve problems include a nervous system disorder that usually begins in the hands and feet and nerve damage causing weakness or numbness in various parts of the body. In rare cases, patients develop a condition called posterior reversible encephalopathy syndrome. Central nervous system problems can vary and include bleeding in the brain, strokes without bleeding, and inflammation of the membranes that surround the brain and spinal cord.

During a physical examination, doctors might find skin sores on the arms and legs, fever, rapid breathing, and a fast heartbeat. Specific skin findings can include a type of inflammation called leukocytoclastic angiitis, reddish-purple spots, network patterns on the skin, skin ulcers, tissue death or gangrene, nodules, digital ischemia (where fingers or toes aren’t getting enough blood), and hives. Lung exams might find abnormal breathing sounds. Nerve exams might find abnormal muscle strength or sensation in certain parts of the body. Heart findings can include high blood pressure, signs of heart failure, a blocked blood supply to the heart, and heart inflammation. Digestive system symptoms may include bleeding, lack of blood supply to the intestines and stomach, and intestinal perforation. Eye exams might reveal bleeding in the retina, inflammation of the white part of the eye, and inflammation within the eye. Other findings will vary depending on which small blood vessels throughout the body are affected.

Testing for Microscopic Polyangiitis

If your doctor suspects you have a condition known as microscopic polyangiitis, you’ll likely go through a number of tests. These are done to confirm the diagnosis and understand how much of your body is affected by the disease. Here’s what you can expect:

* The first step is usually a detailed clinical evaluation. In this stage, your doctor will gather information about your symptoms and how they affect different organ systems in your body.
* You will then undergo laboratory tests including a complete blood count (CBC), checks on your electrolyte levels, along with specific tests for antibodies known as MPO and PR3.
* In the CBC test, your doctor will be looking for signs of leukocytosis (high white blood cell count) and anemia (low red blood cell count).
* The erythrocyte sedimentation rate (ESR) tells your doctor whether there’s inflammation in your body. If this rate is high, it may suggest something’s not right.
* Blood urea nitrogen (BUN) and serum creatinine tests provide insight into how well your kidneys are functioning. Elevated levels may indicate kidney issues.
* The urine analysis helps to identify abnormal substances in the urine, such as too much protein, blood, white blood cells or red blood cell casts.

Another significant test is the antineutrophil cytoplasmic antibody (ANCA) test. This test checks for antibodies that often present in 80% of people with microscopic polyangiitis. Depending on the type of ANCA found, your doctor can also understand more specifics about your particular case of the disease.

Your doctor may also look at other areas of your body using imaging techniques. These include a chest X-ray or a computed tomography (CT) scan of the chest to check for lung abnormalities, especially if you have symptoms like coughing up blood or difficulty breathing. Depending on your test results, you may also undergo an abdominal CT scan, an electrocardiogram (ECG) to check for heart issues, a gastrointestinal endoscopy if you have bleeding in your digestive tract, or an electromyography (EMG) to assess nerve function.

Lastly, a biopsy or tissue sample may be taken from your skin, kidney, or lung, and examined under a microscope to check for signs of disease. This process is called histopathological evaluation and it provides in-depth details about the disease’s severity which in turn helps determine the most suitable treatment.

Treatment Options for Microscopic Polyangiitis

Microscopic polyangiitis (MPA) is a condition that causes small blood vessels in your body to become inflamed. It’s often treated with a mix of medications that help reduce inflammation and suppress your body’s immune system. This condition can range from mild with minor systemic inflammation and kidney problems, to severe with fast deterioration of kidney function and lung inflammation leading to breathing difficulties.

Treatment usually follows two main stages: inducing remission (getting the disease under control) and maintaining remission (keeping the disease in check). It’s important to understand that remission doesn’t mean all symptoms are gone, but rather that there aren’t any symptoms due to active inflammation of blood vessels. If MPA returns, the treatments to get it under control again are the same as what’s used to induce remission initially.

