Patients with diabetes mellitus have an increased risk of lower-limb amputation compared to the nondiabetic population. Foot ulcers precede 85 percent of all nontraumatic, lower-limb amputations. Heel ulcers have the poorest prognosis among diabetic foot ulcers, because flap reconstruction of the heel area is difficult and significant debridement or amputation of the heel rarely leaves a functionally walking patient. Recent advances for the treatment of diabetic foot ulcers have not had much reported success in heel ulcers: Growth factors are less effective in ischemic tissue, and bioengineered dressings are difficult to maintain in position on the heel. Ten patients with neuropathic, diabetic, heel ulcers were treated with pressure relief, debridement, and topical becaplermin (rhPDGF-BB) gel. Ulcers were followed with photography, wound tracing, and area measurement. Eight patients (80%) achieved 100-percent healing at between 13 days and 4 months. This series, although small, suggests becaplermin can be effective in treating neuropathic, diabetic, heel ulcers.
Diabetic foot ulceration is a major complication of diabetes mellitus. Among the 10 to 15 million diabetic patients, two to three percent will develop foot ulcers each year, and approximately 15 percent will develop foot ulcers during their lifetimes. The four percent of the US population with diagnosed diabetes mellitus constitute 46 percent of the approximately 162,500 annual hospitalizations for foot ulcers. Foot ulcers precede 85 percent of all nontraumatic, lower-limb amputations, and half of all nontraumatic, lower-limb amputations in the US are performed in persons with diabetes. It is estimated that patients with diabetes mellitus have as much as a 30- to 40-times higher risk of lower-limb amputations compared to the nondiabetic population.
The costs attendant with the large numbers of diabetic foot ulcers and amputations are staggering. The average cost for a single episode of a foot ulcer has been reported to be $4,595.00. The costs for treating foot ulcers can amount to $1.2 billion annually, excluding the costs of surgery, rehabilitation, prostheses, and lost income. The average costs for revascularization surgery or amputation can approach $40,000.00 per patient. In addition, diabetic patients who require lower-limb amputations are at great risk for requiring amputation of the contralateral limbs in less than two years.
Heel ulcers may be considered to have the poorest prognosis among diabetic foot ulcers. Edmonds, et al., reported that heel ulcers tend to be ischemic and that these ischemic heel ulcers heal less than 50 percent of the time. This is compared to a 86-percent healing rate when ischemia was not present and a 74-percent healing rate when ischemia was present in ulcers other than on the heel. Although the forefoot ulcer in the diabetic patient is usually of neuropathic etiology, heel ulcers are more likely to have a mixed neuropathic and ischemic etiology. Atherosclerosis has a predilection for different vessels in diabetic patients versus nondiabetic patients. The tibial and peroneal arteries are more likely to be involved, while the dorsalis pedis and plantar arteries are frequently spared. This puts the heel at risk for decreased perfusion. Also, the footpad under the heel can become atrophied in people with neuropathy, reducing the heel's cushioning ability.
Recent advances in the treatment of diabetic foot ulcers have occurred. The use of topically applied recombinant growth factors or bioengineered dressings has increased the healing rates of foot ulcers. Becaplermin (rhPDGF-BB) and recombinant transforming growth factor beta-2 (rhTGF-beta2) have been reported to improve healing rates in neuropathic diabetic foot ulcers. Two bioengineered skin substitutes have also shown the ability to accelerate healing of diabetic foot ulcers. However, there are inherent problems when applying these new therapies to the heel ulcer. It is difficult to maintain a skin substitute dressing in place on the convex heel without shearing occurring. The biology of topically applied growth factors may be impaired if the heel ulcer has a significant degree of ischemia. The only recombinant growth factor approved by the United States Food and Drug Administration for the treatment of diabetic foot ulcers is becaplermin (rhPDGF-BB)*.
Wu, et al., demonstrated that PDGF receptors are markedly decreased in ischemic wounds. They also showed that in young animals with ischemic wounds, topical PDGF did not reverse wound healing deficits. Later work from the same laboratory suggested that topically applied TGF-beta1 failed to stimulate wound healing in an aged ischemic ulcer model. Because of these theoretical considerations, several recent clinical trials of topically applied growth factors have been limited to forefoot neuropathic ulcers, excluding heel ulcers.
The purpose of this study was to evaluate the usefulness of becaplermin (rhPDGF-BB) in the treatment of a series of recalcitrant diabetic heel ulcers.