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Wegener's granulomatosis is an uncommon disease, in which the blood vessels
are inflamed (vasculitis). This inflammation damages important organs of
the body by limiting blood flow to those organs and destroying normal tissue.
Although the disease can involve any organ system, Wegener's granulomatosis
mainly affects the respiratory tract (sinuses, nose, trachea [windpipe],
and lungs) and the kidneys. This disorder can affect people at any age
and strikes men and women equally. It is rare in African Americans compared
to Caucasians. Health experts do not know what causes Wegener's granulomatosis.
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The first symptoms of Wegener's granulomatosis are often vague and frequently
include upper respiratory tract symptoms, joint pains, weakness, and tiredness.
The most common sign of Wegener's granulomatosis is involvement of the
upper respiratory tract, which occurs in nearly all patients. Symptoms
include sinus pain, discolored or bloody fluid from the nose, and, occasionally,
nasal ulcers. A common sign of the disease is almost constant rhinorrhea
("runny nose") or other cold symptoms that do not respond to usual treatment
or that become increasingly worse.
Rhinorrhea can result from nasal inflammation or sinus drainage and can
cause pain. A hole may develop in the cartilage of the nose, which may
lead to collapse (called saddle-nose deformity). The eustachian tubes,
which are important for normal ear function, may become blocked, causing
chronic ear problems and hearing loss. Bacterial infection can cause Wegener's-related
sinusitis (inflammation of the sinuses) with congestion and chronic sinus
The lungs are affected in most patients with Wegener's granulomatosis,
although no symptoms may be present. If symptoms are present, they include
cough, hemoptysis (coughing up blood), shortness of breath, and chest discomfort.
Kidney involvement, which occurs in more than three-fourths of patients,
usually does not cause symptoms. If detected by blood and urine tests,
the doctor can start proper treatment, preventing long-term damage to the
Pain in the muscles and joints or, occasionally, joint swelling affects
two-thirds of patients with Wegener's granulomatosis. Although joint pain
can be very uncomfortable, it does not lead to permanent joint damage or
Wegener's granulomatosis can affect the eyes in several ways. Patients
- Conjunctivitis (inflammation of the conjunctiva, the inner lining of
- Scleritis (inflammation of the scleral layer, the white part of the
- Episcleritis (inflammation of the episcleral layer, the outer surface
of the sclera)
- Mass lesion behind the eye globe
Symptoms in the eye include redness, burning or pain. Double vision or
a decrease in vision are serious symptoms requiring immediate medical attention.
Nearly half of people with Wegener's granulomatosis develop skin lesions.
These often have the appearance of small red or purple raised areas or
blister-like lesions, ulcers, or nodules that may or may not be painful.
Some patients experience narrowing of the trachea. The symptoms can include
voice change, hoarseness, shortness of breath, or cough.
The nervous system and heart occasionally may be affected. Fever and night
sweats may occur. Fever also may signal an infection, often of the upper
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To treat people with Wegener's granulomatosis most effectively, doctors
must diagnose the disease early. There are no blood tests that a doctor
can use to diagnose Wegener's granulomatosis, but blood tests are important
to rule out other causes of illness and to determine which organ sites
may be affected. Most blood tests can only suggest that a person has inflammation
somewhere in the body. Anemia (low red blood cell count), elevated white
blood cell count and platelet count, and an elevated sedimentation rate
are commonly found in people with Wegener's granulomatosis. If the kidneys
are involved, a health professional can see red blood cells and structures
called red blood cell casts in the urine when viewed under a microscope,
and the blood tests measuring kidney function may show abnormalities.
X-ray results can be very helpful in diagnosing Wegener's granulomatosis.
People with lung problems will have abnormal chest x-rays. Computed tomography
(CT) scans in people with sinus problems may show thickening of the sinus
Many patients with active Wegener's granulomatosis have a blood test that
shows the presence of a specific type of antibody called antineutrophil
cytoplasmic antibodies (ANCA) (an antibody is a disease-fighting protein).
Although a positive ANCA test is useful to support a suspected diagnosis
of Wegener's granulomatosis, in most instances health professionals do
not use it by itself to diagnose this disorder. The ANCA test may be negative
in some patients with active Wegener's granulomatosis.
Currently, the only clear-cut way to diagnose Wegener's granulomatosis
is by performing a biopsy (removing a tiny piece of tissue) of an involved
organ (usually the sinuses, lung, or kidney). A health professional will
examine tissue from the organ under the microscope to confirm the presence
of vasculitis and granulomas (a specific type of inflammation), which together
are features of Wegener's granulomatosis. A biopsy is very important both
to confirm the presence of the disease and also to make sure other disorders
that may have similar signs and symptoms are not present.
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With the appropriate treatment, the outlook is good for patients with
Wegener's granulomatosis. In a study of 158 patients who were treated with
prednisone and cyclophosphamide at the National Institutes of Health (NIH),
91 percent of them markedly improved. After 6 months to 24 years of follow-up,
80 percent of the patients survived.
