Practitioners conduct a clinical study to determine the possibilities of minimising the risk of secondary hyperpigmentation after laser resurfacing and phenol peels
We have conducted a study to determine the possibility of reducing the risk of secondary hyperpigmentation after phenol peels and laser resurfacing of the face. It has been previously established that pigmentation disturbances during recovery after moderately and severely traumatic treatments are one of the key problems concerning the patients’ wellbeing and satisfaction.1,2
During the course of this study, the patients applied a water-soluble product (serum) with 0.5% niacinamide and a complex of plant ingredients (the extracts of cane sugar, maple sugar, aloe vera, blueberry leaves and berries, sweet orange and citron) for seven to 10 days before their phenol peel treatment (35% phenol's solution) or ablative laser resurfacing.
Following the treatments, the patients continued applying the serum for 30 days. In the phenol peel group (Group 1), there were 20 patients that applied the serum, plus nine patients in the control group. In Group 2, which underwent fractional ablative erbium laser resurfacing, there were 15 patients that applied the serum and 10 patients in the control group.
All patients noted the serum’s high tolerability, skin brightening effect and the absence of skin irritation. No side effects, including post-inflammatory and transitory pigmentation, were registered in either group of patients (20 phenol peel patients and 15 laser resurfacing patients).
In the control groups, one case of post-inflammatory pigmentation was recorded after phenol peel, and one case of post-inflammatory pigmentation after laser resurfacing. The data stayed consistent after three months. Both groups using the serum noted a shorter recovery period: the shedding of post-treatment scabs took three to four days, whereas in the control group it was five to seven days.
Based on the results obtained thus far, we believe that high tolerability, possible reduction of the side effects and the patients’ faster return to social life led to increased wellbeing and satisfaction, providing sufficient grounds for including such topical solutions in the protocols of pre and post-treatment skincare. Further studies should be conducted to obtain more substantial data on the efficacy of topical solutions for the prevention of post-inflammatory hyperpigmentation.
Laser treatments in aesthetic medicine have been growing increasingly popular in the last decade, and this trend is likely to persist.3,4 Laser can be used for a variety of purposes, from acne therapy to scar and skin tag removal; and controlled epidermal injury plays a significant part in the practice of aesthetic practitioners.
According to research, the risk of side effects and complications resulting from aesthetic laser treatments can be considered low.5-7 However, certain side effects, usually classified as insignificant, cause noticeable discomfort and can lead to patients’ dissatisfaction with the treatment effect, even when the results are satisfactory from an objective point of view.
Among such side effects is pigmentation disturbance caused by epidermal injury and the development of inflammatory changes in the tissue in the process of post-laser recovery.8,9 Post-inflammatory hyperpigmentation (PIH) is one of the most commonly described side effects of laser treatments. Various research data shows that the rate of PIH after non-ablative fractional laser treatment reaches 31% for melasma therapy,10 25% for antiageing,11 and 41% for post-acne scarring removal.12
Ablative laser treatment bears even higher degree of risk; up to 80% of PIH with CO2 laser and 60% with Erbium YAG.13 The power of laser impact correlates with the risk of post-treatment pigmentation.14
Generally, patients with already present melasma need to be informed that laser therapy, including non-ablative laser, may increase pigmentation after a single treatment.15
Thus, PIH prevention must be one of the priorities in the patients’ preparation for laser treatment. In the presence of risk factors, such as melasma, PIH manifestation in the past, the use of photosensitising skincare in the previous few weeks and the taking of photosensitising drugs, prophylactic measures are recommended for at least 14-28 days prior to the treatment.16,17
Today the standard for PIH prevention is applying topical solutions with confirmed anti-tyrosinase activity.18 Most commonly used are solutions based on kojic acid, azelaic acid, arbutin and hydroquinone, the latter often used in combination with tretinoin and topical steroids19 (the use of hydroquinone-containing solutions is banned in EU20). Apart from these, the daily use of sunscreens with SPF UVA UVB 30-50 is routinely recommended to laser patients.21,22
However, most of the above, with the exception of sunscreens, actually increase the skin’s sensitivity to ultraviolet, exposing patients to the risk of PIH in the recovery period after laser or other treatment involving epidermal injury.23
The aim of this research is to explore the possibilities and prospects of PIH prevention with the use of a topical solution with a brightening and anti-inflammatory effect, which does not increase the skin’s sensitivity to UV radiation.
