Doi:10.1016/j.jaad.2006.03.022

Topical treatments for hypertrophic scars Joanna M. Zurada, AB,a David Kriegel, MD,b and Ira C. Davis, MDc Hypertrophic scars represent an abnormal, exaggerated healing response after skin injury. In additionto cosmetic concern, scars may cause pain, pruritus, contractures, and other functional impairments.
Therapeutic modalities include topical medications, intralesional corticosteroids, laser therapy, andcryosurgery. Topical therapies, in particular, have become increasingly popular because of their easeof use, comfort, noninvasiveness, and relatively low cost. This review will discuss the properties andeffectiveness of these agents, including pressure therapy, silicone gel sheeting and ointment, polyurethanedressing, onion extract, imiquimod 5% cream, and vitamins A and E in the prevention and treatment ofhypertrophic scars. ( J Am Acad Dermatol 2006;55:1024-31.) The wound healing process consists of 3 Clinically, hypertrophic scars are raised, red, stages—inflammation, granulation, and ma- nodular lesions that occur most commonly in areas of thick skin. They frequently develop within 8 tion, produces exudate from damaged vessels that weeks of a burn, wound closure with excess tension, fills the wound. Neutrophils trigger an inflammatory wound infection, hypoxia, or other traumatic skin cell cascade and macrophages phagocytose cellular and foreign debris. Subsequently, in the granulation growth phase for up to 6 months that may be phase, macrophages secrete cytokines that promote followed by regression during the next 12 to 18 granulation tissue formation consisting of re-epithe- lialization, recreation of an appropriate blood sup- Early recognition of the potential development of ply, and reinforcement of the injured tissue. In the the hypertrophic scar is critical in its management.
final stage of wound healing, matrix remodeling, Because hypertrophic scars are often painful and fibroblasts proliferate and deposit new collagen and difficult to treat, several treatments have been devel- matrix materials at the wound site. The remodeling oped in the past several years in an effort to minimize process of collagen synthesis and lysis can last up to tissue growth and wound contraction. This review will focus on pressure therapy, silicone gel sheeting Hypertrophic scars, by definition, represent an and ointment, polyurethane dressing, onion extract, exaggerated proliferative response to wound heal- imiquimod 5% cream, and vitamins A and E in the ing that stays within the boundaries of the original management of hypertrophic scarring. A summary wound, in contrast to keloids, which have a more of these therapies and a selection of common com- aggressive life cycle and extend beyond the original borders. Because the collagen found is in a disor- ganized, whorllike arrangement rather than inthe normal parallel orientation, hypertrophic scarsare indurated, elevated, and poorly ext Hypertrophic scars are also characterized by hyper- Pressure therapy has been the preferred conser- vascularity, hence, their erythematous appearance.
vative management of scars since the 1970s, espe-cially in treating hypertrophic scarring after burninjury. Pressure therapy is influential primarily while From the Columbia University College of Physicians and Sur- the scar is active and, therefore, loses some efficacy geons,a Mount Sinai Department of Dermatology,b and New after 6 months of treatmeThe garments are typ- York Medical College Department of Dermatology.c ically custom-made from an elastic material with a Funding sources: None.
Conflicts of interest: None identified.
high spandex content and are intended to be worn Reprints not available from the authors.
for approximately 1 year until the scar matures.To Correspondence to: Ira C. Davis, MD, 280 North Central Park Ave, prevent a decrease in elasticity, garments should Published online September 19, 2006.
of compression therapy include its limited use in 0190-9622/$32.00ª 2006 by the American Academy of Dermatology, Inc.
anatomic depressions, flexures, or areas of high movement; patient discomfort; the need to be sions, or high-motion but few studies have subjective pressuremeasurements; sideeffects of local skinmaceration hypertrophic scars andsome evidence thatimproves mature scars Studies have shown: ÿ, no adequate benefit; ÿ/1, equivocal results; 1, some benefit; 11, marked benefit.
