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.

Pigmented actinic lichen planus: a case report.

Actinic lichen planus (ALP) is a rare photosensitive subtype of lichen planus (LP) with four major forms recognized: annular, pigmented (melasma-like), dyschromic, and classic lichenoid. The prevalence is highest among dark-skinned younger females residing in tropical and subtropical regions. There are very few reports of ALP across Europe, with most of the cases among individuals living in warm countries or in people of Middle Eastern and Indian ancestry. We report a case of a 68-year-old white man that presented with a 9-year history of a mildly pruritic solitary hyperpigmented patch on the tip of his nose. Histopathological examination demonstrated signs of classic LP with epidermal atrophy, pigmentary incontinence, and signs of solar elastosis. Based on these findings, a diagnosis of pigmented ALP was established. Topical pimecrolimus and tretinoin along with rigorous photoprotection proved effective, with mild residual hyperpigmentation after 6 months of treatment. Many differential diagnostic possibilities should be considered for such a lesion. Nevertheless, a biopsy and correlation of histopathological and clinical findings can shorten the time from onset to a proper diagnosis. Treating both the hyperpigmented and inflammatory component of this dermatosis is necessary, as well as strict long-term photoprotection to prevent recurrences.

Treatment of Acne Vulgaris-Associated Post-Inflammatory Dyschromia With Combination of Non-Ablative Laser Therapy and Topical Antioxidants.

Acne can cause disfiguring sequelae, such as scarring, post-inflammatory erythema (PIE), and post-inflammatory hyperpigmentation (PIH). These post-inflammatory dyschromias pose a significant psychological burden on patients. This burden disproportionately affects skin of color (SOC) patients and can be the most distressing aspect of acne in SOC patients with skin types IV to VI. Multiple non-ablative lasers are used in the treatment of acne-related PIE and PIH. Combination therapies have shown promise in conditions such as rosacea, acne, and post-inflammatory dyschromia. Addressing both the inflammatory and scarring components of acne is key. Given the role of oxidation in the inflammatory cascade, including antioxidants could be an efficacious adjuvant with non-ablative lasers. This is a single-site, randomized, controlled clinical study of 25 subjects with skin types I to VI with facial PIE and/or PIH from acne. The primary objective was to investigate the clinical efficacy of non-ablative laser therapy followed by the topical application of Silymarin/Salicylic Acid/L-Ascorbic Acid/Ferulic Acid (SSAF) or control in the improvement in oily skin patients with facial PIE and PIH due to acne lesions. There was a statistically significant decrease in PIH and intralesional melanin in patients treated with a combination SSAF and non-ablative laser therapy. Improvement of both PIE and PIH was augmented in combination with SSAF and laser-treated patients compared with the laser-only group, with a concomitant increase in collagen density. This was even more strikingly marked in the SOC subjects, potentially providing an energy-based device (EBD)-based therapy in this population. Limitations of this study include small sample size and length of post-treatment follow-up. J Drugs Dermatol. 2024;23(9):769-773. doi:10.36849/JDD.8309.

Noninvasive high-intensity focused ultrasound for skin brightening efficacy using a topical agent containing glutathione and hyaluronic acid.

BACKGROUND: High-intensity focused ultrasound (HIFU) is well-documented for skin rejuvenation, lifting, and tightening. However, its synergistic effects with topical agents, enhanced by HIFU-induced vibration and heat, remain underexplored. OBJECTIVE: To evaluate clinical and photographic outcomes of HIFU combined with a topical agent versus the topical agent alone. METHOD: This non-randomized controlled trial involved 20 female volunteers (ages 30-55) divided into two groups. Group A (n = 10) received two HIFU sessions combined with a topical agent containing glutathione and hyaluronic acid. Group B (n = 10) received the topical agent alone. Outcomes were assessed using digital photography, patient satisfaction surveys, and the A-One Smart™ system for fine wrinkles, hyperpigmentation, and hydration. Skin brightening was evaluated with the Global Esthetic Improvement Scale (GAIS). RESULTS: Group A showed significant reductions in fine wrinkles (6.25 ± 2.00 mm to 3.10 ± 1.62 mm), improved hyperpigmentation (3.50 ± 0.80 to 2.10 ± 1.05), and increased hydration (28 ± 10 to 55 ± 11) (all p < 0.05). Over two-thirds of Group A reported significant improvements, with no complications. Group B showed minimal, non-significant changes (p > 0.05), with only 30% reporting noticeable improvements. CONCLUSION: Combining HIFU with a topical agent significantly enhances skin quality and brightness without adverse effects.

