Fast freezing inhibits melanin synthesis of melanocytes by modulating the Wnt/ß-catenin signalling pathway.

Skin hyperpigmentation is mainly caused by excessive synthesis of melanin; however, there is still no safe and effective therapy for its removal. Here, we found that the dermal freezer was able to improve UVB-induced hyperpigmentation of guinea pigs without causing obvious epidermal damage. We also mimic freezing stimulation at the cellular level by rapid freezing and observed that freezing treatments <2.5 min could not decrease cell viability or induce cell apoptosis in B16F10 and Melan-A cells. Critically, melanin content and tyrosinase activity in two cells were greatly reduced after freezing treatments. The dramatic decrease in tyrosinase activity was associated with the downregulation of MITF, TYR, TRP-1 and TRP-2 protein expression in response to freezing treatments for two cells. Furthermore, our results first demonstrated that freezing treatments significantly reduced the levels of p-GSK3ß and ß-catenin and the nuclear accumulation of ß-catenin in B16F10 and Melan-A cells. Together, these data suggest that fast freezing treatments can inhibit melanogenesis-related gene expression in melanocytes by regulating the Wnt/ß-catenin signalling pathway. The inhibition of melanin production eventually contributed to the improvement in skin hyperpigmentation induced by UVB. Therefore, fast freezing treatments may be a new alternative of skin whitening in the clinic in the future.

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.

A systematic review of procedural modalities in the treatment of notalgia paresthetica.

BACKGROUND: Notalgia paresthetica (NP) is a rare condition characterized by localized pain and pruritus of the upper back, associated with a distinct area of hyperpigmentation. Given the lack of standardized treatment and the uncertain efficacy of available options, applying procedural methods is of growing interest in treating NP. AIMS: We sought to comprehensively evaluate the role of procedural treatments for NP. METHODS: We systematically searched PubMed/Medline, Ovid Embase, and Web of Science until November 14th, 2023. We also performed a citation search to detect all relevant studies. Original clinical studies published in the English language were included. RESULTS: Out of 243 articles, sixteen studies have reported various procedural modalities, with or without pharmacological components, in treating NP. Pharmacological procedures, including injections of botulinum toxin, lidocaine, and corticosteroids, led to a level of improvement in case reports and case series. However, botulinum toxin did not show acceptable results in a clinical trial. Moreover, non-pharmacological procedures were as follows: physical therapy, exercise therapy, kinesiotherapy, acupuncture and dry needling, electrical muscle stimulation, surgical decompression, and phototherapy. These treatments result in significant symptom control in refractory cases. Physical therapy can be considered a first-line choice or an alternative in refractory cases. CONCLUSION: Procedural modalities are critical in the multidisciplinary approach to NP, especially for patients who are refractory to topical and oral treatments. Procedural modalities include a spectrum of options that can be applied based on the disease's symptoms and severity.

Same But Different: An 18-Month Cross-Sectional Study of Cosmetic Procedures in Patients With Skin Phototype I-III Versus IV-VI in Toronto, Canada.

BACKGROUND: Patients with darker skin phototypes self-report less facial aging than their lighter-skinned counterparts. However, the association of skin phototype with the type of cosmetic procedures received, is yet to be established in a Canadian context. OBJECTIVE: To compare the pattern of nonsurgical cosmetic procedures performed on people with different Fitzpatrick SPTs. MATERIALS AND METHODS: Cross-sectional study of patient encounters from October 2020-April 2022. Charts and photographs were reviewed and analyzed for age, sex, SPT, and procedure type. Participants were stratified by SPT into 2 cohorts: SPT I-III and SPT IV-VI. SPTs were collapsed into groups based on definitions of "skin of color" (SPT IV-VI) in previous literature. RESULTS: We analyzed 350 patients with mean age 43.4, of whom 320 (91%) were female and 30 (9%) were male. The SPT I-III cohort was older (mean age 45 vs 38.5 years, p < .0001) and more frequently underwent neuromodulator injection. The SPT IV-VI cohort more frequently underwent microneedling, platelet-rich plasma, or electrodessication. CONCLUSION: There are distinct patterns of cosmetic procedures performed. The SPT I-III cohort more commonly received procedures to manage facial aging. The SPT IV-VI cohort was younger and more commonly underwent procedures to manage hyperpigmentation.

