Aesthetic Dermatology

Cosmetic procedures continued to increase in popularity in 2019, and body sculpting and laser/light/energy-based procedures led the way, according to a survey by the American Society of Dermatologic Surgery.

The number of cosmetic procedures performed by dermatologic surgeons increased by 14% from 2018 to 2019, with body-sculpting procedures jumping by almost 62%, the largest proportional rise among the major categories of cosmetic procedures, the ASDS reported in its annual member survey.

Use of laser/light/energy-based devices was up by a much lower 18%, but the increase in the actual number of procedures – nearly 637,000 more than 2018 – was larger than any other category, the ASDS said.

Procedures categorized as “other rejuvenation” – microneedling, platelet-rich plasma, hair rejuvenation, and thread lifts – were another bright spot in the cosmetic lineup in 2019, rising 38% over their 2018 volume. Injectable neuromodulator treatments, which were second in overall volume with almost 2.4 million procedures, were up by 12.5% in 2019, compared with 2018, the ASDS said.

The injectable soft-tissue fillers, however, did not produce any noteworthy gain in the volume of procedures for the second consecutive year. Meanwhile, the number of chemical peel procedures dropped by almost 16% in 2019 after rising for the last 2 years, the ASDS reported.

A closer look at the body-sculpting sector also shows some declines in 2019, despite the overall success: Cryolipolysis procedures were down by 10.3% and deoxycholic acid procedures slipped 13.7%. The biggest addition – over 157,000 procedures – came from muscle-toning devices, which were new to the survey last year, the ASDS noted.

The survey was conducted among the society’s members from May 7 to July 31, 2020, and the 514 responses were generalized to the entire ASDS membership of over 6,400 physicians.

[email protected]

Cosmetic procedures continued to increase in popularity in 2019, and body sculpting and laser/light/energy-based procedures led the way, according to a survey by the American Society of Dermatologic Surgery.

The number of cosmetic procedures performed by dermatologic surgeons increased by 14% from 2018 to 2019, with body-sculpting procedures jumping by almost 62%, the largest proportional rise among the major categories of cosmetic procedures, the ASDS reported in its annual member survey.

Use of laser/light/energy-based devices was up by a much lower 18%, but the increase in the actual number of procedures – nearly 637,000 more than 2018 – was larger than any other category, the ASDS said.

Procedures categorized as “other rejuvenation” – microneedling, platelet-rich plasma, hair rejuvenation, and thread lifts – were another bright spot in the cosmetic lineup in 2019, rising 38% over their 2018 volume. Injectable neuromodulator treatments, which were second in overall volume with almost 2.4 million procedures, were up by 12.5% in 2019, compared with 2018, the ASDS said.

The injectable soft-tissue fillers, however, did not produce any noteworthy gain in the volume of procedures for the second consecutive year. Meanwhile, the number of chemical peel procedures dropped by almost 16% in 2019 after rising for the last 2 years, the ASDS reported.

A closer look at the body-sculpting sector also shows some declines in 2019, despite the overall success: Cryolipolysis procedures were down by 10.3% and deoxycholic acid procedures slipped 13.7%. The biggest addition – over 157,000 procedures – came from muscle-toning devices, which were new to the survey last year, the ASDS noted.

The survey was conducted among the society’s members from May 7 to July 31, 2020, and the 514 responses were generalized to the entire ASDS membership of over 6,400 physicians.

[email protected]

Cosmetic procedures continued to increase in popularity in 2019, and body sculpting and laser/light/energy-based procedures led the way, according to a survey by the American Society of Dermatologic Surgery.

The number of cosmetic procedures performed by dermatologic surgeons increased by 14% from 2018 to 2019, with body-sculpting procedures jumping by almost 62%, the largest proportional rise among the major categories of cosmetic procedures, the ASDS reported in its annual member survey.

Use of laser/light/energy-based devices was up by a much lower 18%, but the increase in the actual number of procedures – nearly 637,000 more than 2018 – was larger than any other category, the ASDS said.

Procedures categorized as “other rejuvenation” – microneedling, platelet-rich plasma, hair rejuvenation, and thread lifts – were another bright spot in the cosmetic lineup in 2019, rising 38% over their 2018 volume. Injectable neuromodulator treatments, which were second in overall volume with almost 2.4 million procedures, were up by 12.5% in 2019, compared with 2018, the ASDS said.

The injectable soft-tissue fillers, however, did not produce any noteworthy gain in the volume of procedures for the second consecutive year. Meanwhile, the number of chemical peel procedures dropped by almost 16% in 2019 after rising for the last 2 years, the ASDS reported.

A closer look at the body-sculpting sector also shows some declines in 2019, despite the overall success: Cryolipolysis procedures were down by 10.3% and deoxycholic acid procedures slipped 13.7%. The biggest addition – over 157,000 procedures – came from muscle-toning devices, which were new to the survey last year, the ASDS noted.

The survey was conducted among the society’s members from May 7 to July 31, 2020, and the 514 responses were generalized to the entire ASDS membership of over 6,400 physicians.

[email protected]

By addressing the vascular component of melasma, off-label use of oral tranexamic acid has been a beneficial adjunct for this difficult-to-treat condition. For on-label use treating menorrhagia (the oral form) and short-term prophylaxis of bleeding in hemophilia patients undergoing dental procedures – (the injectable form), tranexamic acid acts as an antifibrinolytic.

By inhibiting plasminogen activation, according to a 2018 review article “tranexamic acid mitigates UV radiation–induced melanogenesis and neovascularization,” both exhibited in the clinical manifestations of melasma.¹ In addition to inhibiting fibrinolysis, tranexamic acid has direct effects on UV-induced pigmentation, “via its inhibitory effects on UV light–induced plasminogen activator on keratinocytes and [subsequent] plasmin activity,” the article states. “Plasminogen activator induces tyrosinase activity, resulting in increased melanin synthesis. The presence of plasmin [which dissolves clots by degrading fibrin] results in increased production of both arachidonic acid and fibroblast growth factor, which stimulate melanogenesis and neovascularization, respectively.”

With oral use, the risk of clot formation, especially in those who have a history of blood clots, clotting disorders (such as factor V Leiden), smoking, or other hypercoagulability risks should be weighed.

Topical tranexamic acid used locally mitigates systemic risk, and according to published studies, has been found to be efficacious for hemostasis in knee and hip arthroplasty surgery and for epistaxis. However, clinical outcomes with the topical treatment have largely not been on par with regards to efficacy for melasma when compared with oral tranexamic acid.

A potentially more efficacious way to deliver topical tranexamic acid for treating melasma and

pigmentation is with laser-assisted delivery. Topical tranexamic acid, in my experience, when applied immediately after fractional 1927-nm diode laser treatment, not only has been noted by patients to feel soothing, but anecdotally has been found to improve pigmentation.

Moreover, there are now several peer-reviewed studies showing some benefit for treating pigmentation from photodamage or melasma with laser-assisted delivery of topical tranexamic acid. Treatment of these conditions may also benefit from nonablative 1927-nm laser alone.

In one recently published study, 10 female melasma patients, Fitzpatrick skin types II-IV, underwent five full-face low-energy, low-density (power 4-5 W, fluence 2-8 mJ, 2-8 passes) 1927-nm fractional thulium fiber laser treatment.² Topical tranexamic acid was applied immediately after laser treatment and continued twice daily for 7 days. Seven patients completed the study. Based on the Global Aesthetics Improvement Scale (GAIS) ratings, all seven patients noted improvement at day 180, at which time six of the patients were considered to have improved from baseline, according to the investigator GAIS ratings. Using the Melasma Area Severity Index (MASI) score, the greatest degree of improvement was seen at day 90; there were three recurrences of melasma with worsening of the MASI score between day 90 and day 180.

In a split-face, double-blind, randomized controlled study, 46 patients with Fitzpatrick skin types III-V, with recalcitrant melasma received four weekly treatments of full-face fractional 1927-nm thulium laser; topical tranexamic acid was applied to one side of the face and normal saline applied to the other side under occlusion, immediately after treatment.³ At 3 months, significant improvements from baseline were seen with Melanin Index (MI) and modified MASI (mMASI) scores for the sides treated with tranexamic acid and the control side, with no statistically significant differences between the two. However, at month 6, among the 29 patients available for follow-up, significant differences in MI and mMASI scores from baseline were still evident, with the exception of MI scores on the control sides.

No adverse events from using topical tranexamic acid with laser were noted in either study. Split-face randomized control studies with use of topical tranexamic acid after fractional 1927-nm diode laser in comparison to fractional 1927-nm thulium laser would be notable in this vascular and heat-sensitive condition as well.

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.

References

1. Sheu SL. Cutis. 2018 Feb;101(2):E7-E8.

2. Wang, JV et al. J Cosmet Dermatol. 2021 Jan;20(1):105-9.

3. Wanitphakdeedecha R. et al. Lasers Med Sci. 2020 Dec;35(9):2015-21.

By addressing the vascular component of melasma, off-label use of oral tranexamic acid has been a beneficial adjunct for this difficult-to-treat condition. For on-label use treating menorrhagia (the oral form) and short-term prophylaxis of bleeding in hemophilia patients undergoing dental procedures – (the injectable form), tranexamic acid acts as an antifibrinolytic.

By inhibiting plasminogen activation, according to a 2018 review article “tranexamic acid mitigates UV radiation–induced melanogenesis and neovascularization,” both exhibited in the clinical manifestations of melasma.¹ In addition to inhibiting fibrinolysis, tranexamic acid has direct effects on UV-induced pigmentation, “via its inhibitory effects on UV light–induced plasminogen activator on keratinocytes and [subsequent] plasmin activity,” the article states. “Plasminogen activator induces tyrosinase activity, resulting in increased melanin synthesis. The presence of plasmin [which dissolves clots by degrading fibrin] results in increased production of both arachidonic acid and fibroblast growth factor, which stimulate melanogenesis and neovascularization, respectively.”

With oral use, the risk of clot formation, especially in those who have a history of blood clots, clotting disorders (such as factor V Leiden), smoking, or other hypercoagulability risks should be weighed.

Topical tranexamic acid used locally mitigates systemic risk, and according to published studies, has been found to be efficacious for hemostasis in knee and hip arthroplasty surgery and for epistaxis. However, clinical outcomes with the topical treatment have largely not been on par with regards to efficacy for melasma when compared with oral tranexamic acid.

A potentially more efficacious way to deliver topical tranexamic acid for treating melasma and

pigmentation is with laser-assisted delivery. Topical tranexamic acid, in my experience, when applied immediately after fractional 1927-nm diode laser treatment, not only has been noted by patients to feel soothing, but anecdotally has been found to improve pigmentation.

Moreover, there are now several peer-reviewed studies showing some benefit for treating pigmentation from photodamage or melasma with laser-assisted delivery of topical tranexamic acid. Treatment of these conditions may also benefit from nonablative 1927-nm laser alone.

In one recently published study, 10 female melasma patients, Fitzpatrick skin types II-IV, underwent five full-face low-energy, low-density (power 4-5 W, fluence 2-8 mJ, 2-8 passes) 1927-nm fractional thulium fiber laser treatment.² Topical tranexamic acid was applied immediately after laser treatment and continued twice daily for 7 days. Seven patients completed the study. Based on the Global Aesthetics Improvement Scale (GAIS) ratings, all seven patients noted improvement at day 180, at which time six of the patients were considered to have improved from baseline, according to the investigator GAIS ratings. Using the Melasma Area Severity Index (MASI) score, the greatest degree of improvement was seen at day 90; there were three recurrences of melasma with worsening of the MASI score between day 90 and day 180.

In a split-face, double-blind, randomized controlled study, 46 patients with Fitzpatrick skin types III-V, with recalcitrant melasma received four weekly treatments of full-face fractional 1927-nm thulium laser; topical tranexamic acid was applied to one side of the face and normal saline applied to the other side under occlusion, immediately after treatment.³ At 3 months, significant improvements from baseline were seen with Melanin Index (MI) and modified MASI (mMASI) scores for the sides treated with tranexamic acid and the control side, with no statistically significant differences between the two. However, at month 6, among the 29 patients available for follow-up, significant differences in MI and mMASI scores from baseline were still evident, with the exception of MI scores on the control sides.

No adverse events from using topical tranexamic acid with laser were noted in either study. Split-face randomized control studies with use of topical tranexamic acid after fractional 1927-nm diode laser in comparison to fractional 1927-nm thulium laser would be notable in this vascular and heat-sensitive condition as well.

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.

References

1. Sheu SL. Cutis. 2018 Feb;101(2):E7-E8.

2. Wang, JV et al. J Cosmet Dermatol. 2021 Jan;20(1):105-9.

3. Wanitphakdeedecha R. et al. Lasers Med Sci. 2020 Dec;35(9):2015-21.

By addressing the vascular component of melasma, off-label use of oral tranexamic acid has been a beneficial adjunct for this difficult-to-treat condition. For on-label use treating menorrhagia (the oral form) and short-term prophylaxis of bleeding in hemophilia patients undergoing dental procedures – (the injectable form), tranexamic acid acts as an antifibrinolytic.

By inhibiting plasminogen activation, according to a 2018 review article “tranexamic acid mitigates UV radiation–induced melanogenesis and neovascularization,” both exhibited in the clinical manifestations of melasma.¹ In addition to inhibiting fibrinolysis, tranexamic acid has direct effects on UV-induced pigmentation, “via its inhibitory effects on UV light–induced plasminogen activator on keratinocytes and [subsequent] plasmin activity,” the article states. “Plasminogen activator induces tyrosinase activity, resulting in increased melanin synthesis. The presence of plasmin [which dissolves clots by degrading fibrin] results in increased production of both arachidonic acid and fibroblast growth factor, which stimulate melanogenesis and neovascularization, respectively.”

With oral use, the risk of clot formation, especially in those who have a history of blood clots, clotting disorders (such as factor V Leiden), smoking, or other hypercoagulability risks should be weighed.

Topical tranexamic acid used locally mitigates systemic risk, and according to published studies, has been found to be efficacious for hemostasis in knee and hip arthroplasty surgery and for epistaxis. However, clinical outcomes with the topical treatment have largely not been on par with regards to efficacy for melasma when compared with oral tranexamic acid.

A potentially more efficacious way to deliver topical tranexamic acid for treating melasma and

pigmentation is with laser-assisted delivery. Topical tranexamic acid, in my experience, when applied immediately after fractional 1927-nm diode laser treatment, not only has been noted by patients to feel soothing, but anecdotally has been found to improve pigmentation.

Moreover, there are now several peer-reviewed studies showing some benefit for treating pigmentation from photodamage or melasma with laser-assisted delivery of topical tranexamic acid. Treatment of these conditions may also benefit from nonablative 1927-nm laser alone.

In one recently published study, 10 female melasma patients, Fitzpatrick skin types II-IV, underwent five full-face low-energy, low-density (power 4-5 W, fluence 2-8 mJ, 2-8 passes) 1927-nm fractional thulium fiber laser treatment.² Topical tranexamic acid was applied immediately after laser treatment and continued twice daily for 7 days. Seven patients completed the study. Based on the Global Aesthetics Improvement Scale (GAIS) ratings, all seven patients noted improvement at day 180, at which time six of the patients were considered to have improved from baseline, according to the investigator GAIS ratings. Using the Melasma Area Severity Index (MASI) score, the greatest degree of improvement was seen at day 90; there were three recurrences of melasma with worsening of the MASI score between day 90 and day 180.

In a split-face, double-blind, randomized controlled study, 46 patients with Fitzpatrick skin types III-V, with recalcitrant melasma received four weekly treatments of full-face fractional 1927-nm thulium laser; topical tranexamic acid was applied to one side of the face and normal saline applied to the other side under occlusion, immediately after treatment.³ At 3 months, significant improvements from baseline were seen with Melanin Index (MI) and modified MASI (mMASI) scores for the sides treated with tranexamic acid and the control side, with no statistically significant differences between the two. However, at month 6, among the 29 patients available for follow-up, significant differences in MI and mMASI scores from baseline were still evident, with the exception of MI scores on the control sides.

No adverse events from using topical tranexamic acid with laser were noted in either study. Split-face randomized control studies with use of topical tranexamic acid after fractional 1927-nm diode laser in comparison to fractional 1927-nm thulium laser would be notable in this vascular and heat-sensitive condition as well.

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.

References

1. Sheu SL. Cutis. 2018 Feb;101(2):E7-E8.

2. Wang, JV et al. J Cosmet Dermatol. 2021 Jan;20(1):105-9.

3. Wanitphakdeedecha R. et al. Lasers Med Sci. 2020 Dec;35(9):2015-21.

We continue with a focus on circadian rhythms and implications for skin care this month, paying particular attention to research or insights pertaining to specific skin conditions, when possible, as well as clinical studies that may shed light on how to time skin care treatments.

