Definition

Wegener's granulomatosis is a very rare disease that affects many different organs and systems of the body. It mainly attacks the respiratory system (sinuses, nose, windpipe, and the lungs) and the kidneys. One of the main features of the disease is an inflammation of the blood vessels (vasculitis). The inflammation narrows the blood vessels and reduces the blood flow to the affected organs. This destroys tissues and damages vital organs.

  Description

Wegener's granulomatosis (WG) is not a contagious disease, and there is no evidence to suggest that it is hereditary either. It is a very rare disease, affecting only 1 in every 30,000-50,000 people. About 500 new cases are diagnosed each year. The disease can occur at any age, however, it mostly affects individuals in their 30s and 40s. It affects males and females equally. Ninety seven percent of all patients are Caucasian, 2% are Black and 1% are of another race.

  Causes and symptoms

No viral, bacterial, or other causative agent has yet been identified for WG. It is thought to be an autoimmune disease, meaning that the body's immune system attacks "itself," that is, the body's own tissues.

Whenever there is an infection in the body, proteins called antibodies, which are capable of attacking the infectious agent, are formed in the blood. In WG, the antibodies that are formed are directed against the white blood cells of the immune system. They are therefore called "auto-antibodies" (antibodies against one's own body cells). These auto-antibodies bind to the blood cells and forms clumps known as immune complexes. The complexes accumulate in the tissues and the blood vessels, leading to a tumor-like (granulomatous) inflammation of the blood vessels. This slows down the blood flow to the different organs and tissues, causing damage and resulting in the many symptoms of WG.

The symptoms of WG, and the severity of the symptoms, vary from patient to patient. One of the most common features is a chronic runny nose and other cold-like symptoms that do not respond to standard treatment. The cold symptoms gradually worsen and could lead to sinusitis (inflammation of the sinuses), middle ear infection (otitis media), cough, coughing of blood, and inflammation of the lung (pleuritis and pneumonia). Other symptoms include fever, fatigue, loss of appetite, weight loss, joint pain, night sweats, change in urine color, and weakness.

Kidney (renal) disease is the most serious development of WG. Patients who do not have renal disease are said to have "Limited Wegener's."

  Diagnosis

Early diagnosis is critical for the most effective treatment of the disease. However, there are no specific laboratory tests for WG. Blood tests are used to rule out other causes of the symptoms and to determine which organs are affected. The blood tests often show anemia (low red cell count) and high white blood cell counts. If the kidneys are involved, red blood cells are seen in the urine when viewed under a microscope. Also, blood tests aimed at measuring kidney function may show abnormalities.

Chest x rays are used to determine if the lungs are involved. Computed tomography scans (CT scans) of sinuses and lungs, and kidney biopsy, are also important tools used in diagnosing WG.

A specific type of antibody called anti-neutrophil cytoplasmic antibody (ANCA) is seen in the blood of about 90% of the patients with WG. The ANCA are a group of antibodies directed against the individual's own white blood cells (namely, the neutrophils). These anti-neutrophil cytoplasmic antibodies are also found in other inflammatory conditions and diseases (such as HIV infection). Though the ANCA test is useful, it cannot be used by itself to make a diagnosis of WG. However, the amount of ANCA in the blood can be measured and correlates well with the progression of the disease. When there is a relapse or a flare-up, the ANCA levels go up. Levels decrease when the disease is controlled by appropriate treatment.

Since there are no definitive laboratory tests for WG, and the initial symptoms of the disease are not very specific, it takes five-15 months, on an average, to make a diagnosis of WG.

  Treatment

Cyclophosphamide (Cytoxan) which is an anti-cancer drug, and corticosteroids, such as prednisone, are used to treat WG. These are powerful drugs that suppress the immune system. However, they are also very toxic and can have serious side effects. The patient has to be watched carefully by the doctors and the dosage of the drugs has to be adjusted, if needed.

Since the patient's immune system is suppressed while on these drugs, he or she is at an increased risk for contracting infections. Vaccinations for flu and pneumonia are recommended.

  Prognosis

In the past, approximately 80% of the patients with untreated WG died within a year of contracting the disease and 90% died within two years. Today, however, the prognosis has been dramatically improved. With appropriate treatment, patients can survive for much longer periods and lead relatively normal lives.

Approximately 50% of the patients with WG will have a relapse of the disease. This generally happens within two years of stopping the medication, but can occur at any point either during treatment or after stopping treatment. Therefore, it is extremely important that patients continue to see their doctors regularly even after stopping the medications.

  Prevention

At present, there are no preventive measures known for Wegener's granulomatosis.

   Key Terms:

Auto-antibodies An antibody that is produced in, and reacts with, an antigen in the same person or animal. Autoimmune disease Any disease which causes tissue injury due to an immunological reaction of antibodies against the patient's own tissues. Granulomatous Resembling a tumor made of granular material. Immune complexes Clusters or aggregates of antigen and antibody bound together. Vasculitis Inflammation of the walls of the blood vessels.

   Resources:

Books

• Harrison's Principles of Internal Medicine. Ed. Anthony S. Fauci, et al. New York: McGraw-Hill, 1997.
• Merck Manual of Diagnosis and Therapy. 17th ed. Ed. Robert Berkow, et al. Rahway, NJ: Merck Research Laboratories, 1997.

Organizations

• National Organization for Rare Disorders. P.O. Box 8923, New Fairfield, CT 06812-8923. (800) 999-6673. http://www.rarediseases.org
• Wegener's Foundation, Inc. 3705 South George Mason Drive, Suite 1813 South, Falls Church, VA 22041. (703) 931-5852.
• Wegener's Granulomatosis Support Group, Inc. P.O. Box 28660, Kansas City, MO 64188-8660. (800) 277-9474. http://www.wgsg.org/wgsg