Microscopic Polyangiitis

Microscopic polyangiitis is a rare condition where tiny blood vessels throughout the body become inflamed, potentially damaging vital organs like the kidneys and lungs. Understanding this condition can help you recognize symptoms early and work with your healthcare team to manage it effectively.

Table of contents

• What is microscopic polyangiitis?
• Who is affected by microscopic polyangiitis?
• What causes microscopic polyangiitis?
• Signs and symptoms
• How is microscopic polyangiitis diagnosed?
• Treatment options

What is microscopic polyangiitis?

Microscopic polyangiitis, or MPA, is a rare disease that happens when small blood vessels become inflamed. This inflammation is called vasculitis, which means swelling of blood vessels^[1]. When blood vessels are inflamed, they can become weak and stretch, or they may become so thin that they break and bleed into nearby tissue^[1].

The inflammation can also cause blood vessels to narrow so much that they close completely. When this happens, organs don’t get the oxygen and nutrients they need from blood, which can damage them^[1]. MPA affects small to medium-sized blood vessels, including the smallest vessels called capillaries, as well as venules (small branches of veins) and arterioles (small branches of arteries)^[3].

The disease most commonly affects the kidneys, lungs, nerves, skin, and joints^[1]. MPA shares common features with another form of vasculitis called granulomatosis with polyangiitis (formerly called Wegener’s granulomatosis), and treatments for these conditions are similar^[1].

• Kidneys
• Lungs
• Peripheral nerves
• Skin
• Joints
• Digestive tract
• Eyes
• Heart

Who is affected by microscopic polyangiitis?

MPA is very rare, affecting about 13 to 19 people in every million^[1]. The disease can occur at any age, though it most often affects people in their 50s and 60s^[4]. MPA appears to affect men and women equally^[1].

In the United States, the typical MPA patient is a middle-aged white male or female, but there are many exceptions to this pattern^[2]. The disease can occur in people of all ages, both genders, and all ethnic backgrounds^[2].

What causes microscopic polyangiitis?

The cause of MPA is unknown^[1]. What is clear is that MPA is not a form of cancer, is not contagious, and does not usually occur within families^[1].

Research strongly suggests that the immune system plays a critical role in MPA. The immune system’s job is to protect the body from disease by attacking harmful things like viruses. In MPA, the immune system causes blood vessel and tissue inflammation and damage^[1]. People with MPA usually have abnormal antibodies called antineutrophil cytoplasmic antibodies (ANCA) in their blood, which attack certain white blood cells^[6].

Researchers are working to understand what triggers this immune system problem. Possible contributing factors may include certain genes, problems with the immune system itself, infections caused by viruses, or reactions to some types of medicines^[4]. MPA sometimes happens along with an autoimmune disease, such as rheumatoid arthritis^[4].

Signs and symptoms

Because many different organ systems may be involved, a wide range of symptoms and signs are possible in MPA^[1]. The inflammation may come and go, and symptoms can get better or worse at times^[4].

General symptoms

Most people with MPA have a fever, feel tired, and lose weight^[6]. These are called “constitutional” symptoms because the disorder is a systemic disease that broadly affects a patient’s overall condition rather than confining itself to one specific organ^[2]. People may feel generally ill and fatigued, have a fever, or experience a loss of appetite and weight^[1]. Muscles and joints often ache^[6].

Kidney involvement

The kidneys are affected in up to 90% of people with MPA^[6]. Kidney inflammation, called approximately 80% of patients^[2]. This inflammation causes blood and protein to be lost through the urine. This process can occur either slowly or very rapidly in the course of the disease^[2].

Patients with kidney inflammation may experience fatigue, shortness of breath, and swelling of the legs^[2]. However, kidney disease caused by MPA often doesn’t produce symptoms. Inflammation of the kidney may not be apparent until the kidneys begin to stop working^[1]. Blood, protein, and red blood cells appear in the urine, but often there is no sign of kidney malfunction until it is severe. Kidney failure may develop rapidly unless diagnosis and treatment are prompt^[6].

Lung involvement

When MPA affects the lungs, people may have shortness of breath or cough up blood^[1]. If the lungs are affected, bleeding in the lungs may occur, causing people to cough up blood, feel short of breath, or both^[6]. The lungs may fill with fluid, and scar tissue may eventually develop. Fluid buildup and scar tissue cause difficulty breathing^[6]. Bleeding in the lungs, which may occur early in the disorder, requires immediate medical attention^[6].

Skin problems

About one-third of people have a rash of reddish purple or brown spots and bumps, usually on the legs, feet, or buttocks^[6]. Skin lesions in MPA can erupt on various areas of the body, though they tend to favor the “dependent” areas of the body, specifically the feet, lower legs, and in bed-ridden patients, the buttocks^[2]. The skin findings include purplish bumps and spots (called palpable purpura), which range in size from several millimeters in diameter to larger merged areas^[2].

