- Email: [email protected]
Phototherapy in cosmetic dermatology
Phototherapy in Cosmetic Dermatology Joshua Brownell, Stephanie Wang MD, Maria M. Tsoukas MD, PhD PII: DOI: Reference:
S0738-081X(16)30149-3 doi: 10.1016/j.clindermatol.2016.05.013 CID 7061
To appear in:
Clinics in Dermatology
Please cite this article as: Brownell Joshua, Wang Stephanie, Tsoukas Maria M., Phototherapy in Cosmetic Dermatology, Clinics in Dermatology (2016), doi: 10.1016/j.clindermatol.2016.05.013
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Joshua Brownell1, Stephanie Wang MD1, Maria M. Tsoukas MD PhD1* 1
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Department of Dermatology, University of Illinois at Chicago College of Medicine, Chicago IL.
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*Corresponding author: Maria M. Tsoukas MD, PhD University of Illinois, College of Medicine
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808 S. Wood Str, Chicago IL 60612, USA
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Email: [email protected]
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Article title: Phototherapy in Cosmetic Dermatology Funding Sources: None Abstract word count: 82
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Number of Figures: 0
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Article word Count: 2665
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Number of Tables: 0 Number of References: 29
Abstract:
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Conflicts of Interest: The authors declare no conflicts of interest.
Light therapy has been incorporated into the art of healing and cosmesis for thousands of years, and currently, has found utility in many areas of medicine. Various modalities of cosmetic phototherapy are detailed, as well as the indications and mechanism of action for each modality. These modalities can be used to treat many common cosmetic conditions, including acne vulgaris, solar lentigo, and melasma. Phototherapy is considered a safe and effective option in the treatment of many of these disorders.
ACCEPTED MANUSCRIPT Introduction Light therapy has been incorporated into the art of healing and cosmesis for thousands of years.
RI P
T
Ancient cultures understood the value of sun and made the first steps in understanding the science behind it, as it secured life and energy on the planet. Ancient mythology and monuments
SC
are dedicated to sun as humans realized its key role into health and life (e.g. Greek God Apollo and his temples, the Stonehenge, the ancient City of Petra, among many others). Hippocrates and
NU
Herodotus addressed the therapeutic properties of light on skin, muscle, and joint illness. The
MA
Egyptians and Indians stressed the importance of different colors of light in the therapy of skin diseases, while the Chinese expanded their knowledge of the therapeutic effect of light on mental
ED
disorders.
Modern photomedicine has evolved to have utility in medical diagnosis and therapy, utilizing a
PT
broad spectrum of visible and non-visible electromagnetic radiation. We review the contribution
Acne vulgaris Red light
AC
aesthetic practices.
CE
of light therapy (excluding laser devices) in cosmesis, as it is commonly applied to medical and
Cleavage of sebum by Propionibacterium (P.) acnes is an important step in the pathogenesis of inflammation within the sebaceous gland. P. acnes creates lipases that cleave sebum into free fatty acids (FFA). These FFAs stimulate the release of antimicrobial peptides and proinflammatory mediators. P. acnes also activates toll-like receptors that activate the proinflammatory nf-kB. This process ultimately leads to hyperkeratinization of the gland, forming a comedone.1 In an in vitro study, 630nm light was demonstrated to have a statistically significant effect in decreasing lipid production in sebocytes. Squalene, a lipid component of
ACCEPTED MANUSCRIPT sebum, was decreased the most. This effect may be due to regulation of ppar-y by 630nm light, and was dose-dependent.2 Because squalene is exclusively found in sebum, red light may have
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T
an inhibiting effect on sebum production.3 Blue light
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Blue light has been demonstrated to have an anti-proliferative effect on cell lines.4 This effect can be utilized in the treatment of acne. An in vitro stud of irradiation of human sebocytes with
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415nm light reduced their proliferation, and this effect was dose-dependent.2 In reducing the number of sebocytes, the amount of sebum available to P. acnes is reduced, thus decreasing the
MA
ability of P. acnes to induce inflammation.1
ED
Blue light is also known to have a direct antimicrobial effect on P. acnes. P. acnes naturally produces photosensitizing porphyrins. Bacteria exposed to high doses of 407-420nm light
PT
showed decreased culture viability. Exposed cells had an increased coproporphyrin production,
CE
indicating that photoinactivation of these cells may be mediated by this endogenous porphyrin production.5 Blue light is believed to excite these endogenous porphyrins, leading to the
AC
production of cytotoxic reactive oxygen species that cause the death of the bacterium.6 These studies suggest that the effect of blue light is due to effects at two separate points of the pathogenesis of acne: colonization by P. acnes and the production of sebum. This has demonstrated therapeutic efficacy. In one prospective study of 21 patients, 4 weeks of biweekly phototherapy sessions, using exclusively blue light, led to decreased inflammatory lesion counts by 13% and acne grade by 11%; these changes were statistically significant.7
ACCEPTED MANUSCRIPT Photopneumatic devices for acne Photopneumatic delivery of phototherapy facilitates penetration of light. The depth of
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T
penetration of light is dependent on two factors: the wavelength of light, and the amount of skin pigmentation. Blue wavelengths do not penetrate as deeply as red, and even in fair skin, these
SC
wavelengths are quickly absorbed. One study demonstrated that 90% of light at 405nm is absorbed within 0.3mm of the skin surface in skin rated as “very fair,” and darker skin types had
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a higher ratio of absorption. This data were generated by a computer model, however, and was not performed in vivo. Instead, absorption of light by skin was simulated through a modeled
MA
volume fraction of melanosomes.8 This study was sufficient to estimate light absorption by skin,
ED
but it may be important to consider that there may be more variation in penetration in vivo. The limited penetration of blue light is important to remember when prescribing treatment because
PT
sebaceous glands may be located at a depth of up to 1mm.2
CE
The photopneumatic device resolves this issue by mechanically lifting the sebaceous gland towards the surface, opening the pore, and removing contents through the use of a vacuum.