Post-inflammatory hyperpigmentation: A systematic review of treatment outcomes.

Post-inflammatory hyperpigmentation is a common consequence of inflammatory dermatoses. It is more common in patients with darker skin and has significant morbidity. This systematic review summarizes treatment outcomes for post-inflammatory hyperpigmentation to help physicians better predict clinical response and improve patient outcomes. Embase, MEDLINE, PubMed databases and clinicaltrials.gov were searched in accordance with PRISMA guidelines using a combination of relevant search terms. Title, abstract and full text screening were done in duplicate. Studies were included if they met our predetermined PICOS framework criteria. Results are presented in descriptive form. In total, 41 studies representing 877 patients were included. Complete response was achieved by laser and energy-based devices in 18.1% (n = 56/309) of patients, topicals in 5.4% (n = 20/369) and combination therapies in 2.4% (n = 4/166). Partial response was achieved by combination modalities in 84.9% (n = 141/166) of patients, topicals in 72.4% (n = 267/369), laser and energy-based devices in 61.2% (n = 189/309) and peels in 33.3% (n = 5/15). Poor to no response occurred with peels in 66.7% (n = 10/15) of patients, topicals in 22.2% (n = 82/369), laser and energy-based devices in 18.1% (n = 56/309) and combination modalities in 12.7% (n = 21/166). Additionally, in 2.6% (n = 8/309) of patients treated with laser and energy-based devices, post-inflammatory hyperpigmentation worsened. Adverse events were reported in 10 patients, all while using topical treatments. In conclusion, the current treatment approaches yielded unsatisfactory rates of complete response. However, combination therapies, laser and energy-based devices and topical therapies showed high rates of partial response. Of note, the majority of post-inflammatory hyperpigmentation cases included were associated with acne, and therefore, the findings and conclusions drawn may have limited applicability to other types of post-inflammatory hyperpigmentation.

INDIVIDUAL ARTICLE: Skincare in Skin of Color: A Comprehensive Approach to Preprocedure, Intraprocedure, and Postprocedure.

Hyperpigmentation, uneven skin tone, textural changes, and dull skin are common cosmetic concerns in skin of color. Other signs of aging, including fine lines, deeper wrinkles, and skin laxity, also occur but may present in later decades. In-office procedures such as laser treatments, energy devices, toxins, fillers, and chemical peels are useful options for addressing the most common cosmetic concerns in skin of color patients. Skincare can play an important role in improving cosmetic outcomes when used in conjunction with in-office procedures. With the availability of these approaches, clinicians can now integrate in-office procedures with skincare strategies to offer patients with skin of color a comprehensive treatment plan that meets their needs. J Drugs Dermatol. 2024;23:8(Suppl 1):s5-10.

Disorders of hyperpigmentation. Part I. Pathogenesis and clinical features of common pigmentary disorders.

Disorders of hyperpigmentation are common and, depending on the extent and location of involvement, can affect the quality of life and pose a significant psychologic burden for patients. Given the similarities in presentation of the various causes of hyperpigmentation, it is often difficult to elucidate the etiology of these conditions, which is important to guide management. Furthermore, certain disorders, such as lichen planus pigmentosus and ashy dermatosis, have similar clinical and/or histologic presentations, and their classification as distinct entities has been debated upon, leading to additional confusion. In this review, the authors selected commonly encountered disorders of hyperpigmentation of the skin, subdivided into epidermal, dermal, or mixed epidermal-dermal disorders based on the location of pigment deposition, along with disorders of hyperpigmentation of the mucosa and nails. Melanocytic nevi, genetic disorders, and systemic causes of hyperpigmentation were largely excluded and considered to be outside the scope of this review. We discussed the pathogenesis of hyperpigmentation as well as the clinical and histologic features of these conditions, along with challenges encountered in their diagnosis and classification. The second article in this 2-part continuing medical education series focuses on the medical and procedural treatments of hyperpigmentation.