worn at all times; and occasional skin ulceration a thinning of the dermis, decrease in edema, and a from uneven pressure distribution. For these reasons, reduction of blood flow and oxygen.The hypoxic patient compliance can be a major problem, with re- environment is hypothesized to decrease collagen ports of noncompliance ranging from 8.5% to 59% formation and increase collagen lysis and loosen the Pressure treatment is believed to accelerate collagen fibrils aligned to the skin surface, thereby wound maturation by several mechanisms, namely more closely approximating the elastic requirements of the skin.This hypothesis remains controver- (P = .072) that the proportion of patients developing sial, however, as other studies have shown that abnormal scars was lower in the topical silicone qualitative improvements in scar tissue receiving gel-sheeting group. However, of those patients at pressure therapy correlate with increased blood high risk who underwent scar revision there was a significant statistical difference (P = .035) that topical A fair body of evidence supports the use of silicone sheets are effective in reducing the devel- compression therapy but literature is generally lack- opment of abnormal scars after surgical excision.
ing in reports on effectiveness and optimal pressures.
Katzsupported these findings in an examination The consensus is that an applied pressure of 25 mm of 14 patients with 14 hypertrophic scars less than Hg may represent ideal loadingbut more recent 3 months old. Nine patients had long-standing hy- studies suggest that good clinical results may be pertrophic scars that were completely excised and achieved at much lower compression levels.
treated with silicone sheeting soon after re-epitheli- However, given that most often this measurement alization. Five patients had a history of hypertrophic is made clinically by the therapist together with scar formation and were given silicone sheeting feedback from the patient, pressure measurements within 2 months of operation to prevent recurrence.
are subjective and not standardizOverall, there In 11 of these cases (79%), hypertrophic scars did not is some evidence to support that compression ther- recur after at least 6 months of follow-up.
apy may be effective but more definitive research is The mechanism of silicone gel sheeting remains needed to evaluate the most optimum parameters.
unclear, although several hypotheses exist. Studieshave shown that silicone sheets do not change pressure, temperature, or oxygen tension at the Silicone, a soft, semiocclusive scar cover, is com- posed of cross-linked polydimethylsiloxone poly- rative water loss almost half that of skin and have mer that has extensibility similar to that of skin. Since been compared with the stratum corneum. Most its introduction in 1982, topical silicone gel sheeting researchers believe that silicone acts by creating and ointment have been used widely to minimize a hydrated, occluded environment that decreases the size, induration, erythema, pruritus, and exten- capillary activity, thereby reducing fibroblast-in- sibility of pre-existing hypertrophic scars and to duced collagen deposition and scar hypertro- prevent the formation of new ones. Numerous for- mulations exist, in addition to several gels and oint- minimize fibroblast production of collagen and pro- mote wound flatteningInterestingly, the use of The therapeutic effect of topical silicone gel silicone cream alone compared with silicone cream sheeting on pre-existing hypertrophic scars is well with occlusive dressing showed 22% and 82% scar improvement, respectively, with respect to ery- uncontrolled clinical reports stating that silicone thema, tenderness, pruritus, and hardness.These gel sheeting promotes resolution of hypertrophic results supported that occlusion may be synergistic in wound healing and suggested that silicone gel alone may not be as effective as silicone sheeting.
trolled trial of 20 patients who had either evolving Wounds treated with silicone gel sheeting have hypertrophic scars or keloids, silicone gel sheeting negligible amounts of silica in histologic sections.
stopped the development of and softened evolving Therefore, the presence of silicone itself may not hypertrophic lesions in 85% of caSilicone gel sheeting has also been shown to significantly im- showed that silicone gel dressings and nonsilicone prove elasticity of old scars between 1 and 6 months gel dressings were equally effective in improving after treatment when compared with untreated size, induration, and color of hypertrophic scar In another study comparing a silicone-free cream Silicone sheeting also helps minimize new hyper- and occlusive dressing with petrolatum alone, scar trophic scarring when applied about 2 weeks after improvement was significantly greater in the cream- occlusive dressing group with respect to pruritus, in patients at high riskethose who had a significant pain, hardness, elevation, and erythemfurther history of hypertrophic scar or keloid formation after a surgical proceduree29% developed hypertrophic In summary, silicone gel sheeting is efficacious, scars after silicone gel sheeting whereas 44% devel- both in minimizing the severity of hypertrophic scars oped hypertrophic scars after routine postoperative in fresh wounds and in promoting the resolution care. This finding provided only marginal evidence of pre-existing hypertrophic scars. Silicone ointment tacky sheets; varietyof configurations available(standard and large sheets,areola circles, mastopexy,strips, C-strips) colorless, fast-dryingclear gel; once-dailyapplication; suitable undercosmetics in conjunction withEpi-Derm sheetsand SilqueClenz scarand sheet cleanser available in skin-tonedor clear formulations pads; maintain a moistwound environment and helpprevent bacterial contamination clear gel; new separatekid-friendly preparation or gel, although more convenient and suitable for healing environment that may promote re-epitheli- exposed areas, is less effective than silicone sheeting.
