Topical propranolol for a chronic recalcitrant wound

A 68 year-old patient presented to our attention with a deep ulcerating lesion of the right sole. He reported the substance loss had manifested after a corticosteroid infiltration at the same site for anti-inflammatory purposes about 11 months before. He reported no other medical condition. At physical examination a 2 3 1 cm ulcer was present, with irregular and undermined borders. The substance loss involved completely the skin and the subcutaneous tissue, sparing the plantar fascia which was left exposed (FIG. 1). No sign of infection was noticeable. The lesion had been treated with a variety of topical and systemic drugs, including advanced dressings, dermal substitute (Integra), and subcutaneous low molecular weight heparin as well as aspirin, with no significant clinical response whatsoever. At time of consultation, vacuum-assisted closure therapy was proposed, but the patient refused. Based on various reports on successful use of topical timolol for chronic ulcers, we discussed the possibility of using a similar off-label treatment. With written consent, we started the patient on a three times/day topical application of a galenic preparation of 1% propranolol-hydrochloride in a hydrophilic cream, covered by a nonadhering silicone dressing (Adaptic) while withdrawing any other specific treatment. We chose propranolol instead of timolol for the excellent safety profile and minor systemic absorption, as supported by the vast experience on ulcerated infantile hemangiomas (1). After 3 weeks of continued application, the ulcer had dramatically improved, and after another week the lesion had completely healed (FIG. 2). No irritation or other local or systemic adverse effects were noticed. The cream was then suspended; follow up at 1 year did not show any sign of recurrence. b-receptor antagonists have shown great promise in wound healing, as they have been shown to enhance keratinocyte migration (2) as well as angiogenesis in the wound (3). Within the skin, b-adrenergic receptors are present on keratinocytes, fibroblasts, and melanocytes. From a pathogenetic point of view, high levels of circulating catecholamines, associated to burns or traumatic wounds, are known to impair wound healing. High doses of oral propranolol have been shown to block this effect (4). In particular, a double blind randomized controlled trial Address correspondence and reprint requests to: Michelangelo Vestita, MD, Unit of Plastic Surgery, IRCCS, Referral Cancer Center of Basilicata, 1, Via Padre Pio, Rionero in Vulture (Pz), 85028, Italy, or email: michelangelovestita@ gmail.com.