Disorders of hyperpigmentation. Part II. Review of management and treatment options for hyperpigmentation.

Key challenges in the management of pigmentary disorders such as melasma and postinflammatory hyperpigmentation are their resistance to treatment, tendency to recur after treatment, and the risk of exacerbating hyperpigmentation with many treatment modalities. The second article in this 2-part continuing medical education series on pigmentary disorders focuses on the evidence behind medical and procedural treatments of dyschromias, including photoprotection, topical lightening agents, oral agents, chemical peels, and laser therapy.

Cutaneous interaction with visible light: What do we know?

Visible light has been used therapeutically in dermatology for years for a variety of cosmetic and medical indications, including skin rejuvenation and the treatment of inflammatory and neoplastic conditions, among others. Until recently, visible light was thought to be relatively inert compared to its spectral neighbors, ultraviolet and infrared radiation. However, recent literature has described the ability of visible light to cause erythema in light skin and pigmentary changes in individuals with darker skin types. Concern surrounding its potentially damaging cutaneous effects has been raised in both the medical community and social media outlets. In this article, we provide an evidenced-based review describing what is currently known about visible light, focusing on its role in dermatologic diseases including disorders of hyperpigmentation such as melasma and postinflammatory hyperpigmentation.

Treatment recommendations for acne-associated hyperpigmentation: Results of the Delphi consensus process and a literature review.

Acne vulgaris can be associated with hyperpigmentation, particularly in individuals with skin of color. This acne-induced macular hyperpigmentation (AMH), also called postinflammatory hyperpigmentation, is often long lasting and negatively impacts quality of life. Large-scale, randomized, controlled clinical trials with regard to the treatment of acne and AMH are lacking. For this reason, evidence-based treatment recommendations cannot be made. However, AMH is a common condition, and it is important for clinicians to have guidance on management strategies. The authors, a group of 10 board-certified dermatologists, conducted a modified Delphi consensus process to reach a consensus on first-line therapy for AMH and determine whether therapeutic choices change in different patient subgroups. We reached a consensus that most patients with acne and AMH should receive early and efficacious acne treatment with a topical retinoid and benzoyl peroxide. Therapies aimed at addressing AMH-including hydroquinone, azelaic acid, chemical peel, or antioxidants-may also be considered for enhancing the effect of the treatment regimen on acne and pigmentation. Chemical peels may be used as adjunctive or second-line therapy. This article details the results of the Delphi process, reviews relevant literature for providing recommendations for AMH, and discusses appropriate treatment options.

Treatment of burn hypertrophic scar with fractional ablative laser-assisted drug delivery can decrease levels of hyperpigmentation.

