Contemporary Options for the Management of Scars

Yvette C. Terrie , BSPharm, RPh
Jeffrey R. Marcus , MD, FAAP, FACS

By definition, a scar is the end result of the normal healing process. For many individuals, the effects of scarring are nonproblematic. Injuries that only involve the epithelium are not likely to cause significant scarring, but injuries that involve the dermis and deeper tissues have greater potential to leave a visible scar.¹ Scarring occurs along a continuum of expression both across and within populations. Normal scars can be faintly perceptible in some cases and prominent in others. We know that variation in normal scarring is associated with such factors as skin color, skin quality, age, and ethnicity. Scarring is a normal process, but several specific types of scars are abnormal and result from aberrant wound healing. Some individuals or populations may be more susceptible to developing such types of abnormal scarring.

Annually, an estimated 100 million individuals will develop some type of scar. Approximately 55 million will develop problematic scars as the result of elective surgeries, and 25 million will develop scars from operations after trauma or disease.² In addition, 11 million keloid scars and 4 million scars from burns exist, of which 70% occur in children.^2,3 The latter abnormal scars are often described as painful, disfiguring, embarrassing, and even functionally disabling.⁴ Patients may experience pruritus, psychological stress, and loss of motion from contracture.^4,5

Over the past 2 decades, researchers have gained significant insight with regard to the prevention, treatment, and management of scarring. An accurate assessment of the scar is a crucial step prior to initiating possible treatment and management.^2,5 Factors that need to be considered prior to electing to treat a scar include²:

1. Is the scar getting worse or showing signs of improvement?
2. The anatomical location of the scar.
3. Symptoms that the patient presents.
4. Presence and/or severity of functional impairment. (Does the scar affect mobility of joints?)
5. Stigma of the scar. (Evaluate the impact of the scar on the patient's quality of life.)
6. Likelihood of improvement with treatment.

Whereas the severity of a scar can be estimated subjectively, accurate representation (for the purpose of investigation) must be based on objective methodology. Objective assessment provides quantitative data and is a key element in the critical evaluation of treatment efficacy. Many objective tools are available for scar assessment. One example is the Vancouver Scar Scale.

The Vancouver scale is a clinical assessment tool that rates and scores scars according to pigmentation, vascularity, height/elevation, and pliability.^2,6,7 From this assessment, a score is obtained; the lower the score, the better the scar.² The scores can then be compared over periods of time and across potential treatment modalities.^2,6,7 Table 1⁸ shows the Vancouver Scar Scale. In this evolving field, it is important for health care professionals to keep abreast of treatment options and the clinical evidence that support their use. This continuing education article will review the stages of wound healing, the types of abnormal scars, and the treatment options currently available.

Table 1

Pathophysiology of Wound Healing and Scar Formation

For the purposes of this discussion, "injury" refers to any loss of skin continuity whether intentional (surgical) or unintentional (traumatic). The healing process is typically divided into 3 stages that begin immediately after an injury and continue for a period lasting weeks to months to years.^1,9,10 The stages of the healing process include inflammation, proliferation, and maturation (matrix remodeling).^1,9,10 The scar is the discernible end result of this process.^1,9,10

Inflammatory Phase
Although the exact role of the inflammatory response in the progression of scar formation is still not entirely clear, it is evident that early inflammation sets the stage for the production of scar tissue and may contribute to the end result.¹⁰ It appears that the development of the scar is programmed during and by certain parts of the inflammatory process.¹⁰

During the inflammatory phase, which lasts 3 to 4 days, the body responds to injury by preparing the wound for subsequent tissue replacement. This consists of 2 primary processes: hemostasis and inflammation.⁹ Hemostasis is initiated immediately as the first major function of the platelets.^1,11 In response to the initial injury, vasoconstriction in combination with clot formation and platelet aggregation occur.¹¹ The aggregation of platelets results in the formation of the primary platelet plug.¹¹ Aggregation and attachment to exposed collagen surfaces activates the platelets.¹²

Once aggregated, the platelets degranulate and release mediators that assist in the development of the fibrin clot, together with growth factors and chemoattractants.¹¹ The platelets are critical to the initial phase of healing, because they release cytokines such as platelet-derived growth factor, insulinlike growth factor-1, epidermal growth factor (EGF), and transforming growth factor-beta (TGF-beta) into the wound bed.^9,11 Neutrophils and macrophages travel into the wound and secrete additional growth factors, such as transforming growth factor-alpha (TGF-alpha), heparin-binding epidermal growth factor (HB-EGF), and basic fibroblast growth factor, which further the progression of the inflammatory process.¹¹

