Eur J Dermatol 2015; 25(2): 122-6
Therapy Nicola L. SCHOENEWOLF Jürg HAFNER Reinhard DUMMER Inja BOGDAN ALLEMANN University Hospital Zürich, Department of Dermatology, Gloriastr. 31 8091 Zürich, Switzerland
Reprints: I. B. Allemann
Article accepted on 12/12/2014
L
Laser treatment of solar lentigines on dorsum of hands: QS Ruby laser versus ablative CO2 fractional laser – a randomized controlled trial Background: Lentigines solares (LS) on the dorsum of hands are often esthetically disturbing. Q-switched ruby laser treatment is highly effective in the treatment of these lesions. Ablative fractional photothermolysis may be a suitable alternative. We compared the Q-switched ruby laser with ablative CO2 fractional photothermolysis for the treatment of solar lentigines. Objective: To evaluate the efficacy and side-effects of 694nm Q-switched ruby laser (Sinon) with the ablative 10,600nm CO2 fractional laser (Quantel Excel O2) in an intra-individual side-to-side comparison in the treatment of LS on the dorsum of hands. Material and methods: Eleven patients were included in the study. The hands of each patient were randomized for treatment with the two laser systems. Three treatment sessions were scheduled at weeks 0, 4 and 8. Evaluations by patients, treating physician and blinded experts were scheduled at weeks 0, 4, 8, 16 and 24. Results: The Q-switched ruby laser was significantly more efficacious than the ablative CO2 fractional laser for removing LS on the dorsum of hands (p = 0.01). Conclusion: In this first study on this topic, the Q-switched ruby laser was superior to the ablative CO2 fractional laser in the treatment of lentigines solares on the dorsum of hands. Key words: lentigines solares, Q-switched ruby laser, CO2 fractional laser
122
(532 nm), Q-switched ruby (694 nm), Q-switched Alexandrite (755 nm), Q-switched Nd:YAG (1064 nm), CO2 (10,600 nm), and Argon (488-630 nm) diode lasers have been under investigation for the treatment of lentigines solares. All available Q-switched (QS) lasers have been demonstrated to be safe and efficacious in the treatment of lentigines [7] and produce excellent results [8]. With the Q-switched lasers in general, only one to two treatment sessions are necessary in order to achieve a satisfactory treatment response. With its wavelength of 694 nm, pulse durations between 25-40 nanoseconds (ns) and average fluences of 3-10J/cm2 , the Q-switched ruby laser has proven effective in the treatment of pigment disorders, even in light solar lentigines [9-15]. Depending on the skin type and level of fluence applied, the degree of unwanted postinflammatory hyperpigmentation may change [16]. The concept of fractional photothermolysis was introduced in 2003 [17]; by 2007 the technology was further developed with ablative wavelengths. In treatment, a multitude of drill hole-shaped microscopic ablation zones (MAZ) are induced into the skin in a regular, sieve-like pattern. Histologically, the treatment leads to a disrupted stratum corneum, a cylindrical central ablation zone lined by a thin eschar layer, followed by a coagulation zone embedded in the unharmed surrounding tissue. Re-epithelialization, starting from the vital tissue surrounding each damaged zone, occurs rapidly. As for non-ablative fractional EJD, vol. 25, n◦ 2, March-April 2015
To cite this article: Schoenewolf NL, Hafner J, Dummer R, Bogdan Allemann I. Laser treatment of solar lentigines on dorsum of hands: QS Ruby laser versus ablative CO2 fractional laser – a randomized controlled trial. Eur J Dermatol 2015; 25(2): 122-6 doi:10.1684/ejd.2014.2513
doi:10.1684/ejd.2014.2513
entigines solares (LS) are sharply demarcated hyperpigmented macules on photoaged skin. They are also called senile lentigines, senile freckles or age spots. Usually, they can be found on chronically sunexposed areas such as the face, neck and back of the hands. Their number increases with age. Typically, there are multiple lesions. In the age group > 50 years, 90% have LS [1]. These UV-induced hyperpigmentations have no oncogenic potential and do not require medical intervention. However, often they are cosmetically disturbing, hence patients request removal. Nitrogen cryotherapy is considered the standard treatment for solar lentigines, based on the guidelines by the “Pigmentary Disorders Academy” published in 2006 [2]. Although cryotherapy has shown good results, patients complain about discomfort during the treatment and unwanted hypopigmentation as a side effect [3, 4]. A recent study by Hexsel et al. showed a reduction of these adverse effects by combining the cryotherapy with a triple combination cream [5]. Histologically, there is an increased number of pigment granules in the keratinocytes and the condensed stratum corneum [6]. In order to approach the increased melanin content therapeutically, the broad absorption capacity of this chromophore (351-1064 nm), has led to an orientation towards laser assisted treatment of lentigines solares [2]. Since the 1960s, a great multitude of different lasers, such as the pulsed dye (595 nm), frequency-doubled Nd:YAG
photothermolysis, the formation of Microscopic Epidermal Necrotic Debris (MEND) can be observed, which has been shown to contain melanin, elastic tissue and other dermal contents [18]. This is the reason why lightening of pigmentation can be expected upon treatment with ablative fractional photothermolysis, as was shown by Gotkin et al.[19]. So far, no clinical studies are available comparing the efficacy and side-effects of the CO2 ablative fractional laser with the Q-switched sinon ruby laser to remove LS on the dorsum of hands. Therefore, we designed and conducted a prospective randomized split-hand trial over a period of six months – to our knowledge, the first study comparing these technologies.