Francesca Bellini/iStock/Getty Images

It is important to remember that several studies in the last 20 years have revealed cutaneous tendencies based on the time of day. For instance, sebum production is known to be highest around noon, and pH also peaks during the day and is at its lowest at night.^1-5
 

Skin aging

In 2019, Dong and associates showed that blue light at 410 nm reduces PER1 transcription in keratinocytes, indicating that epidermal cells have the capacity to directly sense light and regulate their own clock gene expression. With the introduction of blue light at night, circadian rhythm is disrupted as epidermal skin cells act as if it is daytime. The investigators also considered blue light–induced damage to skin cells at various doses and exposure times in comparison with cells that remained unexposed to light. The production of reactive oxygen species increased in the exposed cells, as did DNA impairment and the emergence of inflammatory mediators, all of which have the potential to hasten aging.6

Early this year, Dong and associates demonstrated that melatonin can dose-dependently stimulate PER1 clock gene expression in normal human dermal fibroblasts and normal human epidermal keratinocytes, and verified that the MT-1 melatonin receptor in such fibroblasts manifests a marked decline with age. The researchers concluded that the melatonin pathway contributes significantly in cutaneous aging and impairment, and that its relationship with skin circadian rhythm points to a possible role in slowing the rate of skin aging through the modulation of cutaneous melatonin receptors.⁷
 

Wound healing

In 2019, Walker and associates investigated the effects of dim artificial light at night on wound healing in female C57BL/6 mice, and found that those conditions prior to wounding reduced healing. They concluded that such information might warrant consideration in prescribing treatment.⁸

Atopic dermatitis

Vaughn and associates contended that alterations in circadian rhythm may contribute to the development of atopic dermatitis.⁹ A good example of the impact of circadian rhythms on cutaneous health is the nocturnal exacerbation of atopic dermatitis, particularly in children.¹⁰

Psoriasis

According to Plikus and associates, recent evidence has emerged showing that the circadian clock regulates UVB-induced DNA damage and cutaneous cancers, and it is also associated with the immune-mediated disorder psoriasis.¹¹

Clinical studies

In 2018, Deshayes and associates conducted a clinical study to evaluate the precursors and stem cell attributes of hHF (human hair follicle keratinocytes), hEpi (human interfollicular epidermal keratinocytes), and hHFDP (hair follicle dermal papilla stem cells) in response to clock pathway changes caused by long-term deregulation of circadian rhythms. A total of 20 women participated in the study, 10 in each group (day workers were the control group and compared with shift workers). Two 3-mm fresh punch biopsies were collected from the occipital region of each participant. The investigators reported that chronic circadian rhythm deregulation influenced clock pathway protein expression and correlated with changes in hHF, hEpi, and hHFDP. They concluded that their findings represented the first data in humans suggesting that deregulation of the clock pathway modulates regenerative activity in human cutaneous and hair precursor cells.¹²

Later that year, Wu and associates reported on the role of the circadian clock in the transcriptional regulation of human epidermis. Investigators sampled 20 human participants through a 24-hour period and a population of 219 people once, finding a potent circadian oscillator in human epidermis at the population level, hundreds of rhythmically expressed genes, as well as a biomarker set for human epidermis that can, with one sample, highlight circadian phase within a 3-hour time frame. The team concluded that rhythms in human epidermis persist at the population level, and that they were able to present an effective single-sample circadian biomarker.¹³ This is important, as Morris pointed out, because the standard practice for measuring an individual’s internal clock is to use a dim-light melatonin onset assay over the course of a day.¹⁴ In 2019, Jia and associates studied the skin surface lipid profiles of young women to evaluate and characterize circadian human facial surface lipid composition. The investigators identified significant markers of circadian rhythm, with glycerolipids most affected. They ascribed changes in skin barrier function, such as variable pH and transepidermal water loss, to alterations in triacylglycerol levels as well as free fatty acid chain lengths and content that were affected by variations in circadian rhythm.¹⁵
 

Sleep and the timing of topicals

Based on their recent review of the literature on circadian rhythm and skin, Lyons and associates argued that an understanding of circadian rhythm helps dermatologists in recommending the optimal times for patients to apply topical medications. They added that urging patients to get sufficient sleep is important because DNA repair of the skin occurs best at that time.¹⁶

Conclusions

Doctors have known for half a century that timing drug delivery to a patient’s circadian clock can enhance outcomes. Chronobiological research into how circadian rhythms work at the cellular level, and in cutaneous cells in particular, is a fascinating and expanding area of inquiry that could help dermatologists more accurately recommend timing for skin care regimens. Much more research, especially in clinical trials, is necessary to further elucidate how to best work with the skin’s natural rhythms.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions, a company that independently tests skin care products and makes recommendations to physicians on skin care technologies. Write to her at [email protected].

References

1. Mehling A et al. Skin Pharmacol Physiol. 2006;19(4):182-9.

2. Latreille J et al. Skin Pharmacol Physiol. 2004 May-Jun;17(3):133-40.

3. Le Fur I et al. J Invest Dermatol. 2001 Sep;117(3):718-24.

4. Verschoore M et al. Chronobiol Int. 1993 Oct;10(5):349-59.

5. Yosipovitch G et al. J Invest Dermatol. 1998 Jan;110(1):20-3.

6. Dong K et al. Int J Cosmet Sci. 2019 Dec;41(6):558-62.

7. Dong K et al. Int J Mol Sci. 2020 Jan 3;21(1):326.

8. Walker WH II et al. Arch Dermatol Res. 2019 Sep;311(7):573-6.

9. Vaughn AR et al. Pediatr Dermatol. 2018 Jan;35(1):152-7.

10. Fishbein AB et al. J Allergy Clin Immunol. 2015 Nov;136(5):1170-7.

11. Plikus MV et al. J Biol Rhythms. 2015 Jun;30(3):163-82.

12. Deshayes N et al. Eur J Dermatol. 2018 Aug 1;28(4):467-75.

13. Wu G et al. Proc Natl Acad Sci U S A. 2018 Nov 27;115(48):12313-8.

14. Morris A. Nat Rev Endocrinol. 2018 Dec;15(1):3.

15. Jia Y et al. Exp Dermatol. 2019 Jul;28(7):858-62.

16. Lyons AB et al. J Clin Aesthet Dermatol. 2019 Sep;12(9):42-5.
 

We continue with a focus on circadian rhythms and implications for skin care this month, paying particular attention to research or insights pertaining to specific skin conditions, when possible, as well as clinical studies that may shed light on how to time skin care treatments.

Francesca Bellini/iStock/Getty Images

It is important to remember that several studies in the last 20 years have revealed cutaneous tendencies based on the time of day. For instance, sebum production is known to be highest around noon, and pH also peaks during the day and is at its lowest at night.^1-5
 

Skin aging

In 2019, Dong and associates showed that blue light at 410 nm reduces PER1 transcription in keratinocytes, indicating that epidermal cells have the capacity to directly sense light and regulate their own clock gene expression. With the introduction of blue light at night, circadian rhythm is disrupted as epidermal skin cells act as if it is daytime. The investigators also considered blue light–induced damage to skin cells at various doses and exposure times in comparison with cells that remained unexposed to light. The production of reactive oxygen species increased in the exposed cells, as did DNA impairment and the emergence of inflammatory mediators, all of which have the potential to hasten aging.6

Early this year, Dong and associates demonstrated that melatonin can dose-dependently stimulate PER1 clock gene expression in normal human dermal fibroblasts and normal human epidermal keratinocytes, and verified that the MT-1 melatonin receptor in such fibroblasts manifests a marked decline with age. The researchers concluded that the melatonin pathway contributes significantly in cutaneous aging and impairment, and that its relationship with skin circadian rhythm points to a possible role in slowing the rate of skin aging through the modulation of cutaneous melatonin receptors.⁷
 

Wound healing

In 2019, Walker and associates investigated the effects of dim artificial light at night on wound healing in female C57BL/6 mice, and found that those conditions prior to wounding reduced healing. They concluded that such information might warrant consideration in prescribing treatment.⁸

Atopic dermatitis

Vaughn and associates contended that alterations in circadian rhythm may contribute to the development of atopic dermatitis.⁹ A good example of the impact of circadian rhythms on cutaneous health is the nocturnal exacerbation of atopic dermatitis, particularly in children.¹⁰

Psoriasis

According to Plikus and associates, recent evidence has emerged showing that the circadian clock regulates UVB-induced DNA damage and cutaneous cancers, and it is also associated with the immune-mediated disorder psoriasis.¹¹

Clinical studies

In 2018, Deshayes and associates conducted a clinical study to evaluate the precursors and stem cell attributes of hHF (human hair follicle keratinocytes), hEpi (human interfollicular epidermal keratinocytes), and hHFDP (hair follicle dermal papilla stem cells) in response to clock pathway changes caused by long-term deregulation of circadian rhythms. A total of 20 women participated in the study, 10 in each group (day workers were the control group and compared with shift workers). Two 3-mm fresh punch biopsies were collected from the occipital region of each participant. The investigators reported that chronic circadian rhythm deregulation influenced clock pathway protein expression and correlated with changes in hHF, hEpi, and hHFDP. They concluded that their findings represented the first data in humans suggesting that deregulation of the clock pathway modulates regenerative activity in human cutaneous and hair precursor cells.¹²

Later that year, Wu and associates reported on the role of the circadian clock in the transcriptional regulation of human epidermis. Investigators sampled 20 human participants through a 24-hour period and a population of 219 people once, finding a potent circadian oscillator in human epidermis at the population level, hundreds of rhythmically expressed genes, as well as a biomarker set for human epidermis that can, with one sample, highlight circadian phase within a 3-hour time frame. The team concluded that rhythms in human epidermis persist at the population level, and that they were able to present an effective single-sample circadian biomarker.¹³ This is important, as Morris pointed out, because the standard practice for measuring an individual’s internal clock is to use a dim-light melatonin onset assay over the course of a day.¹⁴ In 2019, Jia and associates studied the skin surface lipid profiles of young women to evaluate and characterize circadian human facial surface lipid composition. The investigators identified significant markers of circadian rhythm, with glycerolipids most affected. They ascribed changes in skin barrier function, such as variable pH and transepidermal water loss, to alterations in triacylglycerol levels as well as free fatty acid chain lengths and content that were affected by variations in circadian rhythm.¹⁵
 

Sleep and the timing of topicals

Based on their recent review of the literature on circadian rhythm and skin, Lyons and associates argued that an understanding of circadian rhythm helps dermatologists in recommending the optimal times for patients to apply topical medications. They added that urging patients to get sufficient sleep is important because DNA repair of the skin occurs best at that time.¹⁶

Conclusions

Doctors have known for half a century that timing drug delivery to a patient’s circadian clock can enhance outcomes. Chronobiological research into how circadian rhythms work at the cellular level, and in cutaneous cells in particular, is a fascinating and expanding area of inquiry that could help dermatologists more accurately recommend timing for skin care regimens. Much more research, especially in clinical trials, is necessary to further elucidate how to best work with the skin’s natural rhythms.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions, a company that independently tests skin care products and makes recommendations to physicians on skin care technologies. Write to her at [email protected].

References

1. Mehling A et al. Skin Pharmacol Physiol. 2006;19(4):182-9.

2. Latreille J et al. Skin Pharmacol Physiol. 2004 May-Jun;17(3):133-40.

3. Le Fur I et al. J Invest Dermatol. 2001 Sep;117(3):718-24.

4. Verschoore M et al. Chronobiol Int. 1993 Oct;10(5):349-59.

5. Yosipovitch G et al. J Invest Dermatol. 1998 Jan;110(1):20-3.

6. Dong K et al. Int J Cosmet Sci. 2019 Dec;41(6):558-62.

7. Dong K et al. Int J Mol Sci. 2020 Jan 3;21(1):326.

8. Walker WH II et al. Arch Dermatol Res. 2019 Sep;311(7):573-6.

9. Vaughn AR et al. Pediatr Dermatol. 2018 Jan;35(1):152-7.

10. Fishbein AB et al. J Allergy Clin Immunol. 2015 Nov;136(5):1170-7.

11. Plikus MV et al. J Biol Rhythms. 2015 Jun;30(3):163-82.

12. Deshayes N et al. Eur J Dermatol. 2018 Aug 1;28(4):467-75.

13. Wu G et al. Proc Natl Acad Sci U S A. 2018 Nov 27;115(48):12313-8.

14. Morris A. Nat Rev Endocrinol. 2018 Dec;15(1):3.

15. Jia Y et al. Exp Dermatol. 2019 Jul;28(7):858-62.

16. Lyons AB et al. J Clin Aesthet Dermatol. 2019 Sep;12(9):42-5.
 

We continue with a focus on circadian rhythms and implications for skin care this month, paying particular attention to research or insights pertaining to specific skin conditions, when possible, as well as clinical studies that may shed light on how to time skin care treatments.

Francesca Bellini/iStock/Getty Images

It is important to remember that several studies in the last 20 years have revealed cutaneous tendencies based on the time of day. For instance, sebum production is known to be highest around noon, and pH also peaks during the day and is at its lowest at night.^1-5
 

Skin aging

In 2019, Dong and associates showed that blue light at 410 nm reduces PER1 transcription in keratinocytes, indicating that epidermal cells have the capacity to directly sense light and regulate their own clock gene expression. With the introduction of blue light at night, circadian rhythm is disrupted as epidermal skin cells act as if it is daytime. The investigators also considered blue light–induced damage to skin cells at various doses and exposure times in comparison with cells that remained unexposed to light. The production of reactive oxygen species increased in the exposed cells, as did DNA impairment and the emergence of inflammatory mediators, all of which have the potential to hasten aging.6

Early this year, Dong and associates demonstrated that melatonin can dose-dependently stimulate PER1 clock gene expression in normal human dermal fibroblasts and normal human epidermal keratinocytes, and verified that the MT-1 melatonin receptor in such fibroblasts manifests a marked decline with age. The researchers concluded that the melatonin pathway contributes significantly in cutaneous aging and impairment, and that its relationship with skin circadian rhythm points to a possible role in slowing the rate of skin aging through the modulation of cutaneous melatonin receptors.⁷
 

Wound healing

In 2019, Walker and associates investigated the effects of dim artificial light at night on wound healing in female C57BL/6 mice, and found that those conditions prior to wounding reduced healing. They concluded that such information might warrant consideration in prescribing treatment.⁸

Atopic dermatitis

Vaughn and associates contended that alterations in circadian rhythm may contribute to the development of atopic dermatitis.⁹ A good example of the impact of circadian rhythms on cutaneous health is the nocturnal exacerbation of atopic dermatitis, particularly in children.¹⁰

Psoriasis

According to Plikus and associates, recent evidence has emerged showing that the circadian clock regulates UVB-induced DNA damage and cutaneous cancers, and it is also associated with the immune-mediated disorder psoriasis.¹¹

Clinical studies

In 2018, Deshayes and associates conducted a clinical study to evaluate the precursors and stem cell attributes of hHF (human hair follicle keratinocytes), hEpi (human interfollicular epidermal keratinocytes), and hHFDP (hair follicle dermal papilla stem cells) in response to clock pathway changes caused by long-term deregulation of circadian rhythms. A total of 20 women participated in the study, 10 in each group (day workers were the control group and compared with shift workers). Two 3-mm fresh punch biopsies were collected from the occipital region of each participant. The investigators reported that chronic circadian rhythm deregulation influenced clock pathway protein expression and correlated with changes in hHF, hEpi, and hHFDP. They concluded that their findings represented the first data in humans suggesting that deregulation of the clock pathway modulates regenerative activity in human cutaneous and hair precursor cells.¹²

Later that year, Wu and associates reported on the role of the circadian clock in the transcriptional regulation of human epidermis. Investigators sampled 20 human participants through a 24-hour period and a population of 219 people once, finding a potent circadian oscillator in human epidermis at the population level, hundreds of rhythmically expressed genes, as well as a biomarker set for human epidermis that can, with one sample, highlight circadian phase within a 3-hour time frame. The team concluded that rhythms in human epidermis persist at the population level, and that they were able to present an effective single-sample circadian biomarker.¹³ This is important, as Morris pointed out, because the standard practice for measuring an individual’s internal clock is to use a dim-light melatonin onset assay over the course of a day.¹⁴ In 2019, Jia and associates studied the skin surface lipid profiles of young women to evaluate and characterize circadian human facial surface lipid composition. The investigators identified significant markers of circadian rhythm, with glycerolipids most affected. They ascribed changes in skin barrier function, such as variable pH and transepidermal water loss, to alterations in triacylglycerol levels as well as free fatty acid chain lengths and content that were affected by variations in circadian rhythm.¹⁵
 

Sleep and the timing of topicals

Based on their recent review of the literature on circadian rhythm and skin, Lyons and associates argued that an understanding of circadian rhythm helps dermatologists in recommending the optimal times for patients to apply topical medications. They added that urging patients to get sufficient sleep is important because DNA repair of the skin occurs best at that time.¹⁶

Conclusions

Doctors have known for half a century that timing drug delivery to a patient’s circadian clock can enhance outcomes. Chronobiological research into how circadian rhythms work at the cellular level, and in cutaneous cells in particular, is a fascinating and expanding area of inquiry that could help dermatologists more accurately recommend timing for skin care regimens. Much more research, especially in clinical trials, is necessary to further elucidate how to best work with the skin’s natural rhythms.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions, a company that independently tests skin care products and makes recommendations to physicians on skin care technologies. Write to her at [email protected].