After hemostasis is achieved, the active inflammatory process is initiated by chemotactic factors that draw neutrophils into the wound. Under normal circumstances, neutrophils phagocytize debris and bacteria in the wound within 24 to 48 hours.⁹ Platelets also release mediators such as bradykinin, histamine, and prostaglandins into the wound area, thus initiating vasodilation among the surrounding vessels. This process then increases blood flow to the area, allowing further inflammatory and mediator cells to reach the site. As a result, the wound appears erythematous and edematous.^9,12 The final stage of the inflammatory phase is the epithelial migration into the wound.^3,9

Proliferative Phase
During the proliferative phase, the wound is filled with new connective tissue and covered with new epithelium. This phase involves the formation of granulation tissue, which is a collection of fibroblasts and newly synthesized collagen, new capillaries, and inflammatory cells.⁹ Granulation tissue begins forming approximately 3 to 5 days following injury and overlaps with the preceding inflammatory phase.¹² The synthesis of collagen by fibroblasts is directed by cytokines produced by stimulated macrophages.⁹ As granulation tissue is being processed, epithelial cells, which started to migrate during the inflammatory process, resurface the damage of the wound.⁹ The process of epithelialization then signals a down-regulation in proliferation. The final step in the proliferative phase includes the process of wound contraction and involves the mobilization and pulling together of the edges of the wound.⁹

Maturation Phase
The maturation phase, also known as the matrix remodeling phase, is the longest phase and begins at about 3 weeks after an injury.^9,10,12 During this phase, the wound is completely closed by connective tissue and resurfaced by epithelial cells. This phase can continue for as long as 2 years after an injury, depending on the extent of the injury.⁹ This phase involves an ongoing process of the synthesis of collagen with hightensile strength collagen.⁹ Peak tensile strength of a wound occurs approximately 60 days after an injury occurs.¹² The end product is the formation of a scar that has an estimated 70% to 80% of the original strength of the skin that it replaced.^9,12

Factors That Affect Wound Healing

Various factors can interfere with the wound-healing process, affecting any of the 3 phases.³ Multiple factors have been identified as contributing to impaired wound healing. Examples of these factors include advanced age, malnutrition, and impaired tissue perfusion and oxygenation. Oxygen availability is critical to the healing and is limited by smoking, diabetes, anemia, hypotension, peripheral vascular disease, and congestive heart failure.⁹ Radiation is a specific example of impaired perfusion due to microvascular fibrosis. Other examples of factors negatively affecting healing include infection, immunosuppressives, chemotherapy, steroids, and inadequate wound care.^1,9,13,14

Scarring

Scarring is part of the skin's natural wound-healing process and is a sign that a wound is healing. For the formation of a normal scar, the maturation phase involves gradual fading and flattening of the scar tissue which, on average, takes about 12 to 18 months, but can take up to 2 years.^1,9 Scarring follows local skin trauma through injury, disease, or surgery, inflammatory disorders (eg, acne vulgaris, mumps/measles/chickenpox infections), or lacerations/piercings (eg, cuts, bites, tattoos, vaccinations, surgery).⁵ Normal scars initially appear pink or red and raised, but then flatten and fade to varying degrees. Abnormal scars are thought to be caused by disturbances in the wound-healing process. During the maturation phase, the manifestation of abnormal scarring becomes apparent.¹⁵

As mentioned previously, many factors can affect the severity of scarring. These factors can be divided into 4 main elements: injury factors, patient factors, technical factors, and care factors.

Injury factors include the depth, orientation, contamination, mechanism, and extent of the injury. Tissue loss, crush injuries, and irregular tears of the skin are particularly problematic. Surgical incisions, on the other hand, are highly controlled. The injury itself is a significant determinant of longterm scar outcome. Patient factors were discussed earlier and relate to the individual's inherent ability to heal well and the potential predisposition to exuberant scar formation. It is worth mentioning that age plays a significant factor among all populations. During 2 periods of development, the process of healing typically results in less conspicuous scars. These are at 2 extremes—the very young and the elderly. Privileged healing does seem to occur during infancy and extends, perhaps to a lesser degree, for several years. By puberty, the qualities of the skin lend themselves to a more proinflammatory state. This exaggeration of the inflammatory and proliferative phase often results in unsightly and/or abnormal scars during this time. With increasing age, the qualities of the skin continue to change, as does the scar response. In later years, the skin becomes thinner and less elastic. The process of wound healing is less exuberant, and scarring during this period is again diminished.