of 5 J/cm2 , spot size diameter of 3 mm, and frequency of 2 Hz). Immediately after treatment, the treated area was cooled with a cool pack and thereafter Ialugen cream was applied (Natrii hyaluronas, BSA Institut Biochimique SA, Lugano, Switzerland). Patients were instructed to apply Ialugen cream twice daily until the disappearance of crusts. They were furthermore instructed to apply sun blocker (SPF 50) daily and avoid sun exposure of the treated areas throughout the entire study.
Follow up Two follow up visits were performed at weeks 16 and 24.
Assessment of treatment outcome
Patients and methods Patient selection Inclusion criteria: Patients presenting with symmetrically localized hyperpigmentations on both dorsal hands, clinically and dermatoscopically diagnosed as lentigines solares, qualified for inclusion in this study. Additionally, all patients had to provide written informed consent and to agree to the protocol. The study was approved by the local ethics committe, Zurich, Switzerland (Project number 730, 2009). Exclusion criteria: Pregnant or breast-feeding women, patients taking light-sensitizing drugs (including systemic retinoids up to 6 months prior to the study), patients who had undergone other treatments of the lentigines solares six months prior to the study (including topical depigmentation creams such as hydroquinone, azelaic acid, vitamin C or peelings), patients with sun exposure six weeks prior to, during and after treatment, herpes simplex or other infections in the treatment area, immunosuppressed patients and those showing a predisposition for keloid development were not allowed to participate in the study. Eleven patients (ten females and one male) with the following features were enrolled in the study and all but one completed the study. The ages ranged between 48 and 70 years old. The median age was 60 years. One patient dropped out due to major pain sensation. All but one patient had skintype II according to Fitzpatrick. One of the female patients had undergone laser therapy years ago.
Randomization The choice of which hand was treated with which laser system was randomized by flipping a coin.
Laser treatment Three laser treatment sessions were scheduled at 0, 4 and 8 weeks. Laser settings were based on clinical experience and manufacturers’ recommendations: the CO2 fractional ablative laser (Quantel ExelO2; wavelength 10,600 nm) was set at an energy of 15 mJ, pulse duration of 2 ms and spot density of 250 mm points/cm2 . The Q-switched ruby (Sinon; wave length 694 nm) was set at an energy density EJD, vol. 25, n◦ 2, March-April 2015
Standardized digital photographs of both hands were taken before each treatment (one example: figure 1). During the active treatment phase (weeks 0, 4 and 8) and during followup (weeks 16, 24), patients and the treating physician scored the efficacy (degree of lightening) as follows: -1 = worsening, 0 = stable, 1 = 1-25% improvement, 2 = 26-50% improvement, 3 = 51-75% improvement, 4 = 76-100% improvement (figure 2) At the study conclusion, two independent blinded experts evaluated the standardized digital photographs that were taken at the same timepoints (weeks 0, 4, 8, 16, 24) (figure 3). They estimated the efficacy of the two laser systems according to the hyperpigmentation intensity before (“initial grading”) and after the end of the study (“final grading”). The score used was: hyperpigmentation: 0 = no pigmentation (absent), 1 = mild, 2 = moderate, 3 = severe.
Subjective patient satisfaction 1 = very unpleased, 2 = unpleased, 3 = satisfied, 4 = very satisfied (figure 4).
Statistical analysis Statistical analysis was performed with the Wilcoxon matched-pairs signed rank test (Graphpad Prism 5 Software)
Results Efficacy All patients responded to the first treatment session of the Q-switched ruby laser. At visit 2, three patients showed reduced pigmentation of 51-75% improvement (score 3), two improved between 26-50% (score 2), two between 125% (score 1) and three were judged as not having improved (score 0). Under the treatment with the ablative fractionated CO2 laser, one patient’s improvement was scored 3, one patient scored 2, five scored 1, two scored 0 and for one a worsening of the pigmentation was scored (-1). The treatment results for one patient could not be evaluated. The improvement did not significantly differ between the two laser technologies at this time point.
