Aetna considers silicone products (e.g., sheeting, gels, rigid shells) experimental and investigational for the treatment of hypertrophic scars or keloids because there is inadequate evidence from prospective randomized clinical trials in the peer-reviewed published medical literature of the effectiveness of silicone products in alleviating symptoms of hypertrophic scars and keloids.

Aetna considers intralesional 5-fluorouracil or corticosteroids medically necessary for treatment of keloids where medical necessity criteria for keloid removal are met.  See CPB 0031 - Cosmetic Surgery, for medically necessary indications for keloid removal.

Aetna considers the following interventions experimental and investigational for the treatment of hypertrophic scars or keloids because of insufficient evidence in the peer-reviewed literature:

• Etanercept (see CPB 0315 - Enbrel (Etanercept))
• Interferon alpha (see CPB 0404 - Interferons)
• Intralesional botulinum toxin type A injection
• Radiofrequency treatment
• Topical calcipotriol
• Topical retinoids.

See also CPB 0062 - Burn Garments, CPB 0244 - Wound Care, CPB 0551 - Radiation Treatment of Keloids, and CPB 0559 - Pulsed Dye Laser Treatment.

Keloids and hypertrophic scars develop as a result of a proliferation of dermal tissue following skin injury, and are common (keloids develop in 5 % to 15 % of wounds).

Topical silicone gel sheeting is a soft, slightly adherent, semi-occlusive covering which is fabricated from medical grade silicone polymers.  Topical silicone gel sheeting is used to reduce the volume and increase the elasticity of hypertrophic and keloid scars, as a dressing for both donor and recipient sites in skin grafting, and as a treatment of burn wounds.

Examples of brands of silicone gel sheeting available over-the-counter include: Sil-K, Cica-Care, ReJuveness, DuraSil and Silastic Gel Sheeting. Epi-Derm brand of silicone gel sheeting is currently available only by prescription, although the manufacturer of Epi-Derm is pursuing Food and Drug Administration (FDA) clearance for over-the-counter marketing.

Silicone has also been applied as a gel or as rigid custom-molded shell to scars, burns, and skin grafts.  Although several case series have reported improvements in the appearance (scar size, erythema, elasticity) and symptoms (pruritus, burning pain) from the application of silicone sheets, gels, or shells to hypertrophic scars and keloids, these promising results have not been confirmed by subsequent prospective randomized controlled trials (RCTs).  Prospective RCTs of silicone products in treatment of hypertrophic scars and keloids are limited, and the outcomes of these studies have not consistently demonstrated a clinically significant benefit of silicone products in treating hypertrophic scars or keloids over standard wound dressings.

In an open-label pilot study, Lacarrubba et al (2008) assessed the effectiveness and tolerability of a silicone gel in the treatment of hypertrophic scars.  A topical self-drying silicone gel containing polysiloxane and silicone dioxide was applied twice-daily in 8 hypertrophic scars.  After 6 months, all lesions showed evident clinical and/or ultrasound improvement, with a mean scar thickness reduction of 37 % (range of 20 % to 54 %).  The authors stated that although controlled trials in larger series of patients are necessary, these findings suggested that the self-drying silicone gel may represent a safe and effective treatment for hypertrophic scars.

In a prospective, single-blind, RCT, Wittenberg et al (1999) evaluated the effectiveness of the 585-nm flashlamp-pumped pulsed-dye laser and silicone gel sheeting in the treatment of hypertrophic scars in lighter-skinned and darker-skinned patients: 19 completed the laser treatments and 18 completed the silicone gel sheeting treatments.  Clinical measurements included hypertrophic scar blood flow, elasticity, and volume.  Patients' subjective complaints of pruritus, pain, and burning were also monitored.  Histological assessment of fibrosis, number of telangiectasias, and number of mast cells was performed.  Statistically significant improvements in clinical measurements and patients' subjective complaints determined treatment success.  These investigators concluded that clinical results demonstrate that the improvements in scar sections treated with silicone gel sheeting and pulsed-dye laser were no different than those in control sections.

