Decubitus Ulcers; Venous Stasis and Diabetic Ulcers; Traumatic Wounds; Skin Autograft Donor Sites; and Burns

Phenytoin has been used topically to speed the healing of decubitus ulcers, pressure sores, venous stasis and diabetic ulcers, traumatic wounds, skin autograft donor sites, and burns. Ketoprofen may be used to control inflammation and pain, lidocaine provides topical anesthesia, and pentoxifylline may improve microcirculation at the wound margins and promote healing of the injured area. Misoprostol, a prostaglandin analog, is often included in wound care formulations to promote healing. Debridement of necrotic eschar with 40% urea paste may also speed healing. Medications which improve capillary blood flow can be added to a compounded medication to enhance circulation at the wound margins and promote healing of the injured area.

Topical Phenytoin for Wound Healing

The stimulatory effect of orally administered phenytoin on gingival tissue prompted its assessment in wound healing. Phenytoin may promote wound healing by a number of mechanisms, including stimulation of fibroblast proliferation, facilitation of collagen deposition, glucocorticoid antagonism, and antibacterial activity. Phenytoin has been used topically in the healing of pressure sores, venous stasis and diabetic ulcers, traumatic wounds, skin autograft donor sites, and burns.

Rhodes et al compared the healing of stage II decubitus ulcers with topically applied phenytoin and two other standard topical treatment procedures in 47 patients in a long-term care setting. Ulcers were examined for the presence of healthy granulation tissue, reduction in surface dimensions, and time to healing. Topical phenytoin therapy resulted in a shorter time to complete healing and formation of granulation tissue when compared with DuoDerm dressings or triple antibiotic ointment applications. The mean time to healing in the phenytoin group was 35.3 +/- 14.3 days compared with 51.8 +/- 19.6 and 53.8 +/- 8.5 days for the DuoDerm and triple antibiotic ointment groups, respectively. Healthy granulation tissue in the phenytoin group appeared within 2 to 7 days in all subjects, compared to 6 to 21 days in the standard treatment groups. The phenytoin-treated group showed no detectable serum phenytoin concentrations.

Anstead et al. described a patient with a massive grade IV pressure ulcer that was unresponsive to conventional treatment, yet responded rapidly to treatment with topical phenytoin. Song and Cheng reported phenytoin improved wound breaking strength in normal and radiation-impaired wounds. The results of their study indicated that topical phenytoin accelerated normal and irradiation-impaired wound healing by increasing the number of wound macrophages and improving the macrophage function. Pendse et al evaluated the effectiveness of topical phenytoin in healing chronic skin ulcers in a controlled trial of 75 inpatients. At the end of the fourth week, 29 of 40 phenytoin-treated ulcers had healed completely versus 10 of 35 controls. They concluded: "topical phenytoin appears to be an effective, inexpensive, and widely available therapeutic agent in wound healing."

The effectiveness of topical phenytoin as a wound healing agent was compared with that of OpSite and a conventional topical antibiotic dressing (Soframycin) in a controlled study of 60 patients with partial-thickness skin autograft donor sites on the lower extremities. Mean pain scores were lower and mean time to complete healing (complete epithelialization) was best in the phenytoin-treated group (6.2 +/- 1.6 days).  Topical phenytoin compared very favorably with, and in some aspects was superior to, occlusive dressings.

The efficacy of topical phenytoin in the treatment of diabetic foot ulcers was evaluated in a controlled inpatient study. Fifty patients were treated with topical phenytoin, and 50 patients received dry sterile occlusive dressings. Both groups improved, but the ulcers treated with topical phenytoin healed more rapidly. Mean time to complete healing was 21 days with phenytoin and 45 days with control.

No study reported any significant adverse effects secondary to topical phenytoin therapy.

Phenytoin references:

Ann Pharmacother 2001 Jun;35(6):675-81
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Biochem Pharmacol 1999 May 15;57(10):1085-94

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Ann Pharmacother 1996 Jul-Aug;30(7-8):768-75
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Int J Dermatol 1993 Mar;32(3):214-7
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Chung Hua I Hsueh Tsa Chih 1997 Jan;77(1):54-7
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Burns 1993 Aug;19(4):306-10
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Diabetes Care 1991 Oct;14(10):909-11

Benzoyl Peroxide for Treatment of Decubitus Ulcers 

Benzoyl peroxide is a powerful oxidizing agent with broad spectrum germicidal activity and good liposolubility. Therefore, it may represent a good agent for prevention of wound infection in areas with high density of sebaceous glands. Topical treatment of pressure sore with 20% benzoyl peroxide in O/W emulsion yielded very satisfactory results. In another study, 10% benzoyl peroxide gel was used prophylactically once a day for 7 days before surgery. The researchers concluded that topical benzoyl peroxide is an efficacious, harmless, and inexpensive agent for prevention of wound infections in seborrheic regions.

Med Cutan Ibero Lat Am 1988;16(5):427-9

[Benzoyl peroxide in the treatment of decubitus ulcers].

Fernandez Vozmediano JM, Alonso Blasi N, Almenara Barrios J, Alonso Trujillo F, Lafuente L
Servicio de Dermatologia, Hospital Clinico Universitario Moreno de Mora, Cadiz.

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J Dermatol Surg Oncol 1994 Aug;20(8):538-40

Utility of topical benzoyl peroxide for prevention of surgical skin wound infection.

Bencini PL, Galimberti M, Signorini M
Instituto di Clinica Dermatologica I e Dermatologia Pediatrica, Universita di Milano, Italy.

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Miscellaneous

Arch Dermatol. 2001 Oct;137(10):1288-90
Debridement of necrotic eschar with 40% urea paste speeds healing of residual limbs and avoids further surgery.

Pelle MT, Miller OF 3rd.
Department of Dermatology, Geisinger Medical Center, 100 N Academy Ave, Danville, PA 17822, USA.

PMID: 11594851 (no abstract available online)