AC
Phototherapy is then applied. One prospective study of 41 patients applied photopneumatic therapy for four sessions at 1-2 week intervals. This study demonstrated a statistically significant decrease in number of lesions after the four sessions were complete, and this improvement remained through 3 months of follow-up.9
ACCEPTED MANUSCRIPT Home devices for acne A common difficulty with phototherapy regimens is maintaining patient compliance for the
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T
length of time needed to see results. Home units can theoretically increase compliance by decreasing the time commitment required of the patient. One randomized, controlled study of 15
SC
patients with grade 2-4 acne investigated the use of a home phototherapy unit, the “OCimple Light Therapy System MP 200” (Ceragem Medisys, Korea). Patients in the experimental group
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received treatment with both red and blue light, while those in the control received a sham device
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that delivered nontherapeutic light. The experimental group demonstrated a decrease in inflammatory lesions by 26.3% and noninflammatory lesions by 22.3%; both reductions were
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statistically significant. Additionally, patients in the experimental group had a statistically significant decline in acne grade and visual assessment scale when compared to the control.10
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Another study investigated the “Silk „n Blue” home device (Home Skinovations, Canada), which
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delivers light at the 405-460nm range. This study enrolled 15 patients, and demonstrated a statistically significant decrease in inflammatory lesion counts by 42% after 1 month of
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treatment. This decrease was sustained for three months.11 The success of these trials indicate that home phototherapy units are viable options for patients that are unable to attend regular office visits.
ACCEPTED MANUSCRIPT Intense Pulsed Light therapy (IPL) for acne IPL appears to be an effective mechanism for delivering phototherapy for treatment of acne. A
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study of 50 patients compared a mainstay of treatment, benzoyl peroxide (BP), to IPL at a 530nm filter with a pulse duration of 35ms and a fluence of 35 J/cm2. Both the BP and the IPL groups
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showed a statistically significant decrease in inflammatory lesions at the end of five sessions, at 69.40% and 61.56%, respectively. The difference between these two was not significant.
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Additionally, patients treated with IPL experienced less irritation of the skin during the study duration, indicating it may be a favorable option to patients who experience discomfort from
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topical pharmacotherapy.12
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Acne vulgaris and pregnancy
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Several commonly used treatments for acne have teratogenic effects and are contraindicated in the pregnant patient, including fluoroquinolones, tetracyclines, spironolactone, and isotretinoin.
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This can limit the options available to control acne. Phototherapy has been shown to be safe for
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use in pregnancy, and should be considered in pregnant patients with severe lesions.13 Onychomycosis
Onychomycosis with discoloration and thickening is extremely common. The incidence increases with age; the prevalence amongst those 70 and older is near 50%. Onychomycosis is caused by infection by any of various fungal species, with 80-90% of cases being caused by dermatophytes. The risk of infection increases in patient populations that have decreased peripheral circulation, including the elderly, smokers, and patients with peripheral artery disease.14
ACCEPTED MANUSCRIPT Some studies have begun to determine the role of UV radiation in the treatment of onychomycosis, due to its known antimicrobial properties. One recent in vitro study investigated
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both the antifungal activity and the nail penetration depth of UV light throughout the UV
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spectrum (280-400nm). They found that wavelengths of light below 317nm were not transmitted through toenails with an average thickness of 0.8mm, representing a lower range of wavelengths
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that can be effective in treating onychomycosis. However, wavelengths above 320 were
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ineffective in inhibiting the growth of the dermatophyte, regardless of fluence. This represents a barrier to treatment, in that the wavelengths necessary to penetrate the nail are incapable of
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treating the disease.15 To date, no in vivo studies were found that further investigated this
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potential mode of treatment.
Intense Pulsed Light (IPL) therapy and photorejuvenation
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Technique and effect on telangiectasia
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IPL was first described as a technique for managing dermatologic disease by Goldman and
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Eckhouse in 1996. They conceived of a technique through which telangiectasia and reticular veins could be treated through the use of non-coherent intense pulsed light (IPL). In their model, a continuous range of light wavelengths, from 550nm to about 900nm, were delivered to the skin in 3msec bursts at a fluence of 7.5 J/cm2. The selection of wavelength was calculated to penetrate to a specific depth of skin, while the short bursts were intended to prevent heating of the epidermis to a level that would cause damage. The intention was to selectively target the pathologic blood vessels, causing coagulation and resolving the disease without causing damage surrounding structures. By modifying these variables, they were able to target vessels of varying sizes and depths.16 Since their description of this technique, IPL has been expanded to have demonstrated efficacy in a wide number of cosmetic dermatologic pathologies. Currently several
ACCEPTED MANUSCRIPT dermatologic pathologies have strong evidence supporting treatment with IPL, including melasma, telangiectasia, acne vulgaris, and solar lentigines.17
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Hirsutism
The use of IPL in unwanted hair removal has been well established for nearly twenty years. By
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targeting melanin within the hair shaft, the hair follicle can be targeted for selective photothermolysis, following the same theory as described above for disorders of
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hyperpigmentation. The resulting hair removal is variable, but is often sustained for several
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months.18 Recent developments in this field have demonstrated that home devices can be safe and effective in treating hirsutism. In one investigation, the “Silk‟n glide” device (Home
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Skinovations, Canada) was used, with light filtered at 475nm at a fluence of 5 J/cm2. Fifteen patients completed 6 sessions during the study, and success of the treatment was quantified by
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the average number of hairs per 1x1 cm area. At the onset of the study, the baseline mean was
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22.7; at the one month follow-up after the completion of 6 sessions, the mean hair count was 4.4. This decrease was statistically significant.19 Home IPL devices can be considered in patients who
Scars
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are unable to attend regular in-office phototherapy sessions.