In a discussion of treatment of keloids, Quintal (2002) concluded that “[m]ore in-depth, controlled research is needed to prove or disclaim the therapeutic effect of silicone.”  A recently published systematic review of the literature on treatment of keloid scars concluded that “[t]he effectiveness of silicone gel sheeting and other occlusive dressings in treating keloidal scars cannot be confirmed by existing studies” (Shaffer et al, 2002).

The FDA (2004) classified silicone sheeting intended for use in the management of closed hyper-proliferative (hypertrophic and keloid) scars into class I (general controls).  As a class I device, the device will be exempt from premarket notification requirements.

In a prospective, randomized, placebo-controlled, clinical trial that examined the use of silicone gel in preventing hypertrophic scar development in median sternotomy wound, Chan et al (2005) concluded that the effect of silicone gel in the prevention of hypertrophic scar development in sternotomy wounds is promising.  In a recent review on keloid pathogenesis and treatment, Al-Attar and colleagues (2006) noted that established treatment strategies for keloids include surgery, steroid, and radiation (silicone was not listed as an established treatment for keloids).

A structured assessment of the evidence of silicone gel sheeting for preventing and treating hypertrophic scars and keloids prepared for the Cochrane Collaboration reached the following conclusions (O'Brien and Pandit, 2006): “Trials evaluating silicon gel sheeting as a treatment for hypertrophic and keloid scarring are of poor quality and highly susceptible to bias.  There is weak evidence of a benefit of silicon gel sheeting as a prevention for abnormal scarring in high risk individuals but the poor quality of research means a great deal of uncertainty prevails.”

Stavrou et al (2010) stated that hypertrophic and keloid scars still are among the banes of plastic surgery.  In the treatment arsenal at the disposal of the plastic surgeon, topical silicone therapy usually is considered the first line of treatment or as an adjuvant to other treatment methods.  Yet, knowledge concerning its mechanisms of action, clinical efficacy, and possible adverse effects is rather obscure and sometimes conflicting.  The author summarized the existing literature regarding the silicone elastomer's mechanism of action on scars, the clinical trials regarding its efficacy, a description of some controversial points and contradicting evidence, and possible adverse effects of this treatment method.  Topical silicone therapy probably will continue to be the preferred first-line treatment for hypertrophic scars due to its availability, price, ease of application, lack of serious adverse effects, and relative efficacy.  Hopefully, future RCTs will help to clarify its exact clinical efficacy and appropriate treatment protocols to optimize treatment results.

In a single-center placebo-controlled double-blind trial, Stoffels et al (2010) examined the impact of silicone spray on scar formation.  These investigators reported that after 3 months of treatment the Patient Scar Assessment Scale demonstrated that patient satisfaction with the silicone application was significantly higher compared to placebo.  However, when treatment was stopped after 3 months, the topical silicone spray did not exhibit any lasting long-term impact on the objective results of scar formation.

In a review on "Prevention and management of keloid scars", Lutgendorf et al (2011) noted that "[a]lthough silicone gel sheeting is a well-accepted treatment modality, the studies to date provide level IV evidence, with a lack of controls and increased susceptibility to bias.  A recent Cochrane systematic review on the use of silicone gel sheeting for preventing and treating hypertrophic and keloid scars found that any effects were obscured by the poor quality of research".

Several clinical trials have demonstrated the effectiveness of intralesional 5-fluorouracil in the treatment of keloid scarring (Asilian et al, 2006; Nanda and Reddy, 2004; and Manuskiatti and Fitzpatrick, 2002).  Asilian and colleagues (2006) examined the effectiveness of a combination of intralesional steroid, 5-fluorouracil (5-FU), and pulsed-dye laser in the treatment of hypertrophic scars and keloids.  A total fo 69 patients were randomly assigned to treatment with intralesional triamcinolone acetonide (TA), intralesional TA plus intralesional 5-FU, and TA, 5-FU and pulse-dye laser treatment.  The investigators reported that, after 12 weeks, good to excellent improvements were reported by a blinded observer in 15 % of subjects treated with TA alone, 40 % of subjects treated with TA plus 5-FU, and 70 % of subjects treated with all 3 modalities.

