National report — The threats of skin cancer and bad outcomes from the disease are significantly higher for those who are immunosuppressed
than they are in the general population.
The increase in skin cancer risk for immunosuppressed patients varies depending on the population. It can range from a small
increase with the administration of systemic steroids to a dramatic increase — up to 64-fold — with transplant-associated
immunosuppression, according to Clark C. Otley, M.D., a dermatologist and associate professor of dermatology at the Mayo Clinic,
Rochester, Minn.
Dermatologists play an important role in taking extra precautions with these patients, who include transplant and HIV patients.
Among dermatologists' options, Dr. Otley says, are to aggressively pursue traditional preventive and treatment options, as
well as work closely with the specialists treating these patients to modify drug regimens and enhance immunity.
Transplant patients, skin cancer
Skin cancer is the most prominent of cancers among transplant patients.
"About 50 percent of the cancers that develop in our transplant patients are skin cancers, which outnumbers all the other
cancers combined," Dr. Otley says. "That is because our immunity probably fights cancer development; we also know that some
of the immunosuppressant medications may contribute to cancer formation."
Researchers who have injected cyclosporin into a particular kind of mouse, called a SCID, and exposed these mice to ultraviolet
radiation have found the mice develop cancer at an increased rate. That is, even though they do not have an intact immune
system, suggesting that there might be a carcinogenic effect, according to Dr. Otley.
One way to help transplant patients avoid skin cancer is to modify their use of medicines that could cause the cancer.
"There are about eight lines of evidence suggesting that reduction of immunosuppression may be an effective adjuvant modality
that could reduce the risk of skin cancer in the transplant patients. However, a randomized prospective trial for this specific
indication is yet to be done," Dr. Otley says.
It is likely that many transplant patients on immunosuppressant therapy are on higher doses of medication than they need to
be to optimize their kidney, heart or liver function, according to Dr. Otley.
Dantal J. et al conducted a randomized trial where patients received either high-dose or low-dose cyclosporin one year after
kidney transplantation and found that while there was increased risk of rejection, it was manageable rejection. At the trial's
end, patients did not have any permanent detrimental effects on their organs and developed fewer cancers, including fewer
skin cancers, according to Dr. Otley.
Another strategy is to consider switching patients to a relatively new immunosuppressant called sirolimus, or rapamycin.
"There is early epidemiologic data that suggests that rapamycin might be associated with a lower risk of skin cancer," he
says. "It is important to emphasize, however, that modifying immunosuppressant therapy is not something that dermatologists
do. This is something that we talk with the transplant physicians and ask them to consider. We, however, know how bad the
skin cancer is and it is the dermatologist's job to identify the risk of skin cancer, think about how risky it will be in
the future and then talk to the transplant physician when we feel like it is warranted to reduce the immunosuppression."
In addition to consulting with patients' physicians about modifying their drug regimens, dermatologists would recommend that
patients use vigorous sun protection, with sunscreen and protective clothing. Dermatologists, according to Dr. Otley, should
treat any skin cancers aggressively and consider using a variety of chemotherapy and preventive cream treatments.
HIV-related challenges
Since the development of highly active antiretroviral therapy (HAART), HIV patients have enjoyed longer lives. The resulting
immunosuppression, however, has been associated with elevated risks for a variety of cancers, including skin cancers, lymphomas,
anal cancers, head and neck cancers, myelomas, germ cell tumors, lung cancers and leukemia, according to Dr. Otley.
"In one study, researchers discovered that if you have HIV-associated Kaposi's sarcoma, you respond better to HAART plus a
pegylated liposomal form of doxorubicin, which is chemotherapy, than you do just with the administration of the highly active
antiretroviral therapy," he says.
Dr. Otley has also reviewed data on HIV patients' experiences with other types of skin cancer, including basal cell and squamous
cell carcinomas, where the increase in risk in a community-based registry is about seven-fold higher for patients with HIV
than for non-HIV patients.
"The risk is not agreed upon in terms of melanoma and HIV patients," he says. "Some studies do not show an increased risk.
We have shown that if you have melanoma and HIV, your disease-free survival and overall likelihood of surviving is less than
if you are a person who does not have HIV."
The evidence suggests that HIV patients are more likely to have bad outcomes with squamous cell carcinoma than the general
population.
The message to dermatologists, Dr. Otley says, is to treat the skin cancer in this patient population cautiously so that dermatologists
are sure to minimize the chances of recurrence.
Preventive measures with HIV patients include working with infectious disease or primary care doctors to optimize HAART and
patients' immune status, using strong sun protective practices, seeing these patients regularly for treatment of early precancerous
lesions and using chemo-preventive or cancer-preventing medications, according to Dr. Otley.
Other at-risk groups
People who take immunosuppressant medications because they have autoimmune diseases, such as rheumatoid arthritis or lupus,
are also at greater risk for skin cancer.
"Those medications seem to be associated with an increased risk of skin cancer," Dr. Otley says, "It is not as high as if
you have a transplant patient, but we are finding that in patients with psoriasis, for example, their risk of skin cancer
is about six-fold higher than the general population if they are taking cyclosporin, which is a medication also used for transplant
patients."
In addition to the medications they take, these patients often get light therapy, which could contribute to the risk.
"One of the recent descriptions in the research (which I do not think that many people are appreciating) is that systemic
steroids, alone, such as prednisone, can increase the risk of squamous cell and basal cell carcinomas," Dr. Otley says. "Several
well-done studies from the Dartmouth group have shown that, in addition to increasing one's risk for skin cancer, long-term
systemic steroid use can increase the risk of other cancers, such as non-Hodgkin's lymphoma."
Chronic lymphocytic leukemia (CLL) patients not only are at increased risk for skin cancer than the general population but
they also tend to have worse outcomes with standard treatments.
Dr. Otley and colleagues followed a group of Mayo Clinic patients with CLL and found they had a greatly increased risk of
recurrence of basal cell carcinoma, despite having had Mohs surgery. They were 14 times more likely to have a recurrence if
they had CLL than patients who did not have CLL. Likewise, with the squamous cell carcinoma, they had a seven times higher
risk of recurrence if they had CLL than if they did not. They had an 18 percent five-year risk of squamous cell carcinoma
spreading to the lymph nodes and 11 percent of the patients died of their squamous cell carcinoma when they had CLL, according
to Dr. Otley.
"We strongly recommend aggressive treatment of skin cancer in patients with CLL," he says. "We recommend doing Mohs surgery,
taking an extra margin of tissue to submit for pathology and considering the use of adjuvant therapy, such as radiation therapy
or lymph node dissection."