Pigmented basal cell carcinoma mimicking nodular melanoma.

The most common form of primary skin cancer is basal cell carcinoma (BCC). Pigmented BCC is a less common clinical presentation in BCC spectrum, where the tumour contains pigment. Some cases can exhibit morphological features that mimic those of nodular melanoma (NM). We present a woman in her late 40's who had an asymptomatic firm, hyperpigmented nodule on the right cheek resembling pigmented NM. Dermoscopy showed diffuse hyperpigmentation with irregular shiny surface and a solitary haemorrhagic crust. Melanoacanthoma and irritated seborrheic keratosis were the other differentials considered. Punch biopsy showed features of trichoepithelioma initially, subsequent complete excision was suggestive of pigmented BCC.Mortality related to BCC is rare, whereas NM is aggressive. Hence, clinicians need to be aware of this rare presentation of BCC as a hyperpigmented nodule, particularly in dark-skinned individuals. Timely differentiation between melanoma and BCC is crucial given their differing prognosis.

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.

Topical Steroids Sold as Fade Creams in Beauty Supply Stores: A Danger for Cosmetic Consumers.

Topical corticosteroids are used extensively in dermatology. Class 1 high potency topical steroids (HPTS) can result in unwanted side effects such as skin hypopigmentation, atrophy, and acneiform eruptions. HPTS are only legally available by prescription to ensure appropriate use in the United States (US). The authors have noticed a recent increase in patients presenting with steroid acne after buying HPTS products in beauty supply stores. These products are marketed as fade creams to treat hyperpigmentation and uneven skin tone. We assessed skincare products containing HPTS (clobetasol or betamethasone) in 33 beauty supply stores in Miami, FL; Washington, DC; and Baltimore, MD. Out of 33 beauty supply stores, 14 (42.42%) contained HPTS skincare products, and they were all located in Miami. Out of 15 stores visited in Miami, 14 (93.33%) contained skincare products with clobetasol, and 5 (33.33%) contained skincare products with both clobetasol and betamethasone. Of the stores selling HPTS skincare products, the number of different brands available ranged from 1 to 7, with an average of 4.21 different brands per store. Our study reveals that HPTS are readily available in over-the-counter skincare products in many beauty supply stores. HPTS skincare products were only available in one of three cities suggesting there may be a regional supplier distributing these products. It may also indicate that there is less oversight of retail stores in Miami with HPTS products. More studies are needed to quantify the availability of these products in different locations throughout the US. Further Studies can help identify this problem and raise awareness among consumers of the dangers of HPTS skincare products in beauty supply stores. J Drugs Dermatol. 2024;23(9):709-712. doi:10.36849/JDD.7608.

Genomic and transcriptomic landscape to decipher the genetic basis of hyperpigmentation in Lanping black-boned sheep (Ovis aries).

