Postoperative risk assessment of post-inflammatory hyperpigmentation and the efficacy of delayed prevention following 532 nm Q-switched Nd:YAG laser treatment of solar lentigines: a randomized controlled study.

BACKGROUND: Although post-inflammatory hyperpigmentation (PIH) is a common adverse event following laser procedures, studies evaluating its risk remain limited. OBJECTIVE: To analyze PIH risk after 532 nm Q-switched Nd:YAG laser (QSNYL) treatment for solar lentigines and examine the efficacy of triple combination cream (TCC) for its prevention. METHODS: In this single center, investigator-blinded, randomized controlled study, participants with solar lentigo either received TCC or emollient from 2 weeks post-QSNYL treatment. The occurrence of PIH was determined by three independent and blinded dermatologists. In vivo skin measurements and sun exposure questionnaires were examined to evaluate the risk of PIH. RESULTS: A total of 28 patients with 67 solar lentigines were included in the analysis. In the control group, PIH occurred in 55.3% of the lesions. Risk factors for the occurrence of PIH were the increased erythema at weeks 2 (OR, 1.32; p = 0.035) and outdoor activity during 1-5 pm (OR, 8.10; p = 0.038). Treatment with TCC from 2 weeks post-QSNYL treatment significantly decreased the incidence of PIH (31.0% vs. 55.3%, p = 0.048). CONCLUSION: Post-laser erythema and outdoor activity at the daytime are prognostic factors for the occurrence of PIH. Administering TCC could be considered for the prevention of PIH in high-risk patients.

Refractory solar lentigines successfully treated with 532-nm nanosecond Nd:YAG Vasculature Salvage Laser Surgery (VSLS) system: Case series.

BACKGROUND: Solar lentigo, a common epidermal hyperpigmented lesion found in sun-exposed areas, results from the proliferation of melanocytes and the accumulation of melanin. Although various treatments for solar lentigo have been explored, they often lead to complications, including prolonged erythema and post-inflammatory hyperpigmentation (PIH), posing significant concerns. OBJECTIVES AND METHODS: This study evaluated the safety and efficacy of the Vasculature Salvage Laser Surgery (VSLS) system. We treated six Korean patients, each with solar lentigo, in a single session using the 532-nm nanosecond neodymium-doped yttrium aluminum garnet (Nd:YAG) VSLS system, with follow-up periods ranging from 3 to 10 weeks. RESULTS: The treatment led to the complete removal of pigmented lesions in all patients without resulting in PIH, even in cases where previous laser treatments had failed. The only side effect observed was mild erythema, which resolved over the long term in most instances. CONCLUSIONS: The VSLS system emerges as a safe and effective treatment for pigmented lesions, including refractory solar lentigines. Nonetheless, additional studies are required to verify its long-term efficacy.

Nevus Spilus, Partial Unilateral Lentiginosis, and Linear and Whorled Nevoid Hypermelanosis: A Comparison of Clinical Features, Course, and Treatment Response.

Skin diseases manifesting as agminated pigmented lesions have overlapping clinical manifestations. Therefore, accurate differentiation is challenging. The clinical characteristics, histopathological findings, and treatment response of patients diagnosed with partial unilateral lentiginosis, nevus spilus, or linear and whorled nevoid hypermelanosis were retrospectively analysed. Each disease demonstrated distinct demographic and clinical characteristics, and the responses to laser treatment varied. The median age at onset varied significantly among the groups: 0.1, 6.6, and 0.5 years in patients with nevus spilus, partial unilateral lentiginosis, and linear and whorled nevoid hypermelanosis, respectively. Regarding the locations of the skin lesions, partial unilateral lentiginosis occurred predominantly on the head and neck, while approximately half of nevus spilus and linear and whorled nevoid hypermelanosis were observed on the extremities. Although linear and whorled nevoid hypermelanosis and partial unilateral lentiginosis share a similar histological feature of basal hyperpigmentation, patients with linear and whorled nevoid hypermelanosis showed the best response to laser treatment, while patients with partial unilateral lentiginosis demonstrated a poor treatment response. The study's data may provide important clues for the differential diagnosis and clinical decision-making regarding the treatment of these agminated pigmented lesions.

Exploring Fractional Pigment Toning: A Novel Approach for Treating Benign Pigmented Lesions in Asian Patients With Fitzpatrick Skin Types III-V.