References

1. Mehling A et al. Skin Pharmacol Physiol. 2006;19(4):182-9.

2. Latreille J et al. Skin Pharmacol Physiol. 2004 May-Jun;17(3):133-40.

3. Le Fur I et al. J Invest Dermatol. 2001 Sep;117(3):718-24.

4. Verschoore M et al. Chronobiol Int. 1993 Oct;10(5):349-59.

5. Yosipovitch G et al. J Invest Dermatol. 1998 Jan;110(1):20-3.

6. Dong K et al. Int J Cosmet Sci. 2019 Dec;41(6):558-62.

7. Dong K et al. Int J Mol Sci. 2020 Jan 3;21(1):326.

8. Walker WH II et al. Arch Dermatol Res. 2019 Sep;311(7):573-6.

9. Vaughn AR et al. Pediatr Dermatol. 2018 Jan;35(1):152-7.

10. Fishbein AB et al. J Allergy Clin Immunol. 2015 Nov;136(5):1170-7.

11. Plikus MV et al. J Biol Rhythms. 2015 Jun;30(3):163-82.

12. Deshayes N et al. Eur J Dermatol. 2018 Aug 1;28(4):467-75.

13. Wu G et al. Proc Natl Acad Sci U S A. 2018 Nov 27;115(48):12313-8.

14. Morris A. Nat Rev Endocrinol. 2018 Dec;15(1):3.

15. Jia Y et al. Exp Dermatol. 2019 Jul;28(7):858-62.

16. Lyons AB et al. J Clin Aesthet Dermatol. 2019 Sep;12(9):42-5.
 

Full-field ablative laser resurfacing may be an “oldie but a goodie” technique, but it remains a gold standard for skin rejuvenation, according to Brian S. Biesman, MD.

“When performing laser skin resurfacing, our goal is to match the degree of injury to the needs of the patient we’re treating,” Dr. Biesman, an oculofacial plastic surgeon who practices in Nashville, Tenn., said during a virtual course on laser and aesthetic skin therapy.

“If we’re treating a 35-year-old with minimal photoaging, we don’t need to use full-field resurfacing. By the same token, a 60-year-old who’s never had anything but sun exposure is not going to do well with nonablative fractional resurfacing or other modalities that produce only modest changes,” he noted. “Full ablative resurfacing is a useful tool that can be used to treat a variety of patients. We can tailor each treatment to the individual patient. We can simply dial the energy up or down and adjust the density.”

Full-field laser ablation removes the epidermis as well as a part of the dermis, and the degree of dermal injury varies depending on the relative aggressiveness of the treatment. “We can treat very superficially in the dermis or we can do deep dermal treatments,” he said at the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine.

“The residual thermal injury will vary to some degree, depending on our treatment parameters. It does cause immediate collagen contracture. It also stimulates a process of neocollagenesis.”

Two main lasers used for full-field treatments are the erbium:YAG laser and the CO₂ laser at wavelengths of 2,940 nm and 10,600 nm, respectively. “The erbium:YAG is far more highly absorbed by water, by a factor of about 13,” he said. “But both of these wavelengths can be used successfully as long as you understand the physics behind them.”

The short-pulsed erbium:YAG laser ablates effectively, producing about a 10 mcm zone of thermal injury. “That’s not going to induce much by the way of remodeling, but it will be effective in removing tissue from the superficial layers of the skin,” said Dr. Biesman, who is a past president of the American Society for Laser Medicine and Surgery. “There’s also an absorption peak for collagen, so if you’re treating a scar, this laser can be highly effective.”

The CO₂ laser creates more residual thermal injury during full-field resurfacing, compared with the short-pulsed erbium:YAG laser. The long-pulsed erbium:YAG laser can be used in both short- and long-pulsed modes and is more ablative than the CO₂ laser when used in short-pulsed mode. When used in long-pulse mode, it makes it possible to produce results “very similar to CO₂ in terms of the thermal injury profile,” he said. “It’s a versatile device. So, the CO₂ in its native mode produces more thermal injury, while the erbium:YAG laser is more ablative. Both can be used effectively for facial skin rejuvenation.”

Full-field laser resurfacing requires local infiltration with lidocaine 1% or 2% with epinephrine or general anesthesia. “This is not a treatment that you can do comfortably under topical anesthesia, even if you’re using cold air unless you are doing treatments essentially confined to the epidermis and superficial dermis,” Dr. Biesman said. “When working around the eyes or on the face you need to use ocular protection with metal ocular shields. There’s no two ways about it. There is no scenario in which you’re doing an ablative resurfacing around the eye where you don’t use metal corneal shields.”

Energy and density levels can be fine-tuned in order to optimize treatment. For deep rhytides in the perioral region or on the forehead or lateral cheeks, clinicians may choose to treat at a higher density, while rhytides located in other areas may respond well to treatments at a lower density. Relative danger zones include the eyelids in general, especially the medial lower eyelid, as well as the upper lip. “These are the areas that are most prone to developing scarring,” he said.

For the upper eyelids, Dr. Biesman treats from the lashes to the upper brow. “It’s important to protect the lashes and treat from the lower-lid margin all the way down to the orbital rim. I debride relatively aggressively. I want to debride all the eschar created by the first pass and come back with a second pass. I sometimes will decrease the density on the second pass, depending on the type of tissue response that I see. If I see a dramatic response on the second pass I will definitely decrease the density.” He uses Aquaphor to protect the eyebrows. “It’s difficult to do that on the lashes. For the lashes, I usually use a wet tongue blade and keep the lid on stretch as I do my treatments.”

Dr. Biesman recommends feathering to blend full-field treatments with the neck. This means bringing treatments below the mandible. “There are times when we want to conservatively treat the neck,” he said. “The neck does not recover nearly as well after ablative resurfacing as the face does due to the fact that there’s probably about 90% fewer sebaceous glands and hair follicles in the neck relative to the face.”

In Dr. Biesman’s opinion, the important perioperative preparation is counseling the patient, including setting realistic expectations and devising a plan for wound care. “They can expect 7-10 days to heal, depending on the area we’re treating and the relative aggressiveness of the planned treatment,” he said. For patients with a history of herpes simplex virus type 1, he recommends antiviral treatment prior to the procedure. “If you do encounter a herpetic infection postoperatively, you may not see typical clinical signs of blistering as the epidermis has been removed.”

Dr. Biesman uses both antiviral and antibiotic prophylaxis prior to full-field treatments. “The literature by and large says that antibiotic/antiviral prophylaxis is not required prior to full-face ablation,” he said. “The reason I choose to is that I have had some issues with community-acquired MRSA infections. Because it’s so ubiquitous these days, I typically do prescribe an agent that gives good MRSA coverage.”

As for wound care, the literature differs on open versus closed techniques. Dr. Biesman favors using Aquaphor for the first week or so and seeing patients back on posttreatment day 2, “who by that time are usually beyond the inflammatory phase of wound healing,” he said. “A lot of the initial oozing has stopped by then. We clean that off any dried exudate in the office very carefully. We debride gently with warm-water soaks and I like to use PRP [platelet-rich plasma]. There is literature to support the role of PRP in wound healing.”

Even in the most experienced hands, complications can occur from full-field laser resurfacing, including bacterial, viral, or fungal infections. Other potential complications include persistent erythema, hypopigmentation, hyperpigmentation, scarring, and ectropion. “Knowledge of treatment parameters, endpoints, and wound healing is required for safe and successful outcomes,” Dr. Biesman said.

He reported having no relevant disclosures related to his presentation.

[email protected]

Full-field ablative laser resurfacing may be an “oldie but a goodie” technique, but it remains a gold standard for skin rejuvenation, according to Brian S. Biesman, MD.

“When performing laser skin resurfacing, our goal is to match the degree of injury to the needs of the patient we’re treating,” Dr. Biesman, an oculofacial plastic surgeon who practices in Nashville, Tenn., said during a virtual course on laser and aesthetic skin therapy.

“If we’re treating a 35-year-old with minimal photoaging, we don’t need to use full-field resurfacing. By the same token, a 60-year-old who’s never had anything but sun exposure is not going to do well with nonablative fractional resurfacing or other modalities that produce only modest changes,” he noted. “Full ablative resurfacing is a useful tool that can be used to treat a variety of patients. We can tailor each treatment to the individual patient. We can simply dial the energy up or down and adjust the density.”

Full-field laser ablation removes the epidermis as well as a part of the dermis, and the degree of dermal injury varies depending on the relative aggressiveness of the treatment. “We can treat very superficially in the dermis or we can do deep dermal treatments,” he said at the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine.

“The residual thermal injury will vary to some degree, depending on our treatment parameters. It does cause immediate collagen contracture. It also stimulates a process of neocollagenesis.”

Two main lasers used for full-field treatments are the erbium:YAG laser and the CO₂ laser at wavelengths of 2,940 nm and 10,600 nm, respectively. “The erbium:YAG is far more highly absorbed by water, by a factor of about 13,” he said. “But both of these wavelengths can be used successfully as long as you understand the physics behind them.”

The short-pulsed erbium:YAG laser ablates effectively, producing about a 10 mcm zone of thermal injury. “That’s not going to induce much by the way of remodeling, but it will be effective in removing tissue from the superficial layers of the skin,” said Dr. Biesman, who is a past president of the American Society for Laser Medicine and Surgery. “There’s also an absorption peak for collagen, so if you’re treating a scar, this laser can be highly effective.”

The CO₂ laser creates more residual thermal injury during full-field resurfacing, compared with the short-pulsed erbium:YAG laser. The long-pulsed erbium:YAG laser can be used in both short- and long-pulsed modes and is more ablative than the CO₂ laser when used in short-pulsed mode. When used in long-pulse mode, it makes it possible to produce results “very similar to CO₂ in terms of the thermal injury profile,” he said. “It’s a versatile device. So, the CO₂ in its native mode produces more thermal injury, while the erbium:YAG laser is more ablative. Both can be used effectively for facial skin rejuvenation.”

Full-field laser resurfacing requires local infiltration with lidocaine 1% or 2% with epinephrine or general anesthesia. “This is not a treatment that you can do comfortably under topical anesthesia, even if you’re using cold air unless you are doing treatments essentially confined to the epidermis and superficial dermis,” Dr. Biesman said. “When working around the eyes or on the face you need to use ocular protection with metal ocular shields. There’s no two ways about it. There is no scenario in which you’re doing an ablative resurfacing around the eye where you don’t use metal corneal shields.”

Energy and density levels can be fine-tuned in order to optimize treatment. For deep rhytides in the perioral region or on the forehead or lateral cheeks, clinicians may choose to treat at a higher density, while rhytides located in other areas may respond well to treatments at a lower density. Relative danger zones include the eyelids in general, especially the medial lower eyelid, as well as the upper lip. “These are the areas that are most prone to developing scarring,” he said.

For the upper eyelids, Dr. Biesman treats from the lashes to the upper brow. “It’s important to protect the lashes and treat from the lower-lid margin all the way down to the orbital rim. I debride relatively aggressively. I want to debride all the eschar created by the first pass and come back with a second pass. I sometimes will decrease the density on the second pass, depending on the type of tissue response that I see. If I see a dramatic response on the second pass I will definitely decrease the density.” He uses Aquaphor to protect the eyebrows. “It’s difficult to do that on the lashes. For the lashes, I usually use a wet tongue blade and keep the lid on stretch as I do my treatments.”

Dr. Biesman recommends feathering to blend full-field treatments with the neck. This means bringing treatments below the mandible. “There are times when we want to conservatively treat the neck,” he said. “The neck does not recover nearly as well after ablative resurfacing as the face does due to the fact that there’s probably about 90% fewer sebaceous glands and hair follicles in the neck relative to the face.”

In Dr. Biesman’s opinion, the important perioperative preparation is counseling the patient, including setting realistic expectations and devising a plan for wound care. “They can expect 7-10 days to heal, depending on the area we’re treating and the relative aggressiveness of the planned treatment,” he said. For patients with a history of herpes simplex virus type 1, he recommends antiviral treatment prior to the procedure. “If you do encounter a herpetic infection postoperatively, you may not see typical clinical signs of blistering as the epidermis has been removed.”

Dr. Biesman uses both antiviral and antibiotic prophylaxis prior to full-field treatments. “The literature by and large says that antibiotic/antiviral prophylaxis is not required prior to full-face ablation,” he said. “The reason I choose to is that I have had some issues with community-acquired MRSA infections. Because it’s so ubiquitous these days, I typically do prescribe an agent that gives good MRSA coverage.”

As for wound care, the literature differs on open versus closed techniques. Dr. Biesman favors using Aquaphor for the first week or so and seeing patients back on posttreatment day 2, “who by that time are usually beyond the inflammatory phase of wound healing,” he said. “A lot of the initial oozing has stopped by then. We clean that off any dried exudate in the office very carefully. We debride gently with warm-water soaks and I like to use PRP [platelet-rich plasma]. There is literature to support the role of PRP in wound healing.”

Even in the most experienced hands, complications can occur from full-field laser resurfacing, including bacterial, viral, or fungal infections. Other potential complications include persistent erythema, hypopigmentation, hyperpigmentation, scarring, and ectropion. “Knowledge of treatment parameters, endpoints, and wound healing is required for safe and successful outcomes,” Dr. Biesman said.

He reported having no relevant disclosures related to his presentation.

[email protected]

Full-field ablative laser resurfacing may be an “oldie but a goodie” technique, but it remains a gold standard for skin rejuvenation, according to Brian S. Biesman, MD.

“When performing laser skin resurfacing, our goal is to match the degree of injury to the needs of the patient we’re treating,” Dr. Biesman, an oculofacial plastic surgeon who practices in Nashville, Tenn., said during a virtual course on laser and aesthetic skin therapy.

“If we’re treating a 35-year-old with minimal photoaging, we don’t need to use full-field resurfacing. By the same token, a 60-year-old who’s never had anything but sun exposure is not going to do well with nonablative fractional resurfacing or other modalities that produce only modest changes,” he noted. “Full ablative resurfacing is a useful tool that can be used to treat a variety of patients. We can tailor each treatment to the individual patient. We can simply dial the energy up or down and adjust the density.”

Full-field laser ablation removes the epidermis as well as a part of the dermis, and the degree of dermal injury varies depending on the relative aggressiveness of the treatment. “We can treat very superficially in the dermis or we can do deep dermal treatments,” he said at the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine.

“The residual thermal injury will vary to some degree, depending on our treatment parameters. It does cause immediate collagen contracture. It also stimulates a process of neocollagenesis.”

Two main lasers used for full-field treatments are the erbium:YAG laser and the CO₂ laser at wavelengths of 2,940 nm and 10,600 nm, respectively. “The erbium:YAG is far more highly absorbed by water, by a factor of about 13,” he said. “But both of these wavelengths can be used successfully as long as you understand the physics behind them.”

The short-pulsed erbium:YAG laser ablates effectively, producing about a 10 mcm zone of thermal injury. “That’s not going to induce much by the way of remodeling, but it will be effective in removing tissue from the superficial layers of the skin,” said Dr. Biesman, who is a past president of the American Society for Laser Medicine and Surgery. “There’s also an absorption peak for collagen, so if you’re treating a scar, this laser can be highly effective.”

The CO₂ laser creates more residual thermal injury during full-field resurfacing, compared with the short-pulsed erbium:YAG laser. The long-pulsed erbium:YAG laser can be used in both short- and long-pulsed modes and is more ablative than the CO₂ laser when used in short-pulsed mode. When used in long-pulse mode, it makes it possible to produce results “very similar to CO₂ in terms of the thermal injury profile,” he said. “It’s a versatile device. So, the CO₂ in its native mode produces more thermal injury, while the erbium:YAG laser is more ablative. Both can be used effectively for facial skin rejuvenation.”

Full-field laser resurfacing requires local infiltration with lidocaine 1% or 2% with epinephrine or general anesthesia. “This is not a treatment that you can do comfortably under topical anesthesia, even if you’re using cold air unless you are doing treatments essentially confined to the epidermis and superficial dermis,” Dr. Biesman said. “When working around the eyes or on the face you need to use ocular protection with metal ocular shields. There’s no two ways about it. There is no scenario in which you’re doing an ablative resurfacing around the eye where you don’t use metal corneal shields.”

