Lasers in Surgery and Medicine 45:135–140 (2013) Treatment of Hypertrophic Scars Using Laser and Laser Assisted Corticosteroid Delivery Jill S. Waibel, MD,1 Adam J. Wulkan, BS,2 and Peter R. Shumaker, MD3 1 Miami Dermatology, Laser Institute, Miami, Florida 33173 2 University of Miami Miller School of Medicine, Miami, Florida 33136 3 Department of Dermatology Naval Medical Center, San Diego, California, 92134 Background and Objectives: Hypertrophic scars and contractures are common following various types of trauma and procedures despite skilled surgical and wound care. Following ample time for healing and scar maturation, many millions of patients are burdened with persistent symptoms and functional impairments. Cutaneous scars can be complex and thus the approach to therapy is often multimodal. Intralesional corticosteroids have long been a staple in the treatment of hypertrophic and restrictive scars. Recent advances in laser technology and applications now provide additional options for improvements in function, symptoms, and cosmesis. Fractional ablative lasers create zones of ablation at variable depths of the skin with the subsequent induction of a wound healing and collagen remodeling response. Recent reports suggest these ablative zones may also be used in the immediate post-operative period to enhance delivery of drugs and other substances. We present a case series evaluating the efﬁcacy of a novel combination therapy that incorporates the use of an ablative fractional laser with topically applied triamcinolone acetonide suspension in the immediate post-operative period. Methods: This is a prospective case series including 15 consecutive subjects with hypertrophic scars resulting from burns, surgery or traumatic injuries. Subjects were treated according to typical institutional protocol with three to ﬁve treatment sessions at 2- to 3-month intervals consisting of fractional ablative laser treatment and immediate post-operative topical application of triamcinolone acetonide suspension at a concentration of 10 or 20 mg/ml. Three blinded observers evaluated photographs taken at baseline and six months after the ﬁnal treatment session. Scores were assigned using a modiﬁed Manchester quartile score to evaluate enhancements in dyschromia, hypertrophy, texture, and overall improvement. Limitations: Small sample size and lack of a control arm. Results: Combination same session laser therapy and immediate post-operative corticosteroid delivery resulted in average overall improvement of 2.73/3.0. Dyschromia ß 2013 Wiley Periodicals, Inc. showed the least amount of improvement while texture showed the most improvement. Conclusion: Combination same-session therapy with ablative fractional laser-assisted delivery of triamcinolone acetonide potentially offers an efﬁcient, safe and effective combination therapy for challenging hypertrophic and restrictive cutaneous scars. Lasers Surg. Med. 45:135– 140, 2013. ß 2013 Wiley Periodicals, Inc. Key words: drug delivery systems; fractional laser; hypertrophic scar; scar therapy; triamcinolone acetonide; laser assisted delivery systems INTRODUCTION The unprecedented survival of individuals who sustain acute burns and other trauma both on and off the battleﬁeld has increased the necessity for effective modalities in the treatment and rehabilitation of patients [1]. Due to a complex interplay of factors such as injury mechanism and tissue tension, elevated levels of IL-4 and other procollagen cytokines may result in a net excess of collagen contributing to the newly formed hypertrophic scar [2]. Treating severe cutaneous scars is complex, and despite the best surgical care and adequate healing time, many millions of patients continue to have functional impairments and symptoms such as burning, itching, and pain. When treating hypertrophic scars, both functional and aesthetic improvement is the ultimate goal. Multiple therapeutic options have previously been described including surgical revision, laser therapy, pressure therapy, silicone The views expressed in this article are those of the authors and do not necessarily reﬂect the ofﬁcial policy or position of the Department of the Navy, Department of Defense, or the United States Government. Conﬂict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conﬂicts of Interest and none were reported. *Corresponding to: Jill S. Waibel, MD, Miami Dermatology & Laser Institute, 7800 SW 87th Avenue, Miami, FL 33173. Accepted 31 January 2013 Published online 4 March 2013 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/lsm.22120 136 WAIBEL ET AL. gel sheets, intralesional injections, pressure garments, and adjuvant topical drug treatments [3–8]. Successful outcomes have been achieved with vascular-speciﬁc lasers when treating severe hypertrophic scars [9–11]. Alster ﬁrst reported improvement after two treatments with pulsed dye lasers for hypertrophic surgical and traumatic scars. The