BACKGROUND: Lanping black-boned sheep (LPB) represent a distinctive mammalian species characterized by hyperpigmentation, resulting in black bone and muscle features, in contrast to their conventional counterparts exhibiting red muscle and white bone. The genetic basis underlying LPB hyperpigmentation has remained enigmatic. METHODS: In this study, we conducted whole-genome sequencing of 100 LPB and 50 Lanping normal sheep (LPN), and integrated this data with 421 sequenced datasets from wild and domestic sheep, shedding light on the genetic backdrop and genomic variations associated with LPB. Furthermore, we performed comparative RNA-Seq analysis using liver sample to pinpoint genes implicated in the pigmentation process. We generated a comprehensive dataset comprising 97,944,357 SNPs from 571 sheep, facilitating an in-depth exploration of genetic factors. RESULTS: Population genetic structure analysis revealed that the LPB breed traces its origin back to LPN, having evolved into a distinct breed. The integration of positively selected genes with differentially expressed genes identified two candidates, ERBB4 and ROR1, potentially linked to LPB hyperpigmentation. Comparative analysis of ERBB4 and ROR1 mRNA relative expression levels in liver, spleen, and kidney tissues of LPB, in comparison to Diqing sheep, revealed significant upregulation, except for ERBB4 in the liver. Gene expression heatmaps further underscored marked allelic frequency disparities in different populations. CONCLUSION: Our findings establish the evolutionary lineage of the LPB breed from LPN and underscore the involvement of ERBB4 and ROR1 genes in melanin synthesis. These results enhance our comprehension of the molecular basis of hyperpigmentation and contribute to a more comprehensive depiction of sheep diversity.

Schmidt´s syndrome found by tan: a case report.

Addison´s disease can form part of type 2 autoimmune polyglandular syndrome. The article reports the case of a 41-year-old female patient with hypothyroidism and vitiligo, who came to the emergency department complaining of asthenia that had worsened in recent months, as well as anorexia, nausea, and weight loss (6 kg in a year). Cutaneous hyperpigmentation was the main finding on physical examination, together with vitiligo lesions on the face, hands, and armpits. Further study revealed a low serum cortisol level, normal urine-free cortisol, and an elevated adrenocorticotropic hormone (ACTH). Antiperoxidase antibodies and 17-alpha-hidroxylase antibodies were both positive. Treatment was started with prednisolone and fludrocortisone, and a good clinical response was obtained. This case report aims to draw attention to the high level of clinical suspicion required to diagnose Addison´s disease and the need to screen actively for other potentially associated autoimmune diseases that may be associated.

Prospective study of using 1064-nm Q-switched Nd: YAG combined with radiofrequency-imported vitamin C on pigmented infraorbital dark circles.

Infraorbital dark circles are a common manifestation of periorbital melanosis, which is aesthetically defective and bring a negative impact on life quality. However, there is no acknowledged treatment for infraorbital dark circles. The 1064-nm Q-switched Nd: YAG laser (QSNYL) is commonly utilized to treat hyperpigmentation disorders. Radiofrequency (RF) therapy can improve the transdermal absorption rate of drugs. A prospective clinical trial was conducted to investigate the clinical efficacy and safety of 1064-nm QSNYL combined with RF-imported vitamin C for the treatment of infraorbital dark circles. A questionnaire was used to explore the relevant factors affecting the severity of infraorbital dark circles. A total of 30 patients with pigmented infraorbital dark circles were enrolled in this clinical trial. Each participant received 4 treatments and was followed up for at least 12 months after the last treatment.We focused on the overall change in the appearance of the included participants before and after treatment, by using satisfaction evaluation.In order to reduce evaluation bias, the vivo reflectance confocal microscopy images were taken on days 1 and 120 to detect pigmentation. The questionnaire survey before treatment showed that high-frequency makeup was positively and statistically significant with the severity of infraorbital dark circles (p < 0.01). Both participants and independent evaluators found that the hyperpigmentation in the infraorbital region was significantly reduced after combined treatment with high treatment satisfaction. The density of melanin particles in the infraorbital dark circles region showed a decreased trend. No significant side effects were observed. The 1064-nm QSNYL combined with RF-imported vitamin C is a safe and effective treatment for pigmented infraorbital dark circles by reducing melanin particles.

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.

H Syndrome: Three New Cases from Morocco.