This research was conducted in several clinics in Ukraine. It involved 54 women, aged 25-52. Participants were selected to the following criteria:
A complete medical history was taken and all patients signed informed consent forms and the research aims and methods were explained to them in full.
Patients were divided into two groups of 25 and 29 people. The first group of 29 people had a 35% phenol peel. There were 20 patients who were given a topical solution to use in the 14 days prior to their chemical peel, and then resume application on the fifth day after the treatment and continue for 30 days. The control group of 10 patients did not use topical solutions in the pre and post-peel periods.
In the second group, all patients had fractional ablative erbium laser resurfacing. There were 15 patients who were given a topical solution to use in the 14 days prior to their laser treatment, and then they were instructed to resume application on the fifth day after the treatment and continue for 30 days. The control group of 10 patients did not use topical solutions in the pre and post-treatment periods.
Neither group had any information about the composition, manufacturer or price of their topical solution.
The topical solution recommended to research participants was a water solution of:
The expected effects of the solution were: a stronger antioxidant protection of the skin, the smoothing of epidermal keratinous layer, reduced activity of melanocyte-keratinocyte melanin transfer, the decrease of melanin synthesis due to the deactivation of tyrosinase, and restoration of capillary tone in the microcirculatory bed.
It was suspected that the affect would be achieved with synergetic impact of niacinamide and a complex of natural antioxidants in the citruses and blueberry extracts, combined with the effect of maple and sugar cane syrups’ polysaccharides and aloe.
The aim of the solution is to create a protective film on the skin surface, creating favourable conditions for comfortable recovery. At the same time, the solution aims to subdue inflammatory reactions, activate epidermal regeneration and stimulate the syntheses of dermal structural elements.
Topical application of niacinamide has a range of confirmed effects on the skin. In particular, applying niacinamide-containing solutions for several weeks aims to reduce trans-epidermal water loss by up to 24% in four weeks through increasing the contents of free fatty acids (67%) and ceramides (34%) in the keratinous layer of the skin.24
The syntheses of epidermal proteins: keratin, filaggrin and involucrin is also known to increase.25 Together, these proteins optimise the aggregation of keratinocytes in the keratinous layer, preserve the integrity of corneous envelopes of corneocytes and the smooth structure of the keratinous layer.26 Research of niacinamide’s effect on the human fibroblast culture has revealed the increased syntheses of new fibroblasts (20%) and collagen type I (54%).27,28 Niacinamide is widely used as a brightening agent, which is especially active during the therapy of post-traumatic, post-inflammatory and chronic recurring hyperpigmentation. The mechanics of niacinamide action is as follows: niacinamide inhibits the melanocyte-to-keratinocyte transfer of pigment granules (melanosomes) up to 68% in vitro in the co-culture of melanocytes and keratinocytes.29 Niacinamide acts in synergy with certain antioxidants,30 increasing the effect of an antioxidant’s impact and advancing all the results described above.
Blueberry extract contains specific anthocyanins and polyphenols with antioxidant effect. They are also able to reduce the damaging effect of oxidative stress, prevent the skin’s photodamage, especially when connected with UVB damage.31 Anthocyanins are capable of absorbing a wide spectrum of UV rays, helping to reduce the skin’s sensitivity to ultraviolet radiation with daily use. Blueberry anthocyanins, in particular cyanidin-3-glucoside, petunidin-3-glucoside, malvidin-3-glucoside, and delphinidin-3-glucoside, can also prevent the overexpression of genes responsible for the synthesis of metal proteinase and the suppression of collagen synthesis by dermal fibroblasts.32
Aloe barbadensis (aloe vera) juice extract contains more than 75 active agents with pronounced biological effect.33 Polysaccharide glucomannan and gibberellin interact with the fibroblasts’ growth factor receptors and stimulate the proliferative activity of the cells leading to the activation of collagen synthesis.34 The topical application of aloe juice extract is known to increase the synthesis of hyaluronic acid and dermatan sulphate in the granulation tissue after an injury,35 as well as the increase of proliferation-promoting activity of dermal cells in general accelerating healing and oxygenation.36 Aloe juice extract has anti-inflammatory effect as well, due to its ability to inhibit the cyclooxygenase pathway of inflammation and to reduce the activity of prostaglandin E2. It appears that this particular effect of aloe extract is due to its contents of C-glucosyl chromone.37 Finally, aloe has a proven antioxidant effect thanks to glutathione peroxide superoxide dismutase and some phenol derivatives.38
Cane sugar extract contains natural flavonoids and phenolic acids with pronounced antioxidant effect.39 The daily application of solutions with cane sugar extract helps reduce the negative effects of oxidative stress and UV-related damage in various skin structures.40
The maple (Acer rubrum) is a rich source of phenolic compounds which possess galloyl groups. These glucitol-core containing gallotannins (GCGs) have reported antioxidant and anti-glycative effects and also the anti-tyrosinase and anti-melanogenic effects of a proprietary phenolic-enriched red maple leaves extract.41 The extract is able to:
Therefore, the anti-melanogenic effects of red maple GCGs can help reduce a risk of PIH.41
Citrus medica extract is a source of natural ascorbic acid and different flavonoids, including nobiletin,42 hesperidin et al.43 The extract helps smooth and brighten the skin because of tyrosinase inhibition effect, prevents inflammatory reaction and accelerates healing process after an injury.44
Sweet orange extract (citrus aurantium extract) contains a range of low-molecular substances with anti-inflammatory and capillary-strengthening effect, also with a capacity for tyrosinase inhibition (TI) and pigment inhibition.45
All patients in both groups noted good tolerability of the solution, ease of application and lack of pronounced subjective sensations during the application, both in pre- and post-treatment (phenol peel and fractional ablative erbium laser resurfacing) periods. Neither group displayed any side effects potentially connected to the use of the solution.
