SAFETY & EFFICACY REPORT Review of Over-the-Counter Topical Scar Treatment Products Richard Shih, M.D. Joshua Waltzman, M.S.3 Gregory R. D. Evans, M.D. Plastic Surgery Educational Foundation Technology Assessment Committee Orange, Calif.

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ostsurgical, traumatic, and burn scars can be painful, pruritic, erythematous, raised, and cosmetically unacceptable. Although a number of over-the-counter products are available to treat symptomatic scars, the peerreviewed data on the clinical efficacy of these products are limited and/or controversial. Physician and patient choice of which product to use is often based on historical practice or anecdotal evidence. The aim of this review is to evaluate the evidence from published controlled clinical trials in humans on some of the most commonly used over-the-counter products for treatment of symptomatic scars.

PRESSURE DRESSINGS Pressure dressings are a mainstay in burn and hypertrophic scar management, despite a striking lack of supportive evidence. The exact mechanism of action by which pressure decreases hypertrophic scarring is unknown, but some believe that pressure enhances scar maturation through intracellular communication and fibroblast matrix remodeling.1,2 Although retrospective clinical and ultrasonic studies since the 1960s are supportive, the only prospective, randomized study on the efficacy of pressure garments demonstrated no significant difference in wound healing by the Vancouver Burn Scar Assessment criteria, time to wound maturation, or length of hospital stay when patients treated with pressure garments were compared with control subjects.3–7 Not only is there a lack of evidence backing the use of pressure dressings in scar management, but pressure dressings From the Aesthetic and Plastic Surgery Institute, University of California at Irvine. Received for publication September 18, 2006; accepted November 30, 2006. Copyright ©2007 by the American Society of Plastic Surgeons DOI: 10.1097/01.prs.0000255814.75012.35

can be harmful by occasionally causing patient discomfort, uneven pressure distribution, skin breakdown, and ulceration.8 –10 A case study from 2001 describes a 24-year-old woman who underwent premolar extraction in preparation for orthodontic treatment and subsequently experienced severe dental-alveolar deformation after being treated with a Jobst pressure garment for 2 months following facial burns.11 Due to the potential for harm to patients who are treated with pressure dressings, novel tools and methods have been developed to measure the pressure exerted by pressure dressings.12,13 Despite the paucity of published clinical evidence supporting the use of pressure dressings, their place in burn and hypertrophic scar management is difficult to ignore. Many care providers have reported great (though unpublished) success using pressure dressings to treat raised scars over the years, especially in burn care. One area in which pressure therapy has been shown to improve scar healing is the use of pressure earrings as primary or adjuvant therapy to treat and prevent the recurrence of ear keloids.14,15 While further clinical investigation may clarify the role of pressure dressings for scar treatment in the literature, it may not offer much to change care providers’ clinical practice. The fact of the matter is that pressure therapy is largely accepted as an effective treatment for raised scar, and the relative lack of controlled clinical trials of its efficacy may be reflective of its wide acceptance by investigators and the perceived lack of need for further study. Furthermore, conducting a study on the efficacy of pressure likely would be either difficult or unethical, because it would involve withholding an accepted treatment from control subjects.

SCAR HYDRATION OINTMENTS/DRESSINGS Current guidelines state that treating wounds with semiocclusive dressings and/or ointments

