Nearly 6.5 million Americans have wounds that take months or even years to heal. Many of these wounds are a consequence of diabetes, which damages blood vessels and interferes with normal skin repair. But new research from Georgetown University Medical Center in Washington, DC, points to another cause: autoimmune diseases such as rheumatoid arthritis, or RA, and lupus.   

The research was presented at meeting of the American College of Rheumatology in Chicago, by rheumatologist and lead author Victoria Shanmugam, MD. It has been accepted for publication in the International Wound Journal.

Dr. Shanmugam had noticed an unusual number of nonhealing wounds – mostly leg ulcers – in people with autoimmune disorders. "What I saw clinically was that people who had autoimmune disease did not respond as well to the usual wound care treatments. I wanted to try to understand the reason for this by comparing healing times and [skin] graft outcomes," she says.

Treatment for nonhealing wounds depends on the wound, but might include special dressings, hyperbaric oxygen, growth factors, bioengineered skin substitutes and skin grafts. If treatment doesn’t work, the patient faces amputation.

Dr. Shanmugam and her colleagues reviewed the charts of 340 patients who sought care at Georgetown’s Center for Wound Healing and Hyperbaric Medicine during a three-month period in 2009. Only those with open wounds that hadn't healed after at least three months of normal therapy were included.  

Forty-nine percent of these patients had diabetes (both type 1, which is itself an autoimmune condition, or type 2). This isn't unusual – diabetes accounts for about half of all chronic wounds. Others had vascular or arterial diseases that typically cause poor wound healing. What surprised Dr. Shanmugam was that 23 percent had autoimmune disorders – a far greater rate than had been expected or previously reported. The most prevalent autoimmune diseases were RA (28 percent), lupus (14 percent) and livedoid vasculopathy, a vascular disease that causes ulcers on the lower legs (also 14 percent).

Dr. Shanmugam then looked at how the people with underlying autoimmune disease responded to therapy. "These patients had larger wounds at the first visit, had higher pain scores and took significantly longer to heal – 14-and-a-half months compared to just over 10 months for other patients,” she explains. "Clearly, there is something in the autoimmune milieu that is inhibiting wound healing," says Dr. Shanmugam.


 

The next step is a three-year study funded by the National Institutes of Health. Under way since May, the study will monitor autoimmune-related wounds over time. "We are hoping to get some understanding of what happens on the cellular and molecular level in people who don't heal well," Dr. Shanmugam says.

One theory is that diabetes and autoimmune disorders cause wounds to become stalled in the inflammatory stage of repair, when the body normally develops new blood vessels. Why this occurs and what happens at the level of the wound itself are questions she hopes to answer.

She also will explore whether treating underlying autoimmune diseases such as RA improves wound healing. "There is concern about using potent immune suppressants in people with open wounds," she says, noting that immunosuppressive drugs are known to interfere with wound healing after surgery. "But in a cohort of rheumatoid arthritis patients, we found that aggressive treatment before skin graft surgery resulted in better outcomes."   

Eric Matteson, MD, chairman of rheumatology at Mayo Clinic in Rochester, Minn., agrees with the approach. "People with rheumatoid arthritis develop wounds for many reasons. One is that they may have low-grade vasculitis – inflammation affecting the small blood vessels in the skin. When the wound is related to the underlying systemic inflammation of rheumatoid arthritis, not having that inflammation under control makes it much more difficult to achieve good wound healing."

He says that successful wound care requires cooperation and vigilance. "Perhaps the biggest message here is that treating people with autoimmune-related wounds really calls for a team approach among the rheumatologist, wound-care specialist and surgeon,” says Dr. Matteson. “What you often see, unfortunately, is a primary care doctor who can't properly manage the wound because of the complexity of the underlying disorder."

Dr. Shanmugam believes her findings will affect patient care in the future. “Understanding how people respond to wound care on a molecular level can help guide therapy and may reduce the risk of infections, which can lead to surgery and even amputation," she says.

As important, she hopes her research will alert other physicians to this under-recognized problem. "When a patient has a leg ulcer that hasn't healed after three or four months of normal treatment, I hope doctors will check for autoimmune disease," says Dr. Shanmugam.