SYMPTOMS
The first symptoms
of Wegener's granulomatosis are often vague and
frequently include upper respiratory tract symptoms,
joint pains, weakness, and tiredness.
Upper respiratory tract
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 pain.
Lungs
The lungs are affected
in most people 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.
Kidneys
Kidney involvement,
which occurs in more than three-fourths of people
with this disorder, usually does not cause symptoms.
If detected by blood and urine tests, a doctor
can start proper treatment, preventing long-term
damage to the kidneys.
Musculoskeletal system
Pain in the muscles
and joints or, occasionally, joint swelling affects
two-thirds of people with Wegener's granulomatosis.
Although joint pain can be very uncomfortable, it
does not lead to permanent joint damage or deformities.
Eyes
Wegener's granulomatosis
can affect the eyes in several ways. People may
develop
- Conjunctivitis (inflammation
of the conjunctiva, the inner lining of the
eyelid)
- Scleritis (inflammation of
the scleral layer, the white part of the eyeball)
- 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.
Skin lesions
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.
Other symptoms
Some people 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 respiratory tract.
DIAGNOSIS
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 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 care provider
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. CT (computed tomography) scans in people
with sinus problems may show thickening of the sinus
lining.
Many people 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 care providers do not use it by itself to
diagnose this disorder. The ANCA test may be negative
in some people 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 care provider
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.
TREATMENT
With the appropriate
treatment, the outlook is good for people 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,
people 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 doctor and patient.
Approximately
half of people with Wegener's granulomatosis may
experience a return of their disease. This occurs
most frequently within 2 years of stopping medicine
but can occur at any point both during treatment
or after stopping treatment. Thus, it is extremely
important that people continue to see their doctors
regularly, both while they are on these medicines,
as well as after the medicines have been stopped.
Prednisone
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 12 months.
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. People
taking this medicine 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
Cyclophosphamide
(Cytoxan) is the most commonly used cytotoxic drug
used to treat Wegener's granulomatosis. People 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 person'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 was in remission.
The dose of cyclophosphamide was then decreased
gradually and eventually stopped. In more recent
treatment approaches, however, 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 their
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
Methotrexate has
been studied at 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. It also is used to maintain
remission after a person has initially received
cyclophosphamide. Methotrexate is usually given
for 1 to 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 drink alcoholic beverages.
Methotrexate cannot be given to people who have
poor kidney function or who have underlying liver
disease such as hepatitis.
Azathioprine
Azathioprine (also
called Imuran) is used primarily 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 to 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 people 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. People with poor kidney
function or liver disease can take azathioprine.
Other medicines
During the course
of treating Wegener's granulomatosis, doctors often
give their patients other medicines to prevent medicine-related
side effects. These include
- Trimethoprim/sulfamethoxazole
(also called bactrim or septra) is given three
times a week to prevent Pneumocystis carinii
infection (a lung infection)
- A medicine regimen is often
given to prevent prednisone-related bone loss
(osteoporosis)
- Folic acid or folinic acid
(also called leucovorin) are often given to
people taking methotrexate
For
information on patient support groups, contact
Wegener's
Granulomatosis Association
P.O. Box 28660
Kansas City, MO 64188-8660
1-800-277-9474 or 816-436-8211
http://www.wgassociation.org
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