For the most stubborn cases of MPA, intravenous immunoglobulins (proteins that help control immune response) may be used. Common medications used in treating MPA include cyclophosphamide, rituximab, methotrexate, steroids, azathioprine and some biological agents, which are a type of drug made from living organisms.

In the first stage of treatment, a combination of steroids and cyclophosphamide is often used to achieve remission. Rituximab can also do the job as effectively and safely as cyclophosphamide. However, when the disease is very severe, cyclophosphamide with steroids may be the first choice. The process of getting the disease under control may take anywhere from 2 to 6 months.

In cases of severe MPA, treatment may also involve a procedure called plasmapheresis, where components of your blood are separated, with the liquid part (plasma) replaced to help reduce inflammatory substances in your blood. This may be especially effective for cases with lung bleeding and severe kidney problems.

Once remission is achieved, the focus turns to maintaining it. This usually involves using azathioprine, which carries less side-effects compared to cyclophosphamide according to clinical trials. The use of methotrexate and cyclosporine (another immunosupressive drug) has also seen some use in maintaining remission. This part of the treatment typically lasts between one to two years.

When MPA causes life-threatening inflammation in the lungs, leading to bleeding, plasmapheresis is carried out, in addition to high-dose steroids and cyclophosphamide.

Pneumocystis jiroveci, a type of fungus, could cause lung infections in people with weak immune systems like those with MPA. Hence, preventative treatment with a low dose of trimethoprim-sulphamethoxazole, an antibiotic, is necessary.

When you are being evaluated for the conditions known as AAV or MPG, your doctor will need to rule out a number of other possibilities first. This is because many other conditions can show similar signs or symptoms. These include:

Infectious diseases like infective endocarditis, disseminated Gonococcosis, Rocky Mountain spotted fever and other tick-born vascular inflammations, and wide-spread fungal infections
Certain types of cancer such as atrial myxomas, lymphomas, and carcinomatosis
Health problems caused by drug toxicity, including the effects of cocaine, amphetamines, ergot alkaloids, and Levamisole
Other autoimmune conditions such as amyloidosis, Goodpasture disease, sarcoidosis, polyarteritis nodosa, leukocytoclastic vasculitis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, crescentic glomerulonephritis, and cryoglobulinemia

Being sure of the diagnosis is essential to make sure you receive the correct treatment.

What to expect with Microscopic Polyangiitis

Microscopic polyangiitis is a condition that can greatly improve with the right treatment. In fact, about 90% of all cases see significant improvement, with roughly 75% reaching complete recovery or ‘remission’. However, this condition has a 5-year survival rate of about 75%, which is lower compared to similar conditions like Churgg-Strauss syndrome or granulomatosis with polyangiitis. This is likely due to the kidney problems that often come with the onset of the disease.

In a study of 296 patients with Microscopic polyangiitis or granulomatosis with polyangiitis, long-term damage was closely tied to the severity of the initial disease, the number of flare-ups or ‘relapses’, older age, and the length of treatment with glucocorticoids (a type of steroid medication). These findings were based on a 7-year follow-up after diagnosis, with patients being treated with glucocorticoid therapy for an average of about 40 months.

In a separate study with 151 patients with AAV (a group of diseases that includes microscopic polyangiitis), those patients that initially had lung involvement ended up with more damage and higher disease activity after 6, 12, and 24 months. Furthermore, these patients were at a higher risk of developing kidney and heart problems, and were also more likely to develop pulmonary fibrosis, a lung disease that causes scarring in the lungs.

Possible Complications When Diagnosed with Microscopic Polyangiitis

Microscopic polyangiitis (MPA), if not treated, can lead to permanent damage to the body’s organs. The most frequent issue that arises is kidney failure. The exact complications of MPA typically depend on the particular organ that is affected. Studies indicate that people who are older, people with high diastolic blood pressure, and people with a positive PR3-ANCA status, a specific type of blood marker, are more likely to experience heart-related problems.

