Treatment of Surgical Scars Using a 595-nm Pulsed Dye Laser Using Purpuric and Nonpurpuric Parameters: A Comparative Study JULIE AKIKO GLADSJO, MD, PHD,

AND

SHANG I. BRIAN JIANG, MD*

BACKGROUND Many studies have examined laser treatment of scars, but cosmetic results have been variable. Although no studies have examined the effect of purpura on scar improvement using the pulsed dye laser (PDL), many clinicians believe inducing purpura results in better and quicker improvement. OBJECTIVE To determine whether PDL treatment of fresh surgical scars with purpura-inducing settings improves clinical appearance more than non-purpura-inducing settings or no treatment. METHODS Twenty-six subjects with surgical scars enrolled in this prospective study. Scars were divided into three equal segments; treatment was randomized: 595-nm PDL with purpuric (1.5 ms) or nonpurpuric (10 ms) settings or no treatment. Fluences were adjusted to Fitzpatrick skin type. Scars were treated three times, 1 month apart, beginning at suture removal. Outcome measures included Vancouver Scar Scale (VSS) and blind clinical ratings. RESULTS The nonpurpuric condition showed significant improvement on the VSS total score, vascularity, and pliability ratings. The purpuric condition demonstrated a trend for improvement on the VSS total. According to blind observer ratings, all conditions improved, without differences between groups. CONCLUSION Nonpurpuric settings on the PDL resulted in significant improvements in the appearance of fresh surgical scars for vascularity, pliability, and VSS total scores, although all scar segments improved over time. The authors have indicated no significant interest with commercial supporters.

S

cars are an unavoidable consequence of the work of dermatologic surgeons. Although surgical scars rarely cause functional impairment, patients are sometimes unhappy with the perceived disfigurement, which may result in dissatisfaction with their doctor and decrease quality of life. Although the phases and pathophysiology of the wound healing process are beginning to be understood,1 it is still not known why some scars develop into keloid, hypertrophic, or atrophic scars. Aside from basic interventions such as avoidance of postoperative wound infections and good surgical technique to reduce tension across wounds, there is a

lack of evidence of factors that will reliably improve the likelihood of a good cosmetic outcome.2 Consequently, many treatments have been tried to minimize the appearance of scars, including topical and intralesional steroids, silicone gel sheeting, radiation, 5-fluorouracil, and cryosurgery. This abundance of treatments indicates that no available treatment effects a reliable improvement in scar appearance. Several recently published reviews have examined the efficacy of these interventions and found that even widely used methods such as intralesional steroids have little support based on

*Both authors are affiliated with the Division of Dermatology, Department of Medicine, University of California at San Diego, San Diego, California © 2013 by the American Society for Dermatologic Surgery, Inc.  Published by Wiley Periodicals, Inc.  ISSN: 1076-0512  Dermatol Surg 2014;40:118–126  DOI: 10.1111/dsu.12406 118

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controlled clinical trials.2–4 The Cochrane group recently evaluated scar treatment methods and concluded that the evidence for most interventions was poor, with silicone gel bandages having the best, albeit weak, support.5 Researchers began in the mid-1980s to examine the use of lasers in the treatment of scars, especially for keloids,6 hypertrophic surgical scars,7 and burn scars.8 Results of these studies have been mixed at least in part because of differences in the lasers and treatment settings used.9 Laser treatment is based on the principle of selective thermolysis, in which heat is created in the skin when certain chromophores preferentially absorb light.10 The pulsed dye laser (PDL) has emerged as the safest, most-effective laser for treating vascular lesions such as port wine stains, telangiectasias, and hemangiomas. It also appears to benefit scars of various etiologies, with significant long-term reductions in erythema, rigidity, and pruritus.11 Oxyhemoglobin absorbs wavelengths of 585– 600 nm, which penetrate approximately 1.2 mm into the skin. Larger spot sizes allow deeper penetration so that deeper vessels may be targeted. Immediate post-treatment purpura results from microvascular hemorrhage, thrombosis, and capillary destruction when short pulse durations are used. This purpura can generally be avoided with longer pulse durations because immediate vessel rupture is avoided, although late-appearing purpura may occasionally occur. Five recently published reviews2,11–14 evaluated the use of lasers for the treatment of scars and keloids. Although the reviewed studies varied widely in the chronicity of scars treated, the scientific rigor of the research design, and the laser parameters used, in general, the authors concluded that most evidence supported the use of the PDL for treating keloids and hypertrophic scars, with at least moderate efficacy. Improvements in scar erythema, pliability, thickness, and pruritus were reported in a number of studies, and only minor adverse reactions were noted. The mechanism by which the PDL exerts its effects on scars is not yet known. It has been postulated that the

