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.
GPA belongs to a family of arthritic diseases called vasculitis. The word vasculitis means inflammation of blood vessels.
The cause of GPA 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 GPA although this trigger is not known.
Granulomatosis with polyangiitis (GPA) 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.
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.
Granulomatosis with polyangiitis (GPA) 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 GPA 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, GPA 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 GPA 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.
Granulomatosis with polyangiitis (GPA) 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.
GPA 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 GPA
Looking for inflammation: GPA 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.
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.
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
Pulmonary Function Tests (PFTs) looking for lung involvement: A PFT is often used to document the presence of lung involvement and follow the lungs to determine if the disease is improving.
Tests for nerve involvement: EMG or Nerve Conduction Studies can be performed to look for nerve involvement
Test for heart involvement: An echocardiogram (ECG or EKG) is a test that looks for heart involvement
Scientists don’t know what causes granulomatosis with polyangiitis (GPA), 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 GPA although this trigger is not known.
Granulomatosis with polyangiitis (GPA) 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 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 GPA.
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 GPA. 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.
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.
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.
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.
The Disease Modifying Anti-Rheumatic Drugs (DMARDs) 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 the DMARDs 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 DMARDs take about 6-12 weeks before they begin to work. Some people might not feel any effect when they first start taking DMARDs. Even if this happens, it’s important to keep taking DMARDs to help keep inflammation under control and to maintain remission.
Living with GPA
The pain and stiffness caused by GPA can sometimes limit people’s normal activities, including work. There are many things people can do to lessen the impact of GPA on their work and daily routine.
We recommend adjusting features of the workplace to help make working with GPA easier. For example, people that sit for much of the day can adjust the position of chairs and desks for proper posture. Vehicle seats can be adjusted to make driving more comfortable and reduce stress on joints and affected tissues.
Those who find out they have GPA while they’re still young can consider choosing work that isn’t physically demanding on their joints and back.
Exercise is important to overall health. It also helps keep the joints moving properly, and helps protect them by strengthening the muscles around them.
The level and amount of exercise people with GPA can do depends on the activity of their disease.
A trained arthritis physiotherapist is the best person to help design an exercise program tailored to the needs of patients with GPA.
The following are some useful articles on exercising with arthritis:
Exercise and Arthritis: An article by arthritis physiotherapist Marlene Thompson
Exercising in a Flare: Another excellent article by Marlene Thompson on how to cope with flares through your exercise routine.
Alcoholic beverages are not an effective treatment for GPA, and they can interact with many medications.
People with GPA that plan on drinking should ask their doctor about possible negative interactions with the medications they take.
Some examples of medication that mixes poorly with alcohol includes, and is not limited to: the DMARDs methotrexate, Arava (leflunomide), and Imuran (azathioprine).
Smoking is not healthy for people with GPA. It can make symptoms worse and harder to treat.
Research has shown that some arthritis medications do not work as well in people who smoke.
We recommend that smokers quit immediately to reduce the impact of their symptoms, improve the effectiveness of their medications, and improve their overall health.
Smoking significantly increases the risk of cardiovascular disease. The chronic (long-term) inflammation caused by rheumatic diseases like GPA already increases this risk without a big extra boost from smoking.
Travel is still possible when you have GPA.
It is best for people with this disease to get organized well in advance of a trip to ensure a smooth, comfortable, and enjoyable time.
Check out our Travel Checklist page.
Though GPA does not particularly cause a loss of sex drive, it can cause pain, fatigue and emotional hardships. These hardships risk creating barriers to sexual needs, ability, and satisfaction.
People with GPA can take comfort knowing that sex and intimacy can be maintained. In many cases, it can help draw partners closer together, especially through improved communication.
For more information on intimacy and arthritis, a great book is: Rheumatoid Arthritis: Plan to Win by Cheryl Koehn, Taysha Palmer and John Esdaile.
Granulomatosis with Polyangiitis (GPA) has no effect on fertility. The chances of getting pregnant for people with GPA are the same as with people that don’t have it. GPA also has no known effects on the developing fetus or the newborn.
The two main issues doctors worry about with GPA and pregnancy are:
Patients with GPA might be treated with a number of medications that can affect pregancies including NSAIDs, anti-TNF biologics, and occasionally DMARDs. It is important for people with GPA who want to become pregnant to discuss their medications with their doctor and create a pre-pregnancy plan. A plan is important for a number of reasons. For example, discontinuing a particular medication for safety of the newborn might cause GPA to flare, so its wise to have a plan in place to handle these possibilities.
Any type of arthritis that affects the pelvis or the hips can make vaginal delivery difficult. It is important for those planning pregnancy to discuss delivery options with an obstetrician.
Following the basics of healthy eating can help improve health and well-being in everyone, including those with GPA. Keeping a healthy weight helps reduce the load on weight-bearing joints including the spine, hips, and knees, making it easier to live with the disease.
Unfortuantely, no special diet has ever been proven to significantly alter the course of GPA or any other types of arthritis.
In addition, no known natural remedies or complementary therapies have been proven to help GPA in any significant way.
People with GPA should consult with their doctor to make sure that any supplements or alternative therapies they consume will not negatively interact with their medications.
Its very important for people with GPA to attend regularly scheduled appointments with their rheumatologist, and promptly get any tests that are ordered by their doctors.
It is often very important that medications are taken exactly as prescribed. Patients should always talk to their doctor about any issues they experience, or if they would like to change anything.
Granulomatosis with Polyangiitis is a chronic disease and a rheumatologist is the best partner in helping patients achieve the best quality of life possible.