Microscopic Polyangiitis (MPA)

What is microscopic polyangiitis (MPA)?

Microscopic polyangiitis (MPA) is a rare disease. It’s the result of blood vessel inflammation (vasculitis), which can damage organ systems. The areas most commonly affected by MPA include the:

• Kidneys.
• Lung.
• Nerves.
• Skin.
• Joints.

MPA shares common features with another form of vasculitis called granulomatosis with polyangiitis (GPA, formerly called Wegener's granulomatosis). Treatments for these illnesses are similar.

What is vasculitis?

Vasculitis is inflammation of the blood vessels. When inflamed, the blood vessel may become weakened and stretch, forming an aneurysm. Or it may become so thin that it ruptures resulting in bleeding into the tissue.

Vasculitis can also cause blood vessel narrowing to the point of closing off the vessel entirely. This can cause organs to become damaged from loss of oxygen and nutrients that were being supplied by the blood. MPA affects small to medium-sized blood vessels.

Who is affected by microscopic polyangiitis (MPA)?

MPA is very rare (affecting about 13 to 19 people in a million). It can occur in people of all ages, and appears to affect men and women equally.

What causes microscopic polyangiitis (MPA)?

The cause of MPA is unknown. MPA isn’t a form of cancer, isn’t contagious and doesn’t usually occur within families. Research strongly suggests that the immune system plays a critical role in MPA in that the immune system causes blood vessel and tissue inflammation and damage.

What are the symptoms and signs of microscopic polyangiitis (MPA)?

Because many different organ systems may be involved, a wide range of symptoms and signs are possible in MPA.

People who have MPA may feel generally ill and fatigued, have a fever, or a loss of appetite and weight. They usually also have symptoms related to areas of involvement such as rashes, muscle and/or joint pain.

When MPA affects the lungs they may have shortness of breath or cough up of blood. MPA affecting the nerves may cause an abnormal sensation followed by numbness or loss of strength. Any combination of these symptoms may be present.

Kidney disease caused by MPA often doesn’t produce symptoms. Inflammation of the kidney may not be apparent to the patient until the kidneys begin to stop working. So it’s very important for the provider, in dealing with any form of vasculitis, to always examine the urine.

How is microscopic polyangiitis (MPA) diagnosed?

Suspicion for MPA is based on information gathered from a variety of sources, including:

• Medical history to look for the presence of MPA symptoms.
• Physical examination to detect sites of organ involvement and to exclude other illnesses that may have a similar appearance.
• Blood tests to look for sites of organ involvement and testing for antineutrophil cytoplasmic antibodies (ANCA).
• Urinalysis to detect excessive protein or the presence of red blood cells.
• Imaging tests such as X-rays, computed tomography (CT) or magnetic resonance (MR) scans, which can show abnormalities in affected areas such as the lungs.

A positive blood test for ANCA can support a suspected diagnosis of MPA. However, the blood test doesn’t by itself prove the diagnosis of MPA or determine disease activity.

Once the diagnosis of MPA is suspected, a biopsy (tissue sample) of an affected area is often performed to try to confirm the presence of vasculitis. Biopsies are only recommended for organ sites in which there are abnormal findings present by examination, laboratory tests or imaging.

How is microscopic polyangiitis (MPA) treated?

Medications that suppress the immune system form the foundation of treatment for MPA. There are a variety of immunosuppressive medications that are used in MPA, each of which has individual side effects.

People with MPA who have critical organ system involvement are generally treated with corticosteroids combined with another immunosuppressive medication such as cyclophosphamide (Cytoxan ®) or rituximab (Rituxan®). In patients who have less severe MPA, corticosteroids and methotrexate can be used first.

The goal of treatment is to stop all injuries that happen as a result of MPA. If disease activity can be completely "turned off," this is called "remission." Once it’s apparent that the disease is improving, doctors slowly reduce the corticosteroid dose and eventually hope to discontinue it completely.

When cyclophosphamide is used, it’s only given until the time of remission (usually around three to six months), After this, it’s switched to another immunosuppressive agent, such as methotrexate, azathioprine (Imuran®) or mycophenolate mofetil (Cellcept®) to maintain remission.

The treatment time of the maintenance immunosuppressive medication may be different between individuals. In most instances, it’s given for a minimum of one to two years before consideration is given to slowly reducing the dose toward discontinuation.

All of these medications are also used to treat other medical conditions. Azathioprine and mycophenolate mofetil are used to prevent organ transplant rejection. Methotrexate is used to treat rheumatoid arthritis and psoriasis. Both cyclophosphamide and methotrexate are given at high doses as a treatment for certain types of cancer, and are sometimes referred to as chemotherapy. In cancer treatment, these medications work by killing or slowing the growth of rapidly multiplying cancer cells.

However, in vasculitis these medications are given at doses that are 10 to 100 times lower than those used to treat cancer. Their primary job is to influence the behavior of the immune system in a way that results in immunosuppression. Rituximab belongs to a class of medications called biologic agents that target a specific element of the immune system. Recent studies found that rituximab was as effective as cyclophosphamide for treating severe active MPA.

Because these medications suppress the immune system, there’s an increased risk of developing serious infections. Each immunosuppressive drug also has its own set of potential side effects. Monitoring for the side effects of all these drugs is critical to prevent or minimize their occurrence.

Also, an initial tolerance of treatment isn’t a guarantee that tolerance remains the same over time. This makes ongoing monitoring essential, and in some instances, monitoring for long-term side effects may be important even after the drug is stopped.

What is the outlook for patients withmicroscopic polyangiitis(MPA)?

Because MPA is rare, accurate statistics on overall outcomes are approximate. On average, after five years of illness, more than 80% of people have survived the effects of MPA. The outcome is strongly related to the severity of illness. Although MPA can be a progressive and serious illness, many people with MPA do extremely well.

Organ damage can be minimized by beginning treatment early, followed by careful monitoring. Even people with the most severe MPA can achieve remission when treated promptly and followed closely.

After achieving remission, it’s possible for MPA to recur (often referred to as a "relapse"). Relapses occur in about 50% of people with MPA. Such relapses may be similar to what the person experienced at the time of their diagnosis or they may be different.

The chance of a severe relapse can be reduced by immediately reporting any new symptoms to the doctor, regular follow-up care and ongoing monitoring with laboratory tests and imaging. The treatment approach for relapses is similar to that of a newly diagnosed disease. Achieving remission again is possible for most people with MPA.