In Group 1, among the patients who used the solution, there were no cases of PIH, whereas in the control group, one case of PIH was diagnosed and the patient received additional therapy to correct hyperpigmentation. The rate of shedding of the crusts among the patients who used the solution was three to four days, whereas, in the control group it was five to seven days.
Group 2 displayed similar results. Among the patients who used the solution there were no cases of PIH, while in the control group, one case of PIH was diagnosed and additional therapy prescribed. The rate of crust shedding was three to four days for the patients who used the solution, and five to seven days for the patients in the control group. The data is summarised in Table 1.
|Group Number||Method||Number of Patients||Rate of PIH||Rate of crust shedding (days)|
|1||35% phenol peeling, with the solution||20||0%||3-4|
|1||35% phenol peeling, control group ||9||11%||5-7|
|2||Ablative Erbium laser resurfacing, with the solution ||15||0%||3-4|
|2||Ablative Erbium laser resurfacing, control group||10||10%||5-7|
Table 1: The results of the study
Given the results of this research, we can suppose that the application of a topical solution based on plant extracts and niacinamide in the periods of preparation for and rehabilitation after laser treatment or deep chemical peel is highly likely to shorten the recovery period and reduce the risk of post-inflammatory hyperpigmentation (PIH).
A shorter recovery period and a reduced possibility of the most common side effect increases the patients’ satisfaction, improves their socialisation and makes the early rehabilitation period more comfortable, which is beneficial for the remote results of the treatment, and the performance of clinic and its practitioners. Good tolerability and lack of contraindications make the solution suitable for preparation and recovery after laser treatments and chemical peels combined with sun protection.
Disclosure: For the purposes of this research, 100 bottles of Meder Beauty Science Nrj-Soin Serum were provided. The packaging was 50ml airless bottles, unmarked. The serum was provided by Meder Beauty International Ltd (UK). The research participants were not rewarded. The clinical professionals, who participated in the research, did not receive any grants, rewards, payments or any other compensation, material or otherwise. This article was written without any sponsor support from the manufacturing company.
1. Buainain De Castro Maymone M. Skin hyperpigmentation disorders: Association and impact on health-related quality of life. Dissertation Boston University School of Medicine, 2016. By the way, very interesting work!
2. Pollo, C. F., Miot, L. D. B., Meneguin, S., & Miot, H. A. (2018). Factors associated with quality of life in facial melasma: a cross-sectional study. International Journal of Cosmetic Science, 40(3), 313–316.
3. Loesch MM, Somani AK, Kingsley MM, Travers JB, Spandau DF. Skin resurfacing procedures: new and emerging options. Clin Cosmet Investig Dermatol. 2014;7:231–241
4. Aesthetic Lasers Market Analysis by Application (IPL Laser Treatment, Laser Skin Resurfacing, Noninvasive Tightening, Laser-Assisted Lipoplasty, Laser Hair Removal), and Segment Forecasts to 2024 Market Research Report GVR-1-68038-078-1 Aug, 2016.
5. Metelitsa AI, Alster TS. Fractionated laser skin resurfacing treatment complications: a review. Dermatol Surg 2010;36:299–306.
