Skin Cancer Linked To Metal Implants
As reported by ScienceDaily (10/14) - Unusual Skin Cancer Linked To Chronic Allergy From Metal Orthopedic Implant
In rare cases, patients with allergies to metals develop persistent skin rashes
after metal devices are implanted near the skin. New research suggests these
patients may be at increased risk of an unusual and aggressive form of skin
cancer. Metal alloys help make orthopedic implants stronger and more durable. But people
with sensitivity to these metals, which include nickel, cobalt and chromium,
can develop chronic inflammation that promotes the development of skin cancers,
report researchers at Washington University School of Medicine and
Barnes-Jewish Hospital in St. Louis. The team's findings were published online
Oct.8,2014 in the Journal of Clinical Investigation.
The researchers were alerted to the connection by a patient who had surgery at
another hospital to have a metal rod implanted to repair a fractured ankle.
After the surgery, the patient developed a skin rash on her ankle, near the
location of the implant. The patient turned out to be allergic to nickel in the
implant, which led surgeons at the other hospital to remove it. But the rash
persisted, and a few years later, a rare form of skin cancer known as
Marjolin's ulcer developed at the surgical site. The cancer, which had become
painful and ulcerated, was diagnosed and removed by physicians at Barnes-Jewish
The researchers showed in mouse models that chronic skin inflammation caused by
continuous skin contact with allergens contributes to tumor development. The
finding suggests that patients with metal implants near the skin may need to be
monitored for this type of inflammation, according to the researchers. The
results likely also will lead to debate and further research on whether
physicians should test for metal sensitivity in patients preparing for surgery
to get these types of implants. Chronic inflammation from metal implants can
cause joint pain and swelling and contribute to joint failure. And when these
implants are placed near the skin, fewer than 5 percent of patients develop an
inflammatory rash related to the implant.
The patient's diagnosis with Marjolin's ulcer, an invasive and potentially
deadly squamous cell cancer, surprised physicians. The patient was under 50
years old, and Marjolin's ulcer is extremely rare in people who are young and
otherwise healthy. This type of cancer most often is identified in patients
with a previous history of skin cancers, but this
patient had never had skin cancer. To investigate whether inflammation from the
implant contributed to the tumor, the researchers studied mouse models of
contact allergy. "A contact allergy is a different kind of reaction from
allergies to pollen, pet dander or food," said senior author Wayne M. Yokoyama,
MD, a Howard Hughes Medical Institute investigator at the School of Medicine.
"A contact allergy usually develops when an allergen touches the skin or is
close to it. Skin rash in response to nickel and poison ivy are two common
examples of contact allergies."
The researchers showed that contact allergy brings inflammatory cells and
molecules to the site of the allergic reaction. If
the contact allergen remains a long time -- as was the case with the patient's
implant -- different inflammatory cells and
molecules become active at the site of the reaction. The new mix of cells and
molecules promotes the development of
skin tumors. "This model supported cancer development so strongly that some mice
developed invasive squamous cell skin cancers similar to the patient's tumor,"
said lead author Shadmehr Demehri, MD, PhD, a dermatologist and postdoctoral
fellow. When the researchers examined the cells and molecules involved in
chronic contact allergy in mice, they identified several that already had been
linked to tumor development. Some of these cells and molecules also were
present in biopsy samples from the patient's ankle. The scientists are working
to identify which inflammatory cells and molecules are most supportive of
cancer formation. "If you're allergic to something, the first thing to do is to
avoid it, but the patient couldn't," said Yokoyama, the Sam and Audrey Loew
Levin Professor of Medicine. "Some nickel had likely seeped from it into her
tissue and was still present in her skin even after the implant was removed.
It's as if a patient allergic to poison ivy kept putting poison ivy on the
To prevent such adverse events, the researchers suggested that the potential for
allergic reactions to metal implants be assessed in patients who have had the
implants and in patients preparing to receive them. "Allergen-free versions of
some implants are available," Demehri said. "These versions may cost more or be
less durable, but for some patients with sensitivity to metals, they may be the
best option." Similar to metal implants, some dental restoration materials and
tattoo inks contain substances associated with allergic reactions and cancers
on the skin or in the mouth. Those clinical observations also could be
explained by the new
findings. The researchers suggested that the potential for these other allergens
to promote skin cancer needs to be examined further.
The above story is based on materials provided by Washington University in St.