Energy and density levels can be fine-tuned in order to optimize treatment. For deep rhytides in the perioral region or on the forehead or lateral cheeks, clinicians may choose to treat at a higher density, while rhytides located in other areas may respond well to treatments at a lower density. Relative danger zones include the eyelids in general, especially the medial lower eyelid, as well as the upper lip. “These are the areas that are most prone to developing scarring,” he said.

For the upper eyelids, Dr. Biesman treats from the lashes to the upper brow. “It’s important to protect the lashes and treat from the lower-lid margin all the way down to the orbital rim. I debride relatively aggressively. I want to debride all the eschar created by the first pass and come back with a second pass. I sometimes will decrease the density on the second pass, depending on the type of tissue response that I see. If I see a dramatic response on the second pass I will definitely decrease the density.” He uses Aquaphor to protect the eyebrows. “It’s difficult to do that on the lashes. For the lashes, I usually use a wet tongue blade and keep the lid on stretch as I do my treatments.”

Dr. Biesman recommends feathering to blend full-field treatments with the neck. This means bringing treatments below the mandible. “There are times when we want to conservatively treat the neck,” he said. “The neck does not recover nearly as well after ablative resurfacing as the face does due to the fact that there’s probably about 90% fewer sebaceous glands and hair follicles in the neck relative to the face.”

In Dr. Biesman’s opinion, the important perioperative preparation is counseling the patient, including setting realistic expectations and devising a plan for wound care. “They can expect 7-10 days to heal, depending on the area we’re treating and the relative aggressiveness of the planned treatment,” he said. For patients with a history of herpes simplex virus type 1, he recommends antiviral treatment prior to the procedure. “If you do encounter a herpetic infection postoperatively, you may not see typical clinical signs of blistering as the epidermis has been removed.”

Dr. Biesman uses both antiviral and antibiotic prophylaxis prior to full-field treatments. “The literature by and large says that antibiotic/antiviral prophylaxis is not required prior to full-face ablation,” he said. “The reason I choose to is that I have had some issues with community-acquired MRSA infections. Because it’s so ubiquitous these days, I typically do prescribe an agent that gives good MRSA coverage.”

As for wound care, the literature differs on open versus closed techniques. Dr. Biesman favors using Aquaphor for the first week or so and seeing patients back on posttreatment day 2, “who by that time are usually beyond the inflammatory phase of wound healing,” he said. “A lot of the initial oozing has stopped by then. We clean that off any dried exudate in the office very carefully. We debride gently with warm-water soaks and I like to use PRP [platelet-rich plasma]. There is literature to support the role of PRP in wound healing.”

Even in the most experienced hands, complications can occur from full-field laser resurfacing, including bacterial, viral, or fungal infections. Other potential complications include persistent erythema, hypopigmentation, hyperpigmentation, scarring, and ectropion. “Knowledge of treatment parameters, endpoints, and wound healing is required for safe and successful outcomes,” Dr. Biesman said.

He reported having no relevant disclosures related to his presentation.

[email protected]

Evidence that a SARS-CoV-2 vaccine is associated with inflammatory reactions in patients with dermal fillers has led the American Society for Dermatologic Surgery to issue a guidance outlining the potential risk and clinical relevance.

The association is not surprising, since other vaccines, including the influenza vaccine, have also been associated with inflammatory reactions in patients with dermal fillers. A warning about inflammatory events from these and other immunologic triggers should be part of routine informed consent, according to Sue Ellen Cox, MD, a coauthor of the guidance and the ASDS president-elect.

“Patients who have had dermal filler should not be discouraged from receiving the vaccine, and those who have received the vaccine should not be discouraged from receiving dermal filler,” Dr. Cox, who practices in Chapel Hill, N.C., said in an interview.

The only available data to assess the risk came from the trial of the Moderna vaccine. Of a total of 15,184 participants who received at least one dose of mRNA-1273, three developed facial or lip swelling that was presumably related to dermal filler. In the placebo group, there were no comparable inflammatory events.

“This is a very small number, but there is no reliable information about the number of patients in either group who had dermal filler, so we do not know the denominator,” Dr. Cox said.

In all three cases, the swelling at the site of dermal filler was observed within 2 days of the vaccination. None were considered a serious adverse event and all resolved. The filler had been administered 2 weeks prior to vaccination in one case, 6 months prior in a second, and time of administration was unknown in the third.

The resolution of the inflammatory reactions associated with the SARS-CoV-2 vaccine is similar to those related to dermal fillers following other immunologic triggers, which not only include other vaccines, but viral or bacterial illnesses and dental procedures. Typically, they are readily controlled with oral corticosteroids, but also typically resolve even in the absence of treatment, according to Dr. Cox.

“The good news is that these will go away,” Dr. Cox said.

The ASDS guidance is meant to alert clinicians and patients to the potential association between inflammatory events and SARS-CoV-2 vaccination in patients with dermal filler, but Dr. Cox said that it will ultimately have very little effect on her own practice. She already employs an informed consent that includes language warning about the potential risk of local reactions to immunological triggers that include vaccines. SARS-CoV-2 vaccination can now be added to examples of potential triggers, but it does not change the importance of informing patients of such triggers, Dr. Cox explained.

Asked if patients should be informed specifically about the association between dermal filler inflammatory reactions and SARS-CoV-2 vaccine, the current ASDS president and first author of the guidance, Mathew Avram, MD, JD, suggested that they should. Although he emphasized that the side effect is clearly rare, he believes it deserves attention.

“We wanted dermatologists and other physicians to be aware of the potential. We focused on the available data but specifically decided not to provide any treatment recommendations at this time,” he said in an interview.

As new data become available, the Soft-Tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other SARS-CoV-2 vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

“Our guidance was based only on the trial data, but there will soon be tens of millions of patients exposed to several different SARS-CoV-2 vaccines. We may learn things we do not know now, and we plan to communicate to our membership and others any new information as events unfold,” said Dr. Avram, who is director of dermatologic surgery, Massachusetts General Hospital, Boston,

Based on her own expertise in the field, Dr. Cox suggested that administration of SARS-CoV-2 vaccine and administration of dermal filler should be separated by at least 2 weeks regardless of which comes first. Her recommendation is not based on controlled data, but she considers this a prudent interval even if it has not been tested in a controlled study.

The full ASDS guidance is scheduled to appear in an upcoming issue of Dermatologic Surgery.

As new data become available, the Soft-tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other types of vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

This article was updated 1/7/21.

Evidence that a SARS-CoV-2 vaccine is associated with inflammatory reactions in patients with dermal fillers has led the American Society for Dermatologic Surgery to issue a guidance outlining the potential risk and clinical relevance.

The association is not surprising, since other vaccines, including the influenza vaccine, have also been associated with inflammatory reactions in patients with dermal fillers. A warning about inflammatory events from these and other immunologic triggers should be part of routine informed consent, according to Sue Ellen Cox, MD, a coauthor of the guidance and the ASDS president-elect.

“Patients who have had dermal filler should not be discouraged from receiving the vaccine, and those who have received the vaccine should not be discouraged from receiving dermal filler,” Dr. Cox, who practices in Chapel Hill, N.C., said in an interview.

The only available data to assess the risk came from the trial of the Moderna vaccine. Of a total of 15,184 participants who received at least one dose of mRNA-1273, three developed facial or lip swelling that was presumably related to dermal filler. In the placebo group, there were no comparable inflammatory events.

“This is a very small number, but there is no reliable information about the number of patients in either group who had dermal filler, so we do not know the denominator,” Dr. Cox said.

In all three cases, the swelling at the site of dermal filler was observed within 2 days of the vaccination. None were considered a serious adverse event and all resolved. The filler had been administered 2 weeks prior to vaccination in one case, 6 months prior in a second, and time of administration was unknown in the third.

The resolution of the inflammatory reactions associated with the SARS-CoV-2 vaccine is similar to those related to dermal fillers following other immunologic triggers, which not only include other vaccines, but viral or bacterial illnesses and dental procedures. Typically, they are readily controlled with oral corticosteroids, but also typically resolve even in the absence of treatment, according to Dr. Cox.

“The good news is that these will go away,” Dr. Cox said.

The ASDS guidance is meant to alert clinicians and patients to the potential association between inflammatory events and SARS-CoV-2 vaccination in patients with dermal filler, but Dr. Cox said that it will ultimately have very little effect on her own practice. She already employs an informed consent that includes language warning about the potential risk of local reactions to immunological triggers that include vaccines. SARS-CoV-2 vaccination can now be added to examples of potential triggers, but it does not change the importance of informing patients of such triggers, Dr. Cox explained.

Asked if patients should be informed specifically about the association between dermal filler inflammatory reactions and SARS-CoV-2 vaccine, the current ASDS president and first author of the guidance, Mathew Avram, MD, JD, suggested that they should. Although he emphasized that the side effect is clearly rare, he believes it deserves attention.

“We wanted dermatologists and other physicians to be aware of the potential. We focused on the available data but specifically decided not to provide any treatment recommendations at this time,” he said in an interview.

As new data become available, the Soft-Tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other SARS-CoV-2 vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

“Our guidance was based only on the trial data, but there will soon be tens of millions of patients exposed to several different SARS-CoV-2 vaccines. We may learn things we do not know now, and we plan to communicate to our membership and others any new information as events unfold,” said Dr. Avram, who is director of dermatologic surgery, Massachusetts General Hospital, Boston,

Based on her own expertise in the field, Dr. Cox suggested that administration of SARS-CoV-2 vaccine and administration of dermal filler should be separated by at least 2 weeks regardless of which comes first. Her recommendation is not based on controlled data, but she considers this a prudent interval even if it has not been tested in a controlled study.

The full ASDS guidance is scheduled to appear in an upcoming issue of Dermatologic Surgery.

As new data become available, the Soft-tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other types of vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

This article was updated 1/7/21.

Evidence that a SARS-CoV-2 vaccine is associated with inflammatory reactions in patients with dermal fillers has led the American Society for Dermatologic Surgery to issue a guidance outlining the potential risk and clinical relevance.

The association is not surprising, since other vaccines, including the influenza vaccine, have also been associated with inflammatory reactions in patients with dermal fillers. A warning about inflammatory events from these and other immunologic triggers should be part of routine informed consent, according to Sue Ellen Cox, MD, a coauthor of the guidance and the ASDS president-elect.

“Patients who have had dermal filler should not be discouraged from receiving the vaccine, and those who have received the vaccine should not be discouraged from receiving dermal filler,” Dr. Cox, who practices in Chapel Hill, N.C., said in an interview.

The only available data to assess the risk came from the trial of the Moderna vaccine. Of a total of 15,184 participants who received at least one dose of mRNA-1273, three developed facial or lip swelling that was presumably related to dermal filler. In the placebo group, there were no comparable inflammatory events.

“This is a very small number, but there is no reliable information about the number of patients in either group who had dermal filler, so we do not know the denominator,” Dr. Cox said.

In all three cases, the swelling at the site of dermal filler was observed within 2 days of the vaccination. None were considered a serious adverse event and all resolved. The filler had been administered 2 weeks prior to vaccination in one case, 6 months prior in a second, and time of administration was unknown in the third.

The resolution of the inflammatory reactions associated with the SARS-CoV-2 vaccine is similar to those related to dermal fillers following other immunologic triggers, which not only include other vaccines, but viral or bacterial illnesses and dental procedures. Typically, they are readily controlled with oral corticosteroids, but also typically resolve even in the absence of treatment, according to Dr. Cox.

“The good news is that these will go away,” Dr. Cox said.

The ASDS guidance is meant to alert clinicians and patients to the potential association between inflammatory events and SARS-CoV-2 vaccination in patients with dermal filler, but Dr. Cox said that it will ultimately have very little effect on her own practice. She already employs an informed consent that includes language warning about the potential risk of local reactions to immunological triggers that include vaccines. SARS-CoV-2 vaccination can now be added to examples of potential triggers, but it does not change the importance of informing patients of such triggers, Dr. Cox explained.

Asked if patients should be informed specifically about the association between dermal filler inflammatory reactions and SARS-CoV-2 vaccine, the current ASDS president and first author of the guidance, Mathew Avram, MD, JD, suggested that they should. Although he emphasized that the side effect is clearly rare, he believes it deserves attention.

“We wanted dermatologists and other physicians to be aware of the potential. We focused on the available data but specifically decided not to provide any treatment recommendations at this time,” he said in an interview.

As new data become available, the Soft-Tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other SARS-CoV-2 vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

“Our guidance was based only on the trial data, but there will soon be tens of millions of patients exposed to several different SARS-CoV-2 vaccines. We may learn things we do not know now, and we plan to communicate to our membership and others any new information as events unfold,” said Dr. Avram, who is director of dermatologic surgery, Massachusetts General Hospital, Boston,

Based on her own expertise in the field, Dr. Cox suggested that administration of SARS-CoV-2 vaccine and administration of dermal filler should be separated by at least 2 weeks regardless of which comes first. Her recommendation is not based on controlled data, but she considers this a prudent interval even if it has not been tested in a controlled study.

The full ASDS guidance is scheduled to appear in an upcoming issue of Dermatologic Surgery.

As new data become available, the Soft-tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other types of vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

This article was updated 1/7/21.

Optical treatments for acne are emerging as promising alternatives to conventional treatments, a development that inspires clinician researchers such as Fernanda H. Sakamoto, MD, PhD.

“I love treating acne, because it can have a huge impact on our patients’ lives,” Dr. Sakamoto, a dermatologist at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, said during a virtual course on laser and aesthetic skin therapy. “Acne is the most common disease in dermatology, affecting about 80% of our patients. Eleven percent of these patients have difficult-to-treat acne, and it is also the No. 1 cause of depression and suicide among teenagers and young adults. And, even though there’s no strong evidence that optical treatments work better than conventional acne treatments, people still spend a lot on those treatments: more than 220 million in 2019.”

Early results from a pilot study suggest that use of a novel laser system known as Accure in patients with mild to moderate acne resulted in an 80% reduction in acne lesions at 12 weeks. The laser prototype, which uses a 1,726 nm wavelength and is being developed by researchers at the Wellman Center for Photomedicine, features a built-in thermal camera in the handpiece that allows the user to monitor the skin’s temperature during treatment.

In initial pilot studies of the device, Dr. Sakamoto and colleagues observed consistent damage of the sebaceous glands, with no damage to the epidermis, surrounding dermis, or other follicular structures. “But because the contrast of absorption of lipids and water is not very high, we needed to create a laser with features that we have never seen before,” she said. “One of them is a robust cooling system. The second prototype features a built-in thermal camera within the handpiece that allows us to see the temperature while we’re treating the patient. It also has built-in software that would shut down the laser if the temperature is too high. “This is the first laser with some safety features that will give the user direct feedback while treating the patient,” she said, noting that its “unique cooling system and real-time monitoring ... makes it different from any of the lasers we see on the market right now.”

Dr. Sakamoto and colleagues (Emil Tanghetti, MD, in San Diego, Roy Geronemus, MD, in New York, and Joel L. Cohen, MD, in Colorado) are conducting a clinical trial of the device, to evaluate whether Accure can selectively target sebaceous glands. As of Oct. 23, 2020, the study enrolled more than 50 patients, who are followed at 4, 8, 12, and 24 weeks post treatment, she said.

To date, 16 patients have completed the study, and the researchers have observed an average lesion reduction of 80% at 12 weeks post treatment, after four treatment sessions. This amounted to more than 12,000 trigger pulls of the device, with no unexpected adverse events. Average visual analogue scale pain scores immediately after treatment have been 1.09 out of 10.

Histologic assessment of skin samples collected from the study participants have revealed selective damage of the sebaceous glands with a normal epidermis and surrounding dermis. “Because this laser is near infrared, it is not absorbed by melanin, making it possible for a safe treatment in darker skin tones,” Dr. Sakamoto said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine.

“We have shown that it is possible to create a selective laser for acne treatment at 1,726 nm. We have proven it mathematically as well as with histological samples,” she said. “Now we are moving on to a larger clinical trial for the FDA clearance.”

Another strategy being developed for acne treatment is to make nonselective lasers selective by adding gold microparticles into the hair follicle and sebaceous glands, to allow the lasers to be absorbed. In a study that used a free electron laser, Dr. Sakamoto and colleagues demonstrated that these microparticles can stay within the sebaceous glands for selective damage of the sebaceous glands. In a subsequent pilot clinical trial they showed that the addition of the gold microparticles followed by a diode laser treatment made it possible to reduce both inflammatory and noninflammatory lesions.

More recently, an open-label European study of acne treatment with light absorbing gold microparticles and optical pulses demonstrated that the treatment led to an 80%-90% reduction of inflammatory lesions at 12 weeks, with a reduction of Investigator’s Global Assessment scale from 2 to 4.

The Food and Drug Administration cleared the treatment, Sebacia Microparticles, for the treatment of mild to moderate acne in September of 2018, but according to Dr. Sakamoto, “the company has struggled, as they were only commercializing the device in California and Washington, DC.”