123
A 4.5 4
Improvement
3.5 3 2.5 2 1.5 1 0.5 0 4
8
16
24
Timepoints [weeks]
B
C
Figure 1. Overview of lentigines solares of patient one prior to treatment (A), after one treatment (B) and 24 weeks after the initial treatment (C). Left hand (CO2 fractional), right hand (Q-switched Ruby).
At visit 3, five of the Q-switched ruby laser treated patients scored an improvement of 3, three were evaluated at score 2, one patient scored 1 and one did not show an improvement (score 0). One patient dropped out due to unbearable pain sensation and was therefore not included any more in the evaluation. Regarding the ablative fractionated CO2 -Laser treatment at this time point, one patient scored 4 (76-100%), five patients scored 2, three scored 1 and one patient -1. Again the results did not differ significantly between the two laser technologies.
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Figure 2. Objective and subjective improvement after Qswitched Ruby and CO2 fractional treatments at time points 0, 4, 8, 16 and 24 weeks. Red: Q-switched Ruby treatment, subjective improvement. Blue: Q-switched Ruby treatment, objective improvement. Green: CO2 fractional treatment, subjective improvement. Pink: CO2 fractional treatment, objective improvement.
At visit 4, three of the Q-switched Ruby laser treated patients showed an improvement of score 4, six patients scored 3 and one patient showed an improvement of 1-25% (score 1). The ablative fractionated CO2 -laser treatment resulted in score 4 for one patient, score 3 for two patients, score 2 for four patients, score 1 for two patients and score -1 for one patient. Patients now showed a significantly higher improvement under the Q-switched ruby laser treatment (p: 0.0148). At visit 5, the Q-switched ruby laser treatment resulted in score 4 for four patients, five patients were ranked score 3 and one score 1. The improvement differed significantly from the results under the ablative fractionated CO2 -laser treatment. (P: 0.0136), where one patient was scored 4, two patients scored 3, five patients scored 2, one patient scored 1 and one patient scored -1. Over the time period, for most patients treated with the Q-switched Ruby laser, the score was further improved (figure 2). Overall, the ablative fractionated CO2 -laser was scored less efficacious than the QS ruby laser, as assessed by the patients and the treating physician, as well as by the blinded experts, although the difference was not statistically significant.
Adverse effects Most patients reported discomfort during the Q-switched ruby laser treatment. One patient dropped out due to this side effect. Treatment with the ablative fractionated CO2 -laser was generally well tolerated (table 1). Directly after treatment, a spotted erythema and slight edema was observed in the majority of patients on the side treated with the Q-switched ruby laser, while the hand treated with the ablative fractionated CO2 -laser presented with an erythematous area (intensity range shown in table 1). More advanced forms of tissue damage, such as blistering, erosion or ulcerations were not observed immediately post-treatment, nor during the course of the study (table 1). EJD, vol. 25, n◦ 2, March-April 2015
Initial grading
Final grading 1.5
Hyperpigmentation (arbitrary units)
Hyperpigmentation (arbitrary units)
3
2
1
0
1.0
0.5
0.0 Q-switched ruby
CO2 fractional
Q-switched ruby
CO2 fractional
P = 0.0107
Figure 3. Comparison between the initial intensity of hyperpigmentation (left) and final evaluation (right). Scoring was performed after the following grading for hyperpigmentation: 0 = no pigmentation (absent), 1 = mild, 2 = moderate, 3 = severe. Pigmentation is significantly reduced after four treatments with Ruby Q-switched Ruby laser in contrast to four treatments with CO2 fractional) (p = 0.0107).
Discussion 4
Satisfaction
3.5 3 2.5 2 1.5 1 0.5 0
4
16
8
24
Timepoints [weeks]
Figure 4. Satisfaction with treatment results for the Qswitched Ruby (pink graph) and the CO2 fractional (blue graph) for time points 0, 4, 8, 16 and 24 weeks.
Patient satisfaction At the study conclusion patient satisfaction was high (score: 3-4) for the hand treated with the Q-switched ruby laser and moderate (score 1-2) for the hand treated with the ablative fractionated CO2 -laser (figure 4).
