[Clinical and pathological analysis of 345 cases of vulvar lichen sclerosus and a preliminary study on the frequency of maintenance treatment].

Objective: To analyze and summarize the clinical and pathological characteristics, management, and efficacy of patients with vulvar lichen sclerosus (VLS) through a single center large sample study, and preliminarily to explore the frequency of maintenance treatment medication for VLS. Methods: The clinical data of VLS patients in Obstetrics and Gynecology Hospital of Fudan University from 2018 to 2021 were retrospectively collected. The clinicopathological characteristics (patients' age, course of disease, complicated disease history, family history, symptoms, signs and pathology), treatment and effects were retrospectively analyzed. The patients in the maintenance treatment stage were followed up regularly to explore the minimum frequency of individual medication to maintain the stability of the disease. Results: (1) General situation: a total of 345 patients with VLS were included in this study. The average age was (50.4±14.7) years (ranged from 8 to 84 years old), prevalence was highest in the 50-59 years group (30.1%, 104/345). Immune diseases occurred in 18.6% (33/177) of patients, 24.3% (43/177) of patients had allergic skin diseases, and 5.6% (10/177) of the patients' immediate family members had chronic vulvar pruritus or vulvar hypopigmentation. (2) Clinical features: the most common symptom was vulvar pruritus (96.1%, 196/204) among 204 patients with recorded symptoms. The most common sign was hypopigmentation of the vulva (96.3%, 206/214). The most common involved sites were labia minora (70.3%, 142/202), labia majora (67.8%, 137/202), and labial sulcus (59.4%, 120/202). The cumulative number of sites involved in 62 vulvar atrophy patients (2.7±1.1) was significantly higher than that in 152 non-atrophy patients (2.2±1.0; t=3.48, P=0.001). The course of vulvar atrophy was (9.3±8.5) years, which was significantly longer than that of non-atrophy patients [(6.6±5.6) years; t=2.04, P=0.046]. (3) Pathological features: among the 286 patients with electronic pathological sections, the most common pathological feature in the epidermis was epithelial nail process passivation (71.3%, 204/286). The common pathological features in the dermis were interstitial collagenization (84.6%, 242/286), and inflammatory cell infiltration (73.8%, 211/286). (4) Treatment: 177 patients received standardized treatment after diagnosis and were followed up regularly in our hospital. In the initial treatment stage, 26.0% (46/177) of the patients were treated with 0.05% clobetasol propionate cream, and 74.0% (131/177) of the patients were treated with 0.1% mometasone furoate ointment. The complete remission rates of the two methods were respectively 80.4% (37/46) and 74.0% (97/131), and there was no statistically significant difference (χ²=0.76, P=0.385). During maintenance treatment, 27.1% (48/177) of the patients took the medication twice a week, 35.0% (62/177) took the medication once a week, and 37.9% (67/177) took the medication once every 10 days. During follow-up after 6 months of maintenance treatment, there were no patients with recurrence of pruritus or progression of vulvar signs. Conclusions: The majority of VLS patients have itching, hypopigmentation, involvement of labia minora and labia majora, progressive atrophy, and inflammatory infiltration of dermis. Local treatments of mometasone furoate and clobetasol propionate have good initial therapeutic effects. The frequency exploration of individualized maintenance treatment could minimize the occurrence of adverse reactions when ensuring the stability of the patients' condition.

Efficacy and Safety of 5-Fluorouracil Tattooing to Repigment Idiopathic Guttate Hypomelanosis: A Split-Body Randomized Trial.

BACKGROUD: Idiopathic guttate hypomelanosis (IGH) is a common skin disorder with no standard treatment. OBJECTIVE: Assess the efficacy and safety of 5-fluorouracil (5FU) compared with saline, delivered using a tattoo machine, to repigment IGH lesions. METHODS: This split-body randomized single-blinded trial recruited adults with symmetrical IGH lesions. A tattoo machine was used to deliver 5FU in IGH lesions of 1 limb and saline in the contralateral limb. Outcomes were the number of achromic lesions 30 days after treatment compared with baseline, patient satisfaction, and local or systemic adverse events. RESULTS: Twenty-nine patients (28 women) were included. The median number of achromic lesions decreased significantly in 5FU-treated limbs (baseline: 32, interquartile range (IQR) 23-37 × post-treatment: 12, IQR 6-18, p = .000003) and saline-treated limbs (baseline: 31, IQR 24-43 × post-treatment: 21, IQR 16-31, p = .000006), but reduction was significantly more pronounced in 5FU-treated limbs ( p = .00003). All participants were satisfied or very satisfied with results on 5FU-treated limbs. There were no adverse events. CONCLUSION: 5-fluorouracil delivery using a tattoo machine was more effective than saline to repigment IGH lesions, with high patient satisfaction and no adverse events.Clinicaltrials.gov : NCT02904564.

