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 medically necessary for treatment of keloids where medical necessity criteria for keloid removal are met. See CPB 031 - 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:

• interferon alpha (see CPB 404 - Interferons)
• radiofrequency treatment
• topical retinoids

See also CPB 062 - Burn Garments, CPB 244 - Wound Care, CPB 551 - Radiation Treatment of Keloids, and CPB 559 - 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 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 clinical trials. Prospective randomized controlled clinical trials 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 a prospective, single-blind, randomized, controlled study, 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 Food and Drug Administration (2004) classified silicone sheeting intended for use in the management of closed hyperproliferative (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 & 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.”

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

Meshkinpour and associates (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 two 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 triamcinolone (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 triamcinolone (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 intradermal 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 triamcinolone acetonide 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).