Systemic
Sclerosis and Cancer
Certain cancers are more commonly seen
in patients with systemic sclerosis
by Chris T. Derk, M.D., Assistant Professor of Medicine,
Division of Rheumatology, Thomas Jefferson University
(originally published in "Scleroderma Voice,"
2004 #3)
 Editor's
note: This is a long article. You can skip directly
to the subheads that interest you, by clicking on these
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A link between cancer and rheumatic diseases such as
Sjögren’s syndrome and myositis has been
clearly described in the medical literature, while in
systemic sclerosis early clinical studies had failed
to show an association.
Subsequent studies looking at large groups of patients
with systemic sclerosis have now shown that certain
cancers are more commonly seen in patients with systemic
sclerosis.
While the potential causes of why this is the case
are not clearly understood, the awareness by both the
patient and the physician of this increased association
will better help in designing preventive care programs
in patients with systemic sclerosis.
While single reports of many different forms of cancer
have been described in the medical literature, most
of the time this is only because of chance alone.
 |
Figure
1. Squamous Cell Cancer. It is believed that the
skin in systemic sclerosis patients is more sensitive
to ultraviolet light, and thus the reason why
there is a higher incidence of squamous cell and
basal cell skin cancers. |
With this review I will try to touch on the cancers
which have been more strongly associated with systemic
sclerosis.
Skin
An increased frequency of skin cancer has been seen
in relation to systemic sclerosis, usually though not
the melanoma type of skin cancer, but squamous cell
(Figure 1) and basal cell skin cancer.
It is believed that the skin in systemic sclerosis
patients is more sensitive to ultraviolet light and
thus the reason why there is a higher incidence of these
skin cancers.
We usually advise our patients, if they are going to
be in the sun, to use strong sun protection with an
SPF of 45 and above.
In addition to a thorough skin exam by the doctor,
we also advise our patients to examine their skin often
and to look for areas that are scaly and rough. Most
of the time this connotes an early pre-cancerous lesion
called actinic keratosis which may lead to skin cancer,
though if this is removed, usually by freezing it, the
transformation into skin cancer is prevented.
Of some further interest is that patients with morphea
also seem to get these same skin
cancers.
Mouth
(Oral Cavity)
While most studies have not shown an increased frequency
of cancer of the oral cavity, in our own patient data
we have seen an increased incidence of squamous cell
cancer of the oral cavity. The risk for developing this
form of cancer is related most of the time to poor oral
hygiene, tobacco use, and alcohol consumption.
In patients with systemic sclerosis who have tightness
of the skin around their mouth and also if Sjögren’s
syndrome co-exists, which causes a decrease in saliva
production, oral hygiene can become very difficult.
 |
Figure
2. Esophagus. The esophagus in relation to the
rest of the gastrointestinal tract. |
As part of our office exam, we examine a patient’s
oral cavity for masses, and we have the patient see
a dentist twice a year.
We advise against the use of both chewable and smoking
tobacco, as well as heavy alcohol consumption, and finally
describe mouth exercises to our patients to increase
their mouth opening, which in turn will help improve
oral hygiene in these patients.
In patients who also have significant dryness of the
mouth, we recommend different over-the-counter remedies,
as well as prescription medications such as oral pilocarpine
and cevimeline, which increase saliva production.
Esophagus
Indigestion, or acid reflux, is common in patients
with systemic sclerosis because of dysfunction of the
lower part of the esophagus (Figures 2, 3).
The acid that comes up from the stomach into the esophagus
causes damage to the lining of the esophagus. If this
is not treated appropriately with medication that suppresses
stomach acid production, the chronic irritation and
damage to the esophagus can lead to what is called Barrett’s
esophagus (Figure 4), which is a change in the cells
lining the esophagus, and can lead to cancer.
 |
Figure
3. Normal Esophagus. Pathologic specimen of a
normal esophagus. |
Use of medications to suppress stomach acid can prevent
this, though once Barrett’s esophagus is diagnosed
at least a yearly examination by a gastroenterologist
is required.
