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Introduction: While it is
called by many names and comes in different varieties, SScl is
characterized by one basic problem: over-production of
collagen. Collagen is an important protein in the body that
is a component of scar tissue, which allows injuries to heal.
When too much collagen is deposited, however, a number of
problems can arise, and this is the basic obstacle that must
be faced in patients with SScl.
The excess
collagen seen in SScl is triggered by inflammation, which
appears to simulate the cells in the body that make collagen.
While the results of this process are most easily seen in the
skin (�scleroderma� is literally translated �hard skin�), many
other parts of the body can become involved. When this takes
place, life-threatening complications may ensue.
SScl affects
roughly 1 in 7,000 individuals in the United States, begins
most commonly between 30 and 50 years of age, and affects
women nearly 4 times as often as men. Depending on the type
of skin involvement present and the organs that are affected,
between 20-30% of patients will die from complications within
the first 7 years of disease onset. These figures indicate
that SScl is over twice as lethal as systemic lupus
erythematosus (SLE).
Features of SScl: There are two
different categories that patients with SScl fall into:
limited SScl and diffuse SScl. Limited SScl is
sometimes also called �CREST syndrome.� While both subsets of
patients may have involvement of the skin over the face and
neck, those with limited disease demonstrate skin thickening
that is restricted to the areas below the elbows and/or knees,
while those with diffuse disease also experience skin
thickening of the upper arms and/or legs or the trunk.
The appearance
of the skin in such patients is initially �puffy� but in time
become hardened and �leathery.� Changes in skin pigment, loss
of wrinkles, and contractures of fingers or limbs may occur.
Skin thickening of the face typically results in diminished
opening of the mouth. These changes develop at different
rates in different patients, and many with limited SScl may
only have subtle thickening over the fingers. Generally
speaking, the extent of the skin thickening tends to correlate
with the severity of involvement in other organs.
Dilated blood
vessels, known as telangiectasias, often occur on the
cheeks, lips, or fingers of SScl patients. These lesions
appear as small red spots that blanch out when pressure is
applied. Calcium deposits known as calcinosis may
occur under the skin around the elbows, knuckles, and other
locations. Occasionally, these deposits may appear as larger
lumps or may drain a chalky white material.
Just as in SLE,
isolated forms of skin involvement may occur that do not
involved other organs. Morphea is a plaque-like area
of skin thickening that commonly involves the trunk or limbs,
and linear scleroderma is a potentially disfiguring
process that causes streaks or �dents� to appear in the skin.
Neither of these conditions, however, typically results in the
more serious manifestations of SScl that will be discussed
below.
Raynaud�s
phenomenon is present in over 90% of patients with SScl
and may begin even before the onset of skin thickening or
other signs of the disease. This condition is characterized
by spasm of the blood vessels in the fingers or toes with cold
exposure, resulting in white, blue, and/or red color changes.
About 5% of the general population can describe a similar
pattern of symptoms, but in patients with SScl, the loss of
circulation is more severe and can lead to loss of tissue on
the tips of the fingers if left untreated.
Lung disease is
the number one cause of death in SScl. When present, lung
impairment can take the form of interstitial fibrosis,
where scar tissue builds up in the lungs, or pulmonary
hypertension, where blood vessels leading to the lung
become narrowed and place a strain on the right side of the
heart. Most commonly, patients with diffuse SScl develop
fibrosis of the lungs, while a minority of patients with SScl
develops pulmonary hyper-tension.
Involvement of
the esophagus may result in difficulty swallowing food or
heartburn symptoms. Patients with diffuse SScl may also
develop impairment of function in the lower part of the
intestinal tract. This complication often results in
difficulty in digesting food or obstructs the flow of gut
contents, requiring nutritional support.
Other
complications that occur almost exclusively in diffuse SScl
include renal crisis, resulting in severe rises in
blood pressure and progressing to kidney failure; and heart
involvement, resulting in either rhythm disturbances or
inflammation of the lining of the heart known as
pericarditis. At times, SScl may also overlap with other
rheumatic diseases, such as SLE, Sj�gren�s syndrome (SS), or
myositis (see related sections).
Diagnosis:
The finding of skin thickening on
physical examination is generally necessary in order to
diagnose SScl. Rare skin diseases, exposure to various
chemicals, and other rheumatic diseases may at times be
difficult to distinguish from SScl. Uncommonly, a biopsy of
affected skin can help to confirm the diagnosis, but this is
usually not necessary if typical features of SScl are present
elsewhere. When coupled with Raynaud�s phenomenon and/or
other findings consistent with SScl (lung disease, esophageal
disease, etc.), the diagnosis is further strengthened.
The
antinuclear antibody (ANA) is positive in at least
90% of patients with SScl. This antibody is also found in SLE,
SS, and in some individuals who have no obvious rheumatic
disease, but some subsets of this antibody are more typical
for SScl and may aid in the diagnosis. For example, anti-centromere
antibodies tend to be seen in patients with limited SScl,
and anti-Scl-70 antibodies are associated with diffuse
SScl.
