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.

Comparison of the efficacy and safety of a 730 nm picosecond titanium sapphire laser and a 755 nm picosecond alexandrite laser for the treatment of freckles in Asian patients: A two-center randomized, split-face, controlled trial.

OBJECTIVE: The 730 nm picosecond titanium sapphire laser is a novel laser that shows promising results in treating freckles. This study aimed to further investigate the efficacy and safety of the 730 nm picosecond titanium sapphire laser for treating freckles in Asian patients compared with those of the 755 nm picosecond alexandrite laser. METHODS: Each face of 86 participants was split into two parts and randomly assigned either one session of 730 or 755 nm picosecond-laser treatment each. Efficacy and safety were determined based on blinded visual evaluations and self-reports at each follow-up visit. RESULTS: The treatment outcomes of the 730 nm picosecond laser for the treatment of freckles were comparable to those of the 755 nm picosecond laser, with 68.99 ± 7.42% and 69.27 ± 7.75% clearance, respectively (p > 0.05). Participants achieved similar Global Aesthetic Improvement Scale scores (4.04 ± 0.31 vs. 4.02 ± 0.30, respectively [p > 0.05]). Additionally, the 730 nm picosecond laser was perceived to be less painful than the 755 nm picosecond laser (4.69 ± 1.63 vs. 5.65 ± 1.80 nm, p < 0.0001). CONCLUSION: The 730 nm picosecond laser is safe and effective for the treatment of freckles in Asian patients. Besides, the 730 nm picosecond laser is less painful than the 755 nm picosecond laser.

Treatment of facial pigmented disorders with a 785-nm picosecond Ti:sapphire laser in Asians: A report of three cases.

Since the advent of the theory of selective photothermolysis, the importance of targeting the chromophore and minimizing the surrounding damage has been extensively discussed. Picosecond-domain laser (ps-laser) treatment with a wide range of wavelengths is an emerging option for various pigmented lesions; however, no definitive treatment choice has been confirmed. The authors aimed to investigate the efficacy and safety of a ps-laser with a 785-nm wavelength for the treatment of facial pigmented lesions in Asians. Three Korean patients with facial pigmented lesions were recruited for the study. A 785-nm ps-laser with a fractionated and an unfractionated handpiece was utilized to administer the treatment. The clinical outcome was evaluated by a clinician by comparing pre- and post-treatment photographs. All patients exhibited a significant improvement in pigmented lesions including freckles, lentigines, and melasma, after three to four sessions of treatment. No adverse events, including post-inflammatory hyperpigmentation or hypopigmentation were observed. In conclusion, this novel 785-nm Ti:sapphire ps-laser may be an effective and safe modality for treating pigmented lesions in skin of color.

Split-face comparison of the efficacy of picosecond 532 nm Nd:YAG laser and Q-switched 755 nm Alexandrite laser for treatment of freckles.

To date, there has been little study of comparison between picosecond 532 nm laser and 755 nm Q-switched Alexandrite lasers in the treatment of freckles. To evaluate the efficacy and safety of picosecond 532 nm laser (PS 532) and 755 nm Q-switched Alexandrite laser (QSAL) for treatment of freckles in a split-face manner. Eighteen patients with freckles were enrolled in the study. The right and left sides of their faces were randomly assigned to either a QSAL-treated group or PS 532-treated group. The degree of pain, satisfaction with the results, and adverse events associated with the laser treatment were evaluated using a questionnaire. All of the patients were followed up at 4 and 12 weeks after one treatment session. Among the 18 patients, PS 532 was found to be associated with less pain (3.56 ± 2.431) than QSAL (3.94 ± 1.893), but the difference was not statistically significant. The curative effect and satisfaction associated with 755 nm Q-switched Alexandrite laser was greater than that of picosecond 532 nm laser (P < .001). Both picosecond 532 nm laser and QSAL are effective in the treatment of freckles, and QSAL has a greater rate of satisfaction and curative effect.

