Diseases

Granulomatosis with Polyangiitis

Granulomatosis with Polyangiitis (GPA) formerly known as Wegener’s granulomatosis is a rare disorder that results mainly affects small and medium size blood vessels in the respiratory tract, including in the sinuses, nasal cavity and lungs. It can also involve other parts of the body including the kidneys, skin, nerves, and joints.

Granulomatosis with Polyangiitis belongs to a family of arthritic diseases called vasculitis. The word vasculitis means inflammation of blood vessels.

Autoimmune Disease

The cause of Granulomatosis with Polyangiitis isn’t known, but it is thought to be an autoimmune disease. This means that it is thought that the disease is caused by the body’s immune system attacking its own blood vessels causing inflammation.

It’s thought that an environmental trigger is involved in the development of Granulomatosis with Polyangiitis although this trigger is not known.

Importance of Early Treatment

Granulomatosis with polyangiitis is a very serious illness that is best treated as early and aggressively as possible to prevent further damage to the blood vessels and organs.

Who Gets Granulomatosis with Polyangiitis

Granulomatosis with polyangiitis is a rare disorder. It is estimated to affect only 1 person in every 25,000. The disorder usually strikes people in middle age, but younger and older people can also develop the condition.

Understanding Granulomatosis with Polyangiitis

Symptoms

Granulomatosis with polyangiitis often starts slowly with symptoms coming on gradually over time.

The symptoms of fevers, tiredness, aching muscles and weight loss can be confused with infection or even cancer.

Most people with Granulomatosis with Polyangiitis initially seek treatment because of problems with their respiratory tract. Signs that the airways are involved include the following:

  • Chronic (long-term) sinus problems
  • Frequent nose bleeds
  • Open sores in the nose and/or mouth
  • Ear infections or loss of hearing
  • Shortness of breath
  • Chronic cough
  • Coughing up blood
  • Lots of lung infections (pneumonia) that are not caused by an infection
  • Swollen trachea (windpipe) – although this is rare, it can be serious if it closes off

Less commonly, Granulomatosis with Polyangiitis affects the kidneys. Signs that the kidneys are involved include swelling of the legs, arms, or face due to fluid retention and frothy urine caused by protein in the urine.

Some people with Granulomatosis with Polyangiitis have joint or muscle aches and pains, a skin rash, or inflammation of the eyes (uveitis or iritis).

Rarely, a person with Granulomatosis with Polyangiitis might suddenly have a nerve problem that causes a sudden loss of strength (e.g. “foot drop”).

Very rarely, Inflammation of the tissue around the heart (called pericarditis) can also occur.

Diagnosis

Granulomatosis with polyangiitis can come on very gradually and it can take time before it’s accurately diagnosed. In some people, it may take several years before a correct diagnosis is made. In other people, the disorder is more obvious from the start.

Granulomatosis with Polyangiitis is usually diagnosed by a specialist physician, depending on what areas of the body are affected. Often times, the disease is diagnosed by a rheumatologist (a specialist in arthritis and autoimmune disease). If the airways are a problem, it might be diagnosed by a respirologist(respiratory and lung specialist). If the kidneys are involved, it might be a nephrologist (a kidney specialist).

Your physician will take a complete history and perform a thorough physical examination. This is usually followed by blood tests, x-rays and other types of tests.

Common Tests to Diagnose Granulomatosis with Polyangiitis

Blood Tests

Looking for inflammation: Granulomatosis with Polyangiitis causes inflammation in the body so these tests are expected to have abnormal results. Common tests include a Complete Blood Count (CBC), Erythrocyte Sedimentation Rate (ESR), and C-Reactive Protein (CRP).

Looking for an immune response against white blood cells: The Anti-Neutrophil Cytoplasmic Antibody (ANCA) test looks for antibodies that attack proteins associated with neutrophils (white blood cells). The most common ANCA type is the c-ANCA also known as the anti-PR3 antibody.

Looking for anemia (low hemoglobin in the blood): Low hemoglobin (anemia) can result from inflammation. The ferritin levels can be tested which measure iron stores and can tell if the anemia is a result of low iron stores.

Looking at kidney function: Creatinine is a common blood test that looks at how well the kidneys are working. Abnormally high levels of creatinine can indicate a problem and can mean that the kidneys are involved.

Urine Tests

Urinalysis tests for kidney involvement: Urine tests look for protein and/or blood in the urine is a sign that the kidneys may be involved.

