| Management
Fortunately,
many patients with sarcoidosis require no treatment. Symptoms,
after all, are usually not disabling and do tend to disappear
spontaneously.
When therapy
is recommended, the main goal is to keep the lungs and
other affected body organs working and to relieve symptoms.
The disease is considered inactive once the symptoms fade.
After many years of experience with treating the disease,
corticosteroid remain the primary treatment for inflammation
and granuloma formation. Prednisone is probably the corticosteroid
most often prescribed today. There is no treatment at
present to reverse the fibrosis that might be present
in advanced sarcoidosis.
More
than one test is needed to diagnose
sarcoidosis. Tests can also show if you are
getting better.
Occasionally,
a blood test will show a high blood level of calcium accompanying
sarcoidosis. The reasons for this are not clear. Some
scientists believe that this condition is not common.
When it does occur, the patient may be advised to avoid
calcium-rich foods, vitamin D, or sunlight, or to take
prednisone; this corticosteroid quickly reverses the condition.
Because sarcoidosis
can disappear even without therapy, doctors sometimes
disagree on when to start the treatment, what dose to
prescribe, and how long to continue the medicine. The
doctor's decision depends on the organ system involved
and how far the inflammation has progressed. If the disease
appears to be severe-especially in the lungs, eyes, heart,
nervous system, spleen, or kidneys-the doctor may prescribe
corticosteroid.
Corticosteroid
treatment usually results in improvement. Symptoms often
start up again, however, when it is stopped. Treatment,
therefore, may be necessary for several years, sometimes
for as long as the disease remains active or to prevent
relapse.
Frequent checkups
are important so that the doctor can monitor the illness
and, if necessary, adjust the treatment. Corticosteroids,
for example, can have side effects-mood swings, swelling,
and weight gain because the treatment tends to make the
body hold on to water; high blood pressure; high blood
sugar; and craving for food. Long-term use can affect
the stomach, skin, and bones. This situation can bring
on stomach pain, an ulcer, or acne, or cause the loss
of calcium from bones. However, if the corticosteroid
is taken in carefully prescribed, low doses, the benefits
from the treatment are usually far greater than the problems.
Most
people with sarcoidosis lead a normal life.
Besides corticosteroid,
various other drugs have been tried, but their effectiveness
has not been established in controlled studies. These
drugs include chloroquine and D- penicillamine.
Several drugs
such as chlorambucil, azathioprine, methotrexate, and
cyclophosphamide, which might suppress alveolitis by killing
the cells that produce granulomas, have also been used.
None have been evaluated in controlled clinical trials,
and the risk of using these drugs is high, especially
in pregnant women.
Cyclosporine,
a drug used widely in organ transplants to suppress immune
reaction, has been evaluated in one controlled trial.
It was found to be unsuccessful.
| Research
Status in Sarcoidosis: Goals of the National Heart,
Lung, and Blood Institute
There
are many unanswered questions about sarcoidosis.
Identifying the agent that causes the illness,
along with the inflammatory mechanisms that set
the stage for the alveolitis, granuloma formation,
and fibrosis that characterized the disease, is
the major aim of the National Heart, Lung, and
Blood Institute's program on sarcoidosis. Development
of reliable methods of diagnosis, treatment, and
eventually, the prevention of sarcoidosis is the
ultimate goal.
Originally,
scientists thought that sarcoidosis was caused
by an acquired state of immunological inertness
(anergy). This notion was revised a few years
ago, when the technique of bronchoalveolar lavage
provided access to a vast array of cells and cell-derived
mediators operating in the lungs of sarcoidosis
patients. Sarcoidosis is now believed to be associated
with a complex mix of immunological disturbances
involving simultaneous activation, as well as
depression, of certain immunological functions.
Immunological
studies on sarcoidosis patients show that many
of the immune functions associated with thymus-derived
white blood cells, called T-lymphocytes or T-cells,
are depressed. The depression of this cellular
component of systemic immune response is expressed
in the inability of the patients to evoke a delayed
hypersensitivity skin reaction ( a positive skin
test), when tested by the appropriate foreign
substances, or antigen, underneath the skin.
In
addition, the blood of sarcoidosis patients contains
a reduced number of T-cells. These T-cells do
not seem capable of responding normally when treated
with substances known to stimulate the growth
of laboratory-cultured T-cells. Neither do they
produce their normal complement of immunological
mediators, cytokines, through which the cells
modify the behavior of other cells.
In
contrast to the depression of the cellular immune
response, humoral immune response of sarcoidosis
patients is elevated. The humoral immune response
is reflected by the production of circulating
antibodies against a variety of exogenous antigens,
including common viruses. This humoral component
of systemic immune response is mediated by another
class of lymphocytes known as B-lymphocytes, or
B-cells, because they originate in the bone marrow.
In
another indication of heightened humoral response,
sarcoidosis patients seem prone to develop autoantibodies
(antibodies against endogenous antigens) similar
to rheumatoid factors.
With
access to the cells and cell products in the lung
tissue compartments through the bronchoalveolar
technique, it also has become possible for researchers
to complement the above investigations at the
blood level with analysis of local inflammatory
and immune events in the lungs.
In
contrast to what is seen at the systemic level,
the cellular immune response in the lungs seems
to be heightened rather than depressed. The heightened
cellular immune response in the diseased tissue
is characterized by significant increases in activated
T-lymphocytes with certain characteristic cell-surface
antigens, as well as in activated alveolar macrophage.
This
pronounced, localized cellular response is also
accompanied by the appearance in the lung of an
array of mediators that are thought to contribute
to the disease process; these include interleukin-1,
interleukin-2, B-cell growth factor, B-cell differentiation
factor, fibroblast growth factor and fibronectin.
Because
a number of lung diseases follow respiratory tract
infections, ascertaining whether a virus can be
implicated in the events leading to sarcoidosis
remains an important area of research. Some recent
observations seem to provide suggestive leads
on this question. In these studies, the genes
of cytomegalovirus (CMV), a common disease-causing
virus, were introduced into lymphocytes, and the
expression of the viral genes was studied. It
was found that the viral genes were expressed
both during acute infection of the cells and when
the virus was not replicating in the cells. However,
this expression seemed to take place only when
the T-cells were activated by some injurious event.
In
addition, the product of a CMV gene was found
capable of activating the gene in alveolar macrophage
responsible for the production of interleukin-1.
Since interleukin-1 levels are found to increase
in alveolar macrophage from patients with sarcoidosis,
this suggests that certain viral genes can enhance
the production of inflammatory components associated
with sarcoidosis. Whether these findings implicate
viral infections in the disease process in sarcoidosis
is unclear. Future research with viral models
may provide clues to the molecular mechanisms
that trigger alterations in lymphocyte and macrophage
regulation leading to sarcoidosis.
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