authors also noted reductions in erythema, elevation, itching, and pain [12]. Fractional lasers were developed within the last decade and have mainly been applied to cosmetic indications such as the mitigation of rhytides [13,14]. However, there is increasing evidence that fractional lasers are an emerging therapeutic option for the aesthetic restoration and functional enhancement of traumatic scars at virtually any location on the body [14–18]. Fractional lasers create zones of ablation at variable depths determined by the treatment settings. The unique fractional injury induces a molecular cascade including heat shock proteins and other factors that lead to a rapid healing response and prolonged neocollagenesis with subsequent collagen remodeling [14]. The mechanism of improvement after ablative fractional laser therapy therefore likely includes the removal of a portion of ﬁbrotic scar and a relative normalization of collagen structure and composition [19]. Intralesional steroid injections are a well-recognized treatment for hypertrophic scars. The procedure involves a uniform injection of 10–40 mg/ml of triamcinolone acetonide suspension with a 25- to 27-gauge needle [20]. One of the long-standing challenges of using intralesional corticosteroid for scar therapy is precise placement of the drug to avoid adverse sequelae such as fat atrophy. In their report on management of hypertrophic scars and keloids, Mustoe et al. [21] noted a recurrence rate of 45– 100% with surgery alone and less than 50% when surgery was combined with corticosteroid injection. Effective topical delivery of any pharmaceutical agent requires the ability to penetrate the epidermis. Fractional laser therapy creates precise, uniform columns of tissue vaporization which in theory might help to facilitate drug delivery past the epidermal barrier. Haedersdal et al. [22] demonstrated this concept in an animal model, noting enhanced uptake of topical methyl 5-aminolevulinate after ablative fractional laser treatment. In this case series, we evaluated the feasibility and efﬁcacy of same-session ablative fractional laser therapy combined with enhanced topical corticosteroid delivery. Potential beneﬁts include the introduction of a simple, cost-effective strategy to combine two valuable scar therapies and possibly create a synergistic therapeutic response. MATERIALS AND METHODS Subject Population A total of 15 consecutive subjects with hypertrophic scars resulting from burns, surgical, or other traumatic injuries present for at least one year were included (Table 1). Written informed consent was obtained from each patient. Patients were not considered for combination treatment in the setting of pregnancy, breastfeeding, oral retinoids 6 months prior to treatment, active infection, or lesions suspicious for malignancy. Study Design This was a prospective case series conducted to evaluate the efﬁcacy of fractional ablative laser followed by topical triamcinolone acetonide suspension (10 or 20 mg/ml) as a treatment option for severe hypertrophic scars. The chosen concentration of triamcinolone acetonide was dependent on the location and thickness of the scar. Larger TABLE 1. Demographics and Clinical Characteristics of Each Patient Skin Number Age Gender type Type of scar Age of scar (years) 1 2 3 42 42 28 Female Female Female 2 2 2 Hypertrophic burn scar Hypertrophic burn scar Hypertrophic burn scar 22 22 5 4 17 Female 5 Traumatic keloid scar 5 6 22 25 Female Female 2 3 Burn scar Acne keloid scar 21 15 7 8 9 10 11 12 13 14 15 52 42 52 22 22 28 48 23 40 Female Female Female Male Female Female Male Male Female 4 2 2 2 2 3 5 2 3 Hypertrophic burn scar Hypertrophic burn scar Traumatic atrophic scar Erythematous burn scar Mesh graft scar Hemangioma residual scar Acne keloid scar Hypertrophic burn scar Surgical scar 7 22 5 5 21 27 14 4 3 4 Laser type Fractional ablative CO2 3 Fractional ablative CO2 3 Fractional ablative CO2, fractional non-ablative 3 Shave excision and fractional ablative CO2 3 Fractional ablative CO2 3 Shave excision and fractional ablative CO2 3 PDL and fractional ablative CO2 4 Fractional ablative CO2 3 PDL and fractional ablative CO2 3 PDL and fractional ablative CO2 3 Fractional ablative CO2 3 Fractional ablative CO2 2 Fractional ablative CO2 4 Fractional ablative CO2 3 Fractional ablative CO2 3 Kenalog strength (mg) 10 10 20 10 10 10 10 10 10 10 and 40 10 10 10 20 10 TREATMENT OF HYPERTROPHIC SCARS scars in locations of thicker skin, such as the back, would generally receive 20 mg/ml, while scars with a lesser degree of hypertrophy on thinner skin would receive 10 mg/ml. Each subject received a course of three to ﬁve combination treatments at 2- to 3-month intervals. Anesthesia was achieved with a topical anesthetic gel containing 20% benzocaine, 8% lidocaine, and 4% tetracaine for 1–2 hours prior to the procedure. This was followed by fractional ablative carbon dioxide (CO2) laser