Photodynamic therapy (PDT) is also being studied as an acne treatment. “PDT uses a photosensitizer that needs to be activated by a light source,” she noted. “The combination of red light and aminolevulinic acid (ALA) or methyl ester ALA has been shown to damage the sebaceous glands”.

In a recent randomized controlled trial that compared PDT to adapalene gel plus oral doxycycline, PDT showed superiority. “Because PDT induces apoptosis of the sebaceous glands, it causes a lot of pain and side effects after treatment,” Dr. Sakamoto said. “However, it can clear 80%-90% of acne in 80%-90% of patients. But because of the side effects, PDT should be limited to those patients who cannot take conventional treatments.”

Dr. Sakamoto reported having received research funding and/or consulting fees from numerous device and pharmaceutical companies.

[email protected]

Optical treatments for acne are emerging as promising alternatives to conventional treatments, a development that inspires clinician researchers such as Fernanda H. Sakamoto, MD, PhD.

“I love treating acne, because it can have a huge impact on our patients’ lives,” Dr. Sakamoto, a dermatologist at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, said during a virtual course on laser and aesthetic skin therapy. “Acne is the most common disease in dermatology, affecting about 80% of our patients. Eleven percent of these patients have difficult-to-treat acne, and it is also the No. 1 cause of depression and suicide among teenagers and young adults. And, even though there’s no strong evidence that optical treatments work better than conventional acne treatments, people still spend a lot on those treatments: more than 220 million in 2019.”

Early results from a pilot study suggest that use of a novel laser system known as Accure in patients with mild to moderate acne resulted in an 80% reduction in acne lesions at 12 weeks. The laser prototype, which uses a 1,726 nm wavelength and is being developed by researchers at the Wellman Center for Photomedicine, features a built-in thermal camera in the handpiece that allows the user to monitor the skin’s temperature during treatment.

In initial pilot studies of the device, Dr. Sakamoto and colleagues observed consistent damage of the sebaceous glands, with no damage to the epidermis, surrounding dermis, or other follicular structures. “But because the contrast of absorption of lipids and water is not very high, we needed to create a laser with features that we have never seen before,” she said. “One of them is a robust cooling system. The second prototype features a built-in thermal camera within the handpiece that allows us to see the temperature while we’re treating the patient. It also has built-in software that would shut down the laser if the temperature is too high. “This is the first laser with some safety features that will give the user direct feedback while treating the patient,” she said, noting that its “unique cooling system and real-time monitoring ... makes it different from any of the lasers we see on the market right now.”

Dr. Sakamoto and colleagues (Emil Tanghetti, MD, in San Diego, Roy Geronemus, MD, in New York, and Joel L. Cohen, MD, in Colorado) are conducting a clinical trial of the device, to evaluate whether Accure can selectively target sebaceous glands. As of Oct. 23, 2020, the study enrolled more than 50 patients, who are followed at 4, 8, 12, and 24 weeks post treatment, she said.

To date, 16 patients have completed the study, and the researchers have observed an average lesion reduction of 80% at 12 weeks post treatment, after four treatment sessions. This amounted to more than 12,000 trigger pulls of the device, with no unexpected adverse events. Average visual analogue scale pain scores immediately after treatment have been 1.09 out of 10.

Histologic assessment of skin samples collected from the study participants have revealed selective damage of the sebaceous glands with a normal epidermis and surrounding dermis. “Because this laser is near infrared, it is not absorbed by melanin, making it possible for a safe treatment in darker skin tones,” Dr. Sakamoto said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine.

“We have shown that it is possible to create a selective laser for acne treatment at 1,726 nm. We have proven it mathematically as well as with histological samples,” she said. “Now we are moving on to a larger clinical trial for the FDA clearance.”

Another strategy being developed for acne treatment is to make nonselective lasers selective by adding gold microparticles into the hair follicle and sebaceous glands, to allow the lasers to be absorbed. In a study that used a free electron laser, Dr. Sakamoto and colleagues demonstrated that these microparticles can stay within the sebaceous glands for selective damage of the sebaceous glands. In a subsequent pilot clinical trial they showed that the addition of the gold microparticles followed by a diode laser treatment made it possible to reduce both inflammatory and noninflammatory lesions.

More recently, an open-label European study of acne treatment with light absorbing gold microparticles and optical pulses demonstrated that the treatment led to an 80%-90% reduction of inflammatory lesions at 12 weeks, with a reduction of Investigator’s Global Assessment scale from 2 to 4.

The Food and Drug Administration cleared the treatment, Sebacia Microparticles, for the treatment of mild to moderate acne in September of 2018, but according to Dr. Sakamoto, “the company has struggled, as they were only commercializing the device in California and Washington, DC.”

Photodynamic therapy (PDT) is also being studied as an acne treatment. “PDT uses a photosensitizer that needs to be activated by a light source,” she noted. “The combination of red light and aminolevulinic acid (ALA) or methyl ester ALA has been shown to damage the sebaceous glands”.

In a recent randomized controlled trial that compared PDT to adapalene gel plus oral doxycycline, PDT showed superiority. “Because PDT induces apoptosis of the sebaceous glands, it causes a lot of pain and side effects after treatment,” Dr. Sakamoto said. “However, it can clear 80%-90% of acne in 80%-90% of patients. But because of the side effects, PDT should be limited to those patients who cannot take conventional treatments.”

Dr. Sakamoto reported having received research funding and/or consulting fees from numerous device and pharmaceutical companies.

[email protected]

Optical treatments for acne are emerging as promising alternatives to conventional treatments, a development that inspires clinician researchers such as Fernanda H. Sakamoto, MD, PhD.

“I love treating acne, because it can have a huge impact on our patients’ lives,” Dr. Sakamoto, a dermatologist at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, said during a virtual course on laser and aesthetic skin therapy. “Acne is the most common disease in dermatology, affecting about 80% of our patients. Eleven percent of these patients have difficult-to-treat acne, and it is also the No. 1 cause of depression and suicide among teenagers and young adults. And, even though there’s no strong evidence that optical treatments work better than conventional acne treatments, people still spend a lot on those treatments: more than 220 million in 2019.”

Early results from a pilot study suggest that use of a novel laser system known as Accure in patients with mild to moderate acne resulted in an 80% reduction in acne lesions at 12 weeks. The laser prototype, which uses a 1,726 nm wavelength and is being developed by researchers at the Wellman Center for Photomedicine, features a built-in thermal camera in the handpiece that allows the user to monitor the skin’s temperature during treatment.

In initial pilot studies of the device, Dr. Sakamoto and colleagues observed consistent damage of the sebaceous glands, with no damage to the epidermis, surrounding dermis, or other follicular structures. “But because the contrast of absorption of lipids and water is not very high, we needed to create a laser with features that we have never seen before,” she said. “One of them is a robust cooling system. The second prototype features a built-in thermal camera within the handpiece that allows us to see the temperature while we’re treating the patient. It also has built-in software that would shut down the laser if the temperature is too high. “This is the first laser with some safety features that will give the user direct feedback while treating the patient,” she said, noting that its “unique cooling system and real-time monitoring ... makes it different from any of the lasers we see on the market right now.”

Dr. Sakamoto and colleagues (Emil Tanghetti, MD, in San Diego, Roy Geronemus, MD, in New York, and Joel L. Cohen, MD, in Colorado) are conducting a clinical trial of the device, to evaluate whether Accure can selectively target sebaceous glands. As of Oct. 23, 2020, the study enrolled more than 50 patients, who are followed at 4, 8, 12, and 24 weeks post treatment, she said.

To date, 16 patients have completed the study, and the researchers have observed an average lesion reduction of 80% at 12 weeks post treatment, after four treatment sessions. This amounted to more than 12,000 trigger pulls of the device, with no unexpected adverse events. Average visual analogue scale pain scores immediately after treatment have been 1.09 out of 10.

Histologic assessment of skin samples collected from the study participants have revealed selective damage of the sebaceous glands with a normal epidermis and surrounding dermis. “Because this laser is near infrared, it is not absorbed by melanin, making it possible for a safe treatment in darker skin tones,” Dr. Sakamoto said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine.

“We have shown that it is possible to create a selective laser for acne treatment at 1,726 nm. We have proven it mathematically as well as with histological samples,” she said. “Now we are moving on to a larger clinical trial for the FDA clearance.”

Another strategy being developed for acne treatment is to make nonselective lasers selective by adding gold microparticles into the hair follicle and sebaceous glands, to allow the lasers to be absorbed. In a study that used a free electron laser, Dr. Sakamoto and colleagues demonstrated that these microparticles can stay within the sebaceous glands for selective damage of the sebaceous glands. In a subsequent pilot clinical trial they showed that the addition of the gold microparticles followed by a diode laser treatment made it possible to reduce both inflammatory and noninflammatory lesions.

More recently, an open-label European study of acne treatment with light absorbing gold microparticles and optical pulses demonstrated that the treatment led to an 80%-90% reduction of inflammatory lesions at 12 weeks, with a reduction of Investigator’s Global Assessment scale from 2 to 4.

The Food and Drug Administration cleared the treatment, Sebacia Microparticles, for the treatment of mild to moderate acne in September of 2018, but according to Dr. Sakamoto, “the company has struggled, as they were only commercializing the device in California and Washington, DC.”

Photodynamic therapy (PDT) is also being studied as an acne treatment. “PDT uses a photosensitizer that needs to be activated by a light source,” she noted. “The combination of red light and aminolevulinic acid (ALA) or methyl ester ALA has been shown to damage the sebaceous glands”.

In a recent randomized controlled trial that compared PDT to adapalene gel plus oral doxycycline, PDT showed superiority. “Because PDT induces apoptosis of the sebaceous glands, it causes a lot of pain and side effects after treatment,” Dr. Sakamoto said. “However, it can clear 80%-90% of acne in 80%-90% of patients. But because of the side effects, PDT should be limited to those patients who cannot take conventional treatments.”

Dr. Sakamoto reported having received research funding and/or consulting fees from numerous device and pharmaceutical companies.

[email protected]

In 2014, I began taking care of a patient (see photo) who had developed over 25 basal cell carcinomas on her lower legs, which were surgically removed. Given the results of a 2015 study by Chen et al. on the protective effects of nicotinamide in the prevention of nonmelanoma skin cancers, I began her on oral nicotinamide, 500 mg twice daily. She has been clear of any skin cancers in the last 2 years since starting supplementation.

Lily Talakoub, MD

Nicotinamide, also known as niacinamide, is a water soluble form of vitamin B3 that has been shown to enhance the repair of UV-induced DNA damage. Nicotinamide is found naturally in meat, fish, nuts, grains, and legumes, and is a key component of the glycolysis pathway, by generating nicotinamide adenine dinucleotide for adenosine triphosphate production. Nicotinamide deficiency causes photosensitive dermatitis, diarrhea, and dementia. It has been studied for its anti-inflammatory benefits as an adjunct treatment for rosacea, bullous diseases, acne, and melasma.

Nonmelanoma skin cancers are known to be caused primarily by UV radiation. The supplementation of nicotinamide orally twice daily has been shown to reduce the rate of actinic keratoses and new nonmelanoma skin cancers compared with placebo after 1 year in patients who previously had skin cancer. In the phase 3 study published in 2015, a randomized, controlled trial of 386 patients who had at least two nonmelanoma skin cancers within the previous 5-year period, oral nicotinamide 500 mg given twice daily for a 12-month period significantly reduced the number of new nonmelanoma skin cancers by 23% versus those on placebo.

The recommended dose for nicotinamide, which is available over the counter as Vitamin B3, is 500 mg twice a day. Nicotinamide should not be confused with niacin (nicotinic acid), which has been used to treat high cholesterol and cardiovascular disease. There are no significant side effects from long-term use; however nicotinamide should not be used in patients with end-stage kidney disease or chronic kidney disease. (Niacin, however, can cause elevation of liver enzymes, headache, flushing, and increased blood pressure.) Nicotinamide crosses the placenta and should not be used in pregnancy as it has not been studied in pregnant populations.

We should counsel patients that this is not an oral sunscreen, and that sun avoidance, sunscreen, and yearly skin cancer checks are still the mainstay of skin cancer prevention. However, given the safety profile of nicotinamide and the protective effects, should all of our skin cancer patients be taking nicotinamide daily? In my practice they are, all of whom swear by it and have had significant reductions of both actinic keratoses and nonmelanoma skin cancers.

Dr. Talakoub and Dr. Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.

In 2014, I began taking care of a patient (see photo) who had developed over 25 basal cell carcinomas on her lower legs, which were surgically removed. Given the results of a 2015 study by Chen et al. on the protective effects of nicotinamide in the prevention of nonmelanoma skin cancers, I began her on oral nicotinamide, 500 mg twice daily. She has been clear of any skin cancers in the last 2 years since starting supplementation.

Lily Talakoub, MD

Nicotinamide, also known as niacinamide, is a water soluble form of vitamin B3 that has been shown to enhance the repair of UV-induced DNA damage. Nicotinamide is found naturally in meat, fish, nuts, grains, and legumes, and is a key component of the glycolysis pathway, by generating nicotinamide adenine dinucleotide for adenosine triphosphate production. Nicotinamide deficiency causes photosensitive dermatitis, diarrhea, and dementia. It has been studied for its anti-inflammatory benefits as an adjunct treatment for rosacea, bullous diseases, acne, and melasma.

Nonmelanoma skin cancers are known to be caused primarily by UV radiation. The supplementation of nicotinamide orally twice daily has been shown to reduce the rate of actinic keratoses and new nonmelanoma skin cancers compared with placebo after 1 year in patients who previously had skin cancer. In the phase 3 study published in 2015, a randomized, controlled trial of 386 patients who had at least two nonmelanoma skin cancers within the previous 5-year period, oral nicotinamide 500 mg given twice daily for a 12-month period significantly reduced the number of new nonmelanoma skin cancers by 23% versus those on placebo.

The recommended dose for nicotinamide, which is available over the counter as Vitamin B3, is 500 mg twice a day. Nicotinamide should not be confused with niacin (nicotinic acid), which has been used to treat high cholesterol and cardiovascular disease. There are no significant side effects from long-term use; however nicotinamide should not be used in patients with end-stage kidney disease or chronic kidney disease. (Niacin, however, can cause elevation of liver enzymes, headache, flushing, and increased blood pressure.) Nicotinamide crosses the placenta and should not be used in pregnancy as it has not been studied in pregnant populations.

We should counsel patients that this is not an oral sunscreen, and that sun avoidance, sunscreen, and yearly skin cancer checks are still the mainstay of skin cancer prevention. However, given the safety profile of nicotinamide and the protective effects, should all of our skin cancer patients be taking nicotinamide daily? In my practice they are, all of whom swear by it and have had significant reductions of both actinic keratoses and nonmelanoma skin cancers.

Dr. Talakoub and Dr. Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.

In 2014, I began taking care of a patient (see photo) who had developed over 25 basal cell carcinomas on her lower legs, which were surgically removed. Given the results of a 2015 study by Chen et al. on the protective effects of nicotinamide in the prevention of nonmelanoma skin cancers, I began her on oral nicotinamide, 500 mg twice daily. She has been clear of any skin cancers in the last 2 years since starting supplementation.

Lily Talakoub, MD

Nicotinamide, also known as niacinamide, is a water soluble form of vitamin B3 that has been shown to enhance the repair of UV-induced DNA damage. Nicotinamide is found naturally in meat, fish, nuts, grains, and legumes, and is a key component of the glycolysis pathway, by generating nicotinamide adenine dinucleotide for adenosine triphosphate production. Nicotinamide deficiency causes photosensitive dermatitis, diarrhea, and dementia. It has been studied for its anti-inflammatory benefits as an adjunct treatment for rosacea, bullous diseases, acne, and melasma.

Nonmelanoma skin cancers are known to be caused primarily by UV radiation. The supplementation of nicotinamide orally twice daily has been shown to reduce the rate of actinic keratoses and new nonmelanoma skin cancers compared with placebo after 1 year in patients who previously had skin cancer. In the phase 3 study published in 2015, a randomized, controlled trial of 386 patients who had at least two nonmelanoma skin cancers within the previous 5-year period, oral nicotinamide 500 mg given twice daily for a 12-month period significantly reduced the number of new nonmelanoma skin cancers by 23% versus those on placebo.

The recommended dose for nicotinamide, which is available over the counter as Vitamin B3, is 500 mg twice a day. Nicotinamide should not be confused with niacin (nicotinic acid), which has been used to treat high cholesterol and cardiovascular disease. There are no significant side effects from long-term use; however nicotinamide should not be used in patients with end-stage kidney disease or chronic kidney disease. (Niacin, however, can cause elevation of liver enzymes, headache, flushing, and increased blood pressure.) Nicotinamide crosses the placenta and should not be used in pregnancy as it has not been studied in pregnant populations.