Lentigines solares on the dorsum of hands are a very common finding in the age group > 50 years and the request to have these lesions removed with few side effects and satisfying cosmesis is very frequent. Cryosurgery is the most cost-effective method to treat lentigines solares, but sometimes patients experience irreversible hypopigmentation, which is a rare outcome with the QS ruby laser, the current gold standard amongst laser technologies for this indication [2, 4, 9, 15]. The goal of this study was to systematically investigate and directly compare the novel ablative fractionated CO2 -laser technology with the established QS ruby laser in the removal of LS on the dorsum of hands. Ablative fractional lasers are FDA (Food and Drug Association) approved for the treatment of rhytides, furrows, fine lines, textural irregularities, pigmented lesions and dyschromia of the skin [20]. Already after one treatment, improvement has been described for photodamaged skin, skin laxity, facial rhytides and acne scarring. Positive experiences in our own clinical trial using the non-ablative
Table 1. A) Objective evaluation (median) intensity of adverse effects by treating physician directly after therapy (Score: 0 = no, 1 = mild, 2 = moderate, 3 = strong; Q-switched Ruby treatment/CO2 fractional treatment. x = not evaluated due to no treatment at these time points. B) Subjective evaluation intensity (median) of adverse effects by the patients directly after treatment and a few days after at time points: 0, 4, 8, 16 and 24 weeks. Score: 0 = no, 1 = mild, 2 = moderate, 3 = strong; pain intensity: 0 = no pain, 10 = very strong pain; RQ-switched Ruby treatment/CO2 fractional treatment. X = not evaluated due to no treatment at these time points. A
Time (weeks)
Blisters
Erythema
Hypo/Hyperpigmentation
B
0 4 8 16 24 Time (weeks) 0 4 8 16 24
0/0 0/0 0/0 x x Blisters 0/0 0/0 0/0 x x
1.3/0.4 2/0.9 2.3/0.8 x x Pain 3.2/2.3 3.9/3.2 5.2/2.5 x x
0/0 0/0 0/0 X x Crusts 2.2/0.2 2/0.4 1.8/0.6 x x
EJD, vol. 25, n◦ 2, March-April 2015
Hypo/Hyperpigmentation 0/0 0/0 0/0 X x
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fractionated ErYAG-laser to treat melasma [21] motivated us to perform the present study. However, ablative fractionated CO2 -laser (Quantel Excel O2) showed only little efficacy in this indication and was clearly less effective than the standard laser treatment with the QS ruby laser (Sinon). At the moment, we cannot decide yet if this type of laser treatment is principally less effective in this indication or if higher fluences would be required to reach a higher response rate – probably at the cost of (more) side effects. In conclusion, ablative fractionated CO2 -laser technology seems not to be sufficiently efficacious in the treatment of LS of the dorsum of hands – even though this was shown by Gotkin et al.[19]. However, they did not compare the technique with another one. Where a patient decides for laser treatment, the well-established Q-switched lasers remain the mainstay in this indication, even for darker skin types [14]. Disclosure. Financial support: none. Conflict of interest: none.
References
1. Ortonne JP. Pigmentary changes of the ageing skin. Br J Dermatol 1990; 122 Suppl 35: 21-8. 2. Ortonne JP, Pandya AG, Lui H, Hexsel D. Treatment of solar lentigines. J Am Acad Dermatol 2006; 54(5 Suppl 2): S262-71. 3. Stern RS, Dover JS, Levin JA, Arndt KA. Laser therapy versus cryotherapy of lentigines: a comparative trial. J Am Acad Dermatol 1994; 30: 985-7. 4. Todd MM, Rallis TM, Gerwels JW, Hata TR. A comparison of 3 lasers and liquid nitrogen in the treatment of solar lentigines: a randomized, controlled, comparative trial. Arch Dermatol 2000; 136: 841-6. 5. Hexsel D, Hexsel C, Porto MD, Siega C. Triple combination as adjuvant to cryotherapy in the treatment of solar lentigines: investigatorblinded, randomized clinical trial. J Eur Acad Dermatol Venereol 2014. doi: 10.1111/jdv.12484. 6. Kerl H. Histopathologie der Haut. Berlin: Springer, 2003. 7. Dummer RBP. Lasertherapie der Haut. Schweiz Med Forum 2002; 2: 42-7.