treatment (Ultrapulse Encore, Deep FX, Lumenis, Inc., Yokneam, Israel) over the entire scar sheet. Three of the patients also received pulsed dye laser treatment for erythema prior to the fractional treatment. Settings were customized for each patient at each treatment session according to estimated scar thickness. Pulse energies ranged from 12.5 to 20 mJ at a treatment density of 10–15%. Within 2 minutes of fractional laser treatment, a thin layer of triamcinolone acetonide suspension was drizzled over the site and rubbed gently over the ablated columns. Post-Treatment Care After treatment, the treatment areas were cooled with ice packs for 10 minutes. Occlusive dressings were not applied. Patients were instructed to perform acetic acid soaks and use a moisturizer three times a day for several days until healed. Patients were also directed to apply a physical sunscreen and avoid sun exposure while the study was in progress. Clinical Assessment To assess scar response, three blinded observers evaluated photographs taken both at baseline and at 6 months following the ﬁnal therapy session. Photographs were obtained using identical camera settings, lighting conditions, and patient positioning (Nikon D300, 13.1 million total pixels, 12.3 million effective pixels). First, observers determined which photograph was ‘‘before’’ and ‘‘after.’’ They subsequently evaluated the improvements in overall appearance, dyschromia, degree of hypertrophy, and texture using a quartile scale. The following four-point scale was utilized: 0 for <25% improvement, 1 for 25–50% improvement, 2 for 50–75% improvement, 3 for >75% improvement. In no case did the observer order the before and after photographs incorrectly. For each patient, scores in each category were averaged to assign an overall score. 137 Fig. 1. Average improvement scoring for overall, texture, dyschromia, and hypertrophy as determined by three blinded investigators at 6 months post-treatment. overall improvement score by a subject was 3.00, which 11 of 15 patients attained (Fig. 2). Texture Of the 15 patients with hypertrophic scars, 12 patients received the highest possible texture improvement score of 3.00 by all blinded observers. The remaining three patients obtained an average improvement between 2.00 and 2.49. The range for average texture improvement was between 2.33 and 3.00. The mean improvement in texture was 2.84. Hypertrophy The mean improvement for scar hypertrophy was 2.76 with a range from 1.67 to 3.00. Eleven patients earned an average score of 3.00 out of 3.00. One patient received an average score of 1.50–1.99, two patients an average score of 2.00–2.49, and one patient a score of 2.50–2.99. Dyschromia The average improvement score for dyschromia was 2.36, with a range of 0.67–3.00. One patient earned a score between 0.50 and 0.99. One earned a score between 1.00 and 1.49, six between 2.00 and 2.49 and seven subjects earned the highest score of 3.00. RESULTS The observers accurately determined the pre- and postphotographs 45 out of 45 times. Of the four improvement parameters measured, texture received the highest improvement score, while dyschromia displayed the least numeric improvement. Each category assessed achieved an average improvement of greater than 2, corresponding to an improvement of greater than 50% (Fig. 1). Overall The overall average score assessed by the three-blinded observers was 2.73 on a 0–3 scale. The highest average Fig. 2. Overall response to treatment averaged by three blinded investigators at 6 months post-treatment. 138 WAIBEL ET AL. Fig. 3. Before and 6 months after Laser Assisted Delivery Systems Treatment using triamcinolone acetonide for hypertrophic burn scar. A: Twenty-eight-year-old female (patient number 3 in Table 1) patient at initial presentation of a 5-year-old hypertrophic contracture scar sustained from house ﬁre. Patient had severely decreased range of motion in wrist joint. Treated with three treatments of non-ablative fractional followed by two treatments of ablative fractional laser 20 mJ with 10% density and topical triamcinolone acetonide 20 mg/ml immediately after the fractional ablative laser. B: Six months after ﬁve laser and triamcinolone acetonide sessions showing decrease in hypertrophy and improvement of dyschromia. Patient also reported increased range of motion in wrist doing activities of daily life. Most subjects experienced mild to moderate erythema and edema immediately post-treatment; no subjects experienced severe pain, erythema or edema after any treatment. Treatments were well-tolerated and no adverse effects were reported (Figs. 3–5). DISCUSSION Treatment of severe cutaneous scars can be complex and often requires a multimodal approach to therapy. Intralesional corticosteroids have been a mainstay in the treatment of hypertrophic scars for decades, leading to improvements through a variety of mechanisms including Fig. 4. Before and 