We should counsel patients that this is not an oral sunscreen, and that sun avoidance, sunscreen, and yearly skin cancer checks are still the mainstay of skin cancer prevention. However, given the safety profile of nicotinamide and the protective effects, should all of our skin cancer patients be taking nicotinamide daily? In my practice they are, all of whom swear by it and have had significant reductions of both actinic keratoses and nonmelanoma skin cancers.

Dr. Talakoub and Dr. Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.

The majority of human cells, including skin and hair cells, keep their own time; that is, they manifest autonomous clocks and the genes that regulate their functioning.¹ During the day, one primary function of the skin is protection; at night, repairing any damage (particularly DNA impairment) incurred during the day prevails.^2-4 These activities are driven through circadian rhythms using clock genes that exist in all cutaneous cells.² Important cutaneous functions such as blood flow, transepidermal water loss, and capacitance are affected by circadian rhythms.⁵ Hydration and inflammation are also among the several functions pertaining to epidermal homeostasis affected by circadian rhythms.⁶ In addition, some collagens and extracellular matrix proteases are diurnally regulated, and approximately 10% of the transcriptome, including the extracellular matrix, is thought to be controlled by circadian rhythms.⁷

Emerging research on the circadian rhythms displayed in the skin yield implications related to skin care. Cutaneous cell migration and proliferation, wound healing, and tissue vulnerability to harm from UV exposure, oxidative stress, and protease activity, for example, are affected by circadian rhythms, Sherratt et al. noted in suggesting that chronotherapy presents promise for enhancing skin therapy.⁷ Indeed, recent research has led to the understanding that cutaneous aging, cellular repair, optimal timing for drug delivery to the skin, and skin cancer development are all affected by the chronobiological functioning of the skin.⁸

We have known for several years that certain types of products should be used at different times of the day. For instance, antioxidants should be used in the morning to protect skin from sun exposure and retinols should be used in the evening because of its induction of light sensitivity. The remainder of this column focuses on research in the last 2 decades that reinforces the notion of circadian rhythms working in the skin, and may alter how we view the timing of skin care. Next month’s column, part two on the circadian rhythms of the skin, will address recent clinical trials and the implications for timing treatments for certain cutaneous conditions.
 

Emerging data on the circadian rhythms of the skin

In 2001, Le Fur et al. studied the cutaneous circadian rhythms in the facial and forearm skin of eight healthy White women during a 48-hour period. They were able to detect such rhythms in facial sebum excretion, transepidermal water loss (TEWL) in the face and forearm, pH in the face, forearm skin temperature, and forearm capacitance using cosinor or analysis of variance methods. The investigators also observed 8- and 12-hour rhythms in TEWL in both areas, and 12 hours for forearm skin temperature. They verified that such rhythms could be measured and that they vary between skin sites. In addition, they were the first to show that ultradian and/or component rhythms can also be found in TEWL, sebum excretion, and skin temperature.⁹

A year later, Kawara et al. showed that mRNA of the circadian clock genes Per1, Clock, and bmal1/mop3 are expressed in normal human-cultured keratinocytes and that low-dose UVB down-regulates these genes and changes their express in keratinocyte cell cultures. They concluded that UV targeting of keratinocytes could alter circadian rhythms.¹⁰

In 2011, Spörl and colleagues characterized an in vitro functional cell autonomous circadian clock in adult human low calcium temperature keratinocytes, demonstrating that the molecular composition of the keratinocyte clock was comparable with peripheral tissue clocks. Notably, they observed that temperature acts as a robust time cue for epidermal traits, such as cholesterol homeostasis and differentiation.¹¹

The next year, Sandu et al. investigated the kinetics of clock gene expression in epidermal and dermal cells collected from the same donor and compared their characteristics. They were able to reveal the presence of functional circadian machinery in primary cultures of fibroblasts, keratinocytes, and melanocytes, with oscillators identified in all skin cell types and thought to be involved in spurring cutaneous rhythmic functions as they exhibited discrete periods and phase relationships between clock genes.¹²

Three years later, Sandu et al. characterized the circadian clocks in rat skin and dermal fibroblasts. They found that skin has a self-sustaining circadian clock that experiences age-dependent alterations, and that dermal fibroblasts manifest circadian rhythms that can be modulated by endogenous (e.g., melatonin) and exogenous (e.g., temperature) influences.¹³

In 2019, Park et al. demonstrated that the diurnal expression of the gene TIMP3, which is thought to evince a circadian rhythm in synchronized human keratinocytes, experiences disruptions in such rhythms by UVB exposure. The inflammation that results can be blocked, they argued, by recovering the circadian expression of TIMP3 using synthetic TIMP3 peptides or bioactive natural ingredients, such as green tea extracts.⁶

Conclusion

Circadian rhythms and the biological clocks by which most cells, including skin and hair cells, regulate themselves represent a ripe and fascinating area of research. Applying evidence in this realm to skin care has been occurring over time and is likely to enhance our practice even more as we continue to elucidate the behavior of cutaneous cells based on the solar day. Based on this information, my recommendations are to use antioxidants and protective products in the morning, and use DNA repair enzymes, retinoids, and other repair products at night.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions, a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].

References

1. Dong K et al. Int J Mol Sci. 2020 Jan 3. doi: 10.3390/ijms21010326.

2. Dong K et al. Int J Cosmet Sci. 2019 Dec;41(6):558-62.

3. Lyons AB et al. J Clin Aesthet Dermatol. 2019 Sep;12(9):42-5.

4. Wu G et al. Proc Natl Acad Sci U S A. 2018 Nov 27;115(48):12313-8.

5. Vaughn AR et al. Pediatr Dermatol. 2018 Jan;35(1):152-7.

6. Park S et al. Int J Mol Sci. 2019 Feb 16. doi: 10.3390/ijms20040862.

7. Sherratt MJ et al. Matrix Biol. 2019 Nov;84:97-110.

8. Luber AJ et al. J Drugs Dermatol. 2014 Feb;13(2):130-4.

9. Le Fur I et al. J Invest Dermatol. 2001 Sep;117(3):718-24.

10. Kawara S et al. J Invest Dermatol. 2002 Dec;119(6):1220-3.

11. Spörl F et al. J Invest Dermatol. 2011 Feb;131(2):338-48.

12. Sandu C et al. Cell Mol Life Sci. 2012 Oct;69(19):3329-39.

13. Sandu C et al. Cell Mol Life Sci. 2015 Jun;72(11):2237-48.

The majority of human cells, including skin and hair cells, keep their own time; that is, they manifest autonomous clocks and the genes that regulate their functioning.¹ During the day, one primary function of the skin is protection; at night, repairing any damage (particularly DNA impairment) incurred during the day prevails.^2-4 These activities are driven through circadian rhythms using clock genes that exist in all cutaneous cells.² Important cutaneous functions such as blood flow, transepidermal water loss, and capacitance are affected by circadian rhythms.⁵ Hydration and inflammation are also among the several functions pertaining to epidermal homeostasis affected by circadian rhythms.⁶ In addition, some collagens and extracellular matrix proteases are diurnally regulated, and approximately 10% of the transcriptome, including the extracellular matrix, is thought to be controlled by circadian rhythms.⁷

Emerging research on the circadian rhythms displayed in the skin yield implications related to skin care. Cutaneous cell migration and proliferation, wound healing, and tissue vulnerability to harm from UV exposure, oxidative stress, and protease activity, for example, are affected by circadian rhythms, Sherratt et al. noted in suggesting that chronotherapy presents promise for enhancing skin therapy.⁷ Indeed, recent research has led to the understanding that cutaneous aging, cellular repair, optimal timing for drug delivery to the skin, and skin cancer development are all affected by the chronobiological functioning of the skin.⁸

We have known for several years that certain types of products should be used at different times of the day. For instance, antioxidants should be used in the morning to protect skin from sun exposure and retinols should be used in the evening because of its induction of light sensitivity. The remainder of this column focuses on research in the last 2 decades that reinforces the notion of circadian rhythms working in the skin, and may alter how we view the timing of skin care. Next month’s column, part two on the circadian rhythms of the skin, will address recent clinical trials and the implications for timing treatments for certain cutaneous conditions.
 

Emerging data on the circadian rhythms of the skin

In 2001, Le Fur et al. studied the cutaneous circadian rhythms in the facial and forearm skin of eight healthy White women during a 48-hour period. They were able to detect such rhythms in facial sebum excretion, transepidermal water loss (TEWL) in the face and forearm, pH in the face, forearm skin temperature, and forearm capacitance using cosinor or analysis of variance methods. The investigators also observed 8- and 12-hour rhythms in TEWL in both areas, and 12 hours for forearm skin temperature. They verified that such rhythms could be measured and that they vary between skin sites. In addition, they were the first to show that ultradian and/or component rhythms can also be found in TEWL, sebum excretion, and skin temperature.⁹

A year later, Kawara et al. showed that mRNA of the circadian clock genes Per1, Clock, and bmal1/mop3 are expressed in normal human-cultured keratinocytes and that low-dose UVB down-regulates these genes and changes their express in keratinocyte cell cultures. They concluded that UV targeting of keratinocytes could alter circadian rhythms.¹⁰

In 2011, Spörl and colleagues characterized an in vitro functional cell autonomous circadian clock in adult human low calcium temperature keratinocytes, demonstrating that the molecular composition of the keratinocyte clock was comparable with peripheral tissue clocks. Notably, they observed that temperature acts as a robust time cue for epidermal traits, such as cholesterol homeostasis and differentiation.¹¹

The next year, Sandu et al. investigated the kinetics of clock gene expression in epidermal and dermal cells collected from the same donor and compared their characteristics. They were able to reveal the presence of functional circadian machinery in primary cultures of fibroblasts, keratinocytes, and melanocytes, with oscillators identified in all skin cell types and thought to be involved in spurring cutaneous rhythmic functions as they exhibited discrete periods and phase relationships between clock genes.¹²

Three years later, Sandu et al. characterized the circadian clocks in rat skin and dermal fibroblasts. They found that skin has a self-sustaining circadian clock that experiences age-dependent alterations, and that dermal fibroblasts manifest circadian rhythms that can be modulated by endogenous (e.g., melatonin) and exogenous (e.g., temperature) influences.¹³

In 2019, Park et al. demonstrated that the diurnal expression of the gene TIMP3, which is thought to evince a circadian rhythm in synchronized human keratinocytes, experiences disruptions in such rhythms by UVB exposure. The inflammation that results can be blocked, they argued, by recovering the circadian expression of TIMP3 using synthetic TIMP3 peptides or bioactive natural ingredients, such as green tea extracts.⁶

Conclusion

Circadian rhythms and the biological clocks by which most cells, including skin and hair cells, regulate themselves represent a ripe and fascinating area of research. Applying evidence in this realm to skin care has been occurring over time and is likely to enhance our practice even more as we continue to elucidate the behavior of cutaneous cells based on the solar day. Based on this information, my recommendations are to use antioxidants and protective products in the morning, and use DNA repair enzymes, retinoids, and other repair products at night.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions, a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].

References

1. Dong K et al. Int J Mol Sci. 2020 Jan 3. doi: 10.3390/ijms21010326.

2. Dong K et al. Int J Cosmet Sci. 2019 Dec;41(6):558-62.

3. Lyons AB et al. J Clin Aesthet Dermatol. 2019 Sep;12(9):42-5.

4. Wu G et al. Proc Natl Acad Sci U S A. 2018 Nov 27;115(48):12313-8.

5. Vaughn AR et al. Pediatr Dermatol. 2018 Jan;35(1):152-7.

6. Park S et al. Int J Mol Sci. 2019 Feb 16. doi: 10.3390/ijms20040862.

7. Sherratt MJ et al. Matrix Biol. 2019 Nov;84:97-110.

8. Luber AJ et al. J Drugs Dermatol. 2014 Feb;13(2):130-4.

9. Le Fur I et al. J Invest Dermatol. 2001 Sep;117(3):718-24.

10. Kawara S et al. J Invest Dermatol. 2002 Dec;119(6):1220-3.

11. Spörl F et al. J Invest Dermatol. 2011 Feb;131(2):338-48.

12. Sandu C et al. Cell Mol Life Sci. 2012 Oct;69(19):3329-39.

13. Sandu C et al. Cell Mol Life Sci. 2015 Jun;72(11):2237-48.

The majority of human cells, including skin and hair cells, keep their own time; that is, they manifest autonomous clocks and the genes that regulate their functioning.¹ During the day, one primary function of the skin is protection; at night, repairing any damage (particularly DNA impairment) incurred during the day prevails.^2-4 These activities are driven through circadian rhythms using clock genes that exist in all cutaneous cells.² Important cutaneous functions such as blood flow, transepidermal water loss, and capacitance are affected by circadian rhythms.⁵ Hydration and inflammation are also among the several functions pertaining to epidermal homeostasis affected by circadian rhythms.⁶ In addition, some collagens and extracellular matrix proteases are diurnally regulated, and approximately 10% of the transcriptome, including the extracellular matrix, is thought to be controlled by circadian rhythms.⁷

Emerging research on the circadian rhythms displayed in the skin yield implications related to skin care. Cutaneous cell migration and proliferation, wound healing, and tissue vulnerability to harm from UV exposure, oxidative stress, and protease activity, for example, are affected by circadian rhythms, Sherratt et al. noted in suggesting that chronotherapy presents promise for enhancing skin therapy.⁷ Indeed, recent research has led to the understanding that cutaneous aging, cellular repair, optimal timing for drug delivery to the skin, and skin cancer development are all affected by the chronobiological functioning of the skin.⁸

We have known for several years that certain types of products should be used at different times of the day. For instance, antioxidants should be used in the morning to protect skin from sun exposure and retinols should be used in the evening because of its induction of light sensitivity. The remainder of this column focuses on research in the last 2 decades that reinforces the notion of circadian rhythms working in the skin, and may alter how we view the timing of skin care. Next month’s column, part two on the circadian rhythms of the skin, will address recent clinical trials and the implications for timing treatments for certain cutaneous conditions.
 

Emerging data on the circadian rhythms of the skin

In 2001, Le Fur et al. studied the cutaneous circadian rhythms in the facial and forearm skin of eight healthy White women during a 48-hour period. They were able to detect such rhythms in facial sebum excretion, transepidermal water loss (TEWL) in the face and forearm, pH in the face, forearm skin temperature, and forearm capacitance using cosinor or analysis of variance methods. The investigators also observed 8- and 12-hour rhythms in TEWL in both areas, and 12 hours for forearm skin temperature. They verified that such rhythms could be measured and that they vary between skin sites. In addition, they were the first to show that ultradian and/or component rhythms can also be found in TEWL, sebum excretion, and skin temperature.⁹

A year later, Kawara et al. showed that mRNA of the circadian clock genes Per1, Clock, and bmal1/mop3 are expressed in normal human-cultured keratinocytes and that low-dose UVB down-regulates these genes and changes their express in keratinocyte cell cultures. They concluded that UV targeting of keratinocytes could alter circadian rhythms.¹⁰

In 2011, Spörl and colleagues characterized an in vitro functional cell autonomous circadian clock in adult human low calcium temperature keratinocytes, demonstrating that the molecular composition of the keratinocyte clock was comparable with peripheral tissue clocks. Notably, they observed that temperature acts as a robust time cue for epidermal traits, such as cholesterol homeostasis and differentiation.¹¹

The next year, Sandu et al. investigated the kinetics of clock gene expression in epidermal and dermal cells collected from the same donor and compared their characteristics. They were able to reveal the presence of functional circadian machinery in primary cultures of fibroblasts, keratinocytes, and melanocytes, with oscillators identified in all skin cell types and thought to be involved in spurring cutaneous rhythmic functions as they exhibited discrete periods and phase relationships between clock genes.¹²

Three years later, Sandu et al. characterized the circadian clocks in rat skin and dermal fibroblasts. They found that skin has a self-sustaining circadian clock that experiences age-dependent alterations, and that dermal fibroblasts manifest circadian rhythms that can be modulated by endogenous (e.g., melatonin) and exogenous (e.g., temperature) influences.¹³

In 2019, Park et al. demonstrated that the diurnal expression of the gene TIMP3, which is thought to evince a circadian rhythm in synchronized human keratinocytes, experiences disruptions in such rhythms by UVB exposure. The inflammation that results can be blocked, they argued, by recovering the circadian expression of TIMP3 using synthetic TIMP3 peptides or bioactive natural ingredients, such as green tea extracts.⁶

Conclusion

Circadian rhythms and the biological clocks by which most cells, including skin and hair cells, regulate themselves represent a ripe and fascinating area of research. Applying evidence in this realm to skin care has been occurring over time and is likely to enhance our practice even more as we continue to elucidate the behavior of cutaneous cells based on the solar day. Based on this information, my recommendations are to use antioxidants and protective products in the morning, and use DNA repair enzymes, retinoids, and other repair products at night.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions, a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].