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Plastic and Reconstructive Surgery • March 2007 (i.e., mineral oil, hydrating lotions, petrolatumbased ointments) promotes moist healing and rapid epithelialization, thereby decreasing hypertrophic scar formation.16,17 These therapies may also improve wound healing by preventing egress of important growth factors from the wound bed.18,19 Indeed, since Winter published his landmark articles in Nature more that 40 years ago, the use of ointments and dressings to preserve wound bed moisture and thereby accelerate wound epithelialization has largely become a cornerstone of wound care.20 –22 Clinical studies show that scar hydration strategies are effective in decreasing scar symptoms (i.e., pain, itching, and tightening), but their efficacy in improving scar appearance (i.e., size, color, and texture) is unclear. One randomized, controlled trial demonstrated that treatment of keloids and hypertrophic scars with hydrocolloid dressing or moisturizer decreased itching (p ⬍ 0.03), somewhat decreased pain (p ⬍ 0.08), and increased pliability (10 percent) but did not change the physical parameters (i.e., size, volume, color, and transcutaneous oxygen measurements) of the scar.23 Another randomized clinical study illustrated that treatment of dermabrasion wounds with triple antibiotic ointment resulted in less scarring and decreased pigment changes than treatment with nonocclusive gauze dressings.24 In a French controlled, randomized clinical trial, treatment of facial skin with low-salt spring water spray and petrolatum ointment after laser resurfacing resulted in decreased itching, stinging, erythema, and tightening than treatment with petrolatum alone over a period of 84 days.25 The efficacy of scar hydration strategies in these human trials is supported in the rat model, where one study revealed that carbon dioxide laser burn wounds healed more quickly with composite polyurethane dressings (i.e., OpSite, Smith & Nephew, Hull, U.K.; Spandra, Thermetics, Inc., Woburn, Mass.) (10 days) and petrolatum gauze (13 days) than when they were left open to air (16 days).26 While studies seem to adequately describe the positive effects of scar hydration ointments and dressings on unepithelialized wounds, further investigation may be warranted to establish their effects on epithelialized wounds.

ADHESIVE MICROPOROUS HYPOALLERGENIC PAPER TAPE While the mechanism of action for this product is not understood, some believe that its effects may be related to its action as a pressure dressing (see above) and as a semiocclusive/wound hydration dressing (see above).17 Two uncontrolled studies describe its efficacy.27,28 According to a

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meta-analysis of this product by Mustoe et al.,17 adhesive microporous hypoallergenic paper tape is useful in treating fresh surgical incisions and scars several weeks out, but its efficacy was less than that of “more established treatments such as silicone gel.”

VITAMIN E Vitamin E is the major lipid-soluble antioxidant in the skin and is believed by some to decrease scar formation due to its ability to inhibit fibroblasts and keratocytes in humans and rabbits in vitro.29,30 However, although no studies have demonstrated that vitamin E improves scars, evidence does exist that it causes harm. Vitamin E may be beneficial when combined with silicone gel sheets, though. A review by Parsa in 1988 highlighted the anti-inflammatory effects of vitamin E in animal models but noted that controlled clinical trials in humans demonstrated no improved scar healing and a high incidence of minor adverse reactions.31 A double-blinded, controlled study illustrated that treatment of scars with topical vitamin E did not help in scar reduction but was associated with an increased incidence of contact dermatitis.32 Another double-blinded, controlled study conducted on patients after operative procedures for postburn contractures revealed that treatment with vitamin E provided no benefit in range of motion, scar thickness, change in graft size, or ultimate cosmetic appearance after treatment for 4 months but resulted in an increased incidence of itching and rash (19.9 percent in the treatment group versus 5.9 percent in the control group).33 Interestingly, one Italian simple-blinded clinical trial published in 1995 illustrated that more patients had significant improvement in the pain, itching, redness, swelling, and induration of their hypertrophic and keloid scars when they received silicone gel sheets with added vitamin E compared with patients who received silicone gel sheets alone for 4 (85 percent versus 55 percent) and 8 weeks (95 percent versus 75 percent).34

SILICONE DRESSINGS Several studies illustrate that treatment of scars with silicone gel dressings clinically improves scars, especially in patients at high risk for problematic scarring. The superiority of one form of silicone gel dressing over another, or of a silicone over a nonsilicone gel dressing, however, is controversial. Silicone dressings are believed to decrease scar via wound hydration, increased static charge (i.e., silicone gels contain increased negative static charge), and modulation of growth factors.35,36 A