Injury factors and patient factors cannot be willfully changed; therefore, a significant aspect of determining outcome is out of the control of the caregiver. The final 2 factors, however, can be influenced significantly, and these are the subject of interventions designed to optimize scar formation. Technical factors relate to the surgeon's ability to manage and repair the injury in the most optimal manner. Care factors relate to the manner in which an injury or wound are treated after surgical or nonsurgical treatment. Most types of scar treatments are directed at this aspect of the scar process.

Types of Abnormal Scars

Several types of abnormal scars exist, including keloids, hypertrophic scars, atrophic scars, widened scars, and contractures that can be differentiated by various characteristics (Table 2).

Table 2

Keloid and Hypertrophic Scars
The exact etiology of keloid and hypertrophic scar development remains unclear. Several theories suggest, however, that abnormalities in cell migration, proliferation, inflammation, and the synthesis and secretion of extracellular matrix proteins, cytokines, and remodeling can contribute to keloid and hypertrophic scar formation.¹²

Keloids
In the United States, keloids affect an estimated 15% of the population and are more prevalent among certain ethnic groups, such as African Americans, Asian Americans, Latin Americans, and other darker-pigmented ethnicities.¹⁶ Some studies suggest that keloids are related to an inherited metabolic alteration in collagen.¹⁶ Although keloids can occur at any age, they are rarely found in newborns or among the elderly and tend to have their greatest occurrence rate among individuals between 10 and 30 years of age.^1,5,17 Cosman et al reported that the average age of patients at the time of receiving initial treatment was 25.8 years, and the average age of onset was 22.3 years in women and 22.6 years in men.¹⁸ Furthermore, research has demonstrated that, because keloids typically have accelerated growth during both puberty and pregnancy and, in general, resolve upon menopause, both androgens and estrogen have been considered contributing factors to keloid formation.⁵ Other hormones that may be connected to the formation of keloids include thyroid hormone alterations and melanocyte-stimulating hormones.⁵

Keloids are defined clinically by 2 factors: first, the growth of the keloid extends beyond the boundaries of the initial wound/injury. Second, keloids are typically symptomatic over a prolonged course, described as painful and pruritic.¹⁹ Genetic predisposition coupled with some form of trauma or injury to the skin may play a pivotal role in the development of keloids.^5,17 Examples of skin injuries that may precipitate formation of keloid scars include surgery, ear piercing, abscess, abrasions, lacerations, tattoos, insect bites, burns, vaccinations, and any process that may cause inflammation of the skin, such as acne, chickenpox, or folliculitis.¹⁷ Butler et al states that the formation of keloids is a response to inflammation that is caused by keloidderived fibroblasts, which involve an abnormal secretion of proinflammatory mediators and an abnormal response to other inflammatory signals.¹⁶

Keloids occur more frequently on the shoulders, chest, earlobes, upper arms, upper back, and cheeks, although the reason for this occurrence is unknown.^20-22 Some theories postulate that these areas have increased susceptibility to formation of keloid scars since they are subject to elevated levels of muscle and skin tension.^23,24 The areas of the head and neck that are typically safe from keloid formation include the eyelids and the mucous membranes.²⁴

With the exception of trauma, exact etiologic factors responsible for keloid formation have not been fully understood.²⁵ Keloids are frequently associated with negative wound-healing factors, such as infection, excessive tension, foreign bodies, and repetitive trauma; however, keloids may form in simple clean wounds.²⁵

Many patients with keloids are affected both physically and psychologically and express a significant negative impact on their quality of life.²¹ In the results from one study, Lee et al evaluated 28 patients with keloids and reported that more than 80% of the patients reported keloid-associated pruritus, and an estimated 50% reported pain.²⁶

Hypertrophic Scars
Hypertrophic scars are more common than keloids. Hypertrophic scars may occur in persons of any age or at any site, and they tend to spontaneously regress. In addition, hypertrophic scars are more likely to respond to treatment.⁵ Hypertrophic scars typically develop within 8 weeks of skin injury, such as a burn wound infection. In general, their normal course includes a rapid growth stage for up to 6 months that can then be followed by regression during the next 12 to 18 months.²⁷

Differentiating Between Keloid and Hypertrophic Scars
Both keloid and hypertrophic scars are characterized by an accumulation of excess collagen and are not always easy to differentiate from one another.^16,21 It is important for health care professionals to distinguish between the 2 types of scars, because inappropriate therapy may cause formation of larger scars.³ Crucial differences between these 2 types of abnormal scars include histologic morphology, cellular response to growth factors, and scar appearance.²⁸