References

1. Dong K et al. Int J Mol Sci. 2020 Jan 3. doi: 10.3390/ijms21010326.

2. Dong K et al. Int J Cosmet Sci. 2019 Dec;41(6):558-62.

3. Lyons AB et al. J Clin Aesthet Dermatol. 2019 Sep;12(9):42-5.

4. Wu G et al. Proc Natl Acad Sci U S A. 2018 Nov 27;115(48):12313-8.

5. Vaughn AR et al. Pediatr Dermatol. 2018 Jan;35(1):152-7.

6. Park S et al. Int J Mol Sci. 2019 Feb 16. doi: 10.3390/ijms20040862.

7. Sherratt MJ et al. Matrix Biol. 2019 Nov;84:97-110.

8. Luber AJ et al. J Drugs Dermatol. 2014 Feb;13(2):130-4.

9. Le Fur I et al. J Invest Dermatol. 2001 Sep;117(3):718-24.

10. Kawara S et al. J Invest Dermatol. 2002 Dec;119(6):1220-3.

11. Spörl F et al. J Invest Dermatol. 2011 Feb;131(2):338-48.

12. Sandu C et al. Cell Mol Life Sci. 2012 Oct;69(19):3329-39.

13. Sandu C et al. Cell Mol Life Sci. 2015 Jun;72(11):2237-48.

According to a 2016 Harris Poll, 29% of Americans have at least one tattoo, up from 21% in 2012. At the same time, 23% of Americans polled in 2016 regret having their tattoo, which means big business for dermatologists who practice laser tattoo removal.

Prior to the theory of selective photothermolysis, tattoo removal mostly consisted of chemical or mechanical abrasion, surgical removal, or using some sort of caustic chemical or thermal destruction of the tattoo, Omar A. Ibrahimi, MD, PhD, said during a virtual course on laser and aesthetic skin therapy. “The earliest lasers prior to refinement by the theory of selective photothermolysis also fell into these categories: just basically crudely removing the skin and trying to get under to where the tattoo is,” said Dr. Ibrahimi, a dermatologist with the Connecticut Skin Institute in Stamford. “These would often heal with horrible scarring.”

Today, clinicians use Q-switched nanosecond and picosecond lasers for tattoo removal, though appropriate wavelengths need to be selected based on the tattoo ink color. Tattoo ink particles average about 0.1 mcm in size, and the thermal relaxation size works out to be about 10 nanoseconds. Black is the most common color dermatologists will treat. “For that, you can typically use a 1064, which has the highest absorption, but you can also use many of the other wavelengths,” he said. “The other colors are less common, followed by red, for which you would use a 532-nm wavelength.”

The clinical endpoint to strive for during tattoo removal is a whitening of the ink. That typically fades after about 20 minutes. “This whitening corresponds to cavitation [the production of gas vacuoles in the cells that were holding the ink],” Dr. Ibrahimi explained during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “These vacuoles are what lead to the whitening when using a high-gigawatt laser in a very short pulse. This causes highly localized heating, cavitation, and cell rupture. We don’t fully understand how tattoos are removed today, but the working models include some of the residual ink coming out through transepidermal elimination, some of it being removed via lymphatics, and some of it being removed by rephagocytosis.”

Alice Pien, MD/Wikimedia/CC BY-SA 4.0

For optimal results, determine if the tattoo is professional, amateur, traumatic, or cosmetic. “That’s going to give you some insight as to what kind of expectations to set for the patient,” he said. “Black ink is often the easiest to remove, while certain colors like white are more challenging. Certain colors are more prone to paradoxical ink darkening, like red or orange, or pink. These can undergo a chemical reaction where they darken. This is something important to discuss with patients in advance.”

Older tattoos “tend to be less hearty” and usually respond better to laser, he continued. Location of the tattoo also plays a role. “I find that tattoos below the knee are very slow to respond. Smaller tattoos will respond faster.”

During the focused medical exam, ask patients about any history of keloid scarring, vitiligo or any dermatologic conditions with a Koebner phenomenon, and rule out a history of parental gold salt administration for arthritis. “During your informed consent you want to make sure you address the expected healing time and the risks such as hyper- and hypopigmentation, blistering, and scarring,” Dr. Ibrahimi said. “You also want to set the expectation that this is not going to be a one and done procedure. Laser tattoo removal takes a series of treatments, often more than what we think – sometimes in the range of 15-20. And you may not get complete clearance. I liken it to breaking it up enough so that if somebody sees it, they won’t be able to recognize what the tattoo is. But you won’t be able to erase it 100%.”

Black, dark blue, and red tattoo colors respond best to laser light. Light blue, green, and purple colors are slower to respond, while yellow and orange colors respond poorly. “Now that we have picosecond lasers, we’re a little better at treating these tougher colors, but I think we still have a lot of room for improvement,” Dr. Ibrahimi said.

Melanin is a competing chromophore, which complicates treatment of tanned individuals and those with darker skin types. “The Q-switched 1064-nm laser is the safest device to use for these patients but it’s not effective for many ink colors,” he said.

Options to keep patients comfortable during the procedure include application of ice or forced chilled air. “You can also use topical anesthetics such as EMLA or liposomal lidocaine cream under occlusion,” he said. “You can also use injectable lidocaine. If you go that route, I recommend a ring block. If you inject right into the tattoo sometimes the ink can get leeched out after treatment. As for spot size, a larger spot size will penetrate deeper, so I try to treat tattoos with the biggest spot size. It also results in less bleeding, less splatter, less side effects, and you get better results.”

Common adverse events from tattoo removal include prolonged erythema, blistering, hyperpigmentation, hypopigmentation, and scarring. Less frequent complications include ink darkening, chrysiasis, and transient immunoreactivity. “We don’t really know what’s in a lot of these ink residues,” Dr. Ibrahimi said. “We know they’re getting mobilized and some of it’s going into the lymphatics. What’s happening with these ink particles? We don’t fully know.”

He also warned against using hair-removal devices to treat a tattoo. “It is the wrong pulse duration,” he said. “You need a picosecond or nanosecond device. You cannot use any other pulse durations, or you will horribly scar your patient.”

In 2012, R. Rox Anderson, MD, director of the Wellman Center for Photomedicine at Massachusetts General Hospital, and colleagues published results of a study that compared a single Q-switched laser treatment pass with four treatment passes separated by 20 minutes. After treating 18 tattoos in 12 adults, they found that the technique, known as the R20 method, was more effective than a single-pass treatment (P < .01). “Subsequent papers have shown that this result isn’t as impressive as initially reported, but I think it’s a method that persists,” Dr. Ibrahimi said.

Another recent advance is use of a topical square silicone patch infused with perfluorodecalin patch during tattoo removal, which has been shown to reduce epidermal whitening. “So, instead of waiting 20 minutes you wait 0 minutes,” he said. “This is called the R0 method,” he added, noting that there are also some secondary benefits to using this patch, including possibly helping as an optical clearing agent for deeper penetration of the laser. “Often after treatment you can see ink on the underside of the patch, which speaks to the transdermal elimination mechanism of action for removal of tattoos.”

As for future directions, Dr. Ibrahimi predicted that there will be better picosecond lasers coming down the pike. He also anticipates that Soliton’s Rapid Acoustic Pulse (RAP) device will make a significant impact in the field. The device was cleared for tattoo removal in 2019 and is being investigated as an option to improve the appearance of cellulite. The manufacturer anticipates that an upgraded RAP device will be cleared for use by the end of the first quarter of 2021.

Dr. Ibrahimi disclosed that he has received research funding and speaker honorarium from Cutera, Lumenis, Lutronic, and Syneron-Candela. He also holds stock in Soliton.

[email protected]

According to a 2016 Harris Poll, 29% of Americans have at least one tattoo, up from 21% in 2012. At the same time, 23% of Americans polled in 2016 regret having their tattoo, which means big business for dermatologists who practice laser tattoo removal.

Prior to the theory of selective photothermolysis, tattoo removal mostly consisted of chemical or mechanical abrasion, surgical removal, or using some sort of caustic chemical or thermal destruction of the tattoo, Omar A. Ibrahimi, MD, PhD, said during a virtual course on laser and aesthetic skin therapy. “The earliest lasers prior to refinement by the theory of selective photothermolysis also fell into these categories: just basically crudely removing the skin and trying to get under to where the tattoo is,” said Dr. Ibrahimi, a dermatologist with the Connecticut Skin Institute in Stamford. “These would often heal with horrible scarring.”

Today, clinicians use Q-switched nanosecond and picosecond lasers for tattoo removal, though appropriate wavelengths need to be selected based on the tattoo ink color. Tattoo ink particles average about 0.1 mcm in size, and the thermal relaxation size works out to be about 10 nanoseconds. Black is the most common color dermatologists will treat. “For that, you can typically use a 1064, which has the highest absorption, but you can also use many of the other wavelengths,” he said. “The other colors are less common, followed by red, for which you would use a 532-nm wavelength.”

The clinical endpoint to strive for during tattoo removal is a whitening of the ink. That typically fades after about 20 minutes. “This whitening corresponds to cavitation [the production of gas vacuoles in the cells that were holding the ink],” Dr. Ibrahimi explained during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “These vacuoles are what lead to the whitening when using a high-gigawatt laser in a very short pulse. This causes highly localized heating, cavitation, and cell rupture. We don’t fully understand how tattoos are removed today, but the working models include some of the residual ink coming out through transepidermal elimination, some of it being removed via lymphatics, and some of it being removed by rephagocytosis.”

Alice Pien, MD/Wikimedia/CC BY-SA 4.0

For optimal results, determine if the tattoo is professional, amateur, traumatic, or cosmetic. “That’s going to give you some insight as to what kind of expectations to set for the patient,” he said. “Black ink is often the easiest to remove, while certain colors like white are more challenging. Certain colors are more prone to paradoxical ink darkening, like red or orange, or pink. These can undergo a chemical reaction where they darken. This is something important to discuss with patients in advance.”

Older tattoos “tend to be less hearty” and usually respond better to laser, he continued. Location of the tattoo also plays a role. “I find that tattoos below the knee are very slow to respond. Smaller tattoos will respond faster.”

During the focused medical exam, ask patients about any history of keloid scarring, vitiligo or any dermatologic conditions with a Koebner phenomenon, and rule out a history of parental gold salt administration for arthritis. “During your informed consent you want to make sure you address the expected healing time and the risks such as hyper- and hypopigmentation, blistering, and scarring,” Dr. Ibrahimi said. “You also want to set the expectation that this is not going to be a one and done procedure. Laser tattoo removal takes a series of treatments, often more than what we think – sometimes in the range of 15-20. And you may not get complete clearance. I liken it to breaking it up enough so that if somebody sees it, they won’t be able to recognize what the tattoo is. But you won’t be able to erase it 100%.”

Black, dark blue, and red tattoo colors respond best to laser light. Light blue, green, and purple colors are slower to respond, while yellow and orange colors respond poorly. “Now that we have picosecond lasers, we’re a little better at treating these tougher colors, but I think we still have a lot of room for improvement,” Dr. Ibrahimi said.

Melanin is a competing chromophore, which complicates treatment of tanned individuals and those with darker skin types. “The Q-switched 1064-nm laser is the safest device to use for these patients but it’s not effective for many ink colors,” he said.

Options to keep patients comfortable during the procedure include application of ice or forced chilled air. “You can also use topical anesthetics such as EMLA or liposomal lidocaine cream under occlusion,” he said. “You can also use injectable lidocaine. If you go that route, I recommend a ring block. If you inject right into the tattoo sometimes the ink can get leeched out after treatment. As for spot size, a larger spot size will penetrate deeper, so I try to treat tattoos with the biggest spot size. It also results in less bleeding, less splatter, less side effects, and you get better results.”

Common adverse events from tattoo removal include prolonged erythema, blistering, hyperpigmentation, hypopigmentation, and scarring. Less frequent complications include ink darkening, chrysiasis, and transient immunoreactivity. “We don’t really know what’s in a lot of these ink residues,” Dr. Ibrahimi said. “We know they’re getting mobilized and some of it’s going into the lymphatics. What’s happening with these ink particles? We don’t fully know.”

He also warned against using hair-removal devices to treat a tattoo. “It is the wrong pulse duration,” he said. “You need a picosecond or nanosecond device. You cannot use any other pulse durations, or you will horribly scar your patient.”

In 2012, R. Rox Anderson, MD, director of the Wellman Center for Photomedicine at Massachusetts General Hospital, and colleagues published results of a study that compared a single Q-switched laser treatment pass with four treatment passes separated by 20 minutes. After treating 18 tattoos in 12 adults, they found that the technique, known as the R20 method, was more effective than a single-pass treatment (P < .01). “Subsequent papers have shown that this result isn’t as impressive as initially reported, but I think it’s a method that persists,” Dr. Ibrahimi said.

Another recent advance is use of a topical square silicone patch infused with perfluorodecalin patch during tattoo removal, which has been shown to reduce epidermal whitening. “So, instead of waiting 20 minutes you wait 0 minutes,” he said. “This is called the R0 method,” he added, noting that there are also some secondary benefits to using this patch, including possibly helping as an optical clearing agent for deeper penetration of the laser. “Often after treatment you can see ink on the underside of the patch, which speaks to the transdermal elimination mechanism of action for removal of tattoos.”

As for future directions, Dr. Ibrahimi predicted that there will be better picosecond lasers coming down the pike. He also anticipates that Soliton’s Rapid Acoustic Pulse (RAP) device will make a significant impact in the field. The device was cleared for tattoo removal in 2019 and is being investigated as an option to improve the appearance of cellulite. The manufacturer anticipates that an upgraded RAP device will be cleared for use by the end of the first quarter of 2021.

Dr. Ibrahimi disclosed that he has received research funding and speaker honorarium from Cutera, Lumenis, Lutronic, and Syneron-Candela. He also holds stock in Soliton.

[email protected]

According to a 2016 Harris Poll, 29% of Americans have at least one tattoo, up from 21% in 2012. At the same time, 23% of Americans polled in 2016 regret having their tattoo, which means big business for dermatologists who practice laser tattoo removal.

Prior to the theory of selective photothermolysis, tattoo removal mostly consisted of chemical or mechanical abrasion, surgical removal, or using some sort of caustic chemical or thermal destruction of the tattoo, Omar A. Ibrahimi, MD, PhD, said during a virtual course on laser and aesthetic skin therapy. “The earliest lasers prior to refinement by the theory of selective photothermolysis also fell into these categories: just basically crudely removing the skin and trying to get under to where the tattoo is,” said Dr. Ibrahimi, a dermatologist with the Connecticut Skin Institute in Stamford. “These would often heal with horrible scarring.”

Today, clinicians use Q-switched nanosecond and picosecond lasers for tattoo removal, though appropriate wavelengths need to be selected based on the tattoo ink color. Tattoo ink particles average about 0.1 mcm in size, and the thermal relaxation size works out to be about 10 nanoseconds. Black is the most common color dermatologists will treat. “For that, you can typically use a 1064, which has the highest absorption, but you can also use many of the other wavelengths,” he said. “The other colors are less common, followed by red, for which you would use a 532-nm wavelength.”

The clinical endpoint to strive for during tattoo removal is a whitening of the ink. That typically fades after about 20 minutes. “This whitening corresponds to cavitation [the production of gas vacuoles in the cells that were holding the ink],” Dr. Ibrahimi explained during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “These vacuoles are what lead to the whitening when using a high-gigawatt laser in a very short pulse. This causes highly localized heating, cavitation, and cell rupture. We don’t fully understand how tattoos are removed today, but the working models include some of the residual ink coming out through transepidermal elimination, some of it being removed via lymphatics, and some of it being removed by rephagocytosis.”

Alice Pien, MD/Wikimedia/CC BY-SA 4.0

For optimal results, determine if the tattoo is professional, amateur, traumatic, or cosmetic. “That’s going to give you some insight as to what kind of expectations to set for the patient,” he said. “Black ink is often the easiest to remove, while certain colors like white are more challenging. Certain colors are more prone to paradoxical ink darkening, like red or orange, or pink. These can undergo a chemical reaction where they darken. This is something important to discuss with patients in advance.”

Older tattoos “tend to be less hearty” and usually respond better to laser, he continued. Location of the tattoo also plays a role. “I find that tattoos below the knee are very slow to respond. Smaller tattoos will respond faster.”

During the focused medical exam, ask patients about any history of keloid scarring, vitiligo or any dermatologic conditions with a Koebner phenomenon, and rule out a history of parental gold salt administration for arthritis. “During your informed consent you want to make sure you address the expected healing time and the risks such as hyper- and hypopigmentation, blistering, and scarring,” Dr. Ibrahimi said. “You also want to set the expectation that this is not going to be a one and done procedure. Laser tattoo removal takes a series of treatments, often more than what we think – sometimes in the range of 15-20. And you may not get complete clearance. I liken it to breaking it up enough so that if somebody sees it, they won’t be able to recognize what the tattoo is. But you won’t be able to erase it 100%.”

