Therapeutic modulation of KIT ligand in melanocytic disorders with implications for mast cell diseases.

KIT ligand and its associated receptor KIT serve as a master regulatory system for both melanocytes and mast cells controlling survival, migration, proliferation and activation. Blockade of this pathway results in cell depletion, while overactivation leads to mastocytosis or melanoma. Expression defects are associated with pigmentary and mast cell disorders. KIT ligand regulation is complex but efficient targeting of this system would be of significant benefit to those suffering from melanocytic or mast cell disorders. Herein, we review the known associations of this pathway with cutaneous diseases and the regulators of this system both in skin and in the more well-studied germ cell system. Exogenous agents modulating this pathway will also be presented. Ultimately, we will review potential therapeutic opportunities to help our patients with melanocytic and mast cell disease processes potentially including vitiligo, hair greying, melasma, urticaria, mastocytosis and melanoma.

Excimer Laser Therapy for Pigmented Purpuric Dermatosis: A Case Study.

BACKGROUND Pigmented purpuric dermatosis (PPD) is a rare disease that is poorly understood but thought to result from inflammation of the capillaries causing extravasation of erythrocytes into the soft tissue. There are a variety of potential causes, including medications, such as acetaminophen and aspirin, abnormal humoral immunity, and excessive exercise. Although benign, PPD can be bothersome to patients due to associated pruritus, weeping, and poor cosmetic results. Treatment of this lesion is difficult, with no standardized regimen and a tendency for relapse once treatment is discontinued. CASE REPORT This case reports on a 77-year-old man who presented to an outpatient dermatology clinic with bilateral lower extremity edema with associated weeping and erythema for 1 year. A biopsy was conducted and resulted as PPD. He began treatment with excimer laser therapy after conservative and topical treatment options failed, with resolution of symptoms without recurrence for approximately 1 year. CONCLUSIONS PPD is notoriously difficult to treat, and historic treatment options include topical corticosteroids, oral supplements, and immunomodulators, all of which come with a range of adverse effects. However, new literature supports the use of phototherapy to treat PPD, with varying results. Previously implemented options include but are not limited to phototherapy with psoralen plus ultraviolet A, narrow band ultraviolet B, advanced fluorescence technology pulsed light, and fractional non-ablative 1540-nm erbium: glass laser, each with varying degrees of success. This case discusses the successful treatment of recalcitrant PPD with excimer laser therapy and maintenance of remission for approximately 1 year.

Pigmented fungiform papillae of the tongue.

INTRODUCTION: Pigmented fungiform papillae of the tongue is a benign condition frequent in dark skin patients. It usually appears in the second or third decade of life, and it has been reported as autosomal dominant inheritance pattern. The diagnosis is clinical, but dermoscopy could be helpful: a classical rose petal pattern is observed. The pathogenesis is unknown, and no treatments are effective. CASE REPORT: We report a case of a 15-year-old girl with a pigmented fungiform papillae and a compatible dermatoscopy pattern. CONCLUSIONS: Knowing the existence of this entity and its characteristic dermoscopy, avoids additional invasive medical test. We have to know this entity because it is a variant of normality.

INTRODUCCIÓN: La pigmentación de las papilas fungiformes linguales es una condición benigna y relativamente frecuente en pacientes con piel oscura. Suele aparecer en la segunda o tercera décadas de la vida y se han descrito casos de herencia autosómica dominante. El diagnóstico es clínico, pero la dermatoscopia es de gran ayuda: presenta un patrón clásico en pétalos de rosa. La patogénesis se desconoce y no hay tratamientos efectivos. CASO CLÍNICO: Reportamos el caso de una niña de 15 años con pigmentación de las papilas fungiformes y con patrón dermatoscópico compatible. CONCLUSIONES: Conocer la existencia de esta afección y su característica dermatoscopia evita realizar pruebas invasivas adicionales, ya que se trata una variante de la normalidad.

Using an intense pulsed light (IPL) module for the treatment of pigmented lesions.

BACKGROUND: Pigmented lesions are largely benign and may lead to extreme distress. Various light and lasers may be used to treat pigmentation, often Q-switched lasers are considered the method of choice, while intense pulsed light (IPL) devices may offer a less invasive treatment with a shorter downtime. OBJECTIVE: The purpose of this study is to evaluate the safety and efficacy of a narrowband IPL module for the treatment of pigmented lesions. METHODS: A retrospective study of 20 patients with pigmented lesions underwent treatment with an IPL module. Treatment was assessed by blinded evaluation of clinical photographs using a GAIS scale of 0-10, as well as through patient satisfaction ratings on a scale of 0-10. Throughout the treatment, pain levels and adverse events were monitored. RESULTS: The mean GAIS score was 7.55 ± 1.15 (mean ± SD), and the mean patient satisfaction score was 7.3 ± 1.26 (mean ± SD). There was a strong positive correlation between GAIS and patient satisfaction scores (r = 0.83), and no significant difference between them (p-value = 0.516). The number of treatments did not significantly affect GAIS and patient satisfaction scores (p-values 0.364 and 0.126). Additional positive unexpected outcomes were improved skin firmness and reduced wrinkles. CONCLUSION: The results of the study indicate that the IPL module is both safe and effective in treating pigmented lesions and may have the potential to stimulate collagen production.