Keloids tend to grow beyond the borders of the original wound, invading the surrounding areas of the skin, and they typically do not resolve spontaneously. Hypertrophic scars stay within the boundaries of the original wound and tend to regress spontaneously.^1,5,13,25 In addition, hypertrophic scars are typically visible soon after an injury to tissue and are often related to a contracture across a joint surface, whereas keloids may develop as late as 12 months after an injury.^1,5,24 Hypertrophic scars appear as red, raised, nodular lesions occurring in areas of thick skin, and they may cause pruritus or pain. Keloid scars appear puckered and nodular and are reddish-purple in color and exhibit a prolonged, proliferative phase resulting in the appearance of thick hyalinized collagen bundles similar to those produced by hypertrophic scars.^17,27 Upon palpitation, keloids appear to be firmer when compared with hypertrophic scars and can also be painful and itchy.^1,28

Atrophic Scars
Atrophic scars are flat and depressed below the dermal area. They are generally small in size with an indented or inverted center.^2,3,16,29,30 They are most commonly the result of collagen destruction during the course of an inflammatory skin disease, such as from the result of acne vulgaris, varicella, and immunization sites.^3,28 Initially, atrophic scars appear erythematous and become increasingly fibrotic and hypopigmented as time progresses.³⁰

Widened Scars
Widened scars are described as stretched scars that normally occur in sites of higher tension.^1,5 The response to tension perpendicular to the wound edges is a widened scar regardless of whether there is separation or disruption of the wound.^1,5 Widened scars can occur at any age and have no predisposition to ethnicity, sex, or familial history. The arms, legs, and abdomen are the most common areas of the body that may form a widened scar.⁵ In addition, sun tanning can contribute to scar widening through attenuation of the tissues.⁵

Widened scars initially appear as a pale red color-typically flat, soft, symptomless scars often seen after knee or shoulder surgery, for example.^1,2,5 The stretch marks that often appear during or after pregnancy are a type of widened scar in which there is trauma/injury to the dermis and subcutaneous tissues but the epidermis is unbreached.⁵ Moreover, mature widened scars have no elevation, thickening, or nodularity, which distinguishes them from hypertrophic scars.²

Scars with Contractures
A contracture scar is characterized as a permanent shortening of a scar that can be disfiguring and disabling, because they can limit an individual's movement.² A contracture scar typically occurs when the wound occurs across a joint or when a large area of the dermal area has been damaged, such as when an individual experiences a severe burn.^1,2 Scar contracture is thought to be mediated by myofibroblasts, which are also thought to play a role in other similar disorders of tissue healing.

Treatment

If a scar causes functional or cosmetic concerns, then treatment may be warranted. The treatment of scarring can be categorized into 2 categories: invasive or noninvasive modalities.^1,7 Although advances have been made with regard to the nature of wound healing and scar formation and the modulation of these processes, a consensus in the literature regarding optimal treatment has not been reached.^1,10 The efficacy of many existing treatments is difficult to assess due to the lack of well-controlled clinical trials.^1,10 There remains a need for more in-depth clinical studies, particularly with regard to nonsurgical therapies in double-blind, placebo-controlled, multicenter, randomized trials with objective, evaluative measures.¹⁰

Invasive treatment options include intralesional corticosteroid injections (eg, triamcinolone), surgical excision, injection of interferons and other chemotherapeutic agents, radiotherapy, laser resurfacing, dermabrasion, cryotherapy, and chemical peels. Noninvasive treatment options include silicone gel sheets, silicone gel ointments/ creams, topical vitamin E, topical onion extract (and compounds derived from allivum), pressure/tissue compression, and topical retinoids. The main problem with most nonsurgical treatments is that little or no evidence of efficacy exists.¹ Many of these treatments are supported only by anecdotal or insufficient clinical data.^1,7 Several modalities are discussed below. Based on a 2002 publication, International Clinical Recommendations on Scar Management by Mustoe et al, however, evidence supports only 2 interventions: silicone gel sheets and intralesional corticosteroid injections.^1,7 These guidelines recommend that silicone gel sheeting should be the first line of treatment in the management of scars, particularly in the prevention of keloids and hypertrophic scars.⁷ In addition, it was recommended that silicone gel sheet therapy be considered as first-line prophylaxis following surgical excision.²¹

Noninvasive Treatment Options

Silicone Gel Sheeting and Silicone Gel Ointment
The use of silicone gel sheeting to prevent and treat hypertrophic and keloid scarring is still relatively new; it began in 1981 with the treatment of burn scars.^10,31 The therapeutic efficacy of silicone gel has been well-documented in the literature.^7,10 Studies show that early intervention with silicone gel appears to be ideal but that older scars have also showed improvement from treatment. When used appropriately, improvements in scar thickness, color, and texture have been noted.^17,32

