Wegener's granulomatosis is a rare, potentially life-threatening form of inflammation of the blood vessels, called vasculitis.

The inflammation of Wegener's granulomatosis damages the walls of small- and medium-sized arteries and veins. This damage interferes with normal blood supply to nearby tissues, causing tissue in many parts of the body to be injured and destroyed. Tissues affected by Wegener's granulomatosis show islands of inflamed cells, called granulomas, when examined under the microscope.

Three areas in the body are affected most commonly � the upper airways (including the sinuses, trachea and nose), lungs and kidneys. In the upper airways, tissue destruction related to Wegener's granulomatosis causes chronic (long-lasting) nasal and sinus problems. Ninety percent to 95 percent of people with Wegener's see their doctors at first because of sinusitis, persistent runny nose or frequent bloody nose. In 80 percent of people with Wegener's, inflammation targets the lungs as well, causing a respiratory illness that includes coughing, shortness of breath, wheezing or coughing up blood. Kidney damage affects 80 percent of those with Wegener's, but in many cases, this damage is mild and does not cause any symptoms. In about 20 percent of people with kidney damage from Wegener's, however, the damage is severe enough to cause symptoms of kidney failure caused by an inflammation of the kidneys. Less predictably, Wegener's granulomatosis involves other organs, including the eyes, ears, skin, joints, heart and nerves.

Although the exact cause of the inflamed blood vessels of Wegener's granulomatosis is unknown, research suggests an autoimmune disorder, an illness in which the body's immune defenses mistakenly attack the body's own cells and tissues. In Wegener's granulomatosis, this misdirected immune attack is aimed at the blood vessels, triggering inflammation and damage. So far, researchers have found at least one immune protein that attacks the body that appears to be related to the damage of Wegener's. This immune protein � called antineutrophil cytoplasmic antibody (ANCA) � has been identified in the blood of many people with active Wegener's granulomatosis.

Wegener's granulomatosis is rare, affecting only 11 in every 1 million people each year in the United States. Although it has been reported in people of all races and age groups, it typically affects middle-aged Caucasians, usually beginning at about age 40 to 50. It is slightly more common in men.

When the disease first develops, most people with Wegener's granulomatosis have upper respiratory complaints, especially persistent nasal congestion and nosebleeds. These can occur together with other symptoms such as fever, malaise (a general sick feeling), weakness, fatigue, weight loss, night sweats, joint pain or muscle aches. As the disease gets worse, upper respiratory symptoms usually worsen. Other parts of the body can be affected, too.

Depending on the location and severity of the inflammation, any of the following can occur:

• Symptoms of chronic sinusitis, such as sinus pain, discolored nasal discharge, sores or crusting inside the nose
• Earache and hearing loss
• Lung symptoms, such as cough, shortness of breath, wheezing, coughing up blood or chest discomfort; this may be due to inflammation in the lungs and airways or due to blood clots in the lungs (pulmonary emboli)
• 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 or, in rare cases, weakened vision or double vision
• Skin symptoms, including red or purple patches, small blisters, ulcers or small nodules
• Swollen joints (due to arthritis) or swollen limbs (due to blood clots)
• Symptoms caused by a narrowing of the upper portion of the windpipe (called subglottic stenosis), which can lead to hoarseness, coughing and breathing problems

Your doctor may suspect that you have Wegener's granulomatosis if you have unusually persistent symptoms of sinusitis, respiratory tract infection or respiratory allergies and if your symptoms have worsened despite standard treatment. Because many early symptoms of Wegener's are so similar to those of milder and more common respiratory problems, the average person with Wegener's granulomatosis often has symptoms for months before the correct diagnosis is made.

Your doctor will review your symptoms and medical history, including any treatments that you have received so far. During a thorough physical examination, your doctor will pay special attention to your entire respiratory tract, from the tip of your nose to the base of your lungs, checking for evidence of inflammation and tissue injury. Your doctor may examine your eyes, ears, heart and skin for any signs that Wegener's granulomatosis has affected these areas.