Volume 119, Number 3 • Over-the-Counter Topical Scar Treatments meta-analysis of scar treatment with silicone in the Cochrane Database included 13 trials with a total of 559 subjects and concluded that most studies were of poor quality, making the efficacy of silicone gel sheeting unclear.37 In this article, we focus on the higher-quality, controlled, clinical trials to improve the clinical relevance of the available data. One study demonstrated that scars treated with silicone gel dressings improved without use of positive pressure on the wound.38 A study comparing the efficacy and safety of two commonly used forms of silicone gel dressing, Cica-Care (Smith & Nephew) and Silastic Gel Sheeting (Dow Corning, Midland, Mich.) revealed no difference in efficacy or safety but suggested that Cica-Care was better tolerated by patients (due to superior adhesiveness and comfort).39 Although both silicone gel sheeting and silicone gel cushions clinically improved hypertrophic and keloid scars, in another study, there was no significant difference in efficacy between the two forms of silicone dressing.35 Both silicone and nonsilicone gel dressings have been effective in reducing scar size, induration, and symptoms over controls, but no significant differences have been noted between results from treatment with silicone and treatment with nonsilicone gel dressings.40 Yet another study demonstrated that the use of topical silicone gel sheets improved scars in patients at high risk for unphysiologic scarring but did not significantly improve scars in low-risk patients.41 Clearly, silicone dressings can benefit symptomatic scars, but further clinical investigation may be warranted to demonstrate their effectiveness over nonsilicone gel dressings as well as to identify the role of silicone dressings in patients at low risk for problematic scarring.

TOPICAL ONION EXTRACT OINTMENT (MEDERMA) The newest available over-the-counter scar treatment, topical onion extract (Mederma, Merz Pharmaceuticals, Greensboro, N.C.), has not been shown to improve scar symptoms in humans when compared with petrolatum emollient (Aquaphor, Beiersdorf, Norwalk, Conn.) in published studies. A prospective, double-blind study of Caucasian males conducted in 2006 demonstrated that the effects of topical onion extract on cosmetic appearance, erythema, and hypertrophy of scars in new surgical scars were equivalent to those of petrolatum emollient.42 Interestingly, these findings contradict the pilot study comparing topical onion extract with petrolatum emollient conducted 7 years earlier, in which topical onion extract

caused no improvement in postsurgical scars while petrolatum emollient reduced scar erythema.43 No mechanisms of action have been reported to describe how topical onion extract acts to reduce scar.

HERBAL/ALTERNATIVE MEDICINES Preliminary and anecdotal evidence supports the use of various herbal and alternative medicines to treat symptomatic scars, but no clinical trials have been performed. A French group reported improved wound healing in the rat burn model with extract from the bark of Spathodea campanulata Beauv (Bignoniaceae).44 A Korean group reported the clinical effectiveness of treating systemic scleroderma, abnormal scar formation, and keloids with titrated extract of Centella asiatica.45 An Indian group reported the ability of Anogeissus latifolia bark extract to accelerate wound healing, decrease wound surface area, and increase tensile strength in rat dermal wounds.46 A Malaysian group reported enhanced wound contraction with haruan (Channa striatus) fish extract when it was combined with cetrimide cream in the rat model.47

CONCLUSIONS Controlled human studies of the above overthe-counter scar treatment products are limited and/or controversial. Although the only prospective, randomized study on treating scar with pressure garments demonstrates no benefit, the efficacy of pressure in treating raised scars is widely accepted. Multiple studies describing pressure dressing morbidity warrant consideration of pressure monitoring for patient safety when pressure dressings are used. Further clinical investigation into the effectiveness of pressure dressings likely would be either difficult or unethical, as it would involve withholding an accepted treatment from control subjects. Scar hydration strategies, on the other hand, are well supported by clinical trials as an effective and safe option to treat symptomatic scars. Adhesive, microporous, hypoallergenic paper tape may represent an intersection of the previous two treatments and has modest evidence to support its efficacy. Conversely, the available literature contraindicates the use of vitamin E to treat symptomatic scars but suggests there may be a benefit in combining vitamin E with silicone dressings. Silicone gel dressings appear to be effective in treating symptomatic scars without positive pressure, especially in patients predisposed to raised, tight, painful, pruritic, discolored, or unaesthetic scarring. The benefit of using one form

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Plastic and Reconstructive Surgery • March 2007 of silicone gel dressing over another or over nonsilicone gel dressings, however, has not been demonstrated. The efficacy of topical onion extract over petrolatum emollient has not been proven. Finally, several herbal and alternative medicines may be beneficial to wound healing, but evidence supporting their efficacy is preliminary and anecdotal. Patients and scar care providers would benefit from further human investigations on the efficacy and safety of over-the-counter scar treatment products. Gregory R. D. Evans, M.D. Aesthetic and Plastic Surgery Institute University of California at Irvine UCI Manchester Pavilion 200 S. Manchester Avenue Orange, Calif. 92868 [email protected]

DISCLOSURE

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