6. Ramsdell WM. Fractional CO2 Laser Resurfacing Complications. Semin Plast Surg. 2012;26(3):137–140.
7. GRABER, E. M., TANZI, E. L. and ALSTER, T. S. (2008), Side Effects and Complications of Fractional Laser Photothermolysis: Experience with 961 Treatments. Dermatologic Surgery, 34: 301-307.
8. Weinstein C. Carbon dioxide laser resurfacing. Long-term followup in 2,123 patients. Clin Plast Surg 1998;25:109–30. Review
9. Tierney, E. P., & Hanke, W. C. (2010). Review of the Literature: Treatment of Dyspigmentation with Fractionated Resurfacing. Dermatologic Surgery, 36(10), 1499–1508.
10. Wind BS, Kroon MW, Meesters AA, et al. Non-ablative 1,550 nm fractional laser therapy versus triple topical therapy for the treatment of melasma: a randomized controlled split-face study. Lasers Surg Med. 2010;42(7):607–612
11. Shin MK, Lee JH, Lee SJ, Kim NI. Platelet-rich plasma combined with fractional laser therapy for skin rejuvenation. Dermatol Surg. 2012;38(4):623–630.
12. Alajlan AM, Alsuwaidan SN. Acne scars in ethnic skin treated with both non-ablative fractional 1,550 nm and ablative fractional CO2 lasers: comparative retrospective analysis with recommended guidelines. Lasers Surg Med. 2011;43(8):787–791.
13. You HJ, Kim DW, Yoon ES, Park SH. Comparison of four different lasers for acne scars: Resurfacing and fractional lasers. J Plast Reconstr Aesthet Surg. 2016;69(4): e 87–95.
14. Consensus recommendations on the use of an erbium-doped 1,550-nm fractionated laser and its applications in dermatologic laser surgery. Sherling M, Friedman PM, Adrian R, Burns AJ, Conn H, Fitzpatrick R, Gregory R, Kilmer S, Lask G, Narurkar V, Katz TM, Avram M Dermatol Surg. 2010 Apr; 36(4):461-9.
15. Laser resurfacing for treatment of acne scarring in Fitzpatrick skin types V to VI: practical approaches to maximizing safety. Alexis AF Cutis. 2013 Dec; 92(6):272-3.
16. Passeron, T. (2016). L’hyperpigmentation post-inflammatoire. Annales de Dermatologie et de Vénéréologie, 143, S15–S19.
17. Tomita Y, Maeda K, Tagami H. Melanocyte-stimulating properties of arachidonic acid metabolites: possible role in postinflammatory pigmentation. Pigment Cell Res. 1992;5: 357-361
18. Hearing V.J. Determination of melanin synthetic pathways. J Invest Dermatol. 2011;131:E8–11.
19. Sarkar R., Arora P., Garg K.V. Cosmeceuticals for hyperpigmentation: What is available? J Cutan Aesthet Surg. 2013;6:4–11.
20. GUIDANCE NOTE: THE RESTRICTION TO “PROFESSIONAL USE” IN THE COSMETICS DIRECTIVE 76/768/EEC VERSION 1.0 (DECEMBER 2005) <ec.europa.eu/docsroom/documents/22681/attachments/1/.../pdf>
21. Boukari F, Jourdan E, Fontas E, Montaudié H, Castela E, Lacour JP, Passeron T. Prevention of melasma relapses with sunscreen combining protection against UV and short wavelengths of visible light: a prospective randomized comparative trial. J Am Acad Dermatol. 2015
22. Callender, V.D., St. Surin-Lord, S., Davis, E.C. et al. Am J Clin Dermatol (2011) 12: 87.
23. Rendon, M. I., & Gaviria, J. I. (2006). Review of Skin-Lightening Agents. Dermatologic Surgery, 31, 886–890.
24. Niacinamide-Containing Facial Moisturizer Improves Skin Barrier and Benefits Subjects With Rosacea Zoe Diana Draelos, MD; Keith Ertel, PhD; Cindy Berge, BS
25. Bissett D. Topical niacinamide and barrier enhancement. Cutis. 2002;70(suppl 6):8-12.
26. Tanno O, Ota U, Kitamura N, et al. Nicotinamide increases biosynthesis of ceramides as well as other stra- tum corneum lipids to improve the epidermal perme- ability barrier. Br J Dermatol. 2000;143:524-531.
