A Novel Treatment for Diabetic Foot Ulcers
January 30, 2006 4 minutes read
A Novel Treatment for Diabetic Foot Ulcers
Abstract & Commentary
By Allan J. Wilke, MD, Residency Program Director, Associate Professor of Family Medicine, University of Alabama at Birmingham School of Medicine—Huntsville Regional Medical Campus, Huntsville. Dr. Wilke reports no financial relationship to this field of study.
Synopsis: Tretinoin solution helps heal diabetic foot ulcers.
Source: Tom WL, et al. The effect of short-contact topical tretinoin therapy for foot ulcers in patients with diabetes. Arch Dermatol. 2005;141: 1373-1377.
This prospective, randomized, double-blind, placebo-controlled study was conducted at the Foot Clinic at the Veterans Affairs Medical Center in San Diego from June to September 2002. It enrolled patients with lower extremity ulcers and a diabetes mellitus diagnosis, and excluded patients who couldn't give informed consent, had a bleeding disorder, were pregnant, had infected ulcers, or had ulcers secondary to large artery disease. After exclusion, 24 patients, all men, were available for the study. The patients were randomized to the control group (normal saline) or the study group (topical 5% tretinoin solution, Retin-A®). For 4 weeks the solutions were applied to the ulcers' wound beds for 10 minutes daily. Then the ulcers were rinsed with normal saline and covered with cadexomer iodine gel (Iodosorb®). The ulcers were measured and photographed at the beginning of the study and then every 2 weeks until the ulcers healed or 16 weeks, whichever came first. All patients received routine ulcer care which included special shoes, debridement, and protective dressings.
The 2 groups were well matched with no statistically significant differences in age, duration of diabetes, hemoglobin A1c level, initial ulcer size, depth, location, or duration of ulceration. Two patients dropped out of the study. Of the 22 remaining patients, 20 had single ulcers and two had 2 ulcers. Those two had their ulcers treated with the same solution. More ulcers in the tretinoin group had 50% or greater reduction in size (84.6% vs 45.4%; number-needed-to-treat [NNT] = 2.5) and complete healing (46.2% vs 18.2%; NNT = 3.6). Adverse effects (mild-to-moderate pain and burning) were uncommon and present in both groups. One patient had mild surrounding erythema and edema that cleared, these were not noted in the study group. No wounds developed features of infection and no systemic effects were noted.
Commentary
Foot ulcers are among the most dreaded sequelae of diabetes. The lifetime risk is estimated to be 15%.1 Infected ulcers are the most common reason for hospitalization of diabetic patients in the United States and can lead to sepsis and amputation. Diabetics are prone to foot ulceration because of the combined effects of peripheral neuropathy, peripheral vascular disease, and immunodeficiency. Although many physicians are pessimistic when it comes to treating these ulcers, they usually will heal, although healing can be slow.2 The 4 principles of diabetic ulcer management are eradication of infection, remediation of macrovascular disease, off-loading of pressure, and wound bed preparation, including debridement of necrotic tissue and trimming of callus. The Diabetes Committee of the American Orthopaedic Foot and Ankle Society issued guidelines for diabetic foot care in 20053 and Lancet published a review of diabetic foot ulcers in 2003.4
A study in 2001 demonstrated stimulation of granulation tissue, new vascular tissue, and new collagen formation in chronic leg ulcers with the use of short-contact tretinoin.5 Short contact is important because tretinoin solution can be irritating, as anyone who has used it to treat acne will confirm. The application of tretinoin directly to the wound bed and avoidance of the skin surrounding the ulcers probably helped, too. What is the mechanism of action of tretinoin in wound healing? The authors speculate that tretinion's ability to stimulate angiogenesis and promote mucopolysaccharide collagen and fibronectin synthesis forms the foundation for delivery of oxygen and nutrients and faster re-epithialization. This study was small and its findings should be considered preliminary. If they are replicated, tretinoin will become a welcome addition to our armamentarium for the treatment of diabetic foot ulcers.
References
1. Reiber GE, et al. The burden of diabetic foot ulcers. Am J Surg. 1998;176(2A Suppl):5S-10S.
2. Chipchase SY, et al. Heel ulcers don't heal in diabetes. Or do they? Diabet Med. 2005;22:1258-1262.
3. Pinzur MS, et al. Guidelines for diabetic foot care: recommendations endorsed by the Diabetes Committee of the American Orthopaedic Foot and Ankle Society. Foot Ankle Int. 2005;26:113-119.
4. Jeffcoate WJ, Harding KG. Diabetic foot ulcers. Lancet. 2003;361(9368):1545-1551.
5. Paquette D, et al. Short-contact topical tretinoin therapy to stimulate granulation tissue in chronic wounds. J Am Acad Dermatol. 2001;45:382-386.
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