Granulomatosis with Polyangiitis (GPA, formerly called Wegener’s)

Granulomatosis with polyangiitis (formerly called Wegener’s) is a rare disease of uncertain cause that can affect people of all ages. It is characterized by inflammation in various tissues, including blood vessels (vasculitis), but primarily parts of the respiratory tract and the kidneys.

Granulomatosis with polyangiitis (GPA, formerly called Wegener’s) is a rare disease of uncertain cause. It is the result of inflammation within the tissues called granulomatous inflammation and blood vessel inflammation ("vasculitis"), which can damage organ systems. The areas most commonly affected by GPA include the sinuses, lungs, and kidneys, but any site can be affected.

The cause of GPA is unknown. GPA is not a form of cancer, it is not contagious, and it does not usually occur within families. Evidence from research laboratories strongly supports the idea that the immune system plays a critical role in GPA such that the immune system causes blood vessel and tissue inflammation and damage.

GPA can occur in people of all ages. The peak age groups affected are from 40-60 years. It appears to affect men and women equally.

GPA has symptoms similar to a number of other disorders, which may make it difficult to diagnose. However, for the most effective and successful treatment, early diagnosis is critical.

Once the diagnosis of GPA 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. It is the combination of symptoms, results of physical examinations, laboratory tests, X-rays, and sometimes a biopsy (sample) of affected tissue (skin, nasal membranes, sinus, lung, kidney or other sites) that together prove the diagnosis of GPA. Following treatment, these factors are also critical in judging whether the disease is active or in remission.

A positive blood test for antineutrophil cytoplasmic antibodies (ANCA) can support a suspected diagnosis of the disease. However, this blood test does not by itself prove the diagnosis of GPA or determine disease activity.

GPA often affects the lungs. In patients with GPA that have no lung symptoms (coughing or shortness of breath), imaging tests (conventional X-rays or a CT scan) will show lung abnormalities in up to one third of cases. Therefore, it is important to have lung images performed if active GPA is suspected, even if you do not have any symptoms of lung disease.

Because GPA is often a life-threatening disease, it is treated with a variety of powerful drugs that have been shown to be life-saving. Medications that suppress the immune system form the foundation of treatment for GPA. The severity of the disease in each individual case dictates what immunosuppressive medications are used. There are a variety of immunosuppressive medications that are used in GPA, each of which has individual side effects.

People with GPA 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 GPA, corticosteroids and methotrexate can be used initially. The goal of treatment is to stop all injury that is occurring as a result of GPA. If disease activity can be completely "turned off," this is called "remission." Once it is apparent that the disease is improving, doctors slowly reduce the corticosteroid dose and eventually hope to discontinue it completely. When cyclophosphamide is used, it is only given until the time of remission (usually around 3 to 6 months), after which time it is switched to another immunosuppressive agent, such as methotrexate, azathioprine (Imuran®), or mycophenolate mofetil (Cellcept®) to maintain remission. The treatment duration of the maintenance immunosuppressive medication may vary between individuals. In most instances, it is given for a minimum of 2 years before consideration is given to slowly reduce 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 therefore are sometimes referred to as "chemotherapy." In cancer treatment, these medications work by killing or slowing the growth of rapidly multiplying cancer cells. In vasculitis, these medications are given at doses that are 10 to 100 times lower than those used to treat cancer, and their primary effect is to influence the behavior of the immune system in a manner 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 GPA.