"The Treatment of Scleroderma, 2004 and Beyond"
by Richard Silver, M.D., Professor of Medicine
and Pediatrics, Medical University of South Carolina,
(originally published
in "Scleroderma Voice," 2004 #2)
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| Richard
Silver, M.D. |
The ultimate goal of scleroderma research is to discover
the cause(s) of and the pathogenic pathway(s) leading
to localized and systemic scleroderma.
Although much progress has been made in our understanding
of certain aspects of scleroderma, the underlying cause
and pathogenesis remains unclear and, thus, prevention
and cure remain a quest rather than a reality. Nevertheless,
significant progress is being made and patients, now
more than ever before, can expect to live a longer and
better quality of life.
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Figure 4.
Organ-Specific Treatment: Kidney. The improved
treatments for renal crisis are a success story
for organ-specific treatment in scleroderma. |
Disease-specific therapy versus organ-specific therapy
Treatment for scleroderma can be divided into disease-specific
therapy and organ-specific therapy. Disease-specific
therapy is still in the developmental stage. Any such
treatment must address each of the three cardinal features
of scleroderma: the vascular system, the immune system,
and activated fibroblast (a cell that makes collagen).
For now, no single drug addresses all three of these
important elements, but that is the goal for which those
of us in the scleroderma research community strive.
Treating Vascular Abnormalities
An increasing number of drugs are aimed at ameliorating
the vascular abnormalities of systemic sclerosis, such
as calcium-channel blocking agents, angiotensin-converting
enzyme (ACE) inhibitors and prostaglandin analogues.
Within the past few years three new drugs (Flolan,
Tracleer, and Remodulin) have been approved by the FDA
for the management of pulmonary arterial hypertension,
a potentially lethal vascular complication of systemic
scleroderma. More are under study now.
Other drugs, such as sildenafil (Viagra) and related
compounds, may also prove to be effective in the management
of various vascular complications of scleroderma, e.g.
digital ischemia and pulmonary hypertension.
Immune Suppression Treatments
Since autoimmunity is believed to play a role in the
pathogenesis of scleroderma, a number of drugs and treatments
designed to suppress the immune system are currently
under investigation.
The Scleroderma Lung Study, funded by the National
Heart Lung and Blood Institute (NHLBI), is designed
to test the hypothesis that cyclophosphamide (Cytoxan)
will improve lung function in scleroderma patients with
active lung inflammation. This study has completed enrollment
and early data analysis is anticipated by the end of
this year.
The National Institute of Arthritis and Musculoskeletal
and Skin Disease (NIAMS) branch of the National Institutes
of Health (NIH) is sponsoring another multicenter study
of immune suppression, the Oral Type I Collagen for
Relieving Scleroderma Study, designed to determine whether
or not exogenous (occurring outside the body) collagen
can induce tolerance in scleroderma lymphocytes (a type
of white blood cell), thereby reducing the degree of
immune activation and subsequent fibrosis. Another powerful
immunosuppressive treatment, autologous stem cell transplantation,
is currently under study in both the U.S. and Europe.
Other Treatment Approaches
One of the most exciting areas of therapeutic research
is the interest in biological agents to reduce the quantity
of collagen produced by scleroderma fibroblasts. Antibodies
designed to bind to and inhibit growth factors have
been synthesized and administered to patients in early
clinical trials. Thus far, preliminary studies suggest
this therapy is safe, but it remains to be determined
whether or not such drugs will prove to be effective
treatments for scleroderma.
Another approach currently under study is to administer
drugs that block receptors on the cell surface of fibroblasts
and other cells believed to play important roles in
the pathogenesis of scleroderma. One such study, BUILD2
(Tracleer, Actelion), is currently recruiting study
participants.
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Figure 5.
Organ-Specific Treatment: Pulmonary Fibrosis.
Pulmonary fibrosis has replaced renal crisis as
the leading case of death among scleroderma patients.
Researchers are striving to find a breakthrough
treatment. |
Progress in Managing Organ-Specific Complications
While we await a disease-specific treatment, it is
important to appreciate the incredible progress made
in the management of organ-specific complications of
scleroderma.
For example, the introduction of ACE-inhibitors for
the prevention and treatment of scleroderma renal crisis
was a major breakthrough for scleroderma patients. Newer
drugs may prove to have a similar impact on preventing
death from pulmonary hypertension.
The proton pump inhibitors that suppress gastric acid
secretion not only reduce the severity of gastro-esophageal
reflux but may also prevent complications such as stricture
formation and Barrett’s esophagus, a pre-malignant
lesion.
This Is An Exciting Time
For those of us who manage patients with localized
and systemic scleroderma, this is indeed an exciting
era. At no time has there been more interest in the
development of new and novel therapeutic agents for
scleroderma. While the quest toward cure continues,
we are confident that significant disease-specific treatment
will be developed.
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