BACKGROUND/OBJECTIVE: Laser therapy has emerged as a widely favored treatment option for solar lentigines (SL). However, a significant challenge associated with this treatment, particularly among individuals with darker skin tones, is the notable risk of postinflammatory hyperpigmentation (PIH) induction. In response to these concerns, the authors conducted a prospective, self-controlled study to comprehensively evaluate the safety and effectiveness of 532-nm picosecond laser, both with and without a microlens array (MLA), for the management of SL in patients with Fitzpatrick skin types (FST) III-V. METHODS: Twenty-seven patients with FST III-V and bilateral SL on the face underwent randomized treatment. One side of the face was treated with a 532-nm picosecond laser coupled with an MLA, utilizing the fractional pigment toning (FPT) technique, while the other side received treatment without the MLA, following the conventional technique (CT). The FPT technique utilized a 9-mm spot size with a fluence of 0.47 J/cm2 for two passes covering 40% of the area. In contrast, the CT used a 4.5-mm handpiece with fluence ranging from 0.3 to 0.7 J/cm2. Patients received a single treatment and were evaluated for pigment clearance, occurrence of PIH, and other adverse effects at 2 weeks, 1, 3, and 6 months posttreatment. RESULTS: Twenty-seven participants completed the study protocol. Analysis of pigment clearance, measured via 3D photography, showed significant improvement from 2 weeks to 6 months posttreatment for both the FPT technique (p < 0.001) and CT (p = 0.004). PIH occurred in 64%, 80%, 96%, and 88% of cases on the CT side, compared to 8%, 32%, 36%, and 16% on the FPT technique side at 2 weeks, 1, 3, and 6 months posttreatment, respectively. The incidence of PIH was significantly lower on the FPT technique side compared to the CT side throughout the follow-up periods. Additionally, transient and mild hypopigmentation occurred in one participant (4%) on the FPT technique side and in five participants (20%) on the CT side. No other adverse effects were observed during the study. CONCLUSIONS: The 532-nm picosecond laser emerges as a safe and efficacious treatment modality for SL in individuals with FST III-V. Particularly noteworthy is the efficacy of the FPT technique, which demonstrates comparable effectiveness while significantly reducing the incidence of PIH compared to the CT.

Efficacy and Safety of 577-nm Yellow Laser in the Treatment of Pigmented Epidermal Lesions.

OBJECTIVES: Freckles and lentigines are common pigmented problems which not only cause substantial cosmetic morbidity but also create psychosocial concern. The available modalities for the treatment of pigmented lesions are often unsatisfactory for patients, require a long treatment period, and often cause skin irritation. With the advent of lasers, safe and effective treatment options for epidermal pigmentation have become more varied for different Fitzpatrick skin types. We aimed to evaluate the efficacy and safety of 577-nm yellow laser in the treatment of pigmented epidermal lesions. METHODS: This study was carried out on 50 patients presented with pigmented epidermal lesions (25 presented with freckles and 25 presented with lentigines). Each patient received four treatment sessions with a 577-nm diode laser at 2-week intervals. RESULTS: There was significant improvement in freckles and lentigines, as 23 out of 50 patients showed marked improvement, 11 patients showed moderate improvement, 10 patients showed mild improvement, and only six patients had no changes. Moreover, 23 patients were very satisfied, 18 patients were satisfied, and nine patients were not satisfied. As regards the safety of the 577-nm yellow laser, there was no significant adverse effect among patients except pain, erythema, and hyperpigmentation, which resolved within one month after treatment. CONCLUSIONS: This study showed that the 577-nm yellow laser is an effective, safe, and well-tolerated device in the treatment of freckles and lentigines.

Multi-System-Level Analysis Reveals Differential Expression of Stress Response-Associated Genes in Inflammatory Solar Lentigo.

Although the pathogenesis of solar lentigo (SL) involves chronic ultraviolet (UV) exposure, cellular senescence, and upregulated melanogenesis, underlying molecular-level mechanisms associated with SL remain unclear. The aim of this study was to investigate the gene regulatory mechanisms intimately linked to inflammation in SL. Skin samples from patients with SL with or without histological inflammatory features were obtained. RNA-seq data from the samples were analyzed via multiple analysis approaches, including exploration of core inflammatory gene alterations, identifying functional pathways at both transcription and protein levels, comparison of inflammatory module (gene clusters) activation levels, and analyzing correlations between modules. These analyses disclosed specific core genes implicated in oxidative stress, especially the upregulation of nuclear factor kappa B in the inflammatory SLs, while genes associated with protective mechanisms, such as SLC6A9, were highly expressed in the non-inflammatory SLs. For inflammatory modules, Extracellular Immunity and Mitochondrial Innate Immunity were exclusively upregulated in the inflammatory SL. Analysis of protein-protein interactions revealed the significance of CXCR3 upregulation in the pathogenesis of inflammatory SL. In conclusion, the upregulation of stress response-associated genes and inflammatory pathways in response to UV-induced oxidative stress implies their involvement in the pathogenesis of inflammatory SL.