After the physical examination, your doctor will send you for tests to look for evidence of inflammation and organ damage, especially in your upper respiratory tract, lungs and kidneys. These tests may include:

• Complete blood count to look for evidence of anemia that is common in Wegener's granulomatosis, or an abnormal white blood count or platelet count that might suggest another diagnosis.
• Blood tests, called erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), measures of body-wide inflammation
• Blood chemistry to measure levels of blood urea nitrogen and creatinine (two chemicals in your body that can show how your kidneys are working)
• A blood test for the antineutrophil cytoplasmic antibody (ANCA) because this antibody is found in up to 90 percent of people with Wegener's granulomatosis
• A urinalysis to check for kidney damage
• A chest X-ray to look for evidence of lung damage or nodules
• A sinus X-ray or computed tomography (CT) scan to determine whether you have sinusitis, which is common in Wegener's granulomatosis

These tests also help to check for other illnesses that may cause symptoms similar to Wegener's granulomatosis.

The only way to confirm that you have Wegener's granulomatosis is to have a biopsy. This involves taking tissue from an affected organ (such as the sinuses, lung or kidney) and examining it under a microscope to check for granulomas and areas of inflammation. Although a positive antibody blood test may support the diagnosis in some people, this test alone usually is not enough to confirm Wegener's granulomatosis because other conditions also are associated with this antibody and because some people with Wegener's lack this antibody.

Wegener's granulomatosis can lead to death rapidly in people with multiple affected organs who do not get appropriate treatment. With treatment, symptoms can go away for long periods, although setbacks are common. Most people are in treatment and under a doctor's supervision for at least two years from the time of diagnosis.

There is no way to prevent Wegener's granulomatosis because its cause is unknown.

For active or severe disease, your doctor may recommend treatment with a combination of two drugs: the anti-inflammatory drug prednisone (sold under several brand names) and cyclophosphamide (Cytoxan, Neosar), which is an immune-suppressing medication. For example, when the kidneys and lungs are involved, these powerful drugs can be life saving; however, for milder or more limited disease (for example, when Wegener's affects only the sinuses), less aggressive therapy, such as methotrexate (Folex, Methotrexate LPF, Rheumatrex), may be effective. As your symptoms subside, your doctor can reduce the dosage of each drug gradually. Eventually, you may not need the prednisone at all. Once your Wegener's granulomatosis improves and you've taken cyclophosphamide for three to six months, your doctor may suggest switching to methotrexate or azathioprine for a total of one year of treatment. However, longer courses of therapy may be necessary if disease control is interrupted by periods of active disease.

Because cyclophosphamide is a very strong drug, it can cause serious side effects. In up to half of the people who use it, cyclophosphamide can damage the bladder, causing bleeding (called hemorrhagic cystitis). In other cases, the drug increases a person's risk of serious infection by suppressing the bone marrow's production of infection-fighting white blood cells. In the long term, cyclophosphamide also seems to increase the risk of certain types of cancer, especially bladder cancer and lymphoma. If you develop serious side effects related to cyclophosphamide, your doctor may prescribe either methotrexate or azathioprine (Imuran) as an alternative medication. Also, some studies suggest that mycophenolate mofetil (CellCept) or cyclosporine (Neoral, and others) may be less-toxic options but support for these drugs is limited.

A procedure called plasmapheresis, in which blood is filtered and returned to the body, may be helpful in certain people, perhaps because it removes harmful antibodies thought to cause organ damage. Newly approved treatments for rheumatoid arthritis, such as adalimumab (Humira), rituximab (Rituxan) and infliximab (Remicade) are being studied as potential treatments for Wegener's granulomatosis.

Make an appointment to 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 more likely that you have a sinus or viral infection than Wegener's granulomatosis, which is very rare.

Prior to current treatment options, only 10 percent of people with Wegener's granulomatosis survive 2 years. Now, 5-year survival is about 80 percent or better. With treatment, more than 90 percent of people with Wegener's granulomatosis enter remission, although 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.

National Institute of Allergy and Infectious Diseases (NIAID)
6610 Rockledge Drive, MSC 6612
Bethesda, MD 20892-2520
Toll-Free: 1-866-284-4107
TDD: 1-800-877-8339
http://www.niaid.nih.gov/

Wegener's Granulomatosis Support Group
P.O. Box 28660
Kansas City, MO 64188-8660
Toll-Free: 1-800-277-9474
E-Mail: wga@wgaassociation.org
http://www.wgassociation.org/

American College of Rheumatology
1800 Century Place, Suite 250
Atlanta, GA 30345
Phone: 404-633-3777
Fax: 404-633-1870
E-Mail: acr@rheumatology.org
http://www.rheumatology.org/