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8. Schönewolf N, Rümmelein B, Bogdan-Allemann I, Dummer R. Tätowierungen und wie man sie wieder los wird. Schweiz Med Forum 2010; 10: 340-3. 9. Kopera DU, Hohenleutner M, Landthaler M. Quality-switched ruby laser treatment of solar lentigines and Becker’s nevus: a histopathological and immunohistochemical study. Dermatology 1997; 194: 338-43. 10. Rosenbach A, Lee SJ, Johr RH. Treatment of medium-brown solar lentigines using an alexandrite laser designed for hair reduction. Arch Dermatol 2002; 138: 547-8. 11. Goldman L, Blaney DJ, Kindel DJ Jr, Franke EK. Effect of the laser beam on the skin. Preliminary report. J Invest Dermatol 1963; 40: 1212. 12. Goldman L, Blaney DJ, Kindel DJ Jr, Richfield D, Franke EK. Pathology of the effect of the laser beam on the skin. Nature 1963; 197: 912-4. 13. Stratigos AJ, Dover JS, Arndt KA. Laser treatment of pigmented lesions–2000: how far have we gone? Arch Dermatol 2000; 136: 91521. 14. Jun HJ, Kim SM, Choi WJ, Cho SH, Lee JD, Kim HS. A split-face, evaluator-blind randomized study on the early effects of Q-switched Nd:YAG laser versus Er:YAG micropeel in light solar lentigines in Asians. J Cosmet Laser Ther 2014; 16: 83-8. 15. Sadighha A, Saatee S, Muhaghegh-Zahed G. Efficacy and adverse effects of Q-switched ruby laser on solar lentigines: a prospective study of 91 patients with Fitzpatrick skin type II, III, and IV. Dermatol Surg 2008; 34: 1465-8. 16. Negishi K, Akita H, Tanaka S, Yokoyama Y, Wakamatsu S, Matsunaga K. Comparative study of treatment efficacy and the incidence of post-inflammatory hyperpigmentation with different degrees of irradiation using two different quality-switched lasers for removing solar lentigines on Asian skin. J Eur Acad Dermatol Venereol 2013; 27: 30712. 17. Manstein D, Herron GS, Sink RK, Tanner H, Anderson RR. Fractional photothermolysis: a new concept for cutaneous remodeling using microscopic patterns of thermal injury. Lasers Surg Med 2004; 34: 426-38. 18. Stumpp OF, Bedi VP, Wyatt D, Lac D, Rahman Z, Chan KF. In vivo confocal imaging of epidermal cell migration and dermal changes post nonablative fractional resurfacing: study of the wound healing process with corroborated histopathologic evidence. J Biomed Opt 2009; 14: 024018. 19. Gotkin RH, Sarnoff DS, Cannarozzo G, Sadick NS, AlexiadesArmenakas M. Ablative skin resurfacing with a novel microablative CO2 laser. J Drugs Dermatol 2009; 8: 138-44. 20. Bogdan Allemann I, Kaufman J. Fractional photothermolysis. Curr Probl Dermatol 2011; 42: 56-66. 21. Barysch MJ, Rümmelein B, Kolm I, et al. Split-face study of melasma patients treated with non-ablative fractionated photothermolysis (1540 nm). J Eur Acad Dermatol Venereol 2012; 26: 423-30.
EJD, vol. 25, n◦ 2, March-April 2015
Therapy Nicola L. SCHOENEWOLF Jürg HAFNER Reinhard DUMMER Inja BOGDAN ALLEMANN University Hospital Zürich, Department of Dermatology, Gloriastr. 31 8091 Zürich, Switzerland
Reprints: I. B. Allemann
Article accepted on 12/12/2014
L
Laser treatment of solar lentigines on dorsum of hands: QS Ruby laser versus ablative CO2 fractional laser – a randomized controlled trial Background: Lentigines solares (LS) on the dorsum of hands are often esthetically disturbing. Q-switched ruby laser treatment is highly effective in the treatment of these lesions. Ablative fractional photothermolysis may be a suitable alternative. We compared the Q-switched ruby laser with ablative CO2 fractional photothermolysis for the treatment of solar lentigines. Objective: To evaluate the efficacy and side-effects of 694nm Q-switched ruby laser (Sinon) with the ablative 10,600nm CO2 fractional laser (Quantel Excel O2) in an intra-individual side-to-side comparison in the treatment of LS on the dorsum of hands. Material and methods: Eleven patients were included in the study. The hands of each patient were randomized for treatment with the two laser systems. Three treatment sessions were scheduled at weeks 0, 4 and 8. Evaluations by patients, treating physician and blinded experts were scheduled at weeks 0, 4, 8, 16 and 24. Results: The Q-switched ruby laser was significantly more efficacious than the ablative CO2 fractional laser for removing LS on the dorsum of hands (p = 0.01). Conclusion: In this first study on this topic, the Q-switched ruby laser was superior to the ablative CO2 fractional laser in the treatment of lentigines solares on the dorsum of hands. Key words: lentigines solares, Q-switched ruby laser, CO2 fractional laser
122
(532 nm), Q-switched ruby (694 nm), Q-switched Alexandrite (755 nm), Q-switched Nd:YAG (1064 nm), CO2 (10,600 nm), and Argon (488-630 nm) diode lasers have been under investigation for the treatment of lentigines solares. All available Q-switched (QS) lasers have been demonstrated to be safe and efficacious in the treatment of lentigines [7] and produce excellent results [8]. With the Q-switched lasers in general, only one to two treatment sessions are necessary in order to achieve a satisfactory treatment response. With its wavelength of 694 nm, pulse durations between 25-40 nanoseconds (ns) and average fluences of 3-10J/cm2 , the Q-switched ruby laser has proven effective in the treatment of pigment disorders, even in light solar lentigines [9-15]. Depending on the skin type and level of fluence applied, the degree of unwanted postinflammatory hyperpigmentation may change [16]. The concept of fractional photothermolysis was introduced in 2003 [17]; by 2007 the technology was further developed with ablative wavelengths. In treatment, a multitude of drill hole-shaped microscopic ablation zones (MAZ) are induced into the skin in a regular, sieve-like pattern. Histologically, the treatment leads to a disrupted stratum corneum, a cylindrical central ablation zone lined by a thin eschar layer, followed by a coagulation zone embedded in the unharmed surrounding tissue. Re-epithelialization, starting from the vital tissue surrounding each damaged zone, occurs rapidly. As for non-ablative fractional EJD, vol. 25, n◦ 2, March-April 2015