Q-Switched Nd:YAG (532 nm) Laser Versus Intra-Dermal Tranexamic Acid for Treatment of Facial Ephelides: A Split Face, Randomized, Comparative Trial.

BACKGROUND AND OBJECTIVES: To compare the efficacy and safety of intradermal injection of tranexamic acid (TXA) versus Q switched (QS) KTP (532 nm) in the treatment of facial ephelides. STUDY DESIGN/MATERIALS AND METHODS: A randomized comparative split-face study included a total of 30 female patients with bilateral facial ephelides. One cheek was treated by intra-dermal TXA injections and the other was treated by QS-KTP (532 nm). Patient assessment was performed by photography, pigmentation area, severity index and spectrophotometry at baseline, 1 week after treatment, and 2 months after treatment. RESULTS: A significant difference was found between both sides regarding the percentage change of pigmentation area, severity score (PSI) and melanin index (MI) after treatment and during follow up, favoring laser (P = 0.001). PSI decreased after treatment by 66.5% and 15.4% (laser and TXA sides respectively), further decrease after follow-up was 69.4% with laser and 26.1% with TXA. MI improved by 3.7% after KTP laser to 7.7% after follow-up and by 2.4% after TXA injections to 6.5% after follow-up. Four patients developed post-inflammatory hyperpigmentation following QS-KTP. CONCLUSION: QS-KTP laser is superior to intradermal TXA injection in the treatment of facial ephelides. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Successful Treatment of Pigmentary Disorders in Asians With a Novel 730-nm Picosecond Laser.

BACKGROUND AND OBJECTIVE: Until recently, quality-switched nanosecond lasers have been the workhorse lasers in treating pigmented lesions. However, the recently commercialized picosecond lasers have provided physicians with a novel method to manage pigmented lesions. Most recently, the first picosecond laser with a 730-nm wavelength was developed to specifically target melanin and melanocytes. STUDY DESIGN/MATERIALS AND METHODS: We report on two Asian patients with freckles, lentigines, and melasma who were successfully treated with a novel 730-nm Ti:Sapphire picosecond laser (Picoway®; Syneron Candela, Corp). The clinical outcome was measured by the global percent of clearance, which was evaluated by blinded observers by comparing the post-treatment photographs with the baseline photographs. RESULTS: In both patients, a significant pigmentary reduction was achieved with only one treatment session. In both patients, the treatments were well tolerated with minimal discomfort even without topical anesthesia. No post-inflammatory hyperpigmentation or repigmentation was observed until the 6-week follow-up. The pigmentary conditions treated included freckles, lentigines, and melasma. Both subjects showed clinical improvement, with the best results observed for the treatment of freckles such that 95% of the lesions achieved excellent response (75-94% lightening). CONCLUSION: The results of this case report indicate that a novel 730-nm Ti:Sapphire picosecond laser may be effective and safe in treating pigmentary disorders in darker-skinned patients. Therefore, further well-designed, prospective clinical trials are warranted to establish the potential of 730-nm picosecond lasers and determine the optimal treatment parameters in comparison to existing laser and light modalities. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Epiderm-Abrasion-Assisted Intensive Pulsed Light and Radiofrequency in Aesthetic Treatment Extensive Facial Freckles.