PDL acts through selective destruction of small vessels that feed the scar fibroblasts, through direct collagenolysis, with heat causing breakdown of disulfide bonds, or indirectly through impaired cellular function, induction of apoptosis, or increase in p53 expression,15 but no mechanism has been proven. A recent in vitro study showed that keloid fibroblasts express higher levels of transforming growth factor-beta (TGF-b), especially isotypes 1 and 2, than normal skin, and another study showed that expression of TGF-b1 was significantly lower in keloids after PDL treatment.16 This decrease in TGF-b1 has been shown to be associated with upregulation of matrix metalloproteinase-13, less fibroblast proliferation, and less collagen III deposition.16 Because it is not possible to predict reliably which scars will hypertrophy or have a poor cosmetic outcome, most clinicians would prefer to take a preventative approach, so a number of researchers have examined the use of prophylactic treatment with PDL to prevent the development of hypertrophic scars. Although the initial studies were uncontrolled and varied in treatment parameters used, the results were suggestive of better cosmesis, less stiffness, and flatter scars.17 Only one of the recent reviews of laser treatment of scars focused specifically on active scar prevention.18 These authors concluded that laser energy applied during the early phase of healing exerts a beneficial effect on the resulting scars, although they did not identify the optimal treatment parameters. The six active laser prevention studies can be categorized according to whether the laser treatment would be expected to cause post-treatment purpura. These studies are summarized in Table 1. In the context of the present study, it is helpful to examine their results according to the treatment parameters used. Of those using clinically nonpurpuric laser settings, the fluences were of lower energy levels. All of these nonpurpuric studies found significantly greater improvements in scar appearance than under their control conditions. The three studies using higher-energy purpuric parameters had more

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TABLE 1. Pulsed Dye Laser (PDL) Treatment of Fresh Surgical Scars

Author

N

Wavelength, nm

High energy, purpuric 29* 585 Chan 19 et al.,

Treatments, n

Fluence, J/cm2

Pulse Duration, ms

Spot Size, mm

3–6

7–8

1.5

5

No

Cryocooling

Alam et al.,20

17

595

1

7

1.5

7

Yes

Conologue et al.,21

13

595

3

8

1.5

7

Yes

3

3.5

0.45

10

No

10

No

7

No

Low energy, nonpurpuric 11 585 Nouri et al.,22

Nouri et al.,23

14

585/595

3

3.5

0.45

Nouri et al.,24

20

585

3

4

0.45/1.5

Author Conclusions PDL had no significant improvement on scars < 6 months old No significant improvement with PDL PDL associated with significant differences in VSS total, vascularity, pliability, cosmetic appearance PDL associated with significant differences in VSS total, vascularity, pliability, cosmetic appearance Trends for improvement with PDL (control segment always in center of scar) Both pulse durations better than control, but PDL conditions did not differ

*Scars could be up to 6 months postoperative.

variability in subject populations and study conditions. For example, the study by Alam and colleagues20 administered only a single laser treatment. Unlike the other five studies of fresh surgical scars, the Chan study19 defined their “prevention” group as including surgical scars .36). One month after the final laser treatment, there was a trend toward a significant difference between groups on the VSS total score, with the nonpurpuric segments rated as better than the control and purpuric groups, which did not differ in their scores (v2 = 5.77, df = 2, p = .06). On global cosmetic outcome, according to the blind observer, all three conditions significantly improved over time (purpuric v2 = 26.40, non-purpuric v2 = 26.86, & control v2 = 26.03, df = 3, p < .001). Additional analysis was conducted to examine the effect of segment location on scar ratings. As predicted, in the untreated control condition, the central segment was rated significantly worse in appearance for VSS total and vascularity than the lateral segments (6-week v2 = 6.92, 10 week v2 = 5.03, df = 1, p < .03; Figure 4), although this was true for the untreated control segments only, suggesting that laser treatment had an effect, albeit not statistically significant.