Tosa et al (2009) stated that because intralesional injection of TA, a widely used for the treatment of keloid, is painful, many patients discontinue treatment.  These researchers evaluated the effects of pre-treatment with topical 60 % lidocaine tape on the pain and tolerability of intralesional TA treatment in patients with keloid.  The subjects were 42 patients with keloid who had been treated with intralesional injection of TA but had discontinued treatment owing to intolerable pain.  All patients were pre-treated with 60 % lidocaine tape placed on the keloids for more than 120 mins before intralesional injection of TA.  Patients assessed pain with a 100-mm visual analog scale (VAS) with 0 mm for "no pain" and 100 mm for "worst possible pain".  Pain was assessed with the VAS immediately after TA injection.  Finally, the patients assessed the tolerability of this treatment.  The mean VAS score during intralesional TA injection therapy without pre-treatment with lidocaine tape was 82.6 +/- 14.4 mm.  In contrast, the mean VAS score during intralesional TA injection therapy in the same patients after pre-treatment with lidocaine tape was 18.9 +/- 11.3 mm, which was significantly lower (p < 0.05), and 30 (71.4 %) of the patients tolerated this therapy well.  Pre-treatment with 60 % lidocaine tape significantly reduces the pain associated with intralesional injection of TA.  This approach increases patient comfort and should enable patients to continue the treatment.

Pai and Cummings (2011) examined if surgical excision with or without adjuvant treatment beneficial in reducing the size of the scar in patients with hypertrophic and keloid scarring of the sternotomy wound.  More than 15 papers were found using the reported search, of which 9 represented the best evidence to address this clinical issue.  The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers were tabulated.  One of the studies showed no difference between surgery and adjunctive TA or colchicine.  One study showed that incomplete excision resulted in higher recurrence rates.  Post-operative radiation was found to be useful in 2 of the studies, although 1 study showed that it was not useful.  One RCT showed improvement after laser compared to no treatment; 2 other trials showed no difference between laser, silicone gel, intralesional steroid or 5-FU.  One trial showed that peri-operative systemic steroid application gave rise to no improvement but in fact worsened scar formation.  The authors concluded that small keloids can be treated radically by surgery with adjuvant therapy (radiation or corticosteroid injections) or by non-surgical therapy (corticosteroid injections, laser and anti-tumour/immunosuppressive agents, such as 5-fFU).  Large and multiple keloids are difficult to treat radically and are currently only treatable by multi-modal therapies that aim to relieve symptoms.

An UpToDate review on "Keloids" (Goldstein and Goldstein, 2012) states that "[i]ntralesional corticosteroids are first-line therapy for most keloids.  A systematic review found that up to 70 percent of patients respond to intralesional corticosteroid injection with flattening of keloids, although the recurrence rate is high in some studies (up to 50 percent at five years)".

Meshkinpour et al (2005) examined the safety and effectiveness of the ThermaCool TC radiofrequency system for treatment of hypertrophic and keloid scars and assessed treatment associated collagen changes.  Six subjects with hypertrophic and 4 with keloid scars were treated with the ThermaCool device: 1/3 of the scar received no treatment (control), 1/3 received one treatment and 1/3 received 2 treatments (4-week interval).  Scars were graded before and then 12 and 24 weeks after treatment on symptoms, pigmentation, vascularity, pliability, and height.  Biopsies were taken from 4 subjects with hypertrophic scars and evaluated with hematoxylin and eosin (H & E) staining, multi-photon microscopy, and pro-collagen I and III immunohistochemistry.  No adverse treatment effects occurred.  Clinical and H & E evaluation revealed no significant differences between control and treatment sites.  Differences in collagen morphology were detected in some subjects.  Increased collagen production (type III > type I) was observed, appeared to peak between 6 and 10 weeks post-treatment and had not returned to baseline even after 12 weeks.  The authors concluded that use of the thermage radiofrequency device on hypertrophic scars resulted in collagen fibril morphology and production changes.  ThermaCool alone did not achieve clinical hypertrophic scar or keloid improvement.  They noted that the collagen effects of this device should be studied further to optimize its therapeutic potential for all indications.