Topical silicone gel sheeting and silicone gel ointments have been used with the intent to reduce the size, induration, erythema, and pruritus of preexisting hypertrophic scars and possibly prevent the formation of new scars.²⁷ Silicone is characterized as a soft, semi-occlusive scar cover composed of a cross-linked polydimethylsiloxone polymer that has extensibility comparable with the skin.²⁷

Although the exact mechanism of action of silicone gel is not fully known, several theories exist. Many researchers agree that silicone gel sheets act at the stratum corneum, which reduces evaporation and restores homeostasis.^10,27,33 Silicone gel sheeting has an evaporative water loss almost half that of skin.²⁷ In addition, many researchers postulate that silicone acts by creating a hydrated, occluded environment that reduces activity of the capillaries, thus decreasing fibroblast-induced collagen deposition and scar hypertrophy.^25,34 Studies also have shown that silicone gel sheets do not change the pressure, temperature, or oxygen tension at the site of the wound.²⁵ Results from at least 8 randomized controlled clinical trials and a meta study of 27 trials showed that silicone gel sheeting is a safe and effective treatment option for both hypertrophic and keloid scars.⁷

In a 2008 publication, Tandara and Mustoe tested the hypothesis that the use of silicone sheeting in vivo has a beneficial effect on scarring by reducing keratinocyte stimulation, with a resulting decrease in dermal thickness.³⁵ In the study, sheets of silicone adhesive gel were applied to scars in a rabbit ear model of hypertrophic scarring 14 days postwounding for a total of 16 days. Results from the study reported that the scar evaluation index was greatly decreased after silicone gel sheet application when compared with the untreated scars.³⁵ Total occlusion decreased scar hypertrophy by 80%, compared with semi-occlusion. The epidermal thickness index of untreated scars was increased by more than 100%, compared with uninjured skin. Furthermore, silicone gel treatment significantly reduced epidermal thickness by more than 30%. The findings showed that 2 weeks of silicone gel application at a very early onset of scarring decreased both dermal and epidermal thickness, which appears to be due to a reduction in keratinocyte stimulation.³⁵ The study also concluded that oxygen could be ruled out as a mechanism of action of silicone occlusive treatment. The hydration of the keratinocytes seems to be the key stimulus.³⁵

Silicone gel sheets should never be applied to open wounds and should be applied as soon as the skin shows signs of complete epithelialization and/or after surgical sutures have been removed, if applicable.³ The sheets should be worn for a minimum of 12 hours daily and may require use for as long as 6 months. The sheet can be removed for normal skin washing, and the product can be washed and reused. Many gel sheets will last for 14 to 28 days.¹ Silicone gel sheeting is an easy and pain-free therapeutic option for many individuals, especially children. From a practical standpoint, one difficulty with the use of silicone sheeting is the application to contoured/irregular body surfaces or surfaces that are difficult to conceal, like the face.

Silicone gel is gaining popularity, because it can be applied to a smaller area such as the face.⁵ Silicone gel has demonstrated significant reduction in scar volume when used over time. Additionally, some studies have shown an 80% to 100% overall improvement in hypertrophic scar formation.⁵ Chan et al evaluated the use of silicone gel in the prevention of hypertrophic scar development in median sternotomy wounds. The study concluded that the use of silicone gel in the prevention of hypertrophic scar development in sternotomy wounds was effective.³³ No incidence of adverse effects was reported, and patient compliance was satisfactory.³³ The topical use of silicone gel appears to improve the color, appearance, texture, and thickness of hypertrophic and keloid scars and decreases the incidence of itching.³ It has been shown to soften and reduce hypertrophic scars much more rapidly without interfering with pressure, temperature, or oxygen tension.³ Silicone gel is typically applied 1 to 2 times per day. It is colorless and odorless; it dries on the surface of the skin and is imperceptible. For these reasons, it is a particularly attractive and very welltolerated option for children.