Bilateral acute depigmentation of the iris (BADI) and bilateral acute iris transillumination (BAIT): A case series from a center in Brazil.

Bilateral acute depigmentation of the iris and bilateral acute iris transillumination (BAIT) are similar clinical entities. The former causes acute-onset depigmentation of the iris stroma without transillumination, whereas the latter causes depigmentation of the iris pigment epithelium with transillumination. The etiopathogenesis of these conditions is not yet fully understood, but the proposed causes include the use of systemic antibiotics (especially moxifloxacin) and viral triggers. We present a case series of five female patients with a mean age of 41 (32-45) years, all of whom suffered acute onset of bilateral pain and redness of the eyes after moxifloxacin use (oral or topical). It is important for ophthalmologists to be aware of the two forms of iris depigmentation since this case series suggests that SARS-CoV-2 or its empirical treatment with moxifloxacin may trigger iris depigmentation. If this is the case, clinicians will likely see increased incidences of bilateral acute depigmentation of the iris and bilateral acute iris transillumination during and after the COVID-19 pandemic.

[Analysis of ADAR gene variants in a Chinese pedigree affected with Dyschromatosis symmetrica hereditaria in conjunct with developmental delay].

OBJECTIVE: To explore the clinical characteristics and genetic etiology for a Chinese pedigree affected with Dyschromatosis symmetrica hereditaria (DSH) in conjunct with developmental delay. METHODS: A child who had presented at the First Affiliated Hospital of Zhengzhou University on May 28 2021 for abnormal skin pigmentation of the extremities and growth retardation for over 2 years was selected as the study subject. Clinical data of the child and his pedigree (11 individuals from three generations) was collected. The child was subjected to whole exome sequencing, and candidate variant was verified by Sanger sequencing. RESULTS: The child, a two-year-and-seven-month-old male, had hyper- and hypopigmentation on his hands, feet and face, in addition with delayed development. All members of his pedigree had typical presentation of DSH. A heterozygous c.2657G>A variant was found in exon 8 of the ADAR gene in the child, his mother, and elder sister. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted as likely pathogenic (PM1+PM2_Supporting+PP1+PP3). CONCLUSION: The c.2657G>A variant of the ADAR gene probably underlay the DSH in this pedigree.

Motor control on gait performance among individuals with lower crossed syndrome: A scoping review.

INTRODUCTION: Lower Cross Syndrome (LCS) is a prevalent condition that manifests as muscular tension due to the asymmetry in the strength of the lower extremity muscles. This imbalance could be due to the tautness of the iliopsoas, rectus femoris, tensor fascia latae, adductor group, gastrocnemius, and soleus muscles. LCS causes a postural imbalance in the individual, which triggers low back pain (LBP). When LCS is present alongside LBP, may cause the upper body to sway more in the transverse plane and at the lumbar level, making walking and termination of gait (GT) more difficult. However, the evidence of motor control and gait performance is scarce with inconclusive findings. Thus, this study aimed to review motor control on gait performance among individuals with lower crossed syndrome. This review is conducted to determine the motor control on gait performance in patients with LCS and how the conditions affect gait. MATERIALS AND METHODS: The databases Google Scholar, Science Direct, ResearchGate, PubMed, and Scopus were searched to identify potentially relevant documents. The keywords used for the search included "motor control" OR "motor learning" OR" core stability" AND "lower crossed syndrome" AND "gait". The search includes articles published between 1970 and 2022 and written in English. It is excluded when the paper is not a full-text article. After finding the articles, the information was extracted, including author, year of publication, country, objective, type of study, and motor control analysis summary. RESULTS: There were 107 articles retrieved from the search. but only seventeen articles were included for analysis. The finding demonstrates that LCS may associate with LBP and reduces the motor control of the core muscle stability which indirectly influences gait performance. CONCLUSIONS: This study suggests that individuals with LCS will have an alteration in their gait. However, there is still insufficient information on motor control in gait performance among lower crossed syndrome. Further research is needed to find what factors that may contribute to the adaptation of motor control in gait among LCS population.

Microneedles: A novel clinical technology for evaluating skin characteristics.