Davison et al (2006) ascertained the effectiveness of interferon alpha-2b in keloid management.  These investigators prospectively assessed the effects of interferon alpha-2b as post-excisional adjuvant therapy for keloids.  A total of 39 keloids in 34 patients were photographed, measured, and surgically excised.  The wound bed was injected twice with either interferon alpha-2b (treatment group; n = 13 keloids) or TA (control group; n = 26 keloids) at surgery and 1 week later.  The patients were followed- up in the plastic surgery clinic.  The trial protocol was terminated at mid-trial surveillance.  Among the 13 keloids that were treated with post-operative intralesional interferon alpha-2b, 7 recurred (54 % recurrence rate).  In contrast, in the 26 keloids that received TA (control group), only 4 recurred (15 % recurrence rate).  Recurrence in either group did not correlate with location of the keloid or race.  The authors concluded that interferon does not appear to be effective in the clinical management of keloids.  This finding is consistent with an earlier controlled trial which also found a lack of effectiveness of intralesional interferon alpha in the treatment of keloids (al-Khawajah, 1996).

Al-Attar et al (2006) reviewed the major concepts of keloid pathogenesis and the treatment options stemming from them.  They noted that mechanisms for keloid formation include alterations in growth factors, collagen turnover, tension alignment, and genetic and immunologic contributions.  Treatment strategies for keloids include established (e.g., surgery, steroid, radiation) and experimental (e.g., interferon, retinoid) regimens.  The authors concluded that combination therapy, using surgical excision followed by intra-dermal steroid or other adjuvant therapy, currently appears to be the most effective and safe current regimen for keloid management.

Sharma and colleagues (2007) compared the effectiveness of liquid nitrogen cryosurgery alone with liquid nitrogen cryosurgery plus intralesional TA combination in the treatment of keloids (n = 21; 60 clinically diagnosed lesions of keloids).  The statistical analysis showed synergistic action of cryosurgery and corticosteroids may offer promise in the treatment.  Karrer (2007) noted that keloids are a therapeutic challenge for dermatologists.  Although multiple therapeutic options are available, a reliably effective approach with few side effects remains elusive.  High quality research in evaluating the effectiveness of keloid therapy is also lacking.  This is in agreement with the findings of Durani and Bayat (2008) who reported that the level of evidence (LOE) of cryosurgery in the treatment of keloids is 4 (LOE-1 denotes highest quality while LOE-5 denotes lowest quality).

Berman et al (2008) evaluated the tolerability and efficacy of etanercept as compared to TA for the treatment of keloids.  A total of 20 subjects were randomly assigned to receive monthly intralesional injections of either 25 mg of etanercept or 20 mg of TA for 2 months.  Keloids were evaluated at baseline, week 4, and week 8 by subjects and investigators in a blinded fashion using physical, clinical, and cosmetic parameters.  Photographs were taken and adverse events were noted during each evaluation.  Etanercept improved 5/12 parameters including significant pruritus reduction, while TA improved 11/12 parameters at week 8, although no statistical difference was observed as compared to baseline.  There was no significant difference between the 2 treatment groups.  The authors concluded that etanercept was safe, well-tolerated, improved several keloid parameters, and reduced pruritus to a greater degree than TA therapy.  However, they noted that further studies are needed before it can be recommended for the treatment of keloids.