IPL appears to have moderate efficacy in the treatment of hypertrophic scars and keloids. In one study of 109 patients, IPL was used with a filter of 550-590nm, fluence of 30-40 J/cm2, pulses of 2.1-10ms, and delays of 10-40 ms. Improvement was graded on the average rating between two physicians. This grade was based on visual clinical improvement. At the conclusion of the treatment period, 56.9% of patients had “good” or “excellent” improvement, and 100% of patients showed at least some visual clinical improvement.20
ACCEPTED MANUSCRIPT Combining corticosteroid injection with IPL may increase the efficacy of scar treatment. One study combined intralesional corticosteroid treatment with IPL with a filter of 450nm, fluence of
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30-40 J/cm2, pulses of 2.1-10ms, and delays of 10-40 ms. Eighty-six patients were treated for a
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maximum of eight sessions at intervals of three weeks. Sixty-two patients showed complete recovery at the conclusion of the study. Additionally, male gender and smaller initial size of the
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lesion were found have a statistically significant increase in the success of treatment.21
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IPL may also have efficacy in the treatment of hyperpigmentation secondary to burn scarring, though this has been less studied thus far. One recent small study of 20 used IPL with filters
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ranging from 560-650 nm and average fluence of 15.4 J/cm2 in treating burn scar dyschromia.
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Seventeen patients completed one session, and 3 completed two sessions. Sixteen patients noted mild to significant improvement at 8-week follow up. However, the limited size and duration of
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this study indicates the need for further research into the efficacy of IPL in this patient
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population.22
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Hyperpigmentation disorders
Melasma is a commonly occurring hyperpigmentation disorder that typically affects the face. A combination of several risk factors interact in the pathogenesis of melasma, including UV exposure, genetics, estrogen, and inflammation. The result is the induction of genes encoding tyrosinase and stimulation of melanocytes, causing increased melanosome production in a localized region.23
ACCEPTED MANUSCRIPT In the treatment of melasma, IPL photothermolysis appears to specifically degrade melanosomes in the stratum spinosum and stratum granulosum before they are incorporated into the stratum
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corneum, while simultaneously inducing basal cell differentiation. Pigmentation is initially
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decreased through the removal of existing melanosomes. The excess melanocytes are eventually
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directed upwards by keratinocyte replication and removed, allowing for sustained results.24 IPL has proven to be an efficacious method of treating melasma, in large part due to its ability to
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target both epidermal and dermal lesions. In one study of 38 patients being treated for melasma
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located at varying depths, IPL successfully reduced hyperpigmentation. The settings used on the IPL device were a wavelength of 550nm, pulse duration of 5-10ms, intervals of 10-20ms, and
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fluence of 6-14 J/cm2, depending on the depth of the lesion. Three to five sessions were conducted at intervals of 40-45 days. At the conclusion of the study, 47% of patients had an 80-
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100% reduction in hyperpigmentation area, and an additional 29% had a 60-80% reduction; no
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patients experienced complications from the therapy.25 A second study, including 35 Asian female patients with specifically a mixed dermal/epidermal
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melasma, investigated the efficacy of IPL as a combination therapy. Another standard of treatment, the low fluence Q-switched Nd:YAG laser, is efficacious in treating melasma but requires a large number of treatments and can cause adverse hypopigmentation. Melasma severity was quantified by the modified melasma area and severity index (MASI). In both groups, the laser treatment was applied four times at one week intervals. In the combination group, one session of IPL was performed two weeks before initiating laser treatment. The combination therapy group and the single therapy group showed a decrease in MASI by 59% and 46%, respectively, and this difference was statistically significant. Additionally, 12 of the 20
ACCEPTED MANUSCRIPT patients in the combination group did not require additional treatments past the study period, while all 15 in the single therapy group did, indicating a higher patient satisfaction rate.26
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Solar lentigines are hyperpigmented lesions that commonly occur on the hands and feet in association with age and sun exposure. Rarely, lentigines can form secondary to genetic
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syndromes, including Peutz-Jeghers and LEOPARD syndrome. Histologically, lentigo is marked by excessive proliferation of melanosomes and keratinocytes within the lesion, causing
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hyperpigmentation.27 These lesions have also been successfully treated with IPL. In one study of
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31 female patients with solar lentigo of the hands, 62% of patients had moderate-to-marked improvement in their lesions after 3-5 treatments. The settings used were 515-1200nm light at
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pulses of 4.0ms, a fluence of 12 J/cm2, and 20ms intervals.28 Another mainstay of treatment for these hyperpigmentation disorders is the Q-switched
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alexandrite laser (QSAL), as further analyzed elsewhere in this journal issue. A study comparing
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the treatment of lentigo with this modality to IPL found that the improvement in the pigmentation area and severity index (PSI) was not different after twelve weeks. However,
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QSAL was associated with a greater incidence of post-inflammatory hyperpigmentation (PIH) after treatment. As such, IPL therapy should be preferred in patients at increased risk of this adverse outcome, which is particularly common in patients of Asian descent.29
ACCEPTED MANUSCRIPT Conclusions
Phototherapy encompasses a wide range of modalities that are safe and effective mechanisms to
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use in the treatment of several cosmetic disorders. Strong evidence currently exists to support the use of light in the treatment of melasma, solar lentigo, acne vulgaris, and hirtsuism. It may be
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useful as an adjunct in treating some disorders, such as hypertrophic scarring. Some conditions, such as onychomycosis, are unlikely to be effectively treated with light. However, as the role of
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light in cosmetic dermatology continues to be investigated, we may uncover that it is efficacious
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in other disorders.
ACCEPTED MANUSCRIPT References 1) Das, J, Reynolds, RV.: Recent Advances in Acne Pathogenesis: Implications for Therapy. Am
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J Clin Dermatol. 2014; 15:479-488.