Topical Vitamin E
Topical vitamin E (tocopherol) is classified as a lipid-soluble antioxidant.²⁷ To date, the effects of vitamin E on wound healing and improving the cosmetic effects of burns and other dermal injuries are due to anecdotal claims, with little scientific evidence to support them.^1,27 In a study conducted by Jenkins et al, the effects of vitamin E with regard to reducing scarring after reconstructive surgery were evaluated.^34,36 The study found no significant variances between the control group and the treatment group, and an estimated 20% of the study subjects reported a local reaction to vitamin E such as dermatitis.³⁶

Baumann and Spencer investigated the effect of vitamin E on the cosmetic appearance of scars. The results of the study demonstrated no benefit to the cosmetic appearance of scars after the use of topical vitamin E after surgery.³⁷ In addition, the study found that topical vitamin E might actually be harmful to the appearance of scars, because 33% of the study participants developed contact dermatitis.³⁷ Thus, the study concluded that the use of topical vitamin E should be dissuaded.³⁷

Onion Extract (Allivum Derivatives)
Allium cepa or onion extract is found in several nonprescription products marketed for scar treatment. Due to its simple use, widespread availability, botanical ingredients, and reasonable cost, many patients may elect to use scar treatment products containing this ingredient. Theories suggest that onion extract appears to exhibit antiinflammatory, bacteriostatic, and collagen down-regulatory properties and improves collagen organization in a rabbit ear model. Despite the popularity of this ingredient, a lack of clinical evidence exists regarding the beneficial effects of improving hypertrophic scars, however.²⁷

Jackson and Shelton evaluated the efficacy of topical onion extract gel on both the appearance and symptomatology of postsurgical scars, and the results were compared with those of a topical emollient ointment.³⁸ The study concluded that a significant decrease in erythema was visible in the scars of those using the topical emollient ointment and that the onion extract gel was ineffective in decreasing scar erythema.³⁸

Chung et al compared the effectiveness of onion extract gel and a petrolatum- based emollient with regard to improving the appearance and symptoms of new surgical scars.³⁹ The study concluded that although participants tolerated both treatments without incidence of allergic reactions, no significant differences were noted in the appearance of the scars when comparing both products.³⁹

Hosnuter et al evaluated the therapeutic activity of onion extract gel on both hypertrophic and keloid scars with an emphasis on elevation, redness, hardness, itching, and pain.⁴⁰ The study involved 60 patients divided into 3 groups. Group 1 was treated solely with onion extract gel; group 2 was treated with only silicone gel; and group 3 was treated with a combination of both onion extract gel and silicone gel sheet. After 6 months, the onion gel was more effective with regard to scar color, whereas the silicone gel sheet was superior in reducing the height of the scar. The most effective results were observed in group 3, where both onion extract gel and silicone gel sheeting were used.⁴⁰

In 2008, Draelos evaluated the ability of onion extract gel to improve the appearance of scars following excision.⁴¹ The study involved 60 participants who had symmetrical seborrheic keratoses of at least 8 mm in diameter on the right and left upper chest. The lesions were removed, and the surgical sites were allowed to heal for 2 to 3 weeks.⁴¹ During that time, the subjects were divided into 2 groups with each receiving either topical treatment of onion gel or no treatment at all. Results from the study concluded that the use of topical onion extract gel improved scar softness, redness, texture, and overall appearance at the excision site when assessed by the blinded investigator at study weeks 4, 6, and 10.⁴¹

Topical Retinoids
The use of topical retinoic acid has been successful in the treatment of keloids and hypertrophic scars. Panabiere- Castaings reported both a decrease in size and weight of lesions after a trial period of 12 weeks.⁴² The daily topical application of retinoic acid to both intractable hypertrophic and keloid scars has been shown to cause scar softening as well as decrease the size of scarring and the incidence of pruritus.⁵

It is important to note, however, that although rare, it is possible for topical retinoids to be absorbed systemically and cause adverse effects such as hypervitaminosis and teratogenicity.²⁷ Therefore, topical retinoid use should be limited or avoided, especially among certain patient populations (ie, pregnant women or those concurrently using oral vitamin supplements).²⁷ Furthermore, insufficient data exist regarding the effectiveness of topical retinoids on treating hypertrophic scarring.²⁷

Pressure/Tissue Compression
Since the 1970s, pressure therapy has been considered the preferred conservative treatment for the management of scars and the standard therapy for the treatment of hypertrophic scarring after a burn injury.^7,29 It can also be used for treatment of keloid scars.^3,7

A successful response rate ranging from 90% to 100% has been reported among patients treated with pressure therapy after keloid excisions, especially in those patients with ear lobe keloids.²⁴ The amount of pressure delivered should be between 24 and 30 mm Hg to avoid decreased peripheral blood circulation.²⁴

Pressure treatment is believed to accelerate wound maturation by several mechanisms, namely, a thinning of the dermis, decrease in edema, and a reduction of blood flow and oxygen.²⁷ Pressure therapy is particularly successful when applied while the scar is active; it loses some degree of efficacy after 6 months of treatment.^7,27

Typically, the materials used in pressure therapy are custom-made from an elastic material that contains a high spandex content. To prevent a decrease in the elasticity of the materials, they should be changed every 6 to 8 weeks.²⁷ To be effective, pressure must be applied continuously, and the garments are to be worn for approximately 1 year until the scar heals.^3,27

