"Systemic Sclerosis: Introduction
and Overview"
by John Varga, M.D., Professor of Medicine, University
of Illinois/Chicago College of Medicine, (originally
published in "Scleroderma Voice," 2004 #2)
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John Varga, M.D. |
Systemic sclerosis (SSc) is an autoimmune connective
tissue disease with multi-organ involvement and unpredictable
course.
While still considered incurable, SSc is now viewed
as a chronic treatable disease.
Scleroderma affects the circulation and blood vessels;
causes inflammation and autoimmunity; and results in
fibrosis (scarring) on the skin, lungs, and other organs.
SSc affects 1 in 4,000 adults in the United States.
It is more frequent in women than men and in African-Americans
than whites. The highest prevalence rates (1 in 1,500)
are reported in Choctaw Native Americans.
What Causes Scleroderma?
The cause of SSc is still unknown. Some evidence links
SSc with environmental or occupational exposures to
silica, vinyl chloride and organic solvents. Cells of
maternal origin (maternal microchimerism) can be detected
in the circulation of 22% of healthy individuals and
72% of women with SSc. In SSc, these microchimeric cells
may infiltrate the skin and other affected tissues,
and play some role in the disease.
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Figure 1. What Is Scleroderma? Scleroderma (SSc) is a connective
tissue disease, like rheumatoid arthritis (RA),
systemic lupus erythematosus (SLE), vasculitis,
and polymyositis/dermatomyositis (PM/DM). |
The Key Role of Vascular Injury
The application of powerful new research tools, such
as DNA microarrays, population-based genetic studies
and gene targeting in animals has brought the pathophysiology
of SSc into sharper focus during the past decade. It
is now generally accepted that vascular injury is an
early event that leads to inflammation in the skin,
the lungs, and other target tissues. Something then
happens in the context of the lesional tissue that allows
injury and scarring to persist even after resolution
of the local inflammation. Damage to circulation is
prominent in the small and medium-size blood vessels
of the fingers, lungs, heart, and gastrointestinal tract.
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| Figure
2a. Normal Pulmonary Artery. This slide shows
an enlarged and colored view of a normal pulmonary
artery. |
Raynaud Phenomenon and Renal Crisis
Raynaud phenomenon is a prominent early vascular feature,
and in some patients may progress to severe digital
ischemia. However, many newer treatments are now available,
and in most patients can successfully reduce the frequency
and severity of Raynaud attacks, and prevent the progression
of this complication.
In the kidneys, injury to the medium-sized arteries
can precipitate scleroderma renal crisis (SRC), an acute
syndrome with malignant hypertension and progressive
renal failure.
Pulmonary Hypertension: A Major Complication of Scleroderma
Pulmonary hypertension (PH) is a major underrecognized
complication in systemic scleroderma (SSc). It develops
in 40% of SSc patients, and occurs more frequently in
limited cutaneous scleroderma (lcSSc, also known as
CREST).
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| Figure
2b. Scleroderma Pulmonary Artery. View of a pulmonary
artery in a scleroderma patient with pulmonary
hypertension. |
Risk factors include older age of disease onset and
the presence of antibodies to fibrillarin. While early
PH is asymptomatic, with progression increasing heart
failure develops.
Because patients may have no specific respiratory complaints,
all patients should be screened. Tests for PH include
pulmonary function testing, echocardiogram and CT of
the chest. The gold standard for the diagnosis of PH
remains cardiac catheterization. Many patients with
SSc also develop scarring/fibrosis in the lungs, which
is frequently progressive, ultimately leading to limitation
in exercise tolerance. Screening for this complication
is also essential at time of diagnosis and on an ongoing
basis to detect its presence. Screenings include pulmonary
funtion tests, chest X-ray and High Resolution CT scan.
In addition, many centers perform bronchoscopic lavage
of the lung, in order to look for early evidence of
lung fibrosis.
Scleroderma Treatment
Until recently, therapeutic options for patients with
SSc were few. The relative rarity of SSc, its variable
presentation, and absence of interest from the pharmaceutical
industry all contributed to a dearth of studies of new
treatments. In contrast, many potential treatments are
now becoming available, and the therapeutic pipeline
is rich.
Furthermore, an international group of collaborating
centers is working together to standardize treatments
and their evaluation. SSc should be approached as a
chronic treatable disease, much like diabetes.
Because SSc is a complex and heterogeneous disease
with an unpredictable course and highly variable prognosis,
treatment must be individualized. Patients should be
referred to specialized centers where they can receive
coordinated multispecialty care, and access to investigational
treatments.
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