BACKGROUND: Current methods for evaluating efficacy of cosmetics have limitations because they cannot accurately measure changes in the dermis. Skin sampling using microneedles allows identification of skin-type biomarkers, monitoring treatment for skin inflammatory diseases, and evaluating efficacy of anti-aging and anti-pigmentation products. MATERIALS AND METHODS: Two studies were conducted: First, 20 participants received anti-aging treatment; second, 20 participants received anti-pigmentation treatment. Non-invasive devices measured skin aging (using high-resolution 3D-imaging in the anti-aging study) or pigmentation (using spectrophotometry in the anti-pigmentation study) at weeks 0 and 4, and adverse skin reactions were monitored. Skin samples were collected with biocompatible microneedle patches. Changes in expression of biomarkers for skin aging and pigmentation were analyzed using qRT-PCR. RESULTS: No adverse events were reported. In the anti-aging study, after 4 weeks, skin roughness significantly improved in 17 out of 20 participants. qRT-PCR showed significantly increased expression of skin-aging related biomarkers: PINK1 in 16/20 participants, COL1A1 in 17/20 participants, and MSN in 16/20 participants. In the anti-pigmentation study, after 4 weeks, skin lightness significantly improved in 16/20 participants. qRT-PCR showed significantly increased expression of skin-pigmentation-related biomarkers: SOD1 in 15/20 participants and Vitamin D Receptor (VDR) in 15/20 participants. No significant change in TFAP2A was observed. CONCLUSION: Skin sampling and mRNA analysis for biomarkers provides a novel, objective, quantitative method for measuring changes in the dermis and evaluating the efficacy of cosmetics. This approach complements existing evaluation methods and has potential application in assessing the effectiveness of medical devices, medications, cosmeceuticals, healthy foods, and beauty devices.

Therapeutic Approach in Pigmented Purpuric Dermatoses-A Scoping Review.

Pigmented purpuric dermatoses (PPD) encompass a group of chronic skin conditions characterized by the presence of petechiae, purpura, and pigmentation changes. While generally benign, these dermatoses can be persistent and aesthetically bothersome. Key clinical features include red to brownish patches with a distinctive "cayenne pepper" appearance, predominantly localized on the lower extremities, particularly the shins. Subtypes include Schamberg disease, Majocchi's disease, Gougerot-Blum disease, Ducas and Kapetanakis pigmented purpura, and lichen aureus. Diagnosis relies primarily on clinical evaluation of skin lesions, with biopsy as a confirmatory tool. Although the exact cause of PPD remains unclear, capillary fragility and red blood cell extravasation are implicated. Treatment strategies for PPD aim to alleviate symptoms, considering the generally benign and chronic nature of the condition. As there is no standardized treatment, various methods with varying efficacy are employed. After searching SCOPUS and PubMed databases, we assessed 42 original articles to present current knowledge regarding therapy of PPD. This review will compare treatment approaches specifically in Schamberg disease and other manifestations of pigmented purpuric dermatoses.

The potential of facial nevi in personal identification.

Forensic anthropologists dealing with personal identification (PI) of human remains have recently stressed the need to explore the potential of "secondary identifiers" for identifying victims who died in particular events for whom images often represent the main antemortem data available. Being the face the part most exposed in images, characteristics as pigmented skin lesions (PSLs), can be crucial if combined with other input. Since no data is available on frequencies and distribution of facial PSLs in the general population, this study aims at systematically collecting such data to verify their potential in PI and to open a debate on the aid that "secondary identifiers", regardless of their specific nature, can give to the identification of the deceased in specific forensic contexts. A retrospective analysis on three-dimensional facial models of 1039 Italian subjects (from 4 to 84 years old) was conducted to examine the incidence of PSLs discriminated according to size and position in well-defined facial areas. From the collected data we developed a probabilistic approach providing the likelihood ratio (LR) for two settings: (1) the relative frequencies of nevi in the various facial areas, providing the deriving compound probability of owning a certain facial PSLs pattern; and (2) codes describing the facial nevi pattern of each individual of our population, thus testing their uniqueness and so their potential in PI. The calculated LRs mostly proved high identifying strength, particularly when provided by the compound probability-based approach. Data on incidence and position of facial nevi, their generated codes, and the probabilistic approach here presented, all constitute a starting point for advancing secondary identifiers. Nonetheless, although this preliminary study proved facial PSLs as valuable and potentially useful for identification, their significance and validity should be interpreted with caution as we are still at the first theoretical step clearly based on ideal conditions, and thus further investigations are due on the limitations of their use in practical identifying settings. Therefore, being this systematic study only a preliminary one in its nature, it is recommended not to use this kind of approach until further studies will test its validity in several practical conditions.

Elastofibromatous changes in giant cell fibroma and amalgam tattoo: Unusual findings in common oral lesions.