The nails may contain thin purplish lines indicating bleeding, called splinter hemorrhages. Rarely, the blood supply to the fingers and toes is reduced^[6].

Nerve damage

MPA affecting the nerves may cause an abnormal sensation followed by numbness or loss of strength^[1]. Nerve damage occurs in about 60% of patients^[2]. People may have tingling, numbness, or weakness in a limb^[6].

Digestive system

Abdominal pain, nausea, vomiting, and diarrhea may occur. Stools may contain blood^[6].

Other symptoms

Other symptoms can include sinus problems, ear problems such as pain or infection, and eye problems such as pain or visual disturbance^[4]. Other organs, such as the heart, are affected less often^[6].

How is microscopic polyangiitis diagnosed?

MPA can be hard to diagnose because many MPA symptoms may look like symptoms of other illnesses^[4]. Doctors suspect microscopic polyangiitis based on symptoms^[6]. Suspicion for MPA is based on information gathered from a variety of sources^[1].

Medical history and physical examination

The doctor will take a medical history to look for the presence of MPA symptoms and perform a physical examination to detect sites of organ involvement and to exclude other illnesses that may have a similar appearance^[1].

Blood tests

Blood tests are done to look for sites of organ involvement and to test for antineutrophil cytoplasmic antibodies (ANCA)^[1]. 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^[1].

These tests cannot specifically identify the disorder but can confirm that inflammation is present. Blood tests can also help doctors detect bleeding in the digestive tract^[6]. The level of red blood cells can be very low, indicating severe anemia due to bleeding in the lungs^[6].

Urine tests

A urinalysis is performed to detect excessive protein or the presence of red blood cells^[1]. A sample of urine is tested for red blood cells and protein. This information can help doctors determine whether the kidneys are affected^[6].

Imaging tests

Imaging tests such as X-rays, computed tomography (CT) or magnetic resonance (MR) scans can show abnormalities in affected areas such as the lungs^[1]. Chest imaging is done in people who have respiratory tract symptoms. CT is much more likely than a chest X-ray to reveal small amounts of bleeding in the lungs^[6].

Biopsy

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^[1]. A biopsy of affected tissue, usually the skin, lungs, or kidneys, is done to confirm the diagnosis^[6]. Biopsies are only recommended for organ sites in which there are abnormal findings present by examination, laboratory tests, or imaging^[1].

Bronchoscopy

If there are signs of bleeding in the lungs, a flexible viewing tube may be inserted through the nose or mouth into the airways to directly view the lungs. This procedure, called bronchoscopy, can confirm the presence of bleeding or rule out infection, another possible cause of respiratory tract symptoms^[6].

Treatment options

Treatment of MPA is principally with corticosteroids and other immunosuppressive agents, which are medicines that suppress the immune system^[11]. Treatment consists of two phases: bringing the disease under control (induction) and keeping it under control (maintenance)^[11].

For mild symptoms

If symptoms of MPA are mild, a corticosteroid plus rituximab or methotrexate, which also suppresses the immune system, are given^[6].

For severe symptoms

If symptoms are severe and vital organs are affected, rituximab or cyclophosphamide, and high doses of a corticosteroid are given^[6]. Induction of remission in MPA is customarily achieved with cyclophosphamide and prednisone. Cyclophosphamide is started at 1.5 to 2 milligrams per kilogram per day. The patient should be monitored for low white blood cell counts. Prednisone is started at 1 milligram per kilogram per day and is continued for 1 month^[11].

If significant improvement is seen, the prednisone dose is decreased gradually. After complete remission, the maintenance phase is started^[11].

Reduced glucocorticoid regimens

Recent research has shown that a reduced-dose regimen of glucocorticoids proved noninferior to a standard-dose regimen with respect to the risk of death or end-stage kidney disease, and resulted in a lower risk of serious infections in the first year of treatment^[11].

Avacopan

Avacopan is a newer medication that has been approved for adjunctive treatment of severe MPA, in combination with glucocorticoids. It works as a complement inhibitor and may help reduce exposure to glucocorticoids. However, it is not approved as a substitute for steroids^[11].

Plasma exchange

Plasma exchange should be considered in patients with severe renal impairment and diffuse bleeding in the lungs^[11].

Maintenance therapy

Rituximab is recommended as maintenance therapy to help prevent relapses^[11].

Treatment of relapses

The treatment of relapsed MPA is the same as that of remission induction. Rituximab is the preferred immune suppressive for treatment of relapse^[11].

Importance of early treatment

Early diagnosis and treatment are crucial for improving outcomes, as immunosuppressive therapy is most effective when initiated before significant organ damage occurs^[3].