BACKGROUND: Freckles are typical epidermal pigmented disorders that occur at sun-exposed areas, presenting with dark-brown or light-brown circular hyperpigmentation. A lot of treatment modalities have been used for treatment of freckles like chemicals, electrosurgery and cryotherapy. These treatments may cause undesirable side effects such as scaring (Sarkar et al. in Indian J Dermatol 62(6):578-584, 2017). Microdermabrasion has been used in treatment of freckles; however, the results are not satisfactory, as it removes the outermost layer of the epidermis only (El-Domyati et al. in J Cosmet Dermatol 15(4):503-513, 2016). Also ablative lasers and non-ablative lasers have been used but have not proved to be completely satisfactory and share a common risk of post-inflammatory hyperpigmentation (Jang et al. in Dermatol Surg 26:231-234, 2000). In our study, we have used epiderm-abrasion-assisted intensive pulsed light (IPL) and radiofrequency (RF) to study their effect in treatment of freckles. PATIENTS AND METHODS: this prospective controlled clinical trial was carried out on 48 patients, who presented with extensive facial freckles, in the period between March 2015 and April 2018. The epiderm-abrasion procedure was performed first, and then, electro-photobiomodulation sessions were started two weeks later. RESULTS: This study was carried out on 48 patients, 39 female and 9 males. Their age ranged between 12 and 58 years old. According to Fitzpatrick classification, four patients were type II, 30 patients were type III, and 14 patients were type IV. The results were excellent in 32 cases, good in 12 cases, fair in four cases, and we have no poor results. Side effects like hyperpigmentation were reported in three patients (6.3%), one case grade III and two cases grade IV Fitzpatrick skin type. No cases with hypopigmentation, or scars, were reported. CONCLUSIONS: Epiderm-abrasion and electro-photobiomodulation (IPL&RF) are effective methods in treatment of facial freckles. Some complications may occur post-procedure such as hyperpigmentation, hypopigmentation and abnormal scarring. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Confocal laser scanning microscopy, a diagnostic alternative for five pigmented lesions on the face: An observational study.

OBJECTIVE: To describe the confocal laser scanning microscopy (CLSM) features of five different facial hyperpigmentation diseases and to highlight the features that can be used to differentiate between the diseases. MATERIALS AND METHODS: Confocal laser scanning microscopy features of skin lesions of 406 patients with different facial hyperpigmentation diseases (chloasma, naevus fusco-caeruleus zygomaticus, naevus of Ota, freckles and Riehl melanosis) were retrospectively analysed. All patients were diagnosed clinically. The features of each layer of the skin in the involved regions and at the junction of the lesion with normal skin were studied, and the characteristic features of each disease were identified. The CLSM probe was applied perpendicular to the skin surface. Scanning was performed with medical ultrasonic coupling agent applied between the adhesive window and skin and between the lens and adhesive window. The skin was scanned layer by layer, and the best cross-sectional images were stored in the computer for analysis. RESULTS: Chloasma lesions showed significantly increased pigment content in the epidermal basal layer and, in some cases, varying degrees of pigment particle deposition in the upper dermis. Naevus fusco-caeruleus zygomaticus and naevus of Ota lesions showed normal epidermal pigment content, with cord-like high-refractive pigment masses scattered in the dermis; cord-like or dendritic melanocytes were seen between collagen fibre bundles in the upper and middle dermis, but no inflammatory cell infiltration was seen. Freckles lesions showed increased numbers of pigment particles in the basal layer, but no abnormal changes in the dermis. Riehl melanosis was characterised by liquefaction degeneration of the basal cells, accompanied by considerable monocyte and melanophage infiltration in the dermal papilla. CONCLUSIONS: Used in combination with clinical manifestations, CLSM can be a useful auxiliary method for diagnosis of naevus fusco-caeruleus zygomaticus, naevus of Ota, chloasma, freckles and Riehl melanosis.

Chemical Peeling with a Modified Phenol Formula for the Treatment of Facial Freckles on Asian Skin.

BACKGROUND: Chemical peeling is an efficient method for the treatment of pigment disorders. For freckles, medium-depth to deep peeling using a phenol solution is one of the most effective chemical peels, and modifications of facial skin can be observed up to 20 years after peeling. However, applying phenol to the skin may cause serious side effects. Phenol peeling has been rarely used in Asia due to its tendency to cause permanent pigmentary changes and hypertrophic scars. METHODS: In total, 896 Chinese inpatients with facial freckles were enrolled in this study. The phenol formula was modified with crystalline phenol, dyclonine, camphor, anhydrous alcohol and glycerin and adjusted to a concentration of 73.6-90.0%. The entire peeling treatment was divided into two procedures performed separately on 2 days. RESULTS: All patients exhibited 26% or greater improvement, and 99.66% of patients exhibited 51% or greater improvement (good and excellent). Scarring and systemic complications were not observed in any patient. CONCLUSIONS: The modified phenol formula is very effective and safe for the treatment of facial freckles in Asian patients. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Successful removal of freckles with the bipolar radiofrequency and optical energy.