In most cases, treatment consists of a combination of a glucocorticoid
(a steroid) and a cytotoxic medicine. Although these medicines are helpful
in treating Wegener's granulomatosis, patients and their doctors should
be aware that they potentially have serious side effects. In many instances
these can be minimized or prevented by careful monitoring by both the physician
Approximately half of people with Wegener's granulomatosis may experience
a return of their disease. This occurs most frequently within two years
of stopping medication, but can occur at any point both during treatment
or after stopping treatment. Thus, it is extremely important that patients
continue to see their doctors regularly, both while they are on these medicines,
as well as after the medicines have been stopped.
Prednisone is the most common glucocorticoid that doctors use. Prednisone
is similar to cortisol, the natural glucocorticoid hormone produced by
the body. It is chemically different from the anabolic steroids that have
been used by athletes and is given in doses much higher than the body normally
produces. Doctors usually give prednisone as a single morning dose to try
to imitate how the body normally secretes cortisol.
When the person's illness improves, the prednisone dose is gradually decreased
and converted to an every other day dosing schedule, usually over a period
of 3 to 4 months. With further improvement in the disease, prednisone is
gradually decreased and discontinued completely after approximately 6 to
When prednisone is taken by mouth, the body stops making its own natural
cortisol. As the prednisone dose is gradually reduced, the body will resume
making cortisol again. It is extremely important that prednisone never
be stopped suddenly because the body requires prednisone (or cortisol)
to function and may not be able to immediately make what it needs.
Prednisone can affect the body's ability to fight off infection. Patients
should report immediately any symptoms of infection and, specifically,
any fever to their doctors. Prednisone can also cause weight gain, cataracts,
brittle bones, diabetes, and changes in mood and personality.
Cyclophosphamide (Cytoxan) is the most commonly used cytotoxic drug used
to treat Wegener's granulomatosis. Patients take cyclophosphamide once
a day by mouth and must take the drug all at once in the morning followed
by drinking a large amount of liquid. Although the first dose of cyclophosphamide
is based on the patient's weight and kidney function, the doctor may adjust
the dosage based on blood counts, which are monitored closely to be sure
that the white blood cell count is maintained at a safe level. In the original
regimen, cyclophosphamide was continued for a full year beyond that point
at which the disease is in remission. The dose of cyclophosphamide is then
decreased gradually and eventually stopped. In more recent treatment approaches,
cyclophosphamide is given until remission and then switched to another
medicine such as methotrexate or azathioprine (discussed below).
Cyclophosphamide is a powerful medicine that keeps the immune system from
working normally. The doctor must monitor patients carefully and perform
blood tests frequently. Cyclophosphamide can cause an increased risk of
infection, bone marrow suppression (lowering of blood counts), sterility,
hemorrhagic cystitis (bleeding from the bladder), bladder cancer, as well
as other serious side effects.
Methotrexate has been studied at the NIH for the treatment of Wegener's
granulomatosis since 1990. In people with active, but not immediately threatening,
Wegener's granulomatosis, methotrexate has been used in combination with
prednisone to bring about remission. Another way that it has been used
is to maintain remission after a patient has initially received cyclophosphamide.
Methotrexate is usually given for 1-2 years, after which time if people
stay in remission, it is decreased and stopped.
Methotrexate is given once a week usually by mouth, but occasionally as
an injection under the skin or in the muscle. People taking methotrexate
need to have regular blood work to monitor their response and to watch
for side effects.
The side effects of methotrexate include infection, lowering of the blood
counts, nausea, soreness and ulceration of the mouth lining, irritation
of the lungs (pneumonitis), and inflammation and scarring of the liver.
People taking methotrexate cannot consume alcoholic beverages. Methotrexate
cannot be given to people who have poor kidney function or who have underlying
liver disease such as hepatitis.
Azathioprine (also called imuran) is primarily used to maintain remission
in people who have initially been treated and gone into remission with
cyclophosphamide. It is taken once a day by mouth. Similar to methotrexate,
it is usually given for 1-2 years after which time the dosage is lowered
until it is stopped.
The side effects of azathioprine include infection, lowering of the blood
counts, and rarely an allergic type reaction. In patients who receive azathioprine
to prevent rejection of a transplanted organ, there has been a suggestion
of an increased risk of blood cancers (leukemia and lymphoma) but it is
not clear whether this risk exists in other situations. Azathioprine can
be given to people with poor kidney function or liver disease.
During the course of treating Wegener's granulomatosis, other medications
are often given to prevent medication side effects. These include
- Trimethoprim/sulfamethoxazole (also called bactrim or septra) given
three times a week to prevent Pneumocystis carinii infection
(a lung infection)
- A medication regimen is often given to prevent prednisone-related bone
- Folic acid or folinic acid (also called leucovorin) are often given
to patients taking methotrexate.
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Since the 1970s, research physicians at the National Institute of Allergy
and Infectious Diseases (NIAID), a component of NIH, have been interested
in Wegener's granulomatosis. NIAID scientists first introduced the combination
of glucocorticoids with cyclophosphamide for treating people with this
disease. While this was a dramatic breakthrough for the treatment of Wegener's
granulomatosis, investigators realize that these medicines have serious
side effects and cannot be tolerated by all people. Therefore, NIH researchers
have continued to study Wegener's granulomatosis to understand the causes
of the disease and to develop new treatments. NIAID is conducting several
studies to investigate new treatment regimens. These studies each have
individual entry criteria but are open to patients who have a definitive
diagnosis of Wegener's granulomatosis and who have active disease.
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For information on patient support groups, contact
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