Impact of blue light on skin pigmentation in patients with melasma

Abstract Background The difference in skin pigmentation induced by blue light between melasma patients and healthy people has not been reported. This study aimed to explore the impact of different doses of blue light irradiation on the pigmentation of the skin of non‐exposed areas in female melasma patients with III‐IV‐type skin and healthy women. Materials and methods This observational study enrolled patients with melasma and healthy people at the First Affiliated Hospital of Kunming Medical University between January and April 2021. The outcomes were the degree of pigmentation, ΔL*, and ΔITA* values. Results Forty‐two (21/group) participants were enrolled. After irradiation with different doses of blue light, different degrees of pigmentation could be observed in the irradiated area of the skin of female melasma patients and healthy women. The △L* and △ITA* values in the irradiated area of the skin of healthy women were higher than in female melasma patients after blue light irradiation at 20 J/cm2 (p < 0.05). There were no significant differences in the pigmentation scores, △L* values, and △ITA* values in the irradiated areas of skin at different time points after irradiation with the other doses of blue light (p > 0.05). Conclusion Blue light at 20 J/cm2 induced a smaller change in pigmentation in melasma patients than in healthy women, but the effect of blue light at 40–80 J/cm2 was similar.

Sunlight is divided into extreme ultraviolet (UV) rays, UV rays, visible light, and infrared rays according to the different wavelengths. 8 UV irradiation can induce melanin synthesis, cause pigmentation in the irradiated area, and induce pigmentation diseases, including melasma. 1,9 Visible light (400-700 nm) accounts for about 50% of solar radiation. 10 Visible light, particularly high-energy visible light (400-500 nm), also called blue light, participates in skin aging. 11,12 Blue light can cause skin hyperpigmentation, particularly in dark-skinned people. 13 The degree of pigmentation is more obvious than the pigmentation induced by UV rays, and the blue light-induced pigmentation can last as long as 3 months. 13,14 Blue light can induce immediate melanosis, continuous melanosis, and delayed melanosis. 13,14 These effects can be observed in all skin types, including in patients with pigmentation diseases. 10,15 The reason for this effect of blue light is that melanocyte opsin 3 activates calmodulin-dependent protein kinase II, transcription factor cAMP-responsive element-binding protein, mitogen-activated protein kinase P38, and extracellular regulated protein kinase by sensing external blue light and induces melanin synthesis. 16 In ex vivo skin specimens, gene expression and tyrosinase activity are increased by visible light. 17 Persistent pigment darkening could last up to 10 days when repeated exposures were performed, but pigmentation faded after 24 h when a single exposure was used. 17 Visible light also has effects on the skin barrier function. 18 It could be hypothesized that healthy people will have a more serious degree of melanosis after exposure to blue light than normal people because of lower baseline melanosis. Therefore, this study aimed to explore the impact of blue light irradiation on the pigmentation in the skin of non-exposed areas in female melasma patients with III-IV-type skin and healthy women. The inclusion criteria were 1) diagnosis of melasma, 2) 20-50 years old, 3) not pregnant or breastfeeding, 4) living in Yunnan for ≥3 years, and 5) no folliculitis, atopic dermatitis, port-wine stains, etc., in the irradiated area that could affect the assessments in the irradiated area.

Study design and population
The exclusion criteria were 1) pigmentation diseases on the face, 2) history of immune system diseases, photosensitivity diseases, inflammatory skin diseases, or major organ diseases, or 3) having taken photosensitive drugs recently.
For the healthy women group, age-matched individuals were selected. The selection criteria were the same as for the patients, except for the melasma diagnosis.

Procedure
Blue light with a wavelength of 400-520 nm was produced by a blue light irradiator (Sellamed VIS 400, Sellas, Germany

Outcomes
The pigmentation degree in the irradiated area was assessed according to the Investigator's Global Assessment Scale (IGAS) ( Table S1). 19 The irradiation intensity of the blue light machine was 50 ± 5 mW/cm 2 .
After irradiation, the irradiation site was marked. The values were The larger the ΔITA value is, the more obvious the pigmentation is. 19,20 SPSS 26.0 (IBM Corp., Armonk, NY, USA) was used for data analysis.

Statistical analysis
The continuous data were presented as means ± standard deviation and analyzed using repeated-measures ANOVA to compare the data within a given group among time points and Student's t-test to compare groups. p < 0.05 was statistically significant. women, which did not completely subside after 2 weeks. In addition, it was also observed that after blue light irradiation, transient erythema also appeared in the irradiated area, which subsided within 24 h ( Figure 1).
The IGA scores on the skin of the non-exposed areas in the melasma patient and healthy women groups at 0 h of irradiation of blue light at 20, 40, 60, and 80 J/cm 2 were higher than those at 24 h, 1 week, and 2 weeks. The IGAS were not significantly different between the two groups, and there were no time effects after 20, 49, and 80 J/cm 2 blue light irradiation were all lower than those of the healthy women group, but the melasma patients had higher IGAS after 60 J/cm 2 blue light irradiation, with significant changes in time, but no time × group interaction was observed ( Figure S1 and Table 2).
The mean values of ΔL* and ΔITA* on the skin of the non-exposed areas in the melasma patient and healthy women groups at 0 h with 20, 40, 60, and 80 J/cm 2 blue light irradiation were higher than those at 24 h, 1 week, and 2 weeks (all p < 0.01).
The mean values of ΔL* and ΔITA* of the melasma patient group at different time points were lower than those of the healthy women group after 20 J/cm 2 blue light irradiation (all p > 0.05) ( Figures S2 and   S3 and Table 3).

DISCUSSION
This study suggested that blue light at 20 J/cm 2 induced a smaller change in pigmentation in melasma patients than in healthy women, but the effect of blue light at 40, 60, and 80 J/cm 2 was similar.
Consistent with previous reports, in the present study, blue light could induce pigmentation in III-IV-type skin, and the degree of pigmentation was dose-dependent. [11][12][13] The reason is that opsin 3 in melanocytes senses the stimulation from external blue light, induces an increase in melanin synthesis through a series of signaling cascades pathways, and blue light can also induce melanocytes in type III and IV skin to form the tyrosinase and dopa isomerase protein complex, which ultimately leads to the formation of long-lasting pigmentation. 13,16 Different from Mahmoud et al., 14 it was observed in this study that  In this study, melasma patients and healthy women were exposed to a single dose of 20-80 J/cm 2 blue light irradiation, and there were no significant differences in the IGAS at the irradiation area between groups, suggesting that melasma patients have similar sensitivity to pigmentation induced by blue light than healthy women, that is, a single small-dose of blue light irradiation has limited effects on melasma patients. Blue light can induce immediate melanosis, continuous melanosis, and delayed melanosis. 13,14 In the present study, melanosis was immediate in both groups and was continuous over  This study has limitations. The participants were from a single center, and the sample size was small. Therefore, stratification based on skin phototype could not be performed. Only females were included, and whether males could show similar effects (because of differences in hormones) is unknown. Even if dose equivalence was calculated, the 80 J/cm 2 dose, for example, was given within a much shorter time than 165 min, which could induce reactions that would not be observed in real life.

CONCLUSION
In conclusion, blue light at 20 J/cm 2 induced a smaller change in pigmentation in melasma patients than in healthy women, but the effect of blue light at 40, 60, and 80 J/cm 2 was similar. The effect of blue light irradiation lasted for 2 weeks in melasma patients and healthy individuals. These results may guide evidence-based sun protection strategies in patients with melasma and have implications in the context of electronic device use. These results call for enhancing the general population's awareness of blue light and UV protection.