While theoretically there is a risk in developing
esophageal cancer in patients with systemic sclerosis,
an increased frequency has not been consistently shown
in large studies.
Lungs
One of the most common cancers associated with systemic
sclerosis is lung cancer. It has been shown that patients
with longstanding fibrosis of the lungs are more at
risk to develop such a form of cancer, while smoking
makes this risk higher.
 |
Figure
4. Barrett’s Esophagus. Pathologic specimen
of Barrett’s esophagus. |
In patients with longstanding lung fibrosis, we try
to do at least yearly high-resolution computer tomography
scans (CAT scans) of the lungs, and breathing tests
to evaluate any changes in the pattern of disease.
Early detection is important. Symptoms of increased
shortness of breath, and fluid around the lungs need
to be closely evaluated.
An inherent difficulty in diagnosing this form of cancer
in systemic sclerosis patients is that patients at the
highest risk to develop such a cancer already have significant
abnormalities on their CAT scans. Thus new radiological
abnormalities are difficult to interpret.
Female
Breast
An increased frequency of breast cancer has been shown
in female patients with systemic sclerosis. It appears
that this diagnosis is usually made 2–3 years
before or after the diagnosis of systemic sclerosis,
suggesting an interrelationship as to their cause.
It is known that in some breast cancer there is an
increased production of TGF-b, an agent which has been
shown to have a central role in the development of systemic
sclerosis.
 |
Figure
5. Mammogram. The improved treatments for renal
crisis are a success story for organ-specific
treatment in scleroderma. Copyright 2005, A.D.A.M.,
Inc. |
Frequent patient-performed breast examinations are
recommended, and frequent examinations by a gynecologist,
especially in the first five years after the diagnosis
of systemic sclerosis.
Special attention needs to be given to patients who
have skin fibrotic changes over their breasts, since
breast examination in these patients may be difficult.
Mammography (Figure 5) can be difficult and painful,
and ultrasound examination of the breast tissue is at
times preferred.
We recommend yearly mammograms after the diagnosis
of systemic sclerosis in all female patients, both pre-menopausal
and post-menopausal.
Lymph
Nodes
Cancer of the lymph nodes, or lymphoma, has been shown
in some studies to be more commonly seen in patients
with systemic sclerosis.
Keeping in line with this data, we advise our patients
to immediately bring to our attention any new lumps
that they may detect on their body. Although most lumps
detected are not lymphomas, patient awareness is improved,
which improves early detection.
Again, as part of our physical examination in the office,
we undertake a thorough evaluation of the patient to
detect any enlarged lymph nodes that may need to be
biopsied.
Treatment
of Cancer in Patients with Systemic Sclerosis
Some chemotherapeutic agents have been shown to induce
a scleroderma-like illness; thus their use in systemic
sclerosis patients with cancer should be minimized.
Bleomycin sulfate, a widely used anti-cancer agent,
has not only been shown to cause a
scleroderma-like illness, but it has also been used
by researchers to produce an animal model of scleroderma
for research purposes.
Uracil-tegafur, a second-line anti-cancer agent, has
also been shown to induce scleroderma-like reactions.
Rare cases of scleroderma-like reactions have also
been shown with melphalan and docetaxel, which are also
anti-cancer agents.
Radiation therapy, which is used to treat some forms
of cancer, has been shown to induce scleroderma skin
changes over the skin region that was exposed in both
cancer patients with or without systemic sclerosis,
though in systemic sclerosis patients it can exacerbate
skin fibrosis especially in the skin overlying the area
which has to be radiated, and at times even the underlying
organs. There is controversy as to if radiation therapy
should be used in patients with systemic sclerosis or
if instead a less widespread region around the cancer
is treated with radiation.
Conclusion
An increased frequency of certain types of cancer
has been seen in patients with systemic sclerosis and
it is important for both the patient and the doctor
to develop a concise preventive plan for early detection.
When cancer is diagnosed, it would be recommended that
the cancer doctors who will be treating you, consult
with your scleroderma specialist so that treatment is
specifically tailored to your health needs.
While the above opinions are those of the author, you
should always confer with your own physician, who is
most familiar with your own unique health history.
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