alization and dermal extracellular matrix synthesisand, hence, decrease scarriDespite the the- oretic risk that a moist environment is associated Polyurethane dressing is a self-adherent, flexible, with a higher risk of wound infection, studies have hydroactive pad that should be worn 12 to 24 h/d for shown that occlusive dressings do not increase the a minimum of 8 consecutive weeks.Advantages of this form of treatment are its availability as clear Hydroactive dressings have been shown to pre- pads for use on exposed areas such as the face or vent the formation of hypertrophic scars.A pilot hands and low incidence of skin maceration because study of 60 patients noted significant improvements of the pads’ evaporative properties. Polyurethane in microcirculation and surface qualities in patients occlusive dressings act by creating a moist wound- who were treated with polyurethane dressing for 6 weeks after surgical incisions when compared controlled clinical studies in the United States on the with other patients who were randomized to receive effect of onion extract on human wound healing.
either dry gauze dressing until removal of the sutures, One clinical trial evaluating onion extract in the hydroactive dressing until removal of the sutures, or prophylactic treatment of 17 scars after Mohs micro- dry gauze dressing until removal of sutures followed graphic surgery showed no statistically significant by hydroactive dressing for 6 weeks.In another difference between pretreatment and posttreatment study of 60 patients with acute facial lacerations, a 5- evaluations of erythema and pruritus after 1 month day course of polyurethane dressing after acute skin of 3-times daily applications of onion extract gel injuryedespite initially showing significantly im- In fact, a significant reduction in scar erythema was proved comfort, less erythema, and less potential for demonstrated in control patients who used a petro- scarring when compared with dry gauzeeshowed latum-based ointment for 1 month, possibly because negligible differences between the dry gauze control of the effects of petrolatum on scar hydration.
group after 2 monthsThis suggested that the mag- Another randomized, double-blinded trial evalu- nitude of benefit from occlusive dressings may depend ating 97 patients with new and old scars who were assigned to a Mederma treatment group or placebo Polyurethane dressing also reduces color, prom- gel control group for 2 months showed similar inence, and hardness of mature hypertrophic results. Scar changes were measured using 6 cate- scars.In a comparative study in which 12 pa- gories of scar size, overall improvement, noticeable tients were randomized to 4 groups (hydroactive appearance, elevation, erythema, and softness. The polyurethane dressing alone, polyurethane plus only significant advantage in the treated group was compression, silicone sheeting plus compression, the patient-reported improvements of a softer, less and compression alone for 24 h/d for 8 weeks), the noticeable scar at 2 months.There were no notable most pronounced effects were achieved with either differences with respect to physician-measured polyurethane dressing plus compression or silicone appearance and size nor patient-measured erythema and elevation. More patients in the placebo group compression was slightly superior to silicone plus than treated group reported improvement with a compression in reduction of surface roughness.
less noticeable scar at 1 week and a less red scar These effects lasted for at least 1 year after the after 1 month. The study’s short follow-up time of termination of therapy. Furthermore, polyurethane 2 months, however, was a limitation of this study.
dressing alone was found to provide functional The most recent randomized, double-blinded, and structural improvement in scar tissue that was split-scar study of 24 patients with new surgical slightly superior to that obtained from compression wounds also demonstrated that onion extract gel alone. It was speculated that scar dressings and did not improve scar appearance, erythema, and compression may promote dynamic shear forces hypertrophy when compared with a petrolatum- based ointment.Before enrollment, each patient Currently, polyurethane dressing has unclear ef- tested negatively for an allergic reaction to both fects on the development of new hypertrophic scars treatments by a 48-hour patch test on the forearm.