2) Jung, YR, Kim, SJ, Sohn, KC, et al.: Regulation of lipid production by light-emitting diodes
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in human sebocytes. Arch Dermatol Res. 2015; 307:265-273.
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3) Smith, KR, Thiboutot, DM.: Sebaceous gland lipids: friend or foe? J Lipid Res. 2008; 49:271281.
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4) Liebmann, J, Born, M, Kolb-Bachofen, V.: Blue-Light Irradiation Regulates Proliferation and
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Differentiation in Human Skin Cells. J Invest Dermatol. 2010; 10:259-269. 5) Ashkenazi, H, Malik, Z, Harith, Y, et al.: Eradication of propionibacterum acnes by its
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Microbiol. 2003; 35:17-24.
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endogenic porphyrins after illumination with high intensity blue light. FEMS Immunol Med
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6) Maclean, M, MacGregor, SJ, Anderson, JG, et al.: The role of oxygen in the visible-light inactivation of Staphylococcus aureus. J Photochem Photobiol B. 2008; 92:180-194. 7) Ammad, S, Gonzales, M, Edwards, C, et al.: An assessment of the efficacy of blue light phototherapy in the treatment of acne vulgaris. J Cosmet Dermatol. 2008; 7:180-188. 8) Mustafa, FH, Jaafar, MS.: Comparison of wavelength-dependent penetration depths of lasers in different types of skin in photodynamic therapy. Indian J Physics. 2013; 87:203-209.
ACCEPTED MANUSCRIPT 9) Narurkar, VA, Gold, M, Shamban, AT.: Photopneumatic Technology Used in Combination with Profusion Therapy for the Treatment of Acne. J Clin Aesthet Dermatol. 2013; 6:36-40.
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10) Kwon, HH, Lee, JB, Yoon, JY, et al.: The clinical and histological effect of home-use, combination blue–red LED phototherapy for mild-to-moderate acne vulgaris in Korean patients:
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a doubleblind, randomized controlled trial. Br J Dermatol. 2013; 168:1088-1094. 11) Hellmann, J, Ramirez, CA.: Evaluation of Self-Treatment of Acne Using Silk‟n Blue
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Phototherapy System. JCDSA. 2014; 4:179-184.
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12) El-latif, AA, Hasaan, FA, Elshahed, AR, et al.: Intense pulsed light versus benzoyl peroxide 5% gel in treatment of acne vulgaris. Lasers Med Sci. 2014; 29:1009-1015.
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13) Kong, YL, Tey, HL.: Treatment of Acne Vulgaris During Pregnancy and Lactation. Drugs.
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2013; 73:779-787.
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14) Westerberg, DP, Voyack, MJ.: Onychomycosis: Current trends in diagnosis and treatment.
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Am Fam Physician. 2013; 88:762-770. 15) Cronin, LJ, Mildren, RP, Moffitt, M, et al.: An investigation into the inhibitory effect of ultraviolet light on Trichophytum rubrum. Lasers Med Sci. 2014; 29:157-163. 16) Goldman, MP, Eckhouse, S.: Photothermal sclerosis of leg veins. Dermatol Surg. 1996; 22:323-330. 17) Wat, H, Wu, DC, Rao, J, et al.: Application of intense pulsed light in the treatment of dermatologic disease: A systematic review. Dermatol Surg. 2014; 40:359-377.
ACCEPTED MANUSCRIPT 18) Gold, MH.: Lasers and light sources for the removal of unwanted hair. Clin Dermatol. 2007; 25:443-453.
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19) Gold, MH, Biron, JA, Thompson, B.: Clinical evaluation of a novel intense pulsed light source for facial skin hair removal for home use. J Clin Aesthet Dermatol. 2015; 8:30-35.
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20) Erol, OO, Gurlek, A, Agaoglu, G, et al.: Treatment of hypertrophic scars and keloids using
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intense pulsed light. Aesthetic Plast Surg. 2008; 32:902-909.
21) Meymandi, SS, Rezazadeh, A, Ekhlasi, A.: Studying intense pulsed light method along with
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corticosteroid injection in treating keloid scars. Iran Red Crescent Med J. 2014; 16:e12464. 22) Hultman, CS, Friedstat, JS, Edkins, RE.: Efficacy of intense pulsed light for the treatment of
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burn scar dyschromias: A pilot study to assess patient satisfaction, safety, and willingness to pay.
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Ann Plast Surg. 2015; 74:S204-208.
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23) Lee, AY.: Recent progress in melasma pathogenesis. Pigment Cell Melanoma Res. 2015;
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accepted for publication.
24) Yamashita, T, Negishi, K, Hariya, T, et al.: Intense pulsed light therapy for superficial pigmented lesions evaluated by reflectance-mode confocal microscopy and optical coherence tomography. J Invest Dermatol. 2006; 126:2281-2286. 25) Zoccali, G, Piccolo, D, Allegra, P, et al.: Melasma treated with intense pulsed light. Aesthetic Plast Surg. 2010; 34:486-493.
ACCEPTED MANUSCRIPT 26) Na, SY, Cho, S, Lee, JH.: Better clinical results with long term benefits in melasma patients. J Dermatol Treat. 2013; 24:112-118.
lentigines. Pigment Cell Melanoma Res. 2014; 27:339-350.
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27) Praetorius, C, Sturm, RA, Steingrimsson, E.: Sun induced freckling: Ephelides and solar
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28) Sasaya, H, Kawada, A, Wada, T., et al.: Clinical effectiveness of intense pulsed light therapy
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for solar lentigines of the hands. Dermatol Ther. 2011; 584-586. 29) Wang, CC, Sue, YM, Yahg, CH, et al.: A comparison of Q-switched alexandrite laser and
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intense pulsed light for treatment of freckles and lentigines in Asian persons: A randomized,
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physician-blinded, split-face comparative trial. J Am Acad Dermatol. 2006; 54;804-810.