Medications used to treat MPA can also have negative side effects. For instance, there is a correlation between cyclophosphamide, a drug used in treatment, and bladder cancer. Steroids, another category of treatment, can cause problems like bone loss, high blood sugar, muscle weakness, and skin issues.

Common complications:

Kidney failure
Heart-related problems (particularly in older age, people with high diastolic blood pressure, and people with positive PR3-ANCA status)
Bladder cancer (in those treated with cyclophosphamide)
Bone loss (due to steroid treatment)
High blood sugar (due to steroid treatment)
Muscle weakness (due to steroid treatment)
Skin issues (due to steroid treatment)

Preventing Microscopic Polyangiitis

It’s very important for patients to realize the severity of their illness and understand that they might not be able to regain the same level of health and strength they had before. Sticking to their assigned medication and therapy routines is vital. Keeping a close eye on their health and attending regular check-in appointments is also key. It’s crucial for patients to be closely watched over, especially because they will be on a treatment which suppresses their immune system for probably more than a year. Doctors measure how active the disease is by looking at ANCA levels; ANCA is a type of protein in the body that can indicate disease activity. Patients also need to be made aware of the potential side effects of the medications they’re taking and know when to report these to their doctor.

Frequently asked questions

Microscopic Polyangiitis is a disease where small blood vessels get damaged. It is part of a larger group of diseases known as anti-neutrophil-cytoplasmic-antibody (ANCA)-associated vasculitides (AAV).

Microscopic Polyangiitis occurs at a rate of 3.3 cases per 100,000 people in the United States.

Signs and symptoms of Microscopic Polyangiitis (MPA) include: - Fever - Joint and muscle pain - Weight loss - Issues related to urination - Coughing (sometimes with blood) - Rashes on the skin - Nerve damage causing weakness or numbness - Seizures - Abdominal pain - Digestive system bleeding - Chest pain - Eye pain - Sinus problems - Testicular pain (sometimes) - Rapidly developing severe symptoms like bloody cough or urine, or even complete kidney failure Kidney problems associated with MPA can manifest as rapidly worsening kidney inflammation, ranging from microscopic signs that only lab tests can detect to complete kidney failure that requires dialysis. Common features of kidney problems include bloody urine, protein in the urine, and urinary casts. Lung problems due to MPA affect about a third to half of patients. The most common finding is damage to the air sacs of the lungs, leading to bleeding. Some patients also develop long-term lung scarring that can cause breathing problems. Signs of lung damage include coughing up blood, coughing, trouble breathing, and chest pain. Skin problems in MPA are seen in about a third to half of patients and may be the first indication of the disease. Common skin symptoms include reddish-purple spots (purpura), net-like patterns on the skin (livedo reticularis), hives, skin nodules, and painful skin ulcers with tissue death. Skin symptoms often come with joint pain. Abdominal pain is the most common digestive system problem related to MPA. Digestive system bleeding can occur but severe, life-threatening bleeding is rare. Neurological issues related to MPA often involve the peripheral nerves. The most common nerve problems include a nervous system disorder that usually begins in the hands and feet and nerve damage causing weakness or numbness in various parts of the body. In rare cases, patients may develop a condition called posterior reversible encephalopathy syndrome. Central nervous system problems can vary and include bleeding in the brain, strokes without bleeding, and inflammation of the membranes that surround the brain and spinal cord. During a physical examination, doctors might find skin sores, fever, rapid breathing, and a fast heartbeat. Specific skin findings can include inflammation, reddish-purple spots, network patterns on the skin, skin ulcers, tissue death or gangrene, nodules, digital ischemia, and hives. Lung exams might find abnormal breathing sounds. Nerve exams might find abnormal muscle strength or sensation in certain parts of the body. Heart findings can include high blood pressure, signs of heart failure, a blocked blood supply to the heart, and heart inflammation. Digestive system symptoms may include bleeding, lack of blood supply to the intestines and stomach, and intestinal perforation. Eye exams might reveal bleeding in the retina, inflammation of the white part of the eye, and inflammation within the eye. Other findings will vary depending on which small blood vessels throughout the body are affected.