OBJECTIVES: Freckles are melanocytic lesions frequently seen on the face with red or blond hair. We aim to determine the effectiveness of combined bipolar radiofrequency (RF) and optical energy. METHODS: Thirty patients with facial freckles received four treatment at 3-week intervals with RF and optical energy, combination of broadband light (580-980 nm) + bipolar RF energy 100 J/cm(3). The improvement of the freckles was evaluated using the Freckles Area and Severity Index (FASI), and physician and patient assessment at the end of the sessions, at Months 3 and 12 after the treatment. RESULTS: By the end of the study, assessment of results by physician for 83% at Week 12 and by patients for 70% at Week 52 was excellent or good. On the other hand, 88% at Week 12 and 76% at Week 52 of the patients reported that they were extremely or very satisfied. FASI was noted to be 65.15 at pre-treatment, 25.60 at 12th week, and 27.40 at the end of the follow-up (one year). Mean improvement rate (n = 30), as determined from the difference in mean FASI score, was 70% at 3 months and 66% at 12 months. CONCLUSION: Bipolar radiofrequency and optical energy can be accepted as an alternative treatment modality for the therapy of freckles with few adverse effects and high satisfaction levels.

Genome wide association study and meta-analysis identified multiple new risk loci for freckles in 4813 Chinese individuals.

Freckle is a prevalent pigmentary dermatosis with an obvious hereditary component. Dozens of freckles risk loci have been discovered through research on multiple traits or other diseases, rather than as an independent trait. To discover novel variants associated with freckles, we performed GWAS and meta-analysis in 4813 Chinese individuals. We conducted GWAS and meta-analysis of two cohorts: 197 patients and 1603 controls (Cohort I), and 336 patients and 2677 controls (Cohort II), both from China. Then we performed linkage disequilibrium (LD) analysis, eQTL study, and enrichment analysis with association results for functional implications. Finally, we discovered 59 new SNPs and 13 novel susceptibility genes associated with freckles (Pmeta <5 × 10-8), which has enriched the genetic research on freckles.

The complexity of phosphatase and tensin homolog hamartoma tumor syndrome: A case report.

Germline pathogenic variants found in the phosphatase and tensin homolog gene are associated with a range of rare syndromes that collectively fall under the umbrella of phosphatase and tensin homolog hamartoma tumor syndromes. Due to the wide array of possible clinical presentations and the varying degrees of symptom severity, many individuals with phosphatase and tensin homolog hamartoma tumor syndromes might remain undiagnosed for an extended period. We describe a case of a male child who received the diagnosis at the age of 12. His clinical features included macrocephaly, hypertrophy in the left arm, thyroid nodules, penile freckles, developmental delay, and an autism spectrum disorder. Whole exome sequencing revealed a de novo heterozygous variant in the phosphatase and tensin homolog. The case highlights the diverse and complex nature of phosphatase and tensin homolog hamartoma tumor syndromes, emphasizing the necessity for early diagnosis, multidisciplinary care, and surveillance protocols, offering the potential for improved prognostic outcomes and enhanced quality of life for affected individuals.

Iris Pigmented Lesions and Risk of Cutaneous Melanoma: Case-Control Study in Lithuania.