Scans

Chest x-rays and/or CT scans: looking for signs of airway and lung involvement

CT scans or MRIs of the head and neck: looking for involvement of the upper respiratory tract

Breathing Test

Pulmonary Function Tests (PFTs) looking for lung involvement: Pulomnary Function Testing is often used to document the presence of lung involvement and follow the lungs to determine if the disease is improving.

Nerve Test

Tests for nerve involvement: Electromyography and Nerve Conduction Studies can be performed to look for nerve involvement

Heart Test (ECG/EKG)

Test for heart involvement: An echocardiogram is an ultrasound of the heart that looks for heart involvement

Causes

Scientists don’t know what causes Granulomatosis with Polyangiitis, but it is thought to be an autoimmune disease. This means that it is thought that the disease is caused by the body’s immune system attacking its own blood vessels causing inflammation.

It’s thought that an environmental trigger is involved in the development of Granulomatosis with Polyangiitis although this trigger is not known.

Treatments

Granulomatosis with polyangiitis should be treated as early and aggressively as possible to prevent severe damage to the blood vessels, respiratory tract (including the lungs), kidneys, and other important tissues and organs.

Medications for granulomatosis with polyangiitis fall into two broad groups:

  • The first group includes medications that are used initially to bring the disease under control quickly. These are called induction therapies.
  • The second group of medications control the disease over the long-term and are called maintenance therapies.

Medications for Induction Therapy

Corticosteroids (prednisone), cyclophosphamide and rituximab help to rapidly reduce inflammation and control the symptoms associated with Granulomatosis with Polyangiitis.

Once the disease is in remission (when there are no more symptoms and markers of inflammation are back to normal), induction therapies are often tapered (reduced or even stopped in some cases).

Medications for Maintenance Therapy

Azathioprine, mycophenolate mofetil or mycophenolic acid, and methotrexate are medications that are typically used for maintenance (long-term) therapy of Granulomatosis with Polyangiitis. These medications usually take longer to begin to work. Rituximab is also being used as a chronic maintenance therapy with good success.

Maintenance medications might be overlapped with the induction therapy, but unlike induction therapies, they are usually continued over the long-term to keep the disease under control.

Corticosteroids (prednisone)

Medications like prednisone help control inflammation. They may also prevent long-term damage in some people. Prednisone is a very effective medication to control the inflammation of granulomatosis with polyangiitis. In the short-term, prednisone may be given by intravenous infusion in the hospital. After a few days, this is usually switched to oral prednisone. As symptoms improve and markers of inflammation return to normal, the dose of prednisone can be gradually reduced (tapered).

When used for long periods of time, prednisone can have side effects. You should to discuss the risks and benefits of using prednisone with your doctor. Some patients who have joint involvement also benefit from cortisone injections directly into a joint. This should be discussed with your rheumatologist.

Cyclophosphamide

A medication called cyclophosphamide is often used with prednisone to get the disease under control. Cyclophosphamide can be given by mouth or by intravenous infusion. If there is very serious lung, kidney or nerve involvement, an intravenous infusion may be easier to administer.

Cyclophosphamide can increase your risk of infection (be careful with fevers). Cyclophosphamide can also affect your ability to have children (fertility) – this needs to be discussed with your doctor.

Rituximab

This is a type of therapy called a “biologic” medicine. Rituximab has been shown to be as effective as cyclophosphamide and is now approved for the treatment of granulomatosis with polyangiitis. Although it is more expensive, it may be appealing to women of childbearing age because it does not affect fertility. Rituximab is becoming increasingly popular as a longer term choice for maintenance therapy.

Disease Modifying Anti-Rheumatic Drugs

The Disease Modifying Anti-Rheumatic Drugs are medications that are typically used to treat rheumatoid arthritis. Examples that have been shown to be effective in people with granulomatosis with polyangiitis include azathioprine (Imuran), methotrexate, and mycophenolate mofetil or mycophenolic acid. In many cases these medications are used for maintenance therapy once the disease is under control. In milder cases of granulomatosis with polyangiitis they may be used initially to induce remission.

Most Disease Modifying Anti-Rheumatic Drugs take about 6-12 weeks before they begin to work. Some people might not feel any effect when they first start taking the medications. Even if this happens, it’s important to keep taking the medication to help keep inflammation under control and to maintain remission.