A 19-year-old girl presented with symmetric and bilateral hyperpigmentation, an indurated lesion that initially appeared on the axillary fold at the age of 14, which then extended to the lower back, anterior aspect of both thighs, and popliteal fold. No hypertrichosis was observed (Figure 1).The patient was the youngest of the four children, born from the first-degree consanguineous marriage. She was born at full term and weighed 2,420 g at birth. No similar patient was present in the family. The patient experienced delayed motor acquisition and stature growth (3rd percentile) until the age of 4. Right hypoacusis was diagnosed at the age of 6. She developed hallux valgus, flexion contracture of the fin-gers and toes, barrel deformity of the anterior thorax, and recurrent fever. The laboratory tests, including fasting blood glucose, -triglycerides, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were normal. Her abdominal, pelvic, and transthoracic ultrasound scans were normal, with no hepatosplenomegaly, lymphadenopathy, or cardiac abnormalities. Histologic analysis demonstrated patchy acanthosis of the epidermis, with orthokeratotic hyperkeratosis. Keratinocyte hyperpigmentation and spongiosis at certain areas were observed with moder-ate inflammation because of the infiltration of lymphocytes, histiocytes, and plasma cells. Immunohistochemical analysis showed macrosialin (CD68+) and common gamma chain (γc) CD132. Germline mutations in the SLC29A3 gene were not analyzed. The patient was prescribed dermocorticoids with depigmentation therapy, which demonstrated moderate clinical evolution.

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.

Research note: effects of hyperpigmentation of the visceral peritoneum on body weight and selection method in Chinese yellow-feathered broilers.

We previously identified a dark blue appearance through the skin of abdomen, especially the colored chicken breeds, called hyperpigmentation of the visceral peritoneum (HVP) which characterized by intense pigmentation of connective tissue in the visceral peritoneum. The HVP has recently garnered increasing attention due to its negative impact on carcass appearance, and been an important concern in the poultry industry, especially for the Chinese yellow-feathered broilers. In this study, we measured the in vivo HVP at different time points, and analyzed the correlation between the HVP in vivo and postmortem. Then, established an accurate and reliable HVP phenotypic measuring method in vivo for early selection in chickens and analyzed the association of phenotypic variations with the in vivo HVP traits with growth traits. The results showed that the in vivo HVP at 21 d of age in chickens have a high heritability (h2 = 0.452) through estimating genetic parameters, and in vivo HVP levels at 21 and 42 d were both significantly associated with those postmortem in chickens, suggesting that directional selection on reducing HVP can be implemented as early as at 21 d in the breeding and production of chickens. Although, we found HVP had no effect on the body weight at 1 d, it could significantly reduce the body weight at 21, 42, 70 d and 91 d in chickens. This suggests HVP not only has a negative effect on carcass traits, but also significantly reduces the production in the poultry industry.

Semaxanib, a VEGF inhibitor, suppresses melanogenesis by modulating CRTC3 independently of VEGF signaling.

BACKGROUND: Dysregulation of melanogenesis contributes to the development of skin hyperpigmentation diseases, which poses a treatment challenge. Following the establishment of CRTC3 screening methods to explore small molecules inhibiting melanogenesis for the topical treatment of hyperpigmentation diseases, we identified a candidate molecule, semaxanib. OBJECTIVE: To explore the antimelanogenic effects of semaxanib, a vascular endothelial growth factor receptor (VEGFR) 2 inhibitor, for potential applications in hyperpigmentation management and to unravel the role of VEGF signaling in melanocyte biology by investigating mechanism of action of semaxanib. METHODS: Mouse-derived spontaneously immortalized melanocytes, B16F10, and normal human primary epidermal melanocytes cells were treated with semaxanib, and cellular responses were assessed using cell viability assays and melanin content measurements. Molecular mechanisms were investigated using transcriptional activity assays, reverse-transcription polymerase chain reaction, and immunoblotting analysis. In vivo studies were conducted using an epidermis-humanized transgenic mouse model and ex vivo human skin tissues. RESULTS: Semaxanib ameliorated melanin content in cultured melanocytes by downregulating the expression of melanogenesis-associated genes by suppressing the CRTC3/microphthalmia-associated transcription factors. Topical application of semaxanib reduced melanin accumulation in the ultraviolet B-stimulated ex vivo human epidermis and tail of K14-stem cell factor transgenic mice. Mechanistically, the antimelanogenic effect induced by semaxanib was associated with SIK2-CRTC3-MITF rather than VEGF signaling in melanocytes. CONCLUSION: Semaxanib emerges as a promising candidate for the development of therapeutics for hyperpigmentation, potentially working independently of VEGF signaling in human melanocytes.