S0738-081X(16)30149-3 doi: 10.1016/j.clindermatol.2016.05.013 CID 7061
To appear in:
Clinics in Dermatology
Please cite this article as: Brownell Joshua, Wang Stephanie, Tsoukas Maria M., Phototherapy in Cosmetic Dermatology, Clinics in Dermatology (2016), doi: 10.1016/j.clindermatol.2016.05.013
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Joshua Brownell1, Stephanie Wang MD1, Maria M. Tsoukas MD PhD1* 1
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Department of Dermatology, University of Illinois at Chicago College of Medicine, Chicago IL.
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*Corresponding author: Maria M. Tsoukas MD, PhD University of Illinois, College of Medicine
SC
808 S. Wood Str, Chicago IL 60612, USA
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Email: [email protected]
MA
Article title: Phototherapy in Cosmetic Dermatology Funding Sources: None Abstract word count: 82
PT
Number of Figures: 0
ED
Article word Count: 2665
CE
Number of Tables: 0 Number of References: 29
Abstract:
AC
Conflicts of Interest: The authors declare no conflicts of interest.
Light therapy has been incorporated into the art of healing and cosmesis for thousands of years, and currently, has found utility in many areas of medicine. Various modalities of cosmetic phototherapy are detailed, as well as the indications and mechanism of action for each modality. These modalities can be used to treat many common cosmetic conditions, including acne vulgaris, solar lentigo, and melasma. Phototherapy is considered a safe and effective option in the treatment of many of these disorders.
ACCEPTED MANUSCRIPT Introduction Light therapy has been incorporated into the art of healing and cosmesis for thousands of years.
RI P
T
Ancient cultures understood the value of sun and made the first steps in understanding the science behind it, as it secured life and energy on the planet. Ancient mythology and monuments
SC
are dedicated to sun as humans realized its key role into health and life (e.g. Greek God Apollo and his temples, the Stonehenge, the ancient City of Petra, among many others). Hippocrates and
NU
Herodotus addressed the therapeutic properties of light on skin, muscle, and joint illness. The
MA
Egyptians and Indians stressed the importance of different colors of light in the therapy of skin diseases, while the Chinese expanded their knowledge of the therapeutic effect of light on mental
ED
disorders.
Modern photomedicine has evolved to have utility in medical diagnosis and therapy, utilizing a
PT
broad spectrum of visible and non-visible electromagnetic radiation. We review the contribution
Acne vulgaris Red light
AC
aesthetic practices.
CE
of light therapy (excluding laser devices) in cosmesis, as it is commonly applied to medical and
Cleavage of sebum by Propionibacterium (P.) acnes is an important step in the pathogenesis of inflammation within the sebaceous gland. P. acnes creates lipases that cleave sebum into free fatty acids (FFA). These FFAs stimulate the release of antimicrobial peptides and proinflammatory mediators. P. acnes also activates toll-like receptors that activate the proinflammatory nf-kB. This process ultimately leads to hyperkeratinization of the gland, forming a comedone.1 In an in vitro study, 630nm light was demonstrated to have a statistically significant effect in decreasing lipid production in sebocytes. Squalene, a lipid component of
ACCEPTED MANUSCRIPT sebum, was decreased the most. This effect may be due to regulation of ppar-y by 630nm light, and was dose-dependent.2 Because squalene is exclusively found in sebum, red light may have
RI P
T
an inhibiting effect on sebum production.3 Blue light
SC
Blue light has been demonstrated to have an anti-proliferative effect on cell lines.4 This effect can be utilized in the treatment of acne. An in vitro stud of irradiation of human sebocytes with
NU
415nm light reduced their proliferation, and this effect was dose-dependent.2 In reducing the number of sebocytes, the amount of sebum available to P. acnes is reduced, thus decreasing the
MA
ability of P. acnes to induce inflammation.1
ED
Blue light is also known to have a direct antimicrobial effect on P. acnes. P. acnes naturally produces photosensitizing porphyrins. Bacteria exposed to high doses of 407-420nm light
PT
showed decreased culture viability. Exposed cells had an increased coproporphyrin production,
CE
indicating that photoinactivation of these cells may be mediated by this endogenous porphyrin production.5 Blue light is believed to excite these endogenous porphyrins, leading to the
AC
production of cytotoxic reactive oxygen species that cause the death of the bacterium.6 These studies suggest that the effect of blue light is due to effects at two separate points of the pathogenesis of acne: colonization by P. acnes and the production of sebum. This has demonstrated therapeutic efficacy. In one prospective study of 21 patients, 4 weeks of biweekly phototherapy sessions, using exclusively blue light, led to decreased inflammatory lesion counts by 13% and acne grade by 11%; these changes were statistically significant.7
ACCEPTED MANUSCRIPT Photopneumatic devices for acne Photopneumatic delivery of phototherapy facilitates penetration of light. The depth of
RI P
T
penetration of light is dependent on two factors: the wavelength of light, and the amount of skin pigmentation. Blue wavelengths do not penetrate as deeply as red, and even in fair skin, these
SC
wavelengths are quickly absorbed. One study demonstrated that 90% of light at 405nm is absorbed within 0.3mm of the skin surface in skin rated as “very fair,” and darker skin types had
NU
a higher ratio of absorption. This data were generated by a computer model, however, and was not performed in vivo. Instead, absorption of light by skin was simulated through a modeled
MA
volume fraction of melanosomes.8 This study was sufficient to estimate light absorption by skin,
ED
but it may be important to consider that there may be more variation in penetration in vivo. The limited penetration of blue light is important to remember when prescribing treatment because
PT
sebaceous glands may be located at a depth of up to 1mm.2
CE
The photopneumatic device resolves this issue by mechanically lifting the sebaceous gland towards the surface, opening the pore, and removing contents through the use of a vacuum.