The development of Microscopic Polyangiitis (MPA) is largely thought to be due to the production of anti-neutrophil-cytoplasmic antibodies (ANCA) that cause damage to blood vessels. The creation of these antibodies is a two-step process involving exposure to inflammatory proteins and the production of myeloperoxidase (MPO). Other factors such as genetic predisposition, environmental factors, certain medications, bacterial infections, exposure to silica, and autoimmune responses may also contribute to the development of MPA.

The doctor needs to rule out the following conditions when diagnosing Microscopic Polyangiitis: - Infectious diseases like infective endocarditis, disseminated Gonococcosis, Rocky Mountain spotted fever and other tick-born vascular inflammations, and wide-spread fungal infections - Certain types of cancer such as atrial myxomas, lymphomas, and carcinomatosis - Health problems caused by drug toxicity, including the effects of cocaine, amphetamines, ergot alkaloids, and Levamisole - Other autoimmune conditions such as amyloidosis, Goodpasture disease, sarcoidosis, polyarteritis nodosa, leukocytoclastic vasculitis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, crescentic glomerulonephritis, and cryoglobulinemia

The types of tests that are needed for Microscopic Polyangiitis include: 1. Clinical evaluation: This involves gathering information about symptoms and how they affect different organ systems in the body. 2. Laboratory tests: - Complete blood count (CBC): Looks for signs of leukocytosis and anemia. - Electrolyte level checks. - Specific tests for antibodies known as MPO and PR3. - Erythrocyte sedimentation rate (ESR): Indicates inflammation in the body. - Blood urea nitrogen (BUN) and serum creatinine tests: Assess kidney function. - Urine analysis: Identifies abnormal substances in the urine. 3. Antineutrophil cytoplasmic antibody (ANCA) test: Checks for antibodies commonly found in people with microscopic polyangiitis. 4. Imaging techniques: May include chest X-ray or CT scan of the chest to check for lung abnormalities, abdominal CT scan, electrocardiogram (ECG) to assess heart function, gastrointestinal endoscopy, or electromyography (EMG) to assess nerve function. 5. Biopsy or tissue sample: Taken from the skin, kidney, or lung to examine under a microscope for signs of disease. These tests help confirm the diagnosis, determine the extent of organ involvement, and guide treatment decisions for Microscopic Polyangiitis.

Microscopic Polyangiitis (MPA) is typically treated with a combination of medications that help reduce inflammation and suppress the immune system. The treatment follows two main stages: inducing remission and maintaining remission. In the first stage, a combination of steroids and cyclophosphamide is often used to achieve remission, although rituximab can also be effective. For severe cases, plasmapheresis may be used in addition to high-dose steroids and cyclophosphamide. Once remission is achieved, the focus shifts to maintaining it, which usually involves using medications such as azathioprine, methotrexate, and cyclosporine. Preventative treatment with an antibiotic may also be necessary to prevent lung infections.

The side effects when treating Microscopic Polyangiitis include: - Bladder cancer (in those treated with cyclophosphamide) - Bone loss (due to steroid treatment) - High blood sugar (due to steroid treatment) - Muscle weakness (due to steroid treatment) - Skin issues (due to steroid treatment)

The prognosis for Microscopic Polyangiitis (MPA) can vary, but overall it is a condition that can greatly improve with the right treatment. Approximately 90% of cases see significant improvement, with about 75% reaching complete recovery or 'remission'. However, MPA has a 5-year survival rate of about 75%, which is lower compared to similar conditions like Churgg-Strauss syndrome or granulomatosis with polyangiitis, likely due to the kidney problems often associated with MPA.

You should see a rheumatologist for Microscopic Polyangiitis.

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