As expected, there were significant differences between groups in terms of subjective pain reported. At the 10-week follow-up, the purpuric condition was rated significantly more painful than the nonpurpuric condition (v2 = 30.19, df = 2, p < .001). Subjects did not report any complications or adverse events, although one subject developed a slightly spread atrophic scar (which the VSS does not capture). No scars developed hypertrophy or keloids. As expected, the purpuric treated segments developed transient purpura.

Discussion The daily work of dermatologic surgeons inevitably results in the production of scars. Our goal is to create the most cosmetically acceptable outcome. To this end, numerous interventions have been tried to improve and minimize existing hypertrophic scars, keloids, and other unacceptable results. More recently, the focus has turned to using prophylactic interventions to facilitate optimal outcomes, instead of intervening only after a poor cosmetic outcome has occurred, but the factors that contribute to a poor scar result are not completely understood, and therefore it is difficult to determine how best to intervene. Neovascularization is known to play a role in normal wound healing and in the development of

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hypertrophic scars. Therefore, PDL, which has demonstrated success in treatment of vascular lesions, is a logical candidate for scar treatment. It has reportedly been useful in improving the appearance of fresh and longstanding surgical, burn, and hypertrophic scars. Based on experience with vascular lesions such as port wine stains, many physicians have assumed that use of purpuric parameters would be more effective than nonpurpuric settings for treating scars. We sought to test this hypothesis and to determine whether PDL treatment would result in better cosmetic outcomes than no treatment. Using the VSS, a standard rating scale of scar appearance, we found a significant effect of better cosmetic outcome over time using nonpurpuric long pulse duration settings than with purpuric settings and no treatment, which did not differ. Although this may seem surprising, it confirms the results of several other studies that used PDL with lowerenergy nonpurpuric parameters and showed significant improvements in scar appearance.22–24 At the final evaluation visit, there was a trend toward a significant difference between groups in VSS total score, with the nonpurpuric segments rated as better than the other conditions, although all scar segments improved over time, whether treated or not, when evaluated using global cosmetic ratings. An examination of the VSS subscales revealed that, similar to other PDL studies, the change in scar appearance associated with nonpurpuric treatment was due primarily to changes in vascularity and pliability. There was a nonsignificant trend of improvement in the purpuric condition in vascularity. No subject developed a keloid or hypertrophic scar during the study period, so it is not surprising that the VSS subscale assessing scar height showed no differences between groups at any time point. Likewise, only minimal pigmentary changes were noted. Significant differences in subjective pain rating were noted between the two laser conditions,

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with purpuric settings rated as more painful than nonpurpuric. Because the central segment of the scar is subject to the strongest pulling forces, we were concerned that segment location might exert an effect greater than that of the laser. For this reason, we examined the effect of location on scar ratings. As expected, central segments were rated as significantly worse in appearance on the VSS total and vascularity subscale, although for untreated control segments only. Being randomized to the central location did not appear to affect ratings of the PDL treated conditions, which suggests that PDL treatment somehow mitigated the unfavorable effects of the highesttension location. Evaluating the results of this study in the context of other similar published studies provides further evidence supporting the use of PDL with nonpurpuric settings. Although study designs varied, the three studies using lower-energy nonpurpuric parameters (3.5–4 J/cm2) all found significant differences between the laser-treated and untreated conditions, although only one of the three studies using higher-energy purpuric settings (7–8 J/cm2) found such a difference. Although the lack of a significant difference may have been attributable to other variables, evidence is accumulating that suggests that nonpurpuric settings are superior for treating surgical scars, although the underlying mechanism is unknown. Paradoxically, the fact that virtually all of the scars healed well over a 4-month period, without complications, was a limitation of the current study. This reduced the variability in outcomes that would be necessary to detect an effect of the laser. When all scars heal well without treatment, it is difficult to detect the effect of intervention. In addition, the choice of the VSS as our main outcome measure may well have been a limitation of the study. Although the VSS is widely used, it is less useful in a population that includes no hypertrophic scars or keloids. It also is limited in its ability to capture data