6 months after Laser Assisted Delivery Systems Treatment using triamcinolone acetonide for hypertrophic mesh graft scar. A: Twenty-two-year-old female (patient number 11 in Table 1) after burn ﬁre in home as a child. Acute therapy included debridement and mesh graft at time of injury as a toddler. Photo is during initial consultation for erythematous, hypertrophic burn scar. Scar was 21 years old at the time of consultation. Patient underwent three treatments of fractional ablative laser 15 mJ with 15% density followed by topical triamcinolone acetonide 10 mg/ml immediately after the fractional ablative laser. B: Six months after three fractional ablative laser treatments and triamcinolone acetonide with decreased erythema and improved texture. Mesh graft pattern smoother after laser and triamcinolone acetonide treatment. diminished collagen synthesis and increased collagen degradation [20]. The advent of fractional laser technology within the last decade has signiﬁcantly increased potential treatment options for patients with disﬁguring and disabling scars [15–18]. The results of our series indicate that combination same-session therapy with laser and laser-assisted delivery of triamcinolone acetonide offers TREATMENT OF HYPERTROPHIC SCARS Fig. 5. Before and 6 months after Laser Assisted Delivery Systems Treatment using triamcinolone acetonide. A: Twenty-ﬁve-year-old female (patient number 6 in Table 1) developed spontaneous keloid scars in central chest during puberty after acne eruption. No prior treatment. Patient had pruritus and pain with keloid. Patient underwent three fractional ablative laser treatments 17.5 mJ with 10% density followed by topical triamcinolone acetonide 10 mg/ml immediately after the fractional ablative laser. Lower right and left periphery of scars had shave excision. B: Six months after laser and triamcinolone treatments with ﬂattening of scar. Some tension remains in the central zone which may be addressed with z-plasty surgical reconstruction. efﬁcient, safe, and effective treatment of challenging hypertrophic cutaneous scars. Various aspects of scar assessment such as texture, hypertrophy, and dyschromia were all positively impacted by combination therapy. Ablative fractional laser-assisted corticosteroid delivery may take advantage of the newly formed channels to penetrate uniformly and deeply into dermal scars. Furthermore, injection of triamcinolone acetonide is often painful and consistent dosing is difﬁcult to achieve throughout the scar. In contrast, topical application of triamcinolone acetonide after fractional resurfacing is painless and may be applied with greater uniformity. To our knowledge, this is the ﬁrst case series in the literature evaluating the efﬁcacy of this combination technique in the treatment of hypertrophic scars. While the results of this series are promising, there are signiﬁcant limitations that must be considered. The lack of a control makes it impossible to ascribe synergistic beneﬁts to the combination treatment over the individual treatments alone. However, the results of this series compare favorably with the experience of the 139 authors in both the rapidity and degree of improvement over the individual modalities. Further investigation including prospective controlled trials will certainly be required to determine if same-session combination fractional laser and topical corticosteroid therapy is more effective compared to either modality alone, as well as to determine other variables such as optimal laser settings and drug dosing. One exciting potential application of fractional ablative laser technology is the ability to deliver drugs and other bioactive agents to patients via channels of a predetermined depth into cutaneous tissue. Current ablative fractional laser devices have a signiﬁcant beneﬁt in being tunable and thus creating channels of a predetermined depth and density. Previous histologic studies in normal skin have documented complete re-epithelialization within 48 hours after ablative fractional CO2 laser treatment [23]. The preference of the authors is to apply the triamcinolone within 2 minutes of fractional treatment at the earliest phases of the inﬂammatory cascade. Capillary action likely facilitates the passage of the triamcinolone acetonide suspension through the channels without the need for an occlusive dressing. We have termed this mode of delivery laser assisted delivery systems, or LADS. While this study utilizes triamcinolone acetonide as the agent taking advantage of the microscopic treatment zones created by the laser, this technique holds promise not only for scar treatment but for a multitude of disorders using cell and drug based approaches. REFERENCES 1. Klein MB, Donelan MB, Spence RJ. Reconstructive surgery. J Burn Care Res 28: 2007; 602–606. 2. Kwon SD, Kye YC. Treatment of scars with a pulsed Er:YAG laser. 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