To cite this article: Schoenewolf NL, Hafner J, Dummer R, Bogdan Allemann I. Laser treatment of solar lentigines on dorsum of hands: QS Ruby laser versus ablative CO2 fractional laser – a randomized controlled trial. Eur J Dermatol 2015; 25(2): 122-6 doi:10.1684/ejd.2014.2513
doi:10.1684/ejd.2014.2513
entigines solares (LS) are sharply demarcated hyperpigmented macules on photoaged skin. They are also called senile lentigines, senile freckles or age spots. Usually, they can be found on chronically sunexposed areas such as the face, neck and back of the hands. Their number increases with age. Typically, there are multiple lesions. In the age group > 50 years, 90% have LS [1]. These UV-induced hyperpigmentations have no oncogenic potential and do not require medical intervention. However, often they are cosmetically disturbing, hence patients request removal. Nitrogen cryotherapy is considered the standard treatment for solar lentigines, based on the guidelines by the “Pigmentary Disorders Academy” published in 2006 [2]. Although cryotherapy has shown good results, patients complain about discomfort during the treatment and unwanted hypopigmentation as a side effect [3, 4]. A recent study by Hexsel et al. showed a reduction of these adverse effects by combining the cryotherapy with a triple combination cream [5]. Histologically, there is an increased number of pigment granules in the keratinocytes and the condensed stratum corneum [6]. In order to approach the increased melanin content therapeutically, the broad absorption capacity of this chromophore (351-1064 nm), has led to an orientation towards laser assisted treatment of lentigines solares [2]. Since the 1960s, a great multitude of different lasers, such as the pulsed dye (595 nm), frequency-doubled Nd:YAG
photothermolysis, the formation of Microscopic Epidermal Necrotic Debris (MEND) can be observed, which has been shown to contain melanin, elastic tissue and other dermal contents [18]. This is the reason why lightening of pigmentation can be expected upon treatment with ablative fractional photothermolysis, as was shown by Gotkin et al.[19]. So far, no clinical studies are available comparing the efficacy and side-effects of the CO2 ablative fractional laser with the Q-switched sinon ruby laser to remove LS on the dorsum of hands. Therefore, we designed and conducted a prospective randomized split-hand trial over a period of six months – to our knowledge, the first study comparing these technologies.
of 5 J/cm2 , spot size diameter of 3 mm, and frequency of 2 Hz). Immediately after treatment, the treated area was cooled with a cool pack and thereafter Ialugen cream was applied (Natrii hyaluronas, BSA Institut Biochimique SA, Lugano, Switzerland). Patients were instructed to apply Ialugen cream twice daily until the disappearance of crusts. They were furthermore instructed to apply sun blocker (SPF 50) daily and avoid sun exposure of the treated areas throughout the entire study.
Follow up Two follow up visits were performed at weeks 16 and 24.
Assessment of treatment outcome
Patients and methods Patient selection Inclusion criteria: Patients presenting with symmetrically localized hyperpigmentations on both dorsal hands, clinically and dermatoscopically diagnosed as lentigines solares, qualified for inclusion in this study. Additionally, all patients had to provide written informed consent and to agree to the protocol. The study was approved by the local ethics committe, Zurich, Switzerland (Project number 730, 2009). Exclusion criteria: Pregnant or breast-feeding women, patients taking light-sensitizing drugs (including systemic retinoids up to 6 months prior to the study), patients who had undergone other treatments of the lentigines solares six months prior to the study (including topical depigmentation creams such as hydroquinone, azelaic acid, vitamin C or peelings), patients with sun exposure six weeks prior to, during and after treatment, herpes simplex or other infections in the treatment area, immunosuppressed patients and those showing a predisposition for keloid development were not allowed to participate in the study. Eleven patients (ten females and one male) with the following features were enrolled in the study and all but one completed the study. The ages ranged between 48 and 70 years old. The median age was 60 years. One patient dropped out due to major pain sensation. All but one patient had skintype II according to Fitzpatrick. One of the female patients had undergone laser therapy years ago.