BACKGROUND: Laser treatments have been used to treat a variety of scar symptoms, including the appearance of scars following burn injury. One such symptom is hyperpigmentation. There are several qualitative and quantitative measures of assessing improvement in hyperpigmentation over time. The Patient and Observer Scar Assessment Scale (POSAS) and Vancouver Scar Scale (VSS) are two scales that describe characteristics of scar such as pigmentation level. These scales are limited by their qualitative nature. On the other hand, spectrophotometers provide quantitative measures of pigmentation. Prior studies have reported that laser can change scar pigmentation, but no quantitative values have been reported. The current study examines changes in scar melanin index after CO2 fractional ablative laser scar revision (FLSR) via noninvasive probe measurement in patients of various Fitzpatrick skin types (FST). MATERIALS AND METHODS: Patients with scars of various sizes and etiologies were treated with FLSR. A database was constructed including 189 patients undergoing laser treatment. From this pool, individuals were selected based on the criteria that they completed at least two laser sessions and had Melanin index measurements for both of these sessions and the pre-operative visit. This criteria resulted in 63 patients of various FST in the cohort. Melanin index, POSAS-Observer (O) and -Patient (P) pigmentation and color scores and VSS-pigmentation scores were examined over time. Demographic information (age of patient at time of first treatment, age of scar at time of first treatment, use of laser-assisted drug delivery (LADD), gender, FST, and Ethnicity) were collected from the medical record. Patients were grouped as "responder" if their Melanin index indicated decreased levels of hyperpigmentation after FLSR treatment in more than half of their total number of visits and "nonresponder" if it did not. RESULTS: The majority of patients were responders (41/63). In responder patients, measurements of Melanin index showed significantly improved levels of hyperpigmentation in hypertrophic scars after two FLSR sessions (p < 0.05). Age of patient, gender, FST, age of scar, ethnicity, or type of drug delivered by LADD did not predict responder grouping. POSAS-O and -P pigmentation/color scores showed improved scores after two FLSR sessions within the responder group. POSAS-P color scores showed improved scores after two and three FLSR sessions in the nonresponder group. VSS pigmentation scores showed improved scores after three FLSR sessions in the responder group only. CONCLUSION: Based on Melanin index values, FLSR leads to improvements in hyperpigmentation in certain patients.

Differential diagnosis and management of hyperpigmentation.

There is an increasing recognition of ethnic dermatology to reflect the increase in skin of colour (SOC) populations in the UK. Hyperpigmentary disorder is one of the commonest skin concerns in SOC but there has been limited training available in this field of dermatology. Variations in skin colour are genetically determined by the amount of melanin content, the eumelanin/pheomelanin ratio and the size of melanosomes, but is also influenced by other factors such as hormones and extrinsic factors such as ultraviolet radiation. Hyperpigmentation is a broad term to describe increased pigmentation in the skin, and making a correct diagnosis is an important first step in the successful management of hyperpigmentary disorders. A systematic approach based on the disease pathogenesis (e.g. reactive vs. nonreactive, increased melanin vs. increased number of cells or epidermal vs. dermal pigmentation) aided by a detailed history and clinical examination is the best way to diagnose a hyperpigmentary disorder. Based on its pathogenesis, management can be planned. For epidermal hyperpigmentation caused by increased melanin, topical skin-lightening agents targeting inhibition of tyrosinase or melanosome transfer and promotion of keratinocyte turnover can be used. Hydroquinone-containing cream is the gold-standard treatment for epidermal hyperpigmentation. Alternative treatments include laser toning or chemical peels. However, increased dermal pigmentation is more challenging to target with topical treatments. If hyperpigmentation is due to increased numbers of melanocytes or keratinocytes, high-fluence laser is the most appropriate treatment method.

Getting to the Core of Contemporary Therapies for Post-Inflammatory Hyperpigmentation.

Post-inflammatory hyperpigmentation (PIH) is a typical complication of inflammatory dermatoses that more frequently and severely affects people with darker skin. External insults to the skin, such as burn injuries, dermatologic treatments, and intrinsic skin disorders (eg, eczema and acne), are common causes of PIH. Individuals with darker skin are prone to develop PIH, which can cause substantial psychological suffering. PIH can be prevented or alleviated. When this happens, it is essential to point out what is causing it and treat it as soon as possible to prevent inflammation and PIH from progressing. If the inflammatory symptoms go away or there is no evidence of inflammation at the time of diagnosis, PIH treatments should be evaluated. To hasten the resolution of PIH, treatment should begin as soon as possible. Treatment begins with the care of the initial inflammatory condition. Topical medications, chemical peels, laser and light-based treatment, phototherapy, and other therapeutic modalities are offered to treat PIH. Understanding the therapy options available helps the physician in choosing the best treatment for each patient. With these backgrounds, the current review aimed to discuss the epidemiology, pathogenesis, clinical presentation, and available treatment options for the PIH. J Drugs Dermatol. 2022;21(3):276-283. doi:10.36849/JDD.6485.