Efficacy of isobutylamido thiazolyl resorcinol for prevention of laser-induced post-inflammatory hyperpigmentation: A randomized, controlled trial.

BACKGROUND: Q-switched (QS) Nd: YAG laser is one of the treatment options for solar lentigines (SLs). However, the incidence of post-inflammatory hyperpigmentation (PIH) is a common complication, especially in dark-complexioned skin. Isobutylamido thiazolyl resorcinol (ITR) has been reported as a preventive modality for ultraviolet B (UVB)-induced hyperpigmentation. AIMS: This study aims to evaluate the efficacy and safety of ITR for the prevention of laser-induced PIH. PATIENTS/METHODS: A randomized, evaluator-blinded study including 24 subjects with SLs was conducted. Three SLs of each patient were randomized into three groups, which were to apply ITR twice daily, once daily, and no application for 2 weeks. Thereafter, 532-nm QS Nd: YAG laser was performed. Incidence of laser-induced PIH, relative melanin index (RMI), mean luminance score (L*), hyperpigmentation score, and adverse events were recorded for 2 months post-laser. RESULTS: The incidence of PIH at the 4th week after laser treatment was significantly lower in the ITR twice-daily group compared to the no-application group (20.83% vs. 50%, p = 0.028). There was no statistically significant difference in RMI, mean L*, and hyperpigmentation score between treatments at all visits. No serious adverse events were reported regarding ITR application and laser treatment. CONCLUSION: Two-week application of ITR prior to QS: Nd YAG laser treatment may potentially reduce the incidence of PIH. A longer duration of application, including after the laser procedure, may be more beneficial for the prevention of laser-induced PIH.

A 15% Trichloroacetic Acid + 3% Glycolic Acid Chemical Peel Series Improves Appearance of Hand Lentigines: An Evaluator-Blinded, Split-Hand Prospective Trial.

BACKGROUND: Improving the appearance of lentigines on the hands is a key component to hand rejuvenation. Soft tissue fillers revolumize hands, but do not address pigmentary changes. OBJECTIVE: This study investigated the effiacy of a 15% trichloroacetic acid (TCA) + 3% glycolic acid (GA) combination peel in improvement of appearance of hand lentigines. METHODS: A prospective evaluator-blinded, split-hand study was performed using a 15% TCA + 3% GA peel to treat patients with hand lentigines. Subjects received a total of 3 treatments at 4-week intervals on 1 hand, with the other hand serving as an untreated control. Final photographs were taken 12 weeks after the last treatment. Two blinded board-certified dermatologists graded improvement in hand lentigines using a 5-point scale. RESULTS: Eighteen of 20 patients completed the study (90%). The mean age was 64.4 years (SE 1.6, range 51-71). The mean pain scores were 3.8 (SE 0.4) on a 10-point scale (1 = no pain, 10 = extremely painful). Blinded evaluators correctly identified the after-treatment photographs in 16 patients (88%). Physician and patient-graded mean improvement of lentigines was significant for treated versus control hands ( p < .01). No adverse events were noted. CONCLUSION: A series of three 15% TCA + 3% GA peels are effective and safe in the treatment of hand lentigines.

A chronic pro-inflammatory environment contributes to the physiopathology of actinic lentigines.

Actinic lentigines (AL) or age spots, are skin hyperpigmented lesions associated with age and chronic sun exposure. To better understand the physiopathology of AL, we have characterized the inflammation response in AL of European and Japanese volunteers. Gene expression profile showed that in both populations, 10% of the modulated genes in AL versus adjacent non lesional skin (NL), i.e. 31 genes, are associated with inflammation/immune process. A pro-inflammatory environment in AL is strongly suggested by the activation of the arachidonic acid cascade and the plasmin pathway leading to prostaglandin production, along with the decrease of anti-inflammatory cytokines and the identification of inflammatory upstream regulators. Furthermore, in line with the over-expression of genes associated with the recruitment and activation of immune cells, immunostaining on skin sections revealed a significant infiltration of CD68+ macrophages and CD4+ T-cells in the dermis of AL. Strikingly, investigation of infiltrated macrophage subsets evidenced a significant increase of pro-inflammatory CD80+/CD68+ M1 macrophages in AL compared to NL. In conclusion, a chronic inflammation, sustained by pro-inflammatory mediators and infiltration of immune cells, particularly pro-inflammatory M1 macrophages, takes place in AL. This pro-inflammatory loop should be thus broken to normalize skin and improve the efficacy of age spot treatment.