but has been shown to improve the prominence and Each scar half then received either the onion extract appearance of mature scars in a small randomized or petrolatum ointment 3 times daily for 8 weeks.
trial. Further studies are necessary to elucidate its The scars were evaluated by blinded investigators role in hypertrophic scar treatment.
and patients at 2, 8, and 12 weeks after initiation oftreatment and by blinded patients at 11 monthspostoperatively. None of the scars became hyper- trophic at 11 months, but it was uncertain whether Allium cepa, or onion extract, is found in a num- the patients would have developed abnormal scar- ber of scar treatment products. Patients, in particular, ring without treatments. One limitation of this study, value this remedy because of its ease of use, relatively however, was that all the patients were elderly low cost, ‘‘botanical’’ ingredients, and widespread Caucasians, a group inherently at lower risk for availability. Onion extract exhibits anti-inflammatory, hypertrophic scarring than patients who are younger bacteriostatic, and collagen down-regulatory prop- In summary, despite the wide use of onion extract by patients, there is no evidence that it is beneficial Documented clinical studies of onion extract have in improving hypertrophic scars. In the few studies shown that onion extract does not improve hyper- conducted to date, more patients in the petrolatum trophic scarring. To date, there have been 3 major control group reported greater improvements in wound healing when compared with those who significant 20% reduction in scar size in the 0.05% retinoic acid treatment group compared with the basecream control group. A more recent study of a different form of vitamin A, 0.25% tocoretinate oint- Imiquimod 5% cream, a topical immune response ment, showed marked decreases in the size, stiffness, modifier, is approved for treatment of genital warts, erythema, and pruritus in all mature hypertrophic basal cell carcinoma, and actinic keratoses.Imiqui- scarsOnly 4 hypertrophic scars were examined, mod stimulates proinflammatory cytokines, espe- however, making these data preliminary.
cially interferon-a, which generate a cell-mediated Vitamin A treatment has its downsides, however.
immune response. Interferon-a increases collagen As topical retinoids may be absorbed systemically, breakdown. In addition, imiquimod alters the ex- hypervitaminosis and teratogenicity are potential pression of genes associated with apoptosis.
complications of this form of therapy and, therefore, Therefore, imiquimod has been used in an attempt limit its use, especially in pregnant women and people who take oral vitamin supplements.
Because of the success of imiquimod 5% cream in In general, sufficient data are lacking on the lowering keloid recurrences after operation, its role efficacy of topical vitamin A on hypertrophic scarring in the prevention of hypertrophic scars is currently and its use may be associated with side effects.
under evaluation. A recent randomized, double- Vitamin A should, therefore, not be recommended.
blinded study of 15 patients investigated the use ofimiquimod 5% cream in the prevention of hypertro- phic scarring after breast operTreatment with Vitamin E (tocopherol), a lipid-soluble antioxi- imiquimod consisted of gently rubbing the cream dant, has complex effects on wound healingIt has over the scar for 3 to 5 minutes once every 3 to 4 days been shown to penetrate into the reticular dermis for a period of 8 weeks. At 24 weeks postsurgery, and reduce the formation of oxygen radicals that imiquimod treatment improved scar quality, espe- impede healing and damage DNA, cellular mem- cially color and elevation, when compared with two branes, and lipids. Vitamin E also alters collagen control groups (no treatment and treatment with and glycosaminoglycan production and inhibits the petrolatum.) There was an absence of hypertrophic spread of peroxidation of lipids in cellular mem- scars and keloids in the imiquimod group, although branes, thereby acting as a membrane-stabilizing this might have been related to the small sample size.