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on atrophic or fishmouth type scars. Finally, although our study of PDL treatment of fresh surgical scars includes the largest number of subjects to date, it is still a small study. It is possible that a larger study group and greater power would have resulted in more significant findings. In conclusion, consistent with previously published studies, we found evidence that the PDL, especially using a nonpurpuric (10 ms) pulse duration is helpful for improving the vascularity and pliability of fresh surgical scars. It appeared to be more beneficial than purpuric (1.5 ms) settings at the same fluence. No adverse events were noted. This finding has clinical utility, because patients generally prefer treatments that have the shortest downtime and fewest side effects. Although all scars improved over time, whether treated or not, indirect evidence from the analysis of scar segment location further supported the conclusion that prophylactic PDL treatment improved cosmetic outcome. Our results also reinforce the importance of randomizing location in treatment comparison studies. When treatment effects are subtle, or less than robust, tension forces at the center of a scar may overwhelm the treatment effect.

Acknowledgments We thank Dr. E. Victor Ross for his input on the design of our study. We also appreciate the statistical advice and expertise of Lea Vella, who performed the data analysis. Appendix 1 Vancouver Scar Scale Pigmentation 0 = Normal color (resembles nearby skin); 1 = Hypopigmentation; 2 = Hyperpigmentation.

Pliability 0 = Normal; 1 = Supple (flexible with minimal resistance); 2 = Yielding (giving way to pressure); 3 = Firm (solid/inflexible, not easily moved, resistant to manual pressure); 4 = Banding (rope-like, blanches with extension of scar, does not limit range of motion); 5 = Contracture (permanent shortening of scar producing deformity or distortion; limits range of motion). Height (mm) 0 = Normal (flat); 1 = 2 and 5 mm.

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Vascularity

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0 = Normal; 1 = Pink; 2 = Red; 3 = Purple.

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20. Alam M, Pon K, Van Laborde S, Kaminer MS, et al. Clinical effect of a single pulsed dye laser treatment of fresh surgical scars: randomized controlled trial. Dermatol Surg 2006;32:21– 5. 21. Conologue TC, Norwood C. Treatment of surgical scars with the cryogen-cooled 595 nm pulsed dye laser starting on the day of suture removal. Dermatol Surg 2006;32:13–20. 22. Nouri K, Jimenez GP, Harrison-Balestra C, Elgart GW. 585-nm pulsed dye laser in the treatment of surgical scars starting on the suture removal day. Dermatol Surg 2003;29:65–73. 23. Nouri K, Rivas MP, Stevens M, Ballard CJ, et al. Comparison of the effectiveness of the pulsed dye laser 585 nm versus 595 nm in the treatment of new surgical scars. Lasers Med Sci 2009;24:801–10. 24. Nouri K, Elsaie ML, Vejjabhinanta V, Stevens M, et al. Comparison of the effects of short- and long-pulse durations when using a 585 nm pulsed dye laser in the treatment of new surgical scars. Lasers Med Sci 2010;25:121–6.

Address correspondence and reprint requests to: Shang I. Brian Jiang, MD, 8899 University Center Lane, Suite 350, MC 0975, San Diego, California 92122, or e-mail: [email protected]

Treatment of surgical scars using a 595-nm pulsed dye laser using purpuric and nonpurpuric parameters: a comparative study.

Many studies have examined laser treatment of scars, but cosmetic results have been variable. Although no studies have examined the effect of purpura ...
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