Interventional and device treatment of the periocular area.

Growth in the research, innovation, and development of laser and energy-based technologies over the past few decades has led to dramatic increases in treatment options for dermatologic and cosmetic concerns of the periorbital area. We highlight recent treatment options using laser and energy-based devices for the clearance of periocular pigmented lesions, including solar lentigines and nevus of Ota; vascular lesions, including port-wine birthmarks, infantile hemangiomas, superficial telangiectasias, and reticular veins; laser ablation of benign tumors, such as xanthelasma; cosmetic rejuvenation; treatment of infraorbital dark circles and festoons; laser removal of eyebrow and eyeliner tattoos; and device-based treatment of chronic dry eyes.

Characteristics of dermal vascularity in melasma and solar lentigo.

BACKGROUND /PURPOSE: Melasma and solar lentigo (SL) are major benign hyperpigmented lesions, and both have been shown to involve the dermal vasculature. This review discusses current knowledge regarding the clinical characteristics of dermal vascularity in melasma and SL, as well as the results of relevant molecular biological investigations. METHODS: PubMed and Google Scholar were searched in December 2023 to identify articles related to melasma, SL, and the dermal vasculature in these lesions. RESULTS: Vascular morphologies in melasma and SL have been detected by histological and non-invasive methods, including modalities such as optical coherence tomography. Biological studies have indicated that factors secreted from vascular endothelial cells, such as stem cell factor and endothelin-1, can promote melanogenesis. With respect to phototherapy, blood vessel-targeting laser treatments are expected to provide long-term suppression of pigmentation, but this regimen is only effective when dilated capillaries are visible. CONCLUSION: In both melasma and SL, clinical and experimental investigations are revealing the contributions of dermal vascularity to hyperpigmentation. More effective treatment may require identification of hyperpigmentation subtypes. In the future, knowledge of treatment (including phototherapy) is expected to accumulate through reliable and validated non-invasive measurements.

The correlation between dermoscopy and clinical and pathological tests in the evaluation of skin photoaging.

BACKGROUND: There are no standards for evaluating skin photoaging. Dermoscopy is a non-invasive detection method that might be useful for evaluating photoaging. OBJECTIVE: To assess the correlation between the dermoscopic evaluation of photoaging and clinical and pathological evaluations. METHODS: The age, clinical evaluation (Fitzpatrick classification, Glogau Photoaging Classification, and Chung's standardized image ruler), histopathology (Masson staining and MMP-1 immunohistochemistry), and dermoscopy (Hu's and Isik's) of 40 donor skin samples were analyzed statistically, and Spearman rank correlation analysis was performed. RESULTS: There was a robust correlation between the total Hu scores and Isik dermoscopy. The correlation of dermoscopy with histopathology was higher than that of clinical evaluation methods. There is a strong correlation between telangiectases and lentigo. Xerosis, superficial wrinkle, diffuse erythema, telangiectases, and reticular pigmentation were significantly correlated with the three clinical evaluation methods. Superficial wrinkles were correlated with Masson, MMP-1, various clinical indicators, and other dermoscopic items. CONCLUSION: There is a good correlation between dermoscopy and clinical and histopathological examination. Dermoscopy might help evaluate skin photoaging.

Epidermal turnover and iron metabolism in senile lentigo.

Senile lentigo (SL) is a pigmentary disorder associated with disrupted epidermal turnover. Trace minerals in the skin are known to regulate keratinocyte proliferation and differentiation. To clarify the role of iron in SL, we compared the expression of molecules related to iron metabolism between SL lesion (lesion) and the surrounding normal skin (nonlesion). Our results revealed that proteins involved in iron uptake and utilization such as transferrin receptor 1, iron regulatory protein 1, mitoferrin 1, and divalent metal transporter 1 were expressed in the lower epidermis in the nonlesion, while expression of them was also observed in the upper epidermis in the lesion. Ferroportin (FPN), involved in iron export, was expressed in the upper epidermis in the nonlesion, but was only scarcely expressed in the upper epidermis in the lesion. Hepcidin, which promotes FPN degradation, was expressed in the lower epidermis in the nonlesion; however, its expression was also observed in the upper epidermis in the lesion. These changes in the expression of molecules involved in iron uptake/export/utilization might reflect the altered iron utilization state in SL, resulting in disruption of keratinocyte differentiation and disturbing epidermal turnover. Our results suggest that the metabolism of iron in keratinocytes in SL differs from that in the normal epidermis, and these changes could be associated with the abnormal epidermal turnover and decreased melanin excretion in SL.