27. Oblong, J.E., Bissett, D.L., Ritter, J.L., Kurtz, K.K., and Schnicker, M.S., »Niacinamide stimulates collagen synthesis from human dermal fibroblasts and differentiation marker in normal human epidermal keratinocytes: Potential of niacinamide to normalize aged skin cells to correct homeostatic balance, 59th Annual Meeting American Academy of Dermatology, Washington, 2001.
28. Matts P. Oblong J. Bissett D.L. A review of the range of effects of niacinamide in human skin. IFSCC Mag Vol.5 No 4/2002
29. Hakozaki T, Minwalla L, Zhuang J, et al. The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer. Br J Dermatol 2002; 147: 20-33.
30. Matts P, Oblong J, and Bissett D. A review of the range of effects of niacinamide in human skin. Int Fed Soc Cosmet Chem Mag 2002; 5: 285-289.
31. Anthocyanins in Health and Disease, Edition: 1, Chapter: Role of Anthocyanins in Skin Aging and UVInduced Skin Damage, Publisher: CRC Press 2013, Editors: Taylor C. Wallace and M. Monica Giusti, pp.307-316
32. Bae, J.-Y., Lim, S. S., Kim, S. J., Choi, J.-S., Park, J., Ju, S. M., Han, S. J., Kang, I.-J., and Kang, Y.-H. 2009. Bog blueberry anthocyanins alleviate photoaging in ultraviolet-B irradiation-induced human dermal fibroblasts. Molecular Nutrition and Food Research, 53, 726–738
33. Gupta, V. K., & Malhotra, S. (2012). Pharmacological attribute of Aloe vera: Revalidation through experimental and clinical studies. Ayu, 33(2), 193–196. http://doi.org/10.4103/0974-8520.105237
34. Chithra P, Sajithlal GB, Chandrakasan G J Ethnopharmacol. Influence of Aloe vera on the glycosaminoglycans in the matrix of healing dermal wounds in rats. 1998 Jan; 59(3):179-86.
35. Anti-inflammatory activity of Aloe vera against a spectrum of irritants. Davis RH, Leitner MG, Russo JM, Byrne ME J Am Podiatr Med Assoc. 1989 Jun; 79(6):263-76.
36. Antiinflammatory C-glucosyl chromone from Aloe barbadensis.
37. Hutter JA, Salman M, Stavinoha WB, Satsangi N, Williams RF, Streeper RT, Weintraub ST J Nat Prod. 1996 May; 59(5):541-3.
38. Khan MA, Tania M, Zhang D, Chen H. Antioxidant enzyme and cancer. Chin J Cancer Res. 2010;22:87–92.
39. Antioxidant and nitrite-scavenging capacities of phenolic compounds from sugarcane (Saccharum officinarum L.) tops J Sun, XM He, MM Zhao, L Li, CB Li, Y Dong - Molecules, 2014
40. Kadam, U.S.; Ghosh, S.B.; Strayo, D.; Suprasanna, P. Antioxidant activity in sugarcane juice and its protective role against radiation induced DNA damage. Food Chem. 2008, 106, 1154–1160
41. Ma H, Xu J, DaSilva NA, Wang L, Wei Z, Guo L, Johnson SL, Lu W, Xu J, Gu Q, Seeram NP Cosmetic applications of glucitol-core containing gallotannins from a proprietary phenolic-enriched red maple (Acer rubrum) leaves extract: inhibition of melanogenesis via down-regulation of tyrosinase and melanogenic gene expression in B16F10 melanoma cells. Arch Dermatol Res. 2017 May;309(4):265-274
42. Sasaki K, Yoshizaki F. Nobiletin as a tyrosinase inhibitor from the peel of Citrus fruit. Biol. Pharm. Bull. 2002;25:806–808.
43. H.Parhiz, Roohbakhsh A., Soltani F., Rezaee R., Iranshahi M. Antioxidant and anti-inflammatory properties of the Citrus flavonoids hesperidin and hesperitin: an updated review of their molecular mechanisms and experimental models. Phytotherapy Research Wiley Lib 2014
44. Smit, Nico, Jana Vicanova, and Stan Pavel. “The Hunt for Natural Skin Whitening Agents.” International Journal of Molecular Sciences 10.12 (2009): 5326–5349. PMC. Web. 18 May 2018.
45. Adhikari A, Devkota HP, Takano A, Masuda K, Nakane T, Basnet P, Skalko-Basnet N. Screening of Nepalese crude drugs traditionally used to treat hyperpigmentation: In vitro tyrosinase inhibition. Int. J. Cosmet. Sci. 2008;30:353–360.