Prurigo Pigmentosa: Demographics and Characteristics in 14 Caucasian Patients.

BACKGROUND: Prurigo pigmentosa (PP) is an inflammatory dermatosis typically reported in young Asian women and characterized by recurrent papulovesicular lesions resolving with a postinflammatory reticulated hyperpigmentation. METHODS: We have included all consecutive patients with PP diagnosed in our tertiary center between 2013 and 2020. The clinical information was retrospectively collected from medical records. RESULTS: We identified 14 patients with PP. The median age at the time of diagnosis was 29.5 years (range 17-43 years), while the female-to-male ratio was 13:1. Diagnostic delay varied from 10 days to 10 years (mean of 25 months). Light microscopy studies consistently showed presence of a lymphohistiocytic infiltrate in combination in 40% of cases with neutrophils. Interface changes were found in 60% of cases. In 6 (43%) of 14 cases, there was a chronological relationship between the starting of a new diet and the development of the first flares. Treatment with doxycycline in 9 patients resulted in a complete regression of the lesions. LIMITATION: This was a retrospective study in a tertiary referral hospital. CONCLUSIONS: Our observations indicate that PP is not so rare in Europe as previously thought and is often diagnosed after a long delay. Demographics, clinical characteristics and triggering factors in Caucasian patients are similar to those described in the Asian population. Diagnosis is based on the peculiar recurrent course and distinctive clinicopathological features. Tetracyclines represent the first-line therapy in PP.

Novel Facial Treatment Regimen Improves Aging Skin Appearance.

BACKGROUND: Skin care regimens with multiple active ingredients offer a multimodal approach to anti-aging treatments. OBJECTIVE: The objective of this research was to investigate the efficacy of a multimodal skincare regimen on facial skin appearance after 12 weeks of twice daily use as compared to baseline. METHOD: 35 healthy female subjects 35–65 years of age of Fitzpatrick skin types I–III with mild to moderate facial photoaging characterized by hyperpigmentation were enrolled. Subjects were seen at baseline, week 6, and week 12, and underwent subject and investigator assessments along with noninvasive evaluations (elasticity, corneometry, dermaspectrophotometer) and photography. RESULTS: Most notable at week 12 was a 60% improvement in smoothness, 82% improvement in dryness, 30% improvement in fine lines, and 24% improvement in crow’s feet. There was an 8% reduction in macule hyperpigmentation (P<0.001) at week 12, supporting excellent pigment lightening qualities for the regimen. There was a statistically significant increase in skin firmness (decrease in elasticity) as early as week 6 of 6% with further improvement observed at week 12 of 16% (P=0.002). SUMMARY: A multimodal skincare regimen with antioxidants, retinol, hydrolyzed pearl, caviar extract, peptides, and growth factors including EGF and TGF-β results in an improvement in the appearance of photoaged skin after 12 weeks of twice daily use. J Drugs Dermatol. 2021;20(3):274-278. doi:10.36849/JDD.5791.

Hyperpigmentation after nonsurgical blepharoplasty using plasma technology.

Nitrogen plasma is considered nowadays one of the efficient treatment options for nonsurgical blepharoplasty. Although it is an overall safe treatment, it has some side effects. This short paper addresses the risk of hyperpigmentation following the use of plasma and list few suggestions on how to prevent it.

Home vs hospital narrowband UVB treatment by a hand-held unit for new-onset vitiligo: A pilot randomized controlled study.