Various factors may be considered drawbacks of using pressure therapy, including its limited use in anatomic depressions, flexures, or areas of high movement, and the need to be worn at all times. The patient also may experience discomfort, and there is the possibility of occasional skin ulceration from uneven pressure distribution.²⁷ Many of these drawbacks can contribute to a decrease in patient compliance, with reports of noncompliance ranging from 8.5% to 59%.²⁷

Imiquimod Cream
Imiquimod 5% cream, which is classified as a topical immune response modifier, is FDA-approved for treating genital warts, basal cell carcinoma, and actinic keratoses. Imiquimod has been used in an attempt to reduce keloid recurrences after excision. Because of the success of imiquimod 5% cream in lowering keloid recurrences after operation, its role in the prevention of hypertrophic scars is currently under evaluation.²⁷ Imiquimod has been shown to improve hypertrophic scar quality after operation in a preliminary small, randomized, prospective clinical trial, but further clinical studies with a larger sample size and longer follow- up are needed to ascertain the role of imiquimod 5% cream in hypertrophic scar therapy.²⁷

Invasive Treatment Options

Corticosteroid Injections
Intralesional corticosteroid injections have been widely used to treat keloid and hypertrophic scars since the 1960s.¹⁰ Despite their use over a long period, however, the primary mechanism of action is still unknown.⁷ It is believed that steroids suppress the inflammatory phase of wound healing, decrease collagen production by the fibroblast, and decrease fibroblast proliferation.²⁴ Intralesional corticosteroid injections are considered the first line of therapy for the treatment of keloid scars and the second line of therapy for hypertrophic scars that have not responded to other treatments.^3,7 The most commonly used corticosteroid for scar treatment is triamcinolone.¹⁰ Multiple studies have shown 50% to 100% efficacy of intralesional injection of triamcinolone as a monotherapeutic agent in reducing scars.^7,10

Typically, the treatment of intralesional corticosteroids involves dosages that range from 10 to 100 mg administered every 3 to 6 weeks for several months.¹⁰ Length of administration depends on how well the scar responds to therapy. Because no standard of therapy exists, the patient's length of therapy is geared to the patient's response.³

Although the use of corticosteroids has been proven to be effective in decreasing scar formation, their use is associated with various adverse effects that occur in as many as 63% of patients. Adverse effects around the injection site include hypopigmentation, particularly in patients with darker pigmentation, dermal atrophy, telangiectasia (superficial blood vessels), widening of the scar, and delayed wound healing.^3,7 Intralesional corticosteroid injections also are associated with significant injection pain.^3,7

Other Invasive Therapies
Examples of other invasive therapies used for the treatment and management of scarring include surgical excision, radiotherapy, cryotherapy, laser therapy, chemical peels, and interferon injections. Whereas surgical excision may be beneficial and provide an immediate improvement in appearance, surgical excision of keloids alone is not always favorable, because the recurrence rate of scars can range from 45% to 93%.^21,24

The use of adjuvant therapies such as postexcisional steroid injections should be considered.²¹ Furthermore, data exist suggesting that preoperative steroid injection in combination with postoperative steroid injection offers a substantial reduction in recurrence associated with keloid excision. In addition, data exist suggesting the potential benefits of using topical mitomycin C as an adjunct to surgical excision; however, these are also small studies with short-term follow-up.²¹

Radiation can be used as monotherapy or in combination with surgical excision in order to prevent recurrence.⁴³ Success with monotherapy has not been acceptable, with recurrence rates reaching 100%. Some success has been shown with large doses of monotherapy; however, this may lead to malignant transformation 15 to 30 years later. Thus, large-dose monotherapy is no longer recommended.⁴³

Cryotherapy has been used for smaller hypertrophic scars, severe atrophic scars, and some keloids. The proposed mechanism of action is cell damage, resultant necrosis, leading to decreased scar bulk.²¹ Its use is restricted due to the occurrence of considerable pain and sometimes prolonged healing following treatment. Because multiple treatments are often required, the risk for hypopigmentation in darker-skinned patients is a significant obstacle.²¹

Atrophic scars have shown improvement with chemical peels, cutaneous laser resurfacing, dermabrasion, punch excisions, and the use of soft tissue biologic fillers.²