AC
Phototherapy is then applied. One prospective study of 41 patients applied photopneumatic therapy for four sessions at 1-2 week intervals. This study demonstrated a statistically significant decrease in number of lesions after the four sessions were complete, and this improvement remained through 3 months of follow-up.9
ACCEPTED MANUSCRIPT Home devices for acne A common difficulty with phototherapy regimens is maintaining patient compliance for the
RI P
T
length of time needed to see results. Home units can theoretically increase compliance by decreasing the time commitment required of the patient. One randomized, controlled study of 15
SC
patients with grade 2-4 acne investigated the use of a home phototherapy unit, the “OCimple Light Therapy System MP 200” (Ceragem Medisys, Korea). Patients in the experimental group
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received treatment with both red and blue light, while those in the control received a sham device
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that delivered nontherapeutic light. The experimental group demonstrated a decrease in inflammatory lesions by 26.3% and noninflammatory lesions by 22.3%; both reductions were
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statistically significant. Additionally, patients in the experimental group had a statistically significant decline in acne grade and visual assessment scale when compared to the control.10
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Another study investigated the “Silk „n Blue” home device (Home Skinovations, Canada), which
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delivers light at the 405-460nm range. This study enrolled 15 patients, and demonstrated a statistically significant decrease in inflammatory lesion counts by 42% after 1 month of
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treatment. This decrease was sustained for three months.11 The success of these trials indicate that home phototherapy units are viable options for patients that are unable to attend regular office visits.
ACCEPTED MANUSCRIPT Intense Pulsed Light therapy (IPL) for acne IPL appears to be an effective mechanism for delivering phototherapy for treatment of acne. A
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study of 50 patients compared a mainstay of treatment, benzoyl peroxide (BP), to IPL at a 530nm filter with a pulse duration of 35ms and a fluence of 35 J/cm2. Both the BP and the IPL groups
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showed a statistically significant decrease in inflammatory lesions at the end of five sessions, at 69.40% and 61.56%, respectively. The difference between these two was not significant.
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Additionally, patients treated with IPL experienced less irritation of the skin during the study duration, indicating it may be a favorable option to patients who experience discomfort from
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topical pharmacotherapy.12
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Acne vulgaris and pregnancy
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Several commonly used treatments for acne have teratogenic effects and are contraindicated in the pregnant patient, including fluoroquinolones, tetracyclines, spironolactone, and isotretinoin.
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This can limit the options available to control acne. Phototherapy has been shown to be safe for
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use in pregnancy, and should be considered in pregnant patients with severe lesions.13 Onychomycosis
Onychomycosis with discoloration and thickening is extremely common. The incidence increases with age; the prevalence amongst those 70 and older is near 50%. Onychomycosis is caused by infection by any of various fungal species, with 80-90% of cases being caused by dermatophytes. The risk of infection increases in patient populations that have decreased peripheral circulation, including the elderly, smokers, and patients with peripheral artery disease.14
ACCEPTED MANUSCRIPT Some studies have begun to determine the role of UV radiation in the treatment of onychomycosis, due to its known antimicrobial properties. One recent in vitro study investigated
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both the antifungal activity and the nail penetration depth of UV light throughout the UV
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spectrum (280-400nm). They found that wavelengths of light below 317nm were not transmitted through toenails with an average thickness of 0.8mm, representing a lower range of wavelengths
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that can be effective in treating onychomycosis. However, wavelengths above 320 were
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ineffective in inhibiting the growth of the dermatophyte, regardless of fluence. This represents a barrier to treatment, in that the wavelengths necessary to penetrate the nail are incapable of
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treating the disease.15 To date, no in vivo studies were found that further investigated this
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potential mode of treatment.
Intense Pulsed Light (IPL) therapy and photorejuvenation
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Technique and effect on telangiectasia
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IPL was first described as a technique for managing dermatologic disease by Goldman and
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Eckhouse in 1996. They conceived of a technique through which telangiectasia and reticular veins could be treated through the use of non-coherent intense pulsed light (IPL). In their model, a continuous range of light wavelengths, from 550nm to about 900nm, were delivered to the skin in 3msec bursts at a fluence of 7.5 J/cm2. The selection of wavelength was calculated to penetrate to a specific depth of skin, while the short bursts were intended to prevent heating of the epidermis to a level that would cause damage. The intention was to selectively target the pathologic blood vessels, causing coagulation and resolving the disease without causing damage surrounding structures. By modifying these variables, they were able to target vessels of varying sizes and depths.16 Since their description of this technique, IPL has been expanded to have demonstrated efficacy in a wide number of cosmetic dermatologic pathologies. Currently several
ACCEPTED MANUSCRIPT dermatologic pathologies have strong evidence supporting treatment with IPL, including melasma, telangiectasia, acne vulgaris, and solar lentigines.17
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Hirsutism
The use of IPL in unwanted hair removal has been well established for nearly twenty years. By
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targeting melanin within the hair shaft, the hair follicle can be targeted for selective photothermolysis, following the same theory as described above for disorders of
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hyperpigmentation. The resulting hair removal is variable, but is often sustained for several
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months.18 Recent developments in this field have demonstrated that home devices can be safe and effective in treating hirsutism. In one investigation, the “Silk‟n glide” device (Home
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Skinovations, Canada) was used, with light filtered at 475nm at a fluence of 5 J/cm2. Fifteen patients completed 6 sessions during the study, and success of the treatment was quantified by
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the average number of hairs per 1x1 cm area. At the onset of the study, the baseline mean was
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22.7; at the one month follow-up after the completion of 6 sessions, the mean hair count was 4.4. This decrease was statistically significant.19 Home IPL devices can be considered in patients who
Scars
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are unable to attend regular in-office phototherapy sessions.