The global incidence of cutaneous melanoma (CM) is rising, necessitating early detection and identification of risk factors across different populations. A case-control study with 180 patients with primary diagnosed CM and 182 healthy controls was conducted. Participants underwent ophthalmic and skin examinations, where the identification and counting of common melanocytic nevi (CMN) and atypical melanocytic nevi (AMN) was performed. During ophthalmic examination, high-resolution slit lamp iris images were taken. Images were categorized according to iris periphery, collaret, and freckles. There was no difference in iris periphery and collaret color between groups. However, blue/grey iris periphery and blue collaret with or without freckles were the most common patterns. The presence of pigmented iris lesions and 2-5 mm and ≥5 mm in diameter CMNs was strongly associated with CM risk. The evidence from this study indicates that blue or grey periphery and blue collaret iris pattern with iris freckles are 2.74 times higher in the CM group than controls. Further research is needed to explore iris patterns' association with CM risk in diverse populations.

Kids These Days: Social Media's Influence on Adolescent Behaviors.

We live in an electronic world with near-ubiquitous access to smartphones and social media. One consequence of this new reality is that children and teenagers may be unduly swayed by social media influencers who promote skincare products and practices, colloquially referred to as "skinfluencers," and enjoy unfettered access to emerging trends-not all of which lead to positive results. Herein, we describe two cases of adolescents presenting to a pediatric dermatology department after trying different beauty trends endorsed by social media influencers. The first patient developed allergic contact dermatitis to "snail slime" (96% Snail Secretion Filtrate; COSRX), a popular over-the-counter skincare product that has received notable attention on social media platforms due to its purported skin hydrating effects. The second patient presented urgently due to her mother's concerns of "overnight moles," which, in fact, the patient had acquired after applying makeup using a social media-endorsed "freckle stamp." Clinicians should be aware of these emerging trends to properly educate, manage, and treat patients susceptible to their influence-especially within the particularly impressionable teenage population.

Naturalistic face adaptation: How we adapt to freckles fast and sustainably.

While sunbathing, our skin becomes susceptible to quite remarkable changes in visual appearance, that is, freckles appear or increase in intensity-most obviously on the face. Research on face adaptation repeatedly showed that the inspection of manipulated versions of faces (so-called adaptor faces) leads to robust and sustainable changes in the perception of subsequently presented faces. Therefore, during the adaptation phase of the present study, participants saw faces with either strongly increased or decreased intensities of freckles. After a 5-minute break, during the test phase, participants had to identify the veridical (non-manipulated) face out of two faces (a slightly manipulated face combined with a non-manipulated face). Results showed strong adaptation effects to increased and decreased levels of freckles. We conclude that updating facial representations in memory is relatively fast, and these representation updates seem to sustain over a certain time span (at least 5 minutes). Face-specificity of our effects will be discussed. The results align with our everyday experience that the appearance of freckles in spring is a salient change in a familiar face; however, we seem to not register these changes after a few exposures due to a loss of information quality.

Additional predictions for forensic DNA phenotyping of externally visible characteristics using the ForenSeq and Imagen kits.

Multiplex DNA typing methods using massively parallel sequencing can be used to predict externally visible characteristics (EVCs) in forensic DNA phenotyping through the analysis of single-nucleotide polymorphisms. The focus of EVC determination has focused on hair color, eye color, and skin tone as well as visible biogeographical ancestry features. In this study, we researched off-label applications beyond what is currently marketed by the manufacturer of the Verogen ForenSeq kit primer set B and Imagen primer set E SNP loci. We investigated additional EVC predictions by examining published genome wide sequencing studies and reported allele-specific gene expression and predictive values. We have identified 15 SNPs included in the ForenSeq kit panel and Imagen kits that have additional EVC prediction capabilities beyond what is published in the Verogen manuals. The additional EVCs that can be predicted include hair graying, ephelides hyperpigmented spots, dermatoheliosis, facial pigmented spots, standing height, pattern balding, helix-rolling ear morphology, hair shape, hair thickness, facial morphology, eyebrow thickness, sarcoidosis, obesity, vitiligo, and tanning propensity. The loci can be used to augment and refine phenotype predictions with software such as MetaHuman for missing persons, cold case, and historic case investigations.