PURPOSE: To compare the efficacy and safety of narrowband ultraviolet B (NB-UVB) phototherapy in home vs in hospital for the management of limited new-onset vitiligo. METHODS: Patients with new-onset vitiligo (<3 months) with <5% body surface area involvement were recruited and randomly assigned to either a home-based or a hospital-based treatment group. Both groups were administered NB-UVB phototherapy thrice a week. The body surface area (BSA) involved with vitiligo, Vitiligo Area Scoring Index (VASI), the effectiveness of repigmentation, Vitiligo Quality of Life index (VitiQoL), and the cost of treatment were examined. RESULTS: A total of 100 patients completed the study. Patients in both groups exhibited improvements demonstrated by BSA and VSAI decrease. No significant differences were found between the two groups in terms of skin repigmentation (P > 0.05). Improvements in the VitiQoL scores were reduced to the greatest degree at week 8 for all patients in both groups. Adverse events, such as painful erythema, burning, blistering, and excessive hyperpigmentation, were more frequently observed in the home-based treatment group than in the hospital-based treatment group. The cost of phototherapy in hospital exceeded the cost of home phototherapy after 7 weeks of treatment. CONCLUSIONS: Home NB-UVB phototherapy treatment was as effective as treatment in hospital, but exhibited cost-effective and a better compliance. However, the education of the patients should be strengthened to avoid excessive UVB exposure and related adverse events.

Use of Lasers for Iron-Induced Accidental Tattoos: Experience at a Tertiary Referral Center.

BACKGROUND: Awareness of accidental tattoos after iron injections with paravenous leakage is low. No larger patient cohorts have been analyzed. The lesions are a burden to the patients. The only known treatment is laser therapy. OBJECTIVE: To characterize the clinical appearance and development of iron-induced tattoos and to demonstrate safe and efficient removal with quality-switched (QS) and picosecond lasers. MATERIALS AND METHODS: The authors conducted a retrospective systematic analysis on patients who presented at the Dermatology Department of the University Hospital of Zurich between Year 2008 and 2017 with accidental hyperpigmentations after iron injections. From 29 collected patients, 13 received laser treatment and were analyzed with reference to the lasers used, including wavelength, fluence, spot size, intervals, number of sessions, and overall success. The authors defined the latter as a complete removal or as patients' satisfaction. RESULTS: The authors treated 13 patients and completed the treatment in 8 patients, with an average of 5.6 sessions. No complications occurred. CONCLUSION: Spontaneous regression of iron-induced tattoos is possible within 1 to 2 years, but not guaranteed. Removal with QS ruby, Nd:YAG, and picosecond lasers can be achieved within a mean number of 5.6 sessions. Assuring a valid indication before intravenous iron administration is important.

Atypical Disseminated Variant of Galli-Galli Disease: A Review of the Literature.

Galli-Galli disease (GGD) is a rare genodermatoses within the group of reticulated pigmentary disorders of the skin. Traditionally, its clinical presentation is identical to that of Dowling-Degos disease (DDD), with the additional feature of acantholysis on histopathological examination. We have reviewed the published cases of GGD to provide further support for the hypothesis that in fact, 2 phenotypes of GGD exist: the characteristic flexural GGD associated with KRT5 mutations and a disseminated variant with no mutation identified to date. A review of the literature revealed 53 reported cases of GGD. Fifteen atypical phenotype cases are described, and no KRT5 mutation has yet been identified. There is growing evidence that acantholysis is an underreported feature of DDD and that GGD and DDD are variations of the same disease, or in fact the same entity. This theory is supported by the identification of the c.418dupA missense mutation in both GGD and DDD. This review highlights that there is growing evidence that there are likely 2 clinical phenotypes of GGD with an associated genotypic correlation.

Periorbital Discolouration Diagnosis and Treatment: Evidence-Based Review.

Infraorbital dark circles are a significant esthetic concern with few publications however offering evidence-based recommendations for their classification and consequent management. A literature review has been undertaken to classify dark circles based on etiology: shadowing, vascular, idiopathic hyperpigmentation, post-inflammatory hyperpigmentation, constitutional and offer an analysis of current treatment modalities and their effectiveness in managing specific types of infraorbital circles. This review aims to provide a detailed account of dark circle etiology, assessment and management.