Granulomatosis with polyangiitis

What is it?

Granulomatosis with polyangiitis (GPA) is a rare disease marked by inflammation of the blood vessels. The condition is potentially life-threatening. It was formerly called Wegener's granulomatosis.

In GPA, inflammation damages the walls of small- and medium-sized arteries and veins. This damage interferes with normal blood supply to nearby tissues. As a result, tissues in many parts of the body may be injured and destroyed.

Tissues affected by GPA contain islands of inflamed cells. These are called granulomas.

Three areas in the body are affected most commonly:

• Upper airways (including the sinuses, trachea and nose). In the upper airways, tissue destruction causes chronic (long-lasting) nasal and sinus problems. Many people with GPA first see their doctors because of sinusitis, persistent runny nose or frequent bloody nose.
• Lungs. In most people with GPA, inflammation targets the lungs as well. This causes a respiratory illness. Symptoms include coughing, shortness of breath, wheezing or coughing up blood.
• Kidneys. Kidney damage affects most people with GPA. But in many cases, this damage is mild and does not cause any symptoms. In some people, however, the kidney damage is more severe. It may cause kidney failure.

In some cases, GPA involves other organs. This may include the eyes, ears, skin, joints, heart and nerves.

GPA is believed to be an autoimmune disorder. This means the body's immune defenses mistakenly attack the body's own cells and tissues. In this case, the misdirected immune attack is aimed at the blood vessels. This triggers inflammation and damage.

Symptoms

When GPA first develops, most people have upper respiratory complaints. Common symptoms of GPA include:

• persistent nasal congestion
• nosebleeds
• fever
• malaise (a general sick feeling)
• weakness
• fatigue
• weight loss
• night sweats
• joint pain
• muscle aches.

As the disease gets worse, upper respiratory symptoms usually worsen. Other parts of the body can be affected, too.

The following symptoms may occur, depending on the location and severity of the inflammation:

• symptoms of chronic sinusitis, such as
  • sinus pain
  • discolored nasal discharge
  • sores or crusting inside the nose
• earache and hearing loss
• lung symptoms, including
  • cough
  • shortness of breath
  • wheezing
  • coughing up blood
  • chest discomfort due to
    • inflammation in the lungs and airways
    • blood clots in the lungs
• swollen gums
• "saddle nose deformity," an indentation over the bridge of the nose due to cartilage inflammation
• ulcers on the tonsils
• eye symptoms, such as
  • eye pain
  • redness
  • a burning sensation
  • weakened vision or double vision (this is rare)
• skin symptoms, including
  • red or purple patches
  • small blisters
  • ulcers
  • small nodules
• swollen joints (due to arthritis)
• swollen limbs (due to blood clots)
• symptoms caused by a narrowing of the upper portion of the windpipe, such as
  • hoarseness
  • coughing
  • breathing problems.

Diagnosis

Your doctor may suspect GPA if you have:

• unusually persistent symptoms of sinusitis
• respiratory tract symptoms
• unexplained kidney disease.

And your symptoms have worsened despite treatment for more common conditions, such as pneumonia or a sinus infection.

Many early symptoms of GPA are similar to those of milder and more common respiratory problems. As a result, the average person with GPA often has symptoms for months before the correct diagnosis is made.

Your doctor will review your symptoms and medical history. This will include any treatments that you have received so far.

Your doctor will conduct a thorough physical examination. He or she will carefully check your entire respiratory tract, from the tip of your nose to the base of your lungs. The doctor will look for evidence of inflammation and tissue injury. Your doctor may also examine your eyes, ears, heart and skin.

After the physical exam, your doctor may send you for tests. These tests will look for inflammation and organ damage. The tests will focus on your upper respiratory tract, lungs and kidneys. These tests may include:

• complete blood count (CBC) to look for
  • evidence of anemia (common in GPA)
  • abnormal white blood cell count
  • platelet count abnormalities that might suggest another diagnosis
• blood tests that measure body-wide inflammation
• urine and blood tests to measure kidney function
• a blood test for an antibody that is found in most people with GPA is called anti-neutrophilic cytoplasmic antibody (ANCA)
• chest X-ray or computed tomography (CT) scan to look for evidence of lung damage or nodules
• sinus X-ray or CT scan to determine whether you have sinusitis.

These tests also help to check for other illnesses that may cause symptoms similar to GPA.

The only way to confirm this diagnosis is to have a biopsy. Tissue is taken from an affected organ. It is then examined under a microscope to check for granulomas and areas of inflammation.

Expected duration

Granulomatosis with polyangiitis can rapidly lead to death in people with multiple affected organs that do not get appropriate treatment.

With treatment, symptoms can go away for long periods. However, setbacks are common. Most people are in treatment and under a doctor's supervision for at least two years from the time of diagnosis.

Prevention

There is no known way to prevent granulomatosis with polyangiitis.

Treatment

Initial treatment for granulomatosis with polyangiitis usually includes the anti-inflammatory corticosteroid drug prednisone. For milder or more limited disease, your doctor may also recommend treatment with the drug methotrexate (Folex, Rheumatrex).

For active or severe disease, your doctor may recommend treatment with a combination of two drugs: prednisone along with cyclophosphamide (Cytoxan, Neosar) or rituximab (Rituxan). Cyclophosphamide and rituximab are powerful immune-suppressing medications.

As your symptoms subside, your doctor will try to reduce the dosage of each drug gradually.

Once your condition improves and you've taken cyclophosphamide or rituximab for three to six months, your doctor may suggest switching medications. He or she may recommend methotrexate, azathioprine (Imuran, Azasan), or other immune-suppressing medications. Treatment lasting a year or more is common; longer periods of treatment may be necessary if disease control is interrupted by periods of active disease.

Cyclophosphamide can cause serious side effects such as bladder damage (especially bleeding) and an increased risk of bladder cancer. Cyclophosphamide and rituximab increase a person's risk of serious infections.

If you develop serious side effects related to these medications, your doctor may prescribe an alternative medication.

A procedure called plasmapheresis may help some people. In this procedure, blood is filtered and returned to the body. This procedure may help because it removes harmful antibodies but details about why it may work are unknown.

When to call a professional

See your doctor if you have a chronic stuffy nose, runny nose, nosebleeds or cough. Keep in mind that even with these symptoms, it's likely that you have a sinus or viral infection as these conditions are much more common than granulomatosis with polyangiitis.

Prognosis

With treatment, more than 85% of people with granulomatosis with polyangiitis survive for seven years or longer after diagnosis. With treatment, most people with the condition enter remission. However, as many as half will relapse when medication is reduced or stopped. Those who do not relapse may remain in remission for many years, often without needing more medication.

Additional info

National Institute of Allergy and Infectious Diseases (NIAID)
http://www.niaid.nih.gov/

American College of Rheumatology
http://www.rheumatology.org/

Vasculitis Foundation
https://www.vasculitisfoundation.org/