Co-occurrence of oculocutaneous albinism type 2 and mild sickle cell disease explained by HbS/ßthal genotype in an individual from the Democratic Republic of Congo.

Oculocutaneous albinism type 2 (OCA2) is a pigmentation disorder characterized by hypopigmentation of the skin, hair and eyes and ocular features. Sickle cell disease (SCD) is caused either by homozygosity of the beta globin gene variant c.20A > T/p.Glu6Val giving rise to severe anemia or by combined abnormal hemoglobins (HbS/ßthal) leading to mild SCD. We report a 45 years old female patient from the Democratic Republic of Congo affected with these two disorders. She presented with creamy white skin and numerous pigmented patches called dendritic freckles, nystagmus, foveal hypoplasia grade 2, photophobia and very poor visual acuity. Sequencing of the OCA2 gene identified the common exon 7 deletion and a new pathogenic variant c.1444A > C/p.Thr482Pro. She had mild SCD with a total Hb level of 101 g/l. Hbß sequencing identified variants c.20A > T giving rise to HbS and c.315 + 1 G > A characteristic of ß-thalassemia. A heterozygous 3.7 kb deletion of the α globin gene was also found. The combined Hbß/α globin genotype explains the mild SCD phenotype. Co-occurrence of OCA2 and SCD raises the question whether the patient's phenotype simply results from the addition of the two diseases' phenotypes or whether interaction between the two diseases modulates the phenotype of each other.

A novel missense variant and multiexon deletion causing a delayed presentation of xeroderma pigmentosum, group C.

Pathogenic variants in the XPC complex subunit, DNA damage recognition, and repair factor (XPC) are the cause of xeroderma pigmentosum, group C (MIM: 278720). Xeroderma pigmentosum is an inherited condition characterized by hypersensitivity to ultraviolet (UV) irradiation and increased risk of skin cancer due to a defect in nucleotide excision repair (NER). Here we describe an individual with a novel missense variant and deletion of exons 14-15 in XPC presenting with a history of recurrent melanomas. The proband is a 39-yr-old female evaluated through the Mayo Clinic Department of Clinical Genomics. Prior to age 36, she had more than 60 skin biopsies that showed dysplastic nevi, many of which had atypia. At age 36 she presented with her first melanoma in situ, and since then has had more than 10 melanomas. The proband underwent research whole-exome sequencing (WES) through the Mayo Clinic's Center for Individualized Medicine and a novel heterozygous variant of uncertain significance (VUS) in XPC (c.1709T > G, p.Val570Gly) was identified. Clinical confirmation pursued via XPC gene sequencing and deletion/duplication analysis of XPC revealed a pathogenic heterozygous deletion of ∼1 kb within XPC, including exons 14 and 15. Research studies determined the alterations to be in trans Although variants in XPC generally result in early-onset skin cancer in childhood, the proband is atypical in that she did not present with her first melanoma until age 36. Review of the patient's clinical, pathological, and genetic findings points to a diagnosis of delayed presentation of xeroderma pigmentosum.

Piebaldism Associated with Café-au-lait Macules and Intertriginous Freckling: A Case Report and Review of the Literature.

We present 9-year-old fraternal twins from a family with piebaldism, having congenital depigmented macules and meeting the diagnostic criteria for neurofibromatosis type 1 (NF1) due to the multiple café-au-lait macules (CALMs) and intertriginous freckling at the same time. It's still a debatable issue that CALMs and intertriginous freckling may be seen in the clinical spectrum of piebaldism or these patients should be regarded as coexistence of piebaldism and NF1. However, based on recent literature and our patients' findings, we suggest that this rare phenotypic variant of piebaldism may not need the careful clinical follow-up and molecular testing for NF1. Besides, it may be suitable that these individuals with piebaldism showing NF1-like clinical phenotypes should be further tested for KIT and SPRED1 gene mutations.