Copper chelation by d-penicillamine alleviates melanocyte death induced by rhododendrol without inhibiting tyrosinase.

Oxidative metabolism of rhododendrol (RD), a skin-whitening ingredient, by tyrosinase has caused leukoderma in a certain population of Japanese consumers. Toxic RD metabolites and reactive oxygen species are proposed causes for the melanocyte death. However, the mechanism by which reactive oxygen species are produced during RD metabolism remains elusive. Some phenolic compounds are known to act as suicide substrates for tyrosinase, resulting in release of a copper atom and hydrogen peroxide during its inactivation. We hypothesized that RD may be a suicide substrate for tyrosinase and that the released copper atom may be responsible for the melanocyte death through hydroxyl radical production. In line with this hypothesis, human melanocytes incubated with RD showed an irreversible decrease in tyrosinase activity and underwent cell death. A copper chelator, d-penicillamine, markedly suppressed the RD-dependent cell death without significantly affecting the tyrosinase activity. Peroxide levels in RD-treated cells were not affected by d-penicillamine. Given the unique enzymatic properties of tyrosinase, we conclude that RD acted as a suicide substrate and resulted in release of a copper atom and hydrogen peroxide, which would collectively impair melanocyte viability. These observations further imply that copper chelation may alleviate chemical leukoderma caused by other compounds.

The toxicity of 4-tert-butylphenol in early development of zebrafish: morphological abnormality, cardiotoxicity, and hypopigmentation.

Endocrine disrupting effects of 4-tert-butylphenol (4-t-BP) are well described in literature. However, the evidence regarding developmental toxic effect of 4-t-BP is still vague. The present study used zebrafish as a model organism to investigate the toxic effect of 4-t-BP. The results showed that 4-t-BP exposure at 3, 6, and 12 µM induced developmental toxicity in zebrafish, such as reduced embryo hatchability and abnormality morphological. Flow cytometry analysis showed that 4-t-BP also induced intracellular ROS production. 4-t-BP induced changes in the expression of genes related to cardiac development and melanin synthesis, resulting in cardiotoxicity and hypopigmentation. 4-t-BP also caused oxidative stress, and initiated apoptosis through p53-bcl-2/bax-capase3 pathway. Integrative biomarker response analysis showed time- and dose-dependent effects of 4-t-BP on oxidative damage and developmental toxicity in zebrafish embryos. Overall, this study contributed to a comprehensive evaluation of the toxicity of 4-t-BP, and the findings provided new evidence for early warning of residues in aquatic environments.

Fentanyl transdermal patches induced chemical leucoderma.

Chemical leucoderma is defined as hypopigmentation or vitiligo-like hypomelanosis caused by repeated chemical exposure, and the diagnosis can be made clinically. Chemical leucoderma induced by fentanyl transdermal patches is rare. This case report involves a 53-year-old man with chronic back pain caused by herniated nucleus pulposus at the L4-L5 level. The patient had used fentanyl transdermal patches for about 2 years. Depigmented lesions were observed in the areas where fentanyl transdermal patches had been applied. Chemical leucoderma was the most likely diagnosis. There remains a debate regarding whether there is a fentanyl dose-response relationship and whether the duration of exposure is relevant. Spontaneous repigmentation may occur after discontinuing the chemical exposure, and follow-ups are recommended to monitor whether spontaneous repigmentation occurs. Additionally, several treatment options have been proposed as specific treatments for chemical leucoderma, including psoralens, corticosteroids, calcineurin inhibitors, immunosuppressive agents and phototherapy.

A cell-based evaluation of human tyrosinase-mediated metabolic activation of leukoderma-inducing phenolic compounds.

