Granulomatosis with polyangiitis (GPA), previously known as Wegener's granulomatosis, is a rare and life-threatening disorder that restricts the blood flow to several organs, including the lungs, kidneys, and upper respiratory tract.

It is a type of vasculitis, an inflammation and injury to the blood vessels.

GPA requires long-term immunosuppression. Some patients die due to the toxicity of the treatment.

GPA affects only 3 out of every 100,000 people in the United States.

It can develop at any age, but symptoms normally appear when patients are in their forties or fifties. It affects males and females are equally, and white people seem to be more susceptible than other ethnic groups.

As well as causing inflammation to the blood vessels, GPA produces granulomas around the blood vessels. A granuloma, or granulation, is a kind of localized nodular inflammation found in tissues, a type of inflammatory tissue.

The cause is unknown, but GPA is not a type of cancer or infection.

With early treatment and diagnosis, the symptoms of GPA can go into remission. Untreated, it can lead to kidney failure and death.

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GPA involves inflammation of the blood vessels.

GPA is part of a larger group of vasculitic syndromes.

They all feature an autoimmune attack by an abnormal type of circulating antibody called antineutrophil cytoplasmic antibodies (ANCAs).

These antibodies attack small and medium-sized blood vessels.

Apart from GPA, other examples of vasculitic syndromes include:

  • Churg-Strauss syndrome
  • microscopic polyangiitis

According to a description issued by the 2012 Chapel Hill Consensus Conference (CHCC2012), GPA is a:

"Necrotizing granulomatous inflammation usually involving the upper and lower respiratory tract, and necrotizing vasculitis affecting predominantly small to medium vessels (e.g., capillaries, venules, arterioles, arteries, and veins). Necrotizing glomerulonephritis is common."

CHCC2012 also agreed to rename Wegener's granulomatosis as granulomatosis with polyangiitis (GPA).

Signs and symptoms of GPA can develop either gradually or suddenly.

The first symptom in most patients is rhinitis, a runny and stuffy nose, similar to a severe case of common cold.

Other signs and symptoms may include:

  • persistent runny nose
  • cough, which may include blood
  • ear infections
  • joint aches
  • loss of appetite
  • malaise, or a general feeling of being unwell
  • nosebleeds
  • shortness of breath
  • sinusitis
  • skin sores
  • swelling of joints
  • eye pain
  • burning sensation in the eyes
  • eye redness
  • vision problems
  • fever
  • weakness, often due to anemia
  • unintended weight loss
  • blood in the urine

It can lead to a rapidly progressive glomerulonephritis, a syndrome of the kidney that, if left untreated, rapidly progresses into acute renal, or kidney, failure. About 75 percent of people with the condition go on to develop kidney disease.

Experts do not know what causes GPA.

It appears to develop when an initial inflammation-causing event provokes an abnormal immune system reaction. This leads to inflamed and constricted blood vessels and granulomas, or inflammatory tissue masses.

When a relapse occurs, it is sometimes due to an infection.

Other contributory factors may be environmental toxins, a genetic predisposition, or a combination of both.

It has been linked to parvovirus and to a long-term presence of Staphylococcus aureus (S. aureus) in the nasal passage.

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A blood test can detect ANCA antibodies, often present people with GPA.

Diagnosis can be difficult, because a patient may have no symptoms in the early stages, or symptoms may be nonspecific. It can take from 2 to 20 months to reach a diagnosis, in primary care.

A doctor may suspect GPA if a patient has had relevant, unexplained symptoms for an extended period.

The physician will ask about signs and symptoms, conduct a physical exam, and study the patient's medical history.

Blood tests may detect ANCAs, the antibodies that are present in over 90 percent of patients with active GPA.

ANCAs alone cannot confirm a diagnosis, but they can indicate that the condition may be present.

A blood test can also measure the patient's erythrocyte sedimentation (sed) rate. This is the speed at which red blood cells fall to the bottom of a tube. It usually takes about an hour.

A sed rate test can help determine whether there is inflammation in the body, and if so, how severe it is. When there is inflammation, the red blood cells fall to the bottom faster.

A blood test may also check for anemia, a common problem in patients with this condition. It may also show whether the kidneys are working properly.

Other diagnostic tests may include the following:

  • urine test to determine whether the kidneys are affected
  • chest X-ray to help determine whether a problem stems from GPA or some other lung disease
  • biopsy

A biopsy is the only sure way of detecting GPA. It involves taking small piece of tissue from an affected organ for examination under a microscope. Tissue samples might be taken from the airways, nasal passages, or lungs, and the results can rule out or confirm the presence of granulomas and vasculitis.

Samples may also be taken from the skin or kidneys if the patient has renal, or kidney, failure or cutaneous vasculitis.

Treatment for GPA is usually divided into two stages:

  • The induction of disease remission, which involves getting rid of all the signs and symptoms.
  • Maintenance of disease remission, to prevent a recurrence.

Early diagnosis and treatment improve the patient's chances of going into remission within months. Some patients may require longer.

It is important to monitor the individual after signs and symptoms have gone away, during the remission stage, because the disease can recur.

Corticosteroids, such as prednisone, may be prescribed for initial signs and symptoms. In a few cases, this is the only medication needed.

Other immunosuppressive drugs, such as cyclophosphamide (Cytoxan), azathioprine (Imuran) or methotrexate (Rheumatrex) are also prescribed in most cases. The aim is to stop the body's immune system from overreacting.

Before steroid and cyclophosphamide treatment became available, 82 percent of patients with GPA died within the first year, and average survival was 5 months. Progress made in the last 50 years means that 90 percent of patients will survive, and some can expect another 20 years without remission.

Rituximab, or Rituxan, may be used. This drug which was originally designed to treat non-Hodgkin's lymphoma, a type of cancer. Later, it was approved for the treatment of rheumatoid arthritis (RA). Rituximab reduces the number of B cells in the body. B cells are involved in inflammation. If standard treatments are not effective, some doctors may prescribe Rituximab.

Many drugs used to treat this condition weaken the patient's immune system, so it is important to monitor the patient. A lower immune system is less able to fight off infection.

The following medications can help support the immune system during treatment:

  • Trimethoprim-sulfamethoxazole, such as Bactrim, Septra, can provide protection from lung infections.
  • Bisphosphonates, such as Fosamax, help prevent osteoporosis, or bone loss, which can result when using corticosteroids.
  • Folic acid can prevent sores and other problems that can occur when folate levels are low, for example, as a result of using methotrexate in treatment.

Some patients may need surgery. If kidney failure occurs, the doctor may recommend a kidney transplant.

Complications usually result from a lack of treatment.

They may include any of the following:

  • deafness due to granulated tissue in the middle ear becoming inflamed
  • skin scarring, if sores develop on the skin
  • heart attack, if the arteries of the heart are affected
  • kidney damage, as untreated cases of GPA will often lead to kidney problems

Glomerulonephritis may develop, in which the kidneys cannot filter out waste and excess fluids from the body properly. This can result in an accumulation of waste products in the bloodstream.

When GPA is fatal, this is normally because of kidney failure.