Of note, all patients in the treatment group experi- Despite numerous anecdotal reports claiming enced an inflammatory response characterized by that vitamin E speeds wound healing and improves erythema, local pain, and pinpoint bleeding. This the cosmetic appearance of scars, little scientific response allowed ‘‘blinded’’ physicians to distin- evidence exists to support these claims. Jenkins guish between treatment and control groups that et al,in an attempt to reduce scarring after recon- structive surgery in patients with burn, used topical vitamin E in the postoperative period. No significant improve hypertrophic scar quality after operation differences were found in range of motion, scar in a preliminary small, randomized, prospective thickness, change in graft size, and overall cosmetic clinical trial, but additional studies with a larger appearance between the vitamin E treatment group sample size and longer follow-up are necessary to and base cream control group 1 year after surgery. In determine the role of imiquimod 5% cream in addition, 20% of patients reported local reactions to the vitamin E cream. A subsequent double-blind,placebo-controlled clinical trial evaluating patients who applied emollient with vitamin E and emollient Vitamin A is required to maintain the integrity of alone to each half of their scar from Mohs micro- epithelial and mucosal surfaces. Based on the obser- graphic surgery (twice daily for 4 weeks starting soon vation that oral vitamin A improved the appearance after surgery) also demonstrated similar results.
of keloid scait has been tested in the form of Twelve weeks after surgery, vitamin E did not help 0.05% retinoic acid in wound healing. Daily appli- in improving the cosmetic appearance of scars or cation of retinoic acid to intractable hypertrophic and keloid scars has been shown to reduce size A high incidence (33%) of contact dermatitis was and pruritusand cause scar softening, flattening, noted. Limitations of the study included the use of and fading of color.In a randomized, double-blind the d-a-tocopheryl form of vitamin E, which has study, Daly et demonstrated a statistically been widely associated with contact dermatitis, and the potentially diluted concentration of topical vita- scars lack enough scientific data regarding their effect min E (one crushed capsule of 320 IU in 1 g of on this type of scar. Such topical therapies include aloe vera, vitamin C, corticosteroids, and tacrolimus.
The use of vitamin E in scar management has A new patent-pending product, a botanical QR340 other theoretic limitations. Because of its ability to formula (Quigley Pharma, Doylestown, Pa), has inhibit collagen synthesis, the use of vitamin E early preliminarily demonstrated higher efficacy than in scar therapy may reduce scar tensile strength and, Mederma and placebo in hypertrophic scar improve- hence, lead to the development of widened scars ment. Further studies are necessary to determine these products’ role in hypertrophic scarring.
When used in conjunction with silicone gel In conclusion, there is no single, optimal modality sheets, however, vitamin E has been shown to that can eliminate or prevent hypertrophic scarring.
improve pre-existing hypertrophic scars. In all, 38 Currently, the most accepted treatment for old and patients (95%) who received silicone gel sheets new hypertrophic scars is silicone gel sheeting.
with added vitamin E improved by at least 50% Silicone ointment or gel alone, however, is less with respect to color, size, and cosmetic appearance, effective than silicone sheeting. Pressure therapy whereas only 30 patients (75%) using silicone gel has demonstrated some efficacy but is cumbersome sheets alone improved at least 50% after 2 months of and not standardized. Polyurethane dressing has treatment.This study led to the conclusion that the equivocal effects on the development of new hyper- combination of vitamin E and silicone gel sheeting is trophic scars but may improve the appearance of beneficial in hypertrophic scar treatment, possibly as mature scars. Products in the United States contain- ing onion extract do not improve scar cosmesis or In conclusion, the evidence that topical vitamin E symptomatology when compared with a petrolatum- alone improves the cosmetic appearance of scars is based ointment. Imiquimod 5% cream has been poor. It is also associated with a high incidence of shown to improve the quality of new hypertrophic contact dermatitis. The use of vitamin E should, scars after surgery in a preliminary clinical trial, but further studies are necessary. Vitamin A lacks suffi-cient data and may be associated with side effects, especially in pregnant women. Finally, vitamin E Studies of scar treatments to date are limited for alone may be detrimental to wound healing and a number of reasons. A suitable animal model is often leads to contact dermatitis; it should, therefore, lacking. Many studies on scar treatments did not use controused other confounding methodssuch as pressure or intermittent corticosteroid injec- tions,or applied different methods of scar 1. Alster T, West TB. Treatment of scars: a review. Ann Plast Surg assessment, making it difficult to evaluate the precise effects of each topical treatment. The studies also 2. Kirsner R. Wound healing. In: Bolognia J, editor. Dermatology.
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