IPL appears to have moderate efficacy in the treatment of hypertrophic scars and keloids. In one study of 109 patients, IPL was used with a filter of 550-590nm, fluence of 30-40 J/cm2, pulses of 2.1-10ms, and delays of 10-40 ms. Improvement was graded on the average rating between two physicians. This grade was based on visual clinical improvement. At the conclusion of the treatment period, 56.9% of patients had “good” or “excellent” improvement, and 100% of patients showed at least some visual clinical improvement.20
ACCEPTED MANUSCRIPT Combining corticosteroid injection with IPL may increase the efficacy of scar treatment. One study combined intralesional corticosteroid treatment with IPL with a filter of 450nm, fluence of
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30-40 J/cm2, pulses of 2.1-10ms, and delays of 10-40 ms. Eighty-six patients were treated for a
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maximum of eight sessions at intervals of three weeks. Sixty-two patients showed complete recovery at the conclusion of the study. Additionally, male gender and smaller initial size of the
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lesion were found have a statistically significant increase in the success of treatment.21
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IPL may also have efficacy in the treatment of hyperpigmentation secondary to burn scarring, though this has been less studied thus far. One recent small study of 20 used IPL with filters
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ranging from 560-650 nm and average fluence of 15.4 J/cm2 in treating burn scar dyschromia.
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Seventeen patients completed one session, and 3 completed two sessions. Sixteen patients noted mild to significant improvement at 8-week follow up. However, the limited size and duration of
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this study indicates the need for further research into the efficacy of IPL in this patient
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population.22
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Hyperpigmentation disorders
Melasma is a commonly occurring hyperpigmentation disorder that typically affects the face. A combination of several risk factors interact in the pathogenesis of melasma, including UV exposure, genetics, estrogen, and inflammation. The result is the induction of genes encoding tyrosinase and stimulation of melanocytes, causing increased melanosome production in a localized region.23
ACCEPTED MANUSCRIPT In the treatment of melasma, IPL photothermolysis appears to specifically degrade melanosomes in the stratum spinosum and stratum granulosum before they are incorporated into the stratum
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corneum, while simultaneously inducing basal cell differentiation. Pigmentation is initially
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decreased through the removal of existing melanosomes. The excess melanocytes are eventually
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directed upwards by keratinocyte replication and removed, allowing for sustained results.24 IPL has proven to be an efficacious method of treating melasma, in large part due to its ability to
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target both epidermal and dermal lesions. In one study of 38 patients being treated for melasma
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located at varying depths, IPL successfully reduced hyperpigmentation. The settings used on the IPL device were a wavelength of 550nm, pulse duration of 5-10ms, intervals of 10-20ms, and
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fluence of 6-14 J/cm2, depending on the depth of the lesion. Three to five sessions were conducted at intervals of 40-45 days. At the conclusion of the study, 47% of patients had an 80-
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100% reduction in hyperpigmentation area, and an additional 29% had a 60-80% reduction; no
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patients experienced complications from the therapy.25 A second study, including 35 Asian female patients with specifically a mixed dermal/epidermal
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melasma, investigated the efficacy of IPL as a combination therapy. Another standard of treatment, the low fluence Q-switched Nd:YAG laser, is efficacious in treating melasma but requires a large number of treatments and can cause adverse hypopigmentation. Melasma severity was quantified by the modified melasma area and severity index (MASI). In both groups, the laser treatment was applied four times at one week intervals. In the combination group, one session of IPL was performed two weeks before initiating laser treatment. The combination therapy group and the single therapy group showed a decrease in MASI by 59% and 46%, respectively, and this difference was statistically significant. Additionally, 12 of the 20
ACCEPTED MANUSCRIPT patients in the combination group did not require additional treatments past the study period, while all 15 in the single therapy group did, indicating a higher patient satisfaction rate.26
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Solar lentigines are hyperpigmented lesions that commonly occur on the hands and feet in association with age and sun exposure. Rarely, lentigines can form secondary to genetic
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syndromes, including Peutz-Jeghers and LEOPARD syndrome. Histologically, lentigo is marked by excessive proliferation of melanosomes and keratinocytes within the lesion, causing
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hyperpigmentation.27 These lesions have also been successfully treated with IPL. In one study of
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31 female patients with solar lentigo of the hands, 62% of patients had moderate-to-marked improvement in their lesions after 3-5 treatments. The settings used were 515-1200nm light at
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pulses of 4.0ms, a fluence of 12 J/cm2, and 20ms intervals.28 Another mainstay of treatment for these hyperpigmentation disorders is the Q-switched
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alexandrite laser (QSAL), as further analyzed elsewhere in this journal issue. A study comparing
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the treatment of lentigo with this modality to IPL found that the improvement in the pigmentation area and severity index (PSI) was not different after twelve weeks. However,
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QSAL was associated with a greater incidence of post-inflammatory hyperpigmentation (PIH) after treatment. As such, IPL therapy should be preferred in patients at increased risk of this adverse outcome, which is particularly common in patients of Asian descent.29
ACCEPTED MANUSCRIPT Conclusions
Phototherapy encompasses a wide range of modalities that are safe and effective mechanisms to
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use in the treatment of several cosmetic disorders. Strong evidence currently exists to support the use of light in the treatment of melasma, solar lentigo, acne vulgaris, and hirtsuism. It may be
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useful as an adjunct in treating some disorders, such as hypertrophic scarring. Some conditions, such as onychomycosis, are unlikely to be effectively treated with light. However, as the role of
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light in cosmetic dermatology continues to be investigated, we may uncover that it is efficacious
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in other disorders.
ACCEPTED MANUSCRIPT References 1) Das, J, Reynolds, RV.: Recent Advances in Acne Pathogenesis: Implications for Therapy. Am
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J Clin Dermatol. 2014; 15:479-488.