Randomization The choice of which hand was treated with which laser system was randomized by flipping a coin.
Laser treatment Three laser treatment sessions were scheduled at 0, 4 and 8 weeks. Laser settings were based on clinical experience and manufacturers’ recommendations: the CO2 fractional ablative laser (Quantel ExelO2; wavelength 10,600 nm) was set at an energy of 15 mJ, pulse duration of 2 ms and spot density of 250 mm points/cm2 . The Q-switched ruby (Sinon; wave length 694 nm) was set at an energy density EJD, vol. 25, n◦ 2, March-April 2015
Standardized digital photographs of both hands were taken before each treatment (one example: figure 1). During the active treatment phase (weeks 0, 4 and 8) and during followup (weeks 16, 24), patients and the treating physician scored the efficacy (degree of lightening) as follows: -1 = worsening, 0 = stable, 1 = 1-25% improvement, 2 = 26-50% improvement, 3 = 51-75% improvement, 4 = 76-100% improvement (figure 2) At the study conclusion, two independent blinded experts evaluated the standardized digital photographs that were taken at the same timepoints (weeks 0, 4, 8, 16, 24) (figure 3). They estimated the efficacy of the two laser systems according to the hyperpigmentation intensity before (“initial grading”) and after the end of the study (“final grading”). The score used was: hyperpigmentation: 0 = no pigmentation (absent), 1 = mild, 2 = moderate, 3 = severe.
Subjective patient satisfaction 1 = very unpleased, 2 = unpleased, 3 = satisfied, 4 = very satisfied (figure 4).
Statistical analysis Statistical analysis was performed with the Wilcoxon matched-pairs signed rank test (Graphpad Prism 5 Software)
Results Efficacy All patients responded to the first treatment session of the Q-switched ruby laser. At visit 2, three patients showed reduced pigmentation of 51-75% improvement (score 3), two improved between 26-50% (score 2), two between 125% (score 1) and three were judged as not having improved (score 0). Under the treatment with the ablative fractionated CO2 laser, one patient’s improvement was scored 3, one patient scored 2, five scored 1, two scored 0 and for one a worsening of the pigmentation was scored (-1). The treatment results for one patient could not be evaluated. The improvement did not significantly differ between the two laser technologies at this time point.
123
A 4.5 4
Improvement
3.5 3 2.5 2 1.5 1 0.5 0 4
8
16
24
Timepoints [weeks]
B
C
Figure 1. Overview of lentigines solares of patient one prior to treatment (A), after one treatment (B) and 24 weeks after the initial treatment (C). Left hand (CO2 fractional), right hand (Q-switched Ruby).
At visit 3, five of the Q-switched ruby laser treated patients scored an improvement of 3, three were evaluated at score 2, one patient scored 1 and one did not show an improvement (score 0). One patient dropped out due to unbearable pain sensation and was therefore not included any more in the evaluation. Regarding the ablative fractionated CO2 -Laser treatment at this time point, one patient scored 4 (76-100%), five patients scored 2, three scored 1 and one patient -1. Again the results did not differ significantly between the two laser technologies.
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Figure 2. Objective and subjective improvement after Qswitched Ruby and CO2 fractional treatments at time points 0, 4, 8, 16 and 24 weeks. Red: Q-switched Ruby treatment, subjective improvement. Blue: Q-switched Ruby treatment, objective improvement. Green: CO2 fractional treatment, subjective improvement. Pink: CO2 fractional treatment, objective improvement.
At visit 4, three of the Q-switched Ruby laser treated patients showed an improvement of score 4, six patients scored 3 and one patient showed an improvement of 1-25% (score 1). The ablative fractionated CO2 -laser treatment resulted in score 4 for one patient, score 3 for two patients, score 2 for four patients, score 1 for two patients and score -1 for one patient. Patients now showed a significantly higher improvement under the Q-switched ruby laser treatment (p: 0.0148). At visit 5, the Q-switched ruby laser treatment resulted in score 4 for four patients, five patients were ranked score 3 and one score 1. The improvement differed significantly from the results under the ablative fractionated CO2 -laser treatment. (P: 0.0136), where one patient was scored 4, two patients scored 3, five patients scored 2, one patient scored 1 and one patient scored -1. Over the time period, for most patients treated with the Q-switched Ruby laser, the score was further improved (figure 2). Overall, the ablative fractionated CO2 -laser was scored less efficacious than the QS ruby laser, as assessed by the patients and the treating physician, as well as by the blinded experts, although the difference was not statistically significant.