Emerging Therapies

Recently, several pharmacologic agents have been investigated as emerging and promising treatments for keloid scars. Although only a few clinical studies have been conducted, monotherapy with intralesional 5-fluorouracil (FU) or bleomycin tattooing have reported moderate to significant flattening of keloid scars in 88% of patients treated with 5-FU and in 92% treated with bleomycin.¹⁶ In addition, no recurrences in those scars that initially responded to these treatments were reported.¹⁶

The mechanism by which 5-FU reduces scarring has not been fully elucidated, but it has been shown that 5-FU inhibits fibroblast proliferation by blocking DNA synthesis and transcription through competitive inhibition of thymidylate synthesis.¹⁰

Adverse effects commonly associated with the use of 5-FU with up to 1 year of follow-up include transient hyperpigmentation (100%), tissue sloughing (21.4%-30%), transient burning sensation (7.1%), or pain (100%) at the injection site. No studies to date have reported systemic complications in patients treated with 5-FU for scar reduction. Long-term follow-up studies show no adverse effects.¹⁰

Bleomycin

Various studies have shown that intradermal injections of bleomycin, which is classified as a polypeptide antibiotic with well-known antitumor, antibacterial, or antiviral activity, have resulted in noticeable improvement in both keloid and hypertrophic scars.¹⁰ The exact mechanism by which bleomycin reduces scarring is not fully understood, but studies have shown that bleomycin inhibits collagen synthesis in dermal fibroblasts through decreased stimulation by TGF-beta1.¹⁰

Adverse effects commonly associated with its use include hyperpigmentation (75%) and dermal atrophy in the skin surrounding treated scars (10%-30%).¹⁰ To date, no systemic toxicity has been reported with low doses of bleomycin when used to treat hypertrophic scars. Future investigations will provide more information about the mechanism by which this drug acts and the effectiveness of this agent with regard to scars.¹⁰

Scar Prevention

Ideally, preventing abnormal scarring is better than treating it. The 2 aspects of the scar process that can be controlled are the technical aspects of wound repair and the postoperative management. From a surgical standpoint, the tissues of a laceration or incision should be handled delicately and be approximated meticulously. Initial dressings should be appropriately protective. Healing incisions on the trunk and extremities are often treated with a semi-occlusive dressing for up to 14 days. For facial incisions, dressings are used less frequently. Meticulous cleaning by patients and families is the single most important factor in control of the patient to affect wound healing and scarring. During the first 3 weeks following injury/repair, the focus should be on maintaining a clean incision.

For open wounds, achieving rapid epithelialization by providing a moist healing environment with ointment and semi-occlusive dressing is appropriate.^9,22 When epithelialization is prolonged past a time frame of 10 to 14 days, the likelihood of hypertrophic scarring increases dramatically.²² In burn injuries, early intervention is indicated, such as through the use of silicone and pressure garments after epithelialization has been complete.³

Just as many treatment approaches exist, many options potentially exist for prevention. For routine postoperative care of incision sites in visible locations, such as the face, the author favors an initial period (2-3 weeks) during which attention is focused on maintaining a clean surgical site. This is followed by 6 to 8 weeks of treatment using topical silicone gel. In the event of hypertrophic scar formation, silicone gel or sheets would be continued, and corticosteroid injection would be considered.

A combination of therapies to improve scar appearance probably holds the best possibility for successful treatment of both normal and abnormal scars. Future studies should continue to focus on evaluating the efficacy of various agents and exploring the potential role of emerging and novel agents for scar reduction.¹⁰

As more treatments and strategies for preventing scarring emerge, one of the best tools health care professionals can give patients is a thorough knowledge of the importance of immediate and proper wound care management, which can play a vital role in preventing or reducing the incidence of scarring. Again, the attention to maintaining a clean surgical/repair site cannot be overemphasized. Regarding counseling, patients with a history of keloid scars or familial history of keloids should be advised to avoid getting body piercings or tattoos, and they also should be discouraged from getting elective procedures at highrisk sites such as the upper arms, chest, or ears.^17,21

Because pharmacists are likely to encounter patients seeking counsel regarding wound care and the various scar treatments currently on the market, it is imperative for pharmacists to advise patients not to rely on the use of anecdotal information found on the Internet and to use products with well-demonstrated clinical efficacy. For the effective management of wounds and scars, it is essential for patients to be informed about the proper protocol regarding treatment and management. It is important for pharmacists to make patients aware of the availability of effective, noninvasive scar products—Table 3^27,44-51 lists topical scar products currently available-and encourage those patients with signs of abnormal scarring to seek the advice of their primary health care provider for proper treatment and to prevent further progression. Examples of when to seek medical attention include wounds that appear to enlarge, that are accompanied by discomfort or pain, show any signs of infection, or restrict movement of a joint.^1,9,10

Table 3