Leukomelanoderma Resembling Hyperpigmented Mycosis Fungoides.

Acquired circumscribed hyperpigmented patches and plaques have various differential diagnoses, including post-inflammatory hyperpigmentation and mycosis fungoides (MF). Leukomelanoderma is an uncommon cutaneous condition in which the pathogenesis is not fully elucidated. It has been reported that leukomelanoderma occurs after allergic contact dermatitis from hydroquinone or acute cutaneous graft-versus-host disease (1,2). Hyperpigmented MF is a cutaneous T-cell lymphoma with a frequent CD8+ phenotype (3). Herein, we report a case of leukomelanoderma clinically and histologically resembling hyperpigmented MF. A 55-year-old Japanese woman was referred to our department for evaluation of reticulate pigmentation with pruritic erythema on the face. She had used commercially available depigmenting cosmetic reagents for 20 years and ointment containing 10% hydroquinone for 3 months. Physical examination revealed diffuse hyperpigmentation and demarcated hypopigmented macules on the face and neck (Figure 1, a). Dermoscopy showed depigmented spots and reticulated plus dotted hyperpigmentation; it presented a pseudo-pigment network (Figure 1, b). Histological examination of a tissue specimen biopsied from the lesion showed superficial band-like lymphocytic infiltration in dermis accompanying single cells or small clusters in epidermis (Figure 1, c). Interface changes were observed together with melanophages in the dermis. Melan-A-positive melanocytes were absent. Immunohistochemical analysis demonstrated that the epidermotropic lymphocytes were CD3+CD7-, and they had predominance of CD8+ cells (Figure 1, d). These immunohistochemical results mimicked MF. However, PCR analysis of the T-cell receptor g-gene rearrangement was negative. Closed patch test result with hydroquinone (5% pet.) was graded D2 (+?) and D3 (+). Ten months after discontinuing cosmetic reagents and hydroquinone, the pigmentary changes showed improvement. The pathomechanism of leukomelanoderma is unclear. Although post-inflammatory pigmentation due to allergic or contact dermatitis together with direct depigmenting effects from hydroquinone use has been suggested (1), the immunophenotype of T-cells has not been examined. As observed in our patient, interface changes with melanophages, in addition to frequent CD8+ phenotype of the epidermotropism and dermal infiltrate of lymphocytes, were characteristic for hyperpigmented MF (3). Moreover, minimal CD7 expression was a specific finding for MF (4). T-cell receptor clonality was negative in our patient, but the clonality appears to be detected by PCR in up to 50% of the patients with early MF (3). In contrast, the closed patch test was positive for hydroquinone in our patient, and it is reported that CD8+ T-cells are recruited to the interphase between the epidermis and the dermis of the patients with allergic contact dermatitis (5). CD8+ T-cells might contribute to acute cutaneous graft-versus-host disease-like interface changes and destroy melanocytes in the leukomelanoderma lesion. Allergic contact dermatitis presenting as leukomelanoderma was thus suggested in our patient. However, further reports and studies are required to support this issue. Therefore, we considered it necessary to follow the patient, since MF was not absolutely eliminated.