2) Jung, YR, Kim, SJ, Sohn, KC, et al.: Regulation of lipid production by light-emitting diodes
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in human sebocytes. Arch Dermatol Res. 2015; 307:265-273.
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3) Smith, KR, Thiboutot, DM.: Sebaceous gland lipids: friend or foe? J Lipid Res. 2008; 49:271281.
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4) Liebmann, J, Born, M, Kolb-Bachofen, V.: Blue-Light Irradiation Regulates Proliferation and
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Differentiation in Human Skin Cells. J Invest Dermatol. 2010; 10:259-269. 5) Ashkenazi, H, Malik, Z, Harith, Y, et al.: Eradication of propionibacterum acnes by its
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Microbiol. 2003; 35:17-24.
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endogenic porphyrins after illumination with high intensity blue light. FEMS Immunol Med
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6) Maclean, M, MacGregor, SJ, Anderson, JG, et al.: The role of oxygen in the visible-light inactivation of Staphylococcus aureus. J Photochem Photobiol B. 2008; 92:180-194. 7) Ammad, S, Gonzales, M, Edwards, C, et al.: An assessment of the efficacy of blue light phototherapy in the treatment of acne vulgaris. J Cosmet Dermatol. 2008; 7:180-188. 8) Mustafa, FH, Jaafar, MS.: Comparison of wavelength-dependent penetration depths of lasers in different types of skin in photodynamic therapy. Indian J Physics. 2013; 87:203-209.
ACCEPTED MANUSCRIPT 9) Narurkar, VA, Gold, M, Shamban, AT.: Photopneumatic Technology Used in Combination with Profusion Therapy for the Treatment of Acne. J Clin Aesthet Dermatol. 2013; 6:36-40.
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10) Kwon, HH, Lee, JB, Yoon, JY, et al.: The clinical and histological effect of home-use, combination blue–red LED phototherapy for mild-to-moderate acne vulgaris in Korean patients:
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a doubleblind, randomized controlled trial. Br J Dermatol. 2013; 168:1088-1094. 11) Hellmann, J, Ramirez, CA.: Evaluation of Self-Treatment of Acne Using Silk‟n Blue
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Phototherapy System. JCDSA. 2014; 4:179-184.
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12) El-latif, AA, Hasaan, FA, Elshahed, AR, et al.: Intense pulsed light versus benzoyl peroxide 5% gel in treatment of acne vulgaris. Lasers Med Sci. 2014; 29:1009-1015.
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13) Kong, YL, Tey, HL.: Treatment of Acne Vulgaris During Pregnancy and Lactation. Drugs.
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14) Westerberg, DP, Voyack, MJ.: Onychomycosis: Current trends in diagnosis and treatment.
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Am Fam Physician. 2013; 88:762-770. 15) Cronin, LJ, Mildren, RP, Moffitt, M, et al.: An investigation into the inhibitory effect of ultraviolet light on Trichophytum rubrum. Lasers Med Sci. 2014; 29:157-163. 16) Goldman, MP, Eckhouse, S.: Photothermal sclerosis of leg veins. Dermatol Surg. 1996; 22:323-330. 17) Wat, H, Wu, DC, Rao, J, et al.: Application of intense pulsed light in the treatment of dermatologic disease: A systematic review. Dermatol Surg. 2014; 40:359-377.
ACCEPTED MANUSCRIPT 18) Gold, MH.: Lasers and light sources for the removal of unwanted hair. Clin Dermatol. 2007; 25:443-453.
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19) Gold, MH, Biron, JA, Thompson, B.: Clinical evaluation of a novel intense pulsed light source for facial skin hair removal for home use. J Clin Aesthet Dermatol. 2015; 8:30-35.
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20) Erol, OO, Gurlek, A, Agaoglu, G, et al.: Treatment of hypertrophic scars and keloids using
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intense pulsed light. Aesthetic Plast Surg. 2008; 32:902-909.
21) Meymandi, SS, Rezazadeh, A, Ekhlasi, A.: Studying intense pulsed light method along with
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corticosteroid injection in treating keloid scars. Iran Red Crescent Med J. 2014; 16:e12464. 22) Hultman, CS, Friedstat, JS, Edkins, RE.: Efficacy of intense pulsed light for the treatment of
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burn scar dyschromias: A pilot study to assess patient satisfaction, safety, and willingness to pay.
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Ann Plast Surg. 2015; 74:S204-208.
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23) Lee, AY.: Recent progress in melasma pathogenesis. Pigment Cell Melanoma Res. 2015;
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accepted for publication.
24) Yamashita, T, Negishi, K, Hariya, T, et al.: Intense pulsed light therapy for superficial pigmented lesions evaluated by reflectance-mode confocal microscopy and optical coherence tomography. J Invest Dermatol. 2006; 126:2281-2286. 25) Zoccali, G, Piccolo, D, Allegra, P, et al.: Melasma treated with intense pulsed light. Aesthetic Plast Surg. 2010; 34:486-493.
ACCEPTED MANUSCRIPT 26) Na, SY, Cho, S, Lee, JH.: Better clinical results with long term benefits in melasma patients. J Dermatol Treat. 2013; 24:112-118.
lentigines. Pigment Cell Melanoma Res. 2014; 27:339-350.
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27) Praetorius, C, Sturm, RA, Steingrimsson, E.: Sun induced freckling: Ephelides and solar
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28) Sasaya, H, Kawada, A, Wada, T., et al.: Clinical effectiveness of intense pulsed light therapy
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for solar lentigines of the hands. Dermatol Ther. 2011; 584-586. 29) Wang, CC, Sue, YM, Yahg, CH, et al.: A comparison of Q-switched alexandrite laser and
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intense pulsed light for treatment of freckles and lentigines in Asian persons: A randomized,
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physician-blinded, split-face comparative trial. J Am Acad Dermatol. 2006; 54;804-810.