Often, the
biggest challenge is not making the diagnosis of SScl, but
assessing the extent of involvement of the disease in other
organs. Lung function studies are a good screening test to
detect complications early. If abnormal, computerized
tomographic (CT) scans or other procedures such as
biopsy may be indicated to confirm the presence of lung
involvement. An echocardiogram can be useful to detect
abnormalities of heart function as well as findings suggesting
pulmonary hypertension. Barium procedures performed in the
x-ray department can detect SScl involvement of the esophagus
or intestines. Frequent monitoring of blood pressure,
especially in patients with diffuse SScl, is prudent to detect
early renal crisis.
Treatment: Therapy for SScl is generally less
successful than that of rheumatoid arthritis or SLE.
Nonetheless, advances are being made that are resulting in
improved outcomes, particularly for those with some of the
more severe complications.
Treatment of
skin thickening in SScl is not necessary for every patient,
especially those with limited SScl, who are usually not
significantly impaired by their skin changes. Patients with
progressive skin thickening can logically be treated, but the
results of studies attempting various medical therapies have
been disappointing. Notably, studies of this type are very
difficult to interpret due to the fact that patients with SScl
typically experience a loosening of their skin a few years
after the onset of their disease, raising the question of
whether the drug or the natural course of the disease is
responsible for such changes.
D-penicillamine has
been a traditional choice among physicians due to its effects
on cells producing collagen. Unfortunately, trials of this
medication in SScl have yielded unimpressive results. A
number of other medications that suppress the immune system
have been attempted, including methotrexate and
azathioprine, both of which failed to demonstrate
benefit. Early results suggest that cyclosporine may
be useful in treating the skin thickening of SScl, but further
confirmation is needed. In summary, there are no guidelines
for treating the skin component of SScl. An experienced
physician, in conjunction with the patient, should carefully
weigh the risks and benefits of these therapies before making
treatment decisions.
Raynaud�s phenomenon is treated by avoidance of cold
temperatures, wearing protective clothing, and if still
bothersome by medications. Drugs that dilate blood vessels,
ordinarily used to treat high blood pressure, are preferred by
most physicians (nifedipine and diltiazem,
e.g.). Recent reports also suggest that fluoxetine (Prozac)
has beneficial effects on circulation in Raynaud�s
phenomenon. More aggressive measures, such as intravenous
medications (see treatment of pulmonary hypertension below)
and surgery to reduce the spasm of the blood vessels, are
sometimes necessary when fingertips lose blood supply and
become ulcerated.
Lung fibrosis has been treated with a number of different
medications over the years. Recently, many physicians in the
field of rheumatology have considered cyclophosphamide,
a medication that powerfully suppresses the immune system, as
the treatment of choice to address this complication. Studies
seem to indicate that this medication stabilizes or improves
respiratory function in SScl patients with active inflammation
in their lungs. Other medications such as cyclosporine and
methotrexate have also been suggested as medications to treat
lung fibrosis in SScl, but well-done studies have not been
performed.
Pulmonary hypertension is a serious complication of SScl with
high mortality rates and few effective treatments until recent
years. When severe, this complication can be treated with
medications that must be infused intra-venously on a
continuous basis (epoprostenol, e.g.) but which appear
to improve quality of life and survival. Because this option
is difficult to manage, a new oral medication known as
bosentan (Tracleer) has been developed. This
medication seems to have similar effects on reducing pressures
in the arteries leading to the lungs and possibly improving
survival. Strangely enough, sildenafil (Viagra)
also appears to be a promising therapy for pulmonary
hypertension. Prompt recognition and the sound judgment of an
experienced team of physicians are the best measures to most
effectively treat this challenging problem.
Esophageal disease may be treated with medications that reduce
acid production in the stomach. Renal crisis is best treated
with a class of blood pressure medications known as ACE
inhibitors (captopril, lisinopril, e.g.).
Before the introduction of these drugs, this complication was
the top cause of death in SScl patients. Now, if medications
are started early enough, the kidney function is often
preserved. Moreover, about 1/2 of patients whose kidneys fail
and require dialysis will be able to come off dialysis if
staying on these drugs. Heart-related complications in SScl
are treated by correcting the rhythm abnormality if possible
and giving medications to reduce inflammation when
pericarditis is present.
SScl is challenging to
treat, although not nearly so challenging at times as it is to
live with the complications the disease may cause. Because it
is a relatively uncommon disorder, a qualified specialist or
team of physicians working in conjunction with the primary
care doctor is often needed to provide the best possible
outcomes. As we discover more about this potentially
devastating illness, it is hoped that more effective therapies
will be developed to treat its various manifestations and
enhance both the quality and the duration of patients' lives. |
