When to switch from standard to biologic therapies for foot ulcers?

Acta Eruditorum

Abby Van Voorhees

Dr. Van Voorhees is the physician editor of Dermatology World. She interviews the author of a recent study each month.

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In this month’s Acta Eruditorum column, Physician Editor Abby S. Van Voorhees, M.D., talks with Robert S. Kirsner, MD, PhD, about his recent Archives of Dermatology article, “Advanced biological therapies for diabetic foot ulcers.”

Dr. Van Voorhees: What prompted you to study diabetic foot ulcers?

Dr. Kirsner: Diabetic foot ulcers represent a significant medical problem. There are 23 million Americans with diabetes and by 2050 there will probably be 50 million. This burgeoning epidemic is in large part due to the concurrent obesity epidemic. And unfortunately at least 15 percent, and some estimates suggest 25 percent, of diabetics at some point in their life will get foot ulcers. These foot ulcers have grave consequences. They increase the likelihood that a patient with diabetes will die, especially if their ulcer is unhealed, and as a pathway to that there’s also loss of limb; many of these patients develop bone infections and have amputations. Diabetes is the leading cause of non-traumatic amputations in the United States. So these patients really represent an important group and are at risk.

Dr. Van Voorhees: Does the speed of wound healing affect the likelihood that a patient might go on to have an amputation?

Dr. Kirsner: That’s a critical thing. As dermatologists know, the skin is the primary defense against infection and the longer the wound is open, the more likely they are to get an infection, which seems to be the thing that tips people over toward amputation. An infection increases the risk of having an amputation more than 20 times. It has been shown in trials that the faster you heal wounds, the less likely patients are to have bone infections and amputations.

Dr. Van Voorhees: Have there been optimal treatment recommendations for the treatment of diabetic foot ulcers up to this point?

Dr. Kirsner: The standard of care for treating diabetic neuropathic foot ulcers is debridement and off-loading. The problem is that the gold standard in off-loading, which is casting the wound using a total contact cast, only occurs in a minority of patients, because a lot of people don’t have the ability to cast in their practice or office, and casting is not without its risks, especially if the person applying the cast is not experienced in casting someone. People will use other ways to off-load, but often using other ways to off-load, patients will often be non-adherent, often for good reason; for example, it is difficult to wear a heavy walker every day. Patients tend to take off those removable off-loading devices; studies estimate that only one of every four steps a person takes is taken with the off-loading device. There’s a sense that once they’re home they’re safe but of course that’s not the case. [pagebreak]

Dr. Van Voorhees: Does the choice of an advanced biological therapy shorten wound closure time?

Dr. Kirsner: Patients should first receive the standard of care; and with standard of care a subset of patients will heal and that’s great. You know patients are healing if the wound is getting smaller over a period of about a month. For diabetic foot ulcers, the wound should get at least 50 percent smaller; if it doesn’t, there’s a very small likelihood that they’re going to heal, so you should move on to these advanced modalities. If you have that information at four weeks, any time you wait longer than that is wasted time. There’s no added benefit, only added risk, because the wounds become more difficult to treat the older they are, and patients are at risk for complications.

Dr. Van Voorhees: Does one of these biologic therapies seem to enhance the time for wound closure over others?

Dr. Kirsner: We studied three different biologic therapies: a platelet releasate, a recombinant growth factor, and bilayered living skin. In all the cases, the sooner you use those products, the better off the patient will be. The one that behaved best was the bilayered living skin. More wounds healed and they healed faster.

Dr. Van Voorhees: Was the timing of introduction of these biologic therapies significant?

Dr. Kirsner: We looked at outcomes and then through multivariate analysis looked at things that would predict better outcomes — faster healing and more complete healing. One of the things, independent of what therapy was used, was that if the therapy was instituted sooner, patients did better.

Dr. Van Voorhees: So generally you’re recommending that patients be evaluated after a month with more conventional therapy and then these dressings be instituted?

Dr. Kirsner: We’re not suggesting that advanced therapy should be used from the very first day, because there are patients who will heal on conventional therapy and the products used are not without cost. Advanced therapies should be reserved for patients who fail to demonstrate healing. But once you reach that criterion, the earlier you institute these therapies, the more likely they’re going to have better outcomes. [pagebreak]

Dr. Van Voorhees: Are there some subgroups of patients who seem to be at risk for more poorly healing diabetic ulcers? Are there co-morbidities dermatologists should be aware of that might put someone in a slightly higher risk group?

Dr. Kirsner: Patients who have chronic renal failure or are on dialysis are at dramatic risk for having poor outcomes. It’s not clear that the therapy will make a difference, but it is clear that you don’t want to wait longer for those patients because they’re at highest risk. Typically when I see a patient who has a diabetic foot ulcer who is on dialysis or has chronic renal failure, I have an honest discussion with them that they have a poor prognosis, meaning that there’s a high likelihood that they may lose part of their foot or limb. We have to do everything correctly with those patients. I stress the off-loading and I keep a close eye on how well they’re doing with the standard of care because you don’t have much leeway.

Dr. Van Voorhees: What about the size of the ulcer and how long it’s been present? Does that make a difference?

Dr. Kirsner: For most chronic wounds, two factors have been shown through multiple studies to predict poor healing. One is the duration of the wound and the other is the size. Diabetic foot ulcers tend to be deeper and can go down to the bone, whereas venous leg ulcers tend to be more superficial. Size in diabetic foot ulcers also implies a depth or stage of the ulcer in addition to the area of the wound. Thus in diabetic foot ulcers, size including area, stage, and depth, as well as ulcer duration have all been shown to be important prognostic factors for diabetic foot ulcers. The smaller, the more superficial, and the shorter duration wounds generally do better.

Dr. Van Voorhees: Do you think this information is generalizable to the management of other ulcers we see in practice?

Dr. Kirsner: If a wound isn’t getting better with the treatment you’re applying, the idea not to wait and hope for the best is important. There is good data, especially in common chronic wounds like pressure ulcers, diabetic foot ulcers, and venous leg ulcers, that if a wound is not getting better by four weeks then just continuing to do what you’re doing is a waste of time. I think that message is important for all chronic wounds.



Dr. Kirsner is vice chairman, professor, and the Stiefel Laboratories Chair of Dermatology and Cutaneous Surgery at the University of Miami’s Miller School of Medicine and chief of dermatology at the University of Miami Hospital. His article was published in the August 2010 issue of Archives of Dermatology. Arch Dermatol. 2010; 146 (8): 857-862.