Berman (2010) stated that the potential of various biological agents to reduce or prevent excessive scar formation has now been evaluated in numerous in-vitro studies, experimental animal models and preliminary clinical trials, in some cases with particularly promising results.  Perhaps prominent among this group of biological agents, and, to some degree, possibly representing marketed compounds already being used "off label" to manage excessive scarring, are the tumor necrosis factor alpha antagonist, etanercept, and immune-response modifiers such as interferon-alpha2b and imiquimod.  The author noted that additional assessment of these novel agents is now justified with a view to reducing or preventing hypertrophic scars, keloid scars and the recurrence of post-excision keloid lesions.

In a meta-analysis, Anzarut et al (2009) evaluated the effectiveness of pressure garment therapy (PGT) for the prevention of abnormal scarring after burn injury.  Randomized control trials were identified from CINHAL, EMBASE, MEDLINE, CENTRAL, the "grey literature" and hand searching of the Proceedings of the American Burn Association.  Primary authors and pressure garment manufacturers were contacted to identify eligible trials.  Bibliographies from included studies and reviews were searched.  Study results were pooled to yield weighted mean differences or standardized mean difference and reported using 95 % confidence interval (CI).  The review incorporated 6 unique trials involving 316 patients.  Original data from 1 unpublished trial were included.  Overall, studies were considered to be of high methodological quality.  The meta-analysis was unable to demonstrate a difference between global assessments of PGT-treated scars and control scars [weighted mean differences (WMD): -0.46; 95 % CI: -1.07 to 0.16].  The meta-analysis for scar height showed a small, but statistically significant, decrease in height for the PGT-treated group standardized mean differences (SMD): -0.31; 95 % CI: -0.63 to 0.00.  Results of meta-analyses of secondary outcome measures of scar vascularity, pliability and colour failed to demonstrate a difference between groups.  The authors concluded that PGT does not appear to alter global scar scores.  It does appear to improve scar height, although this difference is small and of questionable clinical importance.  The beneficial effects of PGT remain unproven, while the potential morbidity and cost are not insignificant.  Given current evidence, additional research is needed to examine the effectiveness, risks and costs of PGT.

In a prospective, randomized, clinical trial, Xiao et al (2009) examined the effectiveness of intralesional botulinum toxin type A (BTX-A) injections in the treatment of hypertrophic scars.  A total of 19 patients were enrolled in this study.  At 1-month intervals, BTX-A (2.5 U per cubic centimeter of lesion) was injected in these patients for a total of 3 months.  All the patients were followed-up for at least half a year.  Therapeutic satisfaction was recorded, and the lesions were assessed for erythema, itching sensation, and pliability.  At the half-year follow-up visits, all the patients showed acceptable improvement, and the rate of therapeutic satisfaction was very high.  The erythema score, itching sensation score, and pliability score after the BTX-A injection all were significantly lower than before the BTX-A injection.  The differences all were statistically significant (p < 0.01).  The authors concluded that for the treatment of hypertrophic scars, doctors and patients both found BTX-A acceptable because of its better therapeutic results.  Its effect of eliminating or decreasing hypertrophic scars was promising.  The findings of this preliminary report need to be validated by further investigation.

In a randomized, double-blind, placebo-controlled trial using the reduction mammoplasty wound-healing model, van der Veer et al (2009) assessed the effectiveness of topical application of calcipotriol (a synthetic derivative of calcitriol or vitamin D) to healing wounds in preventing or reducing hypertrophic scar formation and investigated the biochemical properties of the epidermis associated with hypertrophic scar formation.  A total of 30 women who underwent bilateral reduction mammoplasty were included in this study.  For 3 months, scar segments were treated with either topical calcipotriol or placebo.  Three weeks, 3 months, and 12 months post-operatively, the scars were evaluated and punch biopsy samples were collected for immuno-histochemical analysis.  No significant difference in the prevalence of hypertrophic scars was observed between the placebo-treated and calcipotriol-treated scars.  Only scars with activated keratinocytes 3 weeks post-operatively became hypertrophic (p = 0.001).  The authors concluded that topical application of calcipotriol during the first 3 months of wound healing does not affect the incidence of hypertrophic scar formation.