Adverse effects Most patients reported discomfort during the Q-switched ruby laser treatment. One patient dropped out due to this side effect. Treatment with the ablative fractionated CO2 -laser was generally well tolerated (table 1). Directly after treatment, a spotted erythema and slight edema was observed in the majority of patients on the side treated with the Q-switched ruby laser, while the hand treated with the ablative fractionated CO2 -laser presented with an erythematous area (intensity range shown in table 1). More advanced forms of tissue damage, such as blistering, erosion or ulcerations were not observed immediately post-treatment, nor during the course of the study (table 1). EJD, vol. 25, n◦ 2, March-April 2015
Initial grading
Final grading 1.5
Hyperpigmentation (arbitrary units)
Hyperpigmentation (arbitrary units)
3
2
1
0
1.0
0.5
0.0 Q-switched ruby
CO2 fractional
Q-switched ruby
CO2 fractional
P = 0.0107
Figure 3. Comparison between the initial intensity of hyperpigmentation (left) and final evaluation (right). Scoring was performed after the following grading for hyperpigmentation: 0 = no pigmentation (absent), 1 = mild, 2 = moderate, 3 = severe. Pigmentation is significantly reduced after four treatments with Ruby Q-switched Ruby laser in contrast to four treatments with CO2 fractional) (p = 0.0107).
Discussion 4
Satisfaction
3.5 3 2.5 2 1.5 1 0.5 0
4
16
8
24
Timepoints [weeks]
Figure 4. Satisfaction with treatment results for the Qswitched Ruby (pink graph) and the CO2 fractional (blue graph) for time points 0, 4, 8, 16 and 24 weeks.
Patient satisfaction At the study conclusion patient satisfaction was high (score: 3-4) for the hand treated with the Q-switched ruby laser and moderate (score 1-2) for the hand treated with the ablative fractionated CO2 -laser (figure 4).
Lentigines solares on the dorsum of hands are a very common finding in the age group > 50 years and the request to have these lesions removed with few side effects and satisfying cosmesis is very frequent. Cryosurgery is the most cost-effective method to treat lentigines solares, but sometimes patients experience irreversible hypopigmentation, which is a rare outcome with the QS ruby laser, the current gold standard amongst laser technologies for this indication [2, 4, 9, 15]. The goal of this study was to systematically investigate and directly compare the novel ablative fractionated CO2 -laser technology with the established QS ruby laser in the removal of LS on the dorsum of hands. Ablative fractional lasers are FDA (Food and Drug Association) approved for the treatment of rhytides, furrows, fine lines, textural irregularities, pigmented lesions and dyschromia of the skin [20]. Already after one treatment, improvement has been described for photodamaged skin, skin laxity, facial rhytides and acne scarring. Positive experiences in our own clinical trial using the non-ablative
Table 1. A) Objective evaluation (median) intensity of adverse effects by treating physician directly after therapy (Score: 0 = no, 1 = mild, 2 = moderate, 3 = strong; Q-switched Ruby treatment/CO2 fractional treatment. x = not evaluated due to no treatment at these time points. B) Subjective evaluation intensity (median) of adverse effects by the patients directly after treatment and a few days after at time points: 0, 4, 8, 16 and 24 weeks. Score: 0 = no, 1 = mild, 2 = moderate, 3 = strong; pain intensity: 0 = no pain, 10 = very strong pain; RQ-switched Ruby treatment/CO2 fractional treatment. X = not evaluated due to no treatment at these time points. A
Time (weeks)
Blisters
Erythema
Hypo/Hyperpigmentation
B
0 4 8 16 24 Time (weeks) 0 4 8 16 24
0/0 0/0 0/0 x x Blisters 0/0 0/0 0/0 x x
1.3/0.4 2/0.9 2.3/0.8 x x Pain 3.2/2.3 3.9/3.2 5.2/2.5 x x
0/0 0/0 0/0 X x Crusts 2.2/0.2 2/0.4 1.8/0.6 x x
EJD, vol. 25, n◦ 2, March-April 2015
Hypo/Hyperpigmentation 0/0 0/0 0/0 X x
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fractionated ErYAG-laser to treat melasma [21] motivated us to perform the present study. However, ablative fractionated CO2 -laser (Quantel Excel O2) showed only little efficacy in this indication and was clearly less effective than the standard laser treatment with the QS ruby laser (Sinon). At the moment, we cannot decide yet if this type of laser treatment is principally less effective in this indication or if higher fluences would be required to reach a higher response rate – probably at the cost of (more) side effects. In conclusion, ablative fractionated CO2 -laser technology seems not to be sufficiently efficacious in the treatment of LS of the dorsum of hands – even though this was shown by Gotkin et al.[19]. However, they did not compare the technique with another one. Where a patient decides for laser treatment, the well-established Q-switched lasers remain the mainstay in this indication, even for darker skin types [14]. Disclosure. Financial support: none. Conflict of interest: none.
References
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