Several cases of elastofibromatous lesion affecting the oral mucosa have been reported. Clinically, these lesions may appear as small exophytic lesions or less often as white lesions. Therefore, fibrous hyperplasia and leukoplakia are not uncommonly considered in clinical differential diagnosis. Microscopically, elastic and fibrous connective tissue deposition is seen. Rarely, elastofibromatous changes can be detected when assessing intraoral lesions, including cysts, salivary gland neoplasms, and epithelial dysplasia. Here we report two oral lesions showing elastofibromatous changes, expanding their clinicopathological spectrum. The first case was a 46-year-old man with a history of asymptomatic nodular lesion on the palate 1 year ago, diagnosed as giant cell fibroma with elastofibromatous changes. The second case was a 79-year-old woman who presented a pigmented and mildly symptomatic lesion on the mandibular alveolar mucosa several months ago, diagnosed as amalgam tattoo associated with elastofibromatous changes.

Investigation of the pathogenesis of ADAR1 gene in dyschromatosis symmetrica hereditaria.

The pathogenesis of dyschromatosis symmetrica hereditaria (DSH) has not been well defined. In this study, we sought to investigate the influence of the ADAR1 gene on DSH both in vitro and in vivo. Morpholino knockdown of adar1 in zebrafish produced phenotypes characterized by polarity changes, and abnormal migration and distribution of melanocytes. Differential expression of C-KIT and distinct patterns of apoptosis between hyperpigmented and hypopigmented areas in DSH patient were detected by means of immunohistochemical methods and TUNEL assays, respectively. This study revealed that adar1 knockdown in a zebrafish model resulted in abnormal migration and changes in the cell polarity of melanocytes, and provided novel insight into the mechanism of DSH pathogenesis.

Atypical Dyschromia in Skin of Color.

Dyschromia is a concern for many patients, especially persons of color. Postinflammatory hypopigmentation and depigmentation can affect all skin types; however, it is more apparent in those with darker skin. Some members of the dermatology community may not comprehensively understand the mechanisms of these reactions and the extent of the psychosocial effect they have on persons of color. Skin of color patients experiencing a decrease or loss of pigmentation are left with few treatment options, with no available evidence-based treatment established from a sufficient sample size. Several diseases may present with hypopigmentation and/or depigmentation despite this not being a major criterion for these conditions, including atopic dermatitis, lichen planus, discoid lupus erythematosus, polymorphous light eruption, and scleroderma. Here, we present three cases of atypical dyschromia in skin of color to highlight the underlying hypo- and depigmentation that may present with active disease and persist despite appropriate treatment.  Practice Points: 1. These cases foreground the potential for a range of dermatologic conditions to result in atypical pigment changes in persons of color. 2. Postinflammatory hypopigmentation or depigmentation may persist in skin of color despite the regression of active disease.J Drugs Dermatol. 2024;23(2):100-102.     doi:10.36849/JDD.7683.

Skin dark spot mapping and evaluation of brightening product efficacy using Line-field Confocal Optical Coherence Tomography (LC-OCT).

BACKGROUND: Facial dark spots remain a significant challenge for the cosmetic industry, in terms of providing effective treatment. Using Line-field Confocal Optical Coherence Tomography (LC-OCT), we investigated the internal structural features of photo-aging spot areas and evaluated the efficacy of a skin-brightening cosmetic product. MATERIALS AND METHODS: Twenty-six Asian female volunteers, aged between 29 and 65 years, applied a cosmetic product on their entire face twice a day for 2 months. LC-OCT was used to evaluate the dermal-epidermal junction (DEJ) undulation and the volume density of melanin in the epidermis at D0 and D56. Skin brightening and redness were also assessed by photography (SkinCam). RESULTS: Using LC-OCT technology, various microscopic dark spot morphologies, spanning from minimally deformed DEJ to complex DEJ patterns, were identified. Dark spots characterized by slight deformities in the DEJ were predominantly observed in the youngest age group, while older volunteers displayed a wavier pattern. Furthermore, a total of 44 spots were monitored to evaluate the brightening product efficacy. A statistically significant reduction in melanin volumetric density of 7.3% in the spots and 12.3% in their surrounding area was observed after 56 days of product application. In line with these results, an analysis of color parameters using SkinCam reveals a significant increase in brightening and decrease in redness in both pigmented spots and the surrounding skin following application. CONCLUSIONS: LC-OCT proves to be a valuable tool for in-depth dark spots characterization and assessment of skin brightening products, enabling various applications in the field of dermatological sciences.

Zinc deficiency or genetic mutations?-A case report of hair heterochromia in the context of MC1R genetic mutations.

Hair heterochromia may be caused by different mechanisms. At clinical work, we found a Chinese boy whose hair colour gradually turned to red. We record the diagnosis and treatment process and follow-up situation, finally find that altered hair colour phenotype is due to MC1R genetic mutations, rather than zinc deficiency. This rarely red hair colour phenotype improve our understanding of hair heterochromia caused by genetic mutations.