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)

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.

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.

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.

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.

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.

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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