Black, dark blue, and red tattoo colors respond best to laser light. Light blue, green, and purple colors are slower to respond, while yellow and orange colors respond poorly. “Now that we have picosecond lasers, we’re a little better at treating these tougher colors, but I think we still have a lot of room for improvement,” Dr. Ibrahimi said.

Melanin is a competing chromophore, which complicates treatment of tanned individuals and those with darker skin types. “The Q-switched 1064-nm laser is the safest device to use for these patients but it’s not effective for many ink colors,” he said.

Options to keep patients comfortable during the procedure include application of ice or forced chilled air. “You can also use topical anesthetics such as EMLA or liposomal lidocaine cream under occlusion,” he said. “You can also use injectable lidocaine. If you go that route, I recommend a ring block. If you inject right into the tattoo sometimes the ink can get leeched out after treatment. As for spot size, a larger spot size will penetrate deeper, so I try to treat tattoos with the biggest spot size. It also results in less bleeding, less splatter, less side effects, and you get better results.”

Common adverse events from tattoo removal include prolonged erythema, blistering, hyperpigmentation, hypopigmentation, and scarring. Less frequent complications include ink darkening, chrysiasis, and transient immunoreactivity. “We don’t really know what’s in a lot of these ink residues,” Dr. Ibrahimi said. “We know they’re getting mobilized and some of it’s going into the lymphatics. What’s happening with these ink particles? We don’t fully know.”

He also warned against using hair-removal devices to treat a tattoo. “It is the wrong pulse duration,” he said. “You need a picosecond or nanosecond device. You cannot use any other pulse durations, or you will horribly scar your patient.”

In 2012, R. Rox Anderson, MD, director of the Wellman Center for Photomedicine at Massachusetts General Hospital, and colleagues published results of a study that compared a single Q-switched laser treatment pass with four treatment passes separated by 20 minutes. After treating 18 tattoos in 12 adults, they found that the technique, known as the R20 method, was more effective than a single-pass treatment (P < .01). “Subsequent papers have shown that this result isn’t as impressive as initially reported, but I think it’s a method that persists,” Dr. Ibrahimi said.

Another recent advance is use of a topical square silicone patch infused with perfluorodecalin patch during tattoo removal, which has been shown to reduce epidermal whitening. “So, instead of waiting 20 minutes you wait 0 minutes,” he said. “This is called the R0 method,” he added, noting that there are also some secondary benefits to using this patch, including possibly helping as an optical clearing agent for deeper penetration of the laser. “Often after treatment you can see ink on the underside of the patch, which speaks to the transdermal elimination mechanism of action for removal of tattoos.”

As for future directions, Dr. Ibrahimi predicted that there will be better picosecond lasers coming down the pike. He also anticipates that Soliton’s Rapid Acoustic Pulse (RAP) device will make a significant impact in the field. The device was cleared for tattoo removal in 2019 and is being investigated as an option to improve the appearance of cellulite. The manufacturer anticipates that an upgraded RAP device will be cleared for use by the end of the first quarter of 2021.

Dr. Ibrahimi disclosed that he has received research funding and speaker honorarium from Cutera, Lumenis, Lutronic, and Syneron-Candela. He also holds stock in Soliton.

[email protected]

New technologies being developed at the Wellman Center for Photomedicine, Boston, that dermatologists will likely be using in the next 5 years include injection of ice slurry to remove fat, a cooling device for benign pigmented lesions, and a focused laser beam that delivers energy without injuring the skin’s surface.

During a virtual course on laser and aesthetic skin therapy, Lilit Garibyan, MD, PhD, discussed findings from a swine study published online in January 2020 that used an injectable physiologic ice slurry for the nonsurgical removal of fat, a technology that could give CoolSculpting a run for its money. “It does lead to more efficient and effective cryolipolysis,” said Dr. Garibyan, the lead study author who is an assistant professor of dermatology at Harvard University, and director of The Magic Wand Initiative at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston. “The treatment of fat tissue with ice slurry injection can be done in less than 1 minute, as opposed to an hour of cooling with CoolSculpting. In addition, because cooling is delivered directly into target tissue, it is more effective.”

For the study, she and her colleagues at the Wellman Center injected the slurry – a mix of ice, saline, and glycol – into the flanks of swine and followed them for up to 8 weeks. They used ultrasound imaging to show the location of the fat loss and to quantify it. The researchers observed about 40%-50% loss of fat in the treated area, compared with a 60% fat gain in swine who served as controls. “This is because the pig is growing and gaining weight, so the fat is increasing,” she explained.

Gross histologic images also showed fat loss in the subcutaneous fat tissue of treated swine, but not in controls. “When we quantified this loss, there was about a 60% loss of fat after a single injection of ice slurry in the subcutaneous fat,” Dr. Garibyan said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “On histology there was loss of fat in the subcutaneous area and it was replaced by new collagen. No damage to surrounding skin or muscle tissue was seen.”

She characterized the approach as “a minimally invasive and novel method of adipose tissue removal. It’s very simple, because it’s just a simple injection, and it’s very efficient and effective in fat removal. Most importantly, it can target any anatomic site accessible with a needle.”

Human studies are currently underway.

Another emerging technology Dr. Garibyan discussed is a novel controlled skin cooling device for the treatment of benign pigmented lesions. The approach, known as Cryomodulation, was invented by R. Rox Anderson, MD, Dieter Manstein, MD, PhD, and Henry HL Chan, MD, at Massachusetts General Hospital, Boston, and is being commercialized by R2 Technologies. It delivers precise controlled and titratable freezing of benign pigmented lesions without damage to the epidermal barrier. It has been cleared by the Food and Drug Administration, and R2 Technologies plans to launch its first commercial product in the United States in December 2020.

The handpiece of the device, which is placed on top of the skin, provides localized and controlled freezing to targeted benign pigmented lesions. “The cold, or the freeze, is delivered to where the melanocytes reside,” Dr. Garibyan said. “The ice nucleation essentially pauses melanin production. As cell turnover occurs, cells that are melanin-free migrate upward and renew freshly healthy skin. So, melanocyte function is still preserved but there is no destruction to the epidermal barrier. This technology is totally color blind, and there is no persistent inflammatory response.”

After this treatment, histology reveals a reduction of epidermal melanin without destruction of melanocytes. The treatment impairs melanocyte transfer, but not the melanocytes. “Clinically, that is seen as lightening of the skin,” she said. More than 550 patients have been treated with Cryomodulation to demonstrate its safety and effectiveness, described in a study published in 2019, and an ASLMS e-poster.

The final technology Dr. Garibyan discussed is a novel device for removing dermal pigment with a highly focused laser beam. “The problem with current lasers is that the maximum absorption of energy happens at the dermal/epidermal junction,” she said. “This not only increases the risk of epidermal injury, especially in skin of color, but it also leaves very little energy to reach the pigmented target tissue or cells. In addition, there is scattering in the skin, which also reduces the amount of fluence or energy that can reach the target depth, therefore reducing the efficacy of treatment with currently available laser.”

The investigative focused laser beam with high-speed scanning creates a large differential between the fluence at the surface and the fluence at the target, which improves safety. “It’s able to deliver enhanced energy to the target,” she said. “Therefore it’s more effective than destroying the target pigmented cells. There is no injury outside of the focal point, so it offers improved safety, efficacy, and spatial selectivity. The end result on histology is a selective destruction of the pigmented cells, which are typically melanophages.”

Dr. Garibyan predicted that this device will be an ideal therapy for postinflammatory hyperpigmentation and for melasma, “as no effective therapies are available for those conditions.”

She disclosed that she has received royalties/inventorship assigned to MGH. She holds equity in, is a consultant to, and is a member of the scientific advisory board of Brixton Biosciences. She is a consultant to Vyome Therapeutics, Blossom Innovations, Aegle Therapeutics, and ClearifiRx.

[email protected]

New technologies being developed at the Wellman Center for Photomedicine, Boston, that dermatologists will likely be using in the next 5 years include injection of ice slurry to remove fat, a cooling device for benign pigmented lesions, and a focused laser beam that delivers energy without injuring the skin’s surface.

During a virtual course on laser and aesthetic skin therapy, Lilit Garibyan, MD, PhD, discussed findings from a swine study published online in January 2020 that used an injectable physiologic ice slurry for the nonsurgical removal of fat, a technology that could give CoolSculpting a run for its money. “It does lead to more efficient and effective cryolipolysis,” said Dr. Garibyan, the lead study author who is an assistant professor of dermatology at Harvard University, and director of The Magic Wand Initiative at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston. “The treatment of fat tissue with ice slurry injection can be done in less than 1 minute, as opposed to an hour of cooling with CoolSculpting. In addition, because cooling is delivered directly into target tissue, it is more effective.”

For the study, she and her colleagues at the Wellman Center injected the slurry – a mix of ice, saline, and glycol – into the flanks of swine and followed them for up to 8 weeks. They used ultrasound imaging to show the location of the fat loss and to quantify it. The researchers observed about 40%-50% loss of fat in the treated area, compared with a 60% fat gain in swine who served as controls. “This is because the pig is growing and gaining weight, so the fat is increasing,” she explained.

Gross histologic images also showed fat loss in the subcutaneous fat tissue of treated swine, but not in controls. “When we quantified this loss, there was about a 60% loss of fat after a single injection of ice slurry in the subcutaneous fat,” Dr. Garibyan said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “On histology there was loss of fat in the subcutaneous area and it was replaced by new collagen. No damage to surrounding skin or muscle tissue was seen.”

She characterized the approach as “a minimally invasive and novel method of adipose tissue removal. It’s very simple, because it’s just a simple injection, and it’s very efficient and effective in fat removal. Most importantly, it can target any anatomic site accessible with a needle.”

Human studies are currently underway.

Another emerging technology Dr. Garibyan discussed is a novel controlled skin cooling device for the treatment of benign pigmented lesions. The approach, known as Cryomodulation, was invented by R. Rox Anderson, MD, Dieter Manstein, MD, PhD, and Henry HL Chan, MD, at Massachusetts General Hospital, Boston, and is being commercialized by R2 Technologies. It delivers precise controlled and titratable freezing of benign pigmented lesions without damage to the epidermal barrier. It has been cleared by the Food and Drug Administration, and R2 Technologies plans to launch its first commercial product in the United States in December 2020.

The handpiece of the device, which is placed on top of the skin, provides localized and controlled freezing to targeted benign pigmented lesions. “The cold, or the freeze, is delivered to where the melanocytes reside,” Dr. Garibyan said. “The ice nucleation essentially pauses melanin production. As cell turnover occurs, cells that are melanin-free migrate upward and renew freshly healthy skin. So, melanocyte function is still preserved but there is no destruction to the epidermal barrier. This technology is totally color blind, and there is no persistent inflammatory response.”

After this treatment, histology reveals a reduction of epidermal melanin without destruction of melanocytes. The treatment impairs melanocyte transfer, but not the melanocytes. “Clinically, that is seen as lightening of the skin,” she said. More than 550 patients have been treated with Cryomodulation to demonstrate its safety and effectiveness, described in a study published in 2019, and an ASLMS e-poster.

The final technology Dr. Garibyan discussed is a novel device for removing dermal pigment with a highly focused laser beam. “The problem with current lasers is that the maximum absorption of energy happens at the dermal/epidermal junction,” she said. “This not only increases the risk of epidermal injury, especially in skin of color, but it also leaves very little energy to reach the pigmented target tissue or cells. In addition, there is scattering in the skin, which also reduces the amount of fluence or energy that can reach the target depth, therefore reducing the efficacy of treatment with currently available laser.”

The investigative focused laser beam with high-speed scanning creates a large differential between the fluence at the surface and the fluence at the target, which improves safety. “It’s able to deliver enhanced energy to the target,” she said. “Therefore it’s more effective than destroying the target pigmented cells. There is no injury outside of the focal point, so it offers improved safety, efficacy, and spatial selectivity. The end result on histology is a selective destruction of the pigmented cells, which are typically melanophages.”

Dr. Garibyan predicted that this device will be an ideal therapy for postinflammatory hyperpigmentation and for melasma, “as no effective therapies are available for those conditions.”

She disclosed that she has received royalties/inventorship assigned to MGH. She holds equity in, is a consultant to, and is a member of the scientific advisory board of Brixton Biosciences. She is a consultant to Vyome Therapeutics, Blossom Innovations, Aegle Therapeutics, and ClearifiRx.

[email protected]

New technologies being developed at the Wellman Center for Photomedicine, Boston, that dermatologists will likely be using in the next 5 years include injection of ice slurry to remove fat, a cooling device for benign pigmented lesions, and a focused laser beam that delivers energy without injuring the skin’s surface.

During a virtual course on laser and aesthetic skin therapy, Lilit Garibyan, MD, PhD, discussed findings from a swine study published online in January 2020 that used an injectable physiologic ice slurry for the nonsurgical removal of fat, a technology that could give CoolSculpting a run for its money. “It does lead to more efficient and effective cryolipolysis,” said Dr. Garibyan, the lead study author who is an assistant professor of dermatology at Harvard University, and director of The Magic Wand Initiative at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston. “The treatment of fat tissue with ice slurry injection can be done in less than 1 minute, as opposed to an hour of cooling with CoolSculpting. In addition, because cooling is delivered directly into target tissue, it is more effective.”

For the study, she and her colleagues at the Wellman Center injected the slurry – a mix of ice, saline, and glycol – into the flanks of swine and followed them for up to 8 weeks. They used ultrasound imaging to show the location of the fat loss and to quantify it. The researchers observed about 40%-50% loss of fat in the treated area, compared with a 60% fat gain in swine who served as controls. “This is because the pig is growing and gaining weight, so the fat is increasing,” she explained.

Gross histologic images also showed fat loss in the subcutaneous fat tissue of treated swine, but not in controls. “When we quantified this loss, there was about a 60% loss of fat after a single injection of ice slurry in the subcutaneous fat,” Dr. Garibyan said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “On histology there was loss of fat in the subcutaneous area and it was replaced by new collagen. No damage to surrounding skin or muscle tissue was seen.”

She characterized the approach as “a minimally invasive and novel method of adipose tissue removal. It’s very simple, because it’s just a simple injection, and it’s very efficient and effective in fat removal. Most importantly, it can target any anatomic site accessible with a needle.”

Human studies are currently underway.

Another emerging technology Dr. Garibyan discussed is a novel controlled skin cooling device for the treatment of benign pigmented lesions. The approach, known as Cryomodulation, was invented by R. Rox Anderson, MD, Dieter Manstein, MD, PhD, and Henry HL Chan, MD, at Massachusetts General Hospital, Boston, and is being commercialized by R2 Technologies. It delivers precise controlled and titratable freezing of benign pigmented lesions without damage to the epidermal barrier. It has been cleared by the Food and Drug Administration, and R2 Technologies plans to launch its first commercial product in the United States in December 2020.

The handpiece of the device, which is placed on top of the skin, provides localized and controlled freezing to targeted benign pigmented lesions. “The cold, or the freeze, is delivered to where the melanocytes reside,” Dr. Garibyan said. “The ice nucleation essentially pauses melanin production. As cell turnover occurs, cells that are melanin-free migrate upward and renew freshly healthy skin. So, melanocyte function is still preserved but there is no destruction to the epidermal barrier. This technology is totally color blind, and there is no persistent inflammatory response.”

After this treatment, histology reveals a reduction of epidermal melanin without destruction of melanocytes. The treatment impairs melanocyte transfer, but not the melanocytes. “Clinically, that is seen as lightening of the skin,” she said. More than 550 patients have been treated with Cryomodulation to demonstrate its safety and effectiveness, described in a study published in 2019, and an ASLMS e-poster.

The final technology Dr. Garibyan discussed is a novel device for removing dermal pigment with a highly focused laser beam. “The problem with current lasers is that the maximum absorption of energy happens at the dermal/epidermal junction,” she said. “This not only increases the risk of epidermal injury, especially in skin of color, but it also leaves very little energy to reach the pigmented target tissue or cells. In addition, there is scattering in the skin, which also reduces the amount of fluence or energy that can reach the target depth, therefore reducing the efficacy of treatment with currently available laser.”

The investigative focused laser beam with high-speed scanning creates a large differential between the fluence at the surface and the fluence at the target, which improves safety. “It’s able to deliver enhanced energy to the target,” she said. “Therefore it’s more effective than destroying the target pigmented cells. There is no injury outside of the focal point, so it offers improved safety, efficacy, and spatial selectivity. The end result on histology is a selective destruction of the pigmented cells, which are typically melanophages.”

Dr. Garibyan predicted that this device will be an ideal therapy for postinflammatory hyperpigmentation and for melasma, “as no effective therapies are available for those conditions.”

She disclosed that she has received royalties/inventorship assigned to MGH. She holds equity in, is a consultant to, and is a member of the scientific advisory board of Brixton Biosciences. She is a consultant to Vyome Therapeutics, Blossom Innovations, Aegle Therapeutics, and ClearifiRx.

[email protected]