BACKGROUND: Chemical leukoderma is a skin depigmentation disorder induced through contact with certain chemicals, most of which have a p-substituted phenol structure similar to the melanin precursor tyrosine. The tyrosinase-catalyzed oxidation of phenols to highly reactive o-quinone metabolites is a critical step in inducing leukoderma through the production of melanocyte-specific damage and immunological responses. OBJECTIVE: Our aim was to find an effective method to evaluate the formation of o-quinone by human tyrosinase and subsequent cellular reactions. METHODS: Human tyrosinase-expressing 293T cells were exposed to various phenolic compounds, after which the reactive o-quinones generated were identified as adducts of cellular thiols. We further examined whether the o-quinone formation induces reductions in cellular GSH or viability. RESULTS: Among the chemicals tested, all 7 leukoderma-inducing phenols/catechol (rhododendrol, raspberry ketone, monobenzone, 4-tert-butylphenol, 4-tert-butylcatechol, 4-S-cysteaminylphenol and p-cresol) were oxidized to o-quinone metabolites and were detected as adducts of cellular glutathione and cysteine, leading to cellular glutathione reduction, whereas 2-S-cysteaminylphenol and 4-n-butylresorcinol were not. In vitro analysis using a soluble variant of human tyrosinase revealed a similar substrate-specificity. Some leukoderma-inducing phenols exhibited tyrosinase-dependent cytotoxicity in this cell model and in B16BL6 melanoma cells where tyrosinase expression was effectively modulated by siRNA knockdown. CONCLUSION: We developed a cell-based metabolite analytical method to detect human tyrosinase-catalyzed formation of o-quinone from phenolic compounds by analyzing their thiol-adducts. The detailed analysis of each metabolite was superior in sensitivity and specificity compared to cytotoxicity assays for detecting known leukoderma-inducing phenols, providing an effective strategy for safety evaluation of chemicals.

Stellate Hypopigmentation in a Pediatric Patient After Treatment with Intralesionally-Injected Corticosteroid.

BACKGROUND Several factors contribute to keloids in post-operative patients, including skin mechanics, genetics, and inflammatory processes. One of the most widely used treatment modalities for keloidal scars involves the intralesional injection of corticosteroids, such as triamcinolone acetonide (TAC). TAC is a first-line treatment option for keloids due to its proven efficacy and effectiveness in reducing collagen synthesis, glycosaminoglycan synthesis, inflammatory processes, and proliferation of fibroblasts. Some common adverse effects of intralesional corticosteroid injection include localized hypopigmentation, depigmentation, skin atrophy, and lipoatrophy. CASE REPORT In this report, we describe the case of a 3-year-old African American male patient who presented for dermatologic evaluation of a diffused stellate hypopigmentation attributed to intralesional corticosteroid injection following a keloid removal. Specifically, we summarize this case's clinical features, diagnosis, and outcomes. CONCLUSIONS The case illustrates self-limiting hypopigmentation that repigmented successfully without clinical intervention. Although previous reports of corticosteroid injections' adverse effects resulting in hypopigmentation have been published, this condition is uncommon or poorly reported in pediatric patients. This report aims to contribute to our understanding of the effects of administering corticosteroids in pediatric patients by virtue of diversifying the cases reported in the currently available literature.

A framework to mitigate the risk of chemical leukoderma: Consumer products.

Chemical leukoderma is an acquired depigmentation of the skin caused by repeated exposure to specific agents damaging to epidermal melanocytes. Case reports of chemical leukoderma have been associated with some consumer products. To date, there are no well-accepted approaches for evaluating and minimizing this risk. To this end, a framework is presented that evaluates the physical and chemical characteristics of compounds associated with chemical leukoderma and employs structure-activity relationship (SAR) read-across and predictive metabolism tools to determine whether a compound is at increased risk of evoking chemical leukoderma. In addition to in silico approaches, the testing strategy includes in chemico quinone formation and in vitro melanocyte cytotoxicity assays to dimension the risk as part of an overall weight of evidence approach to risk assessment. Cosmetic ingredients raspberry ketone, undecylenoyl phenylalanine, tocopheryl succinate, p-coumaric acid, resveratrol, resveratrol dimethyl ether, sucrose dilaurate, tranexamic acid, niacinamide and caffeic acid are evaluated in this framework and compared to positive controls rhododendrol and hydroquinone. Overall, this framework is considered an important step toward mitigating the risk of chemical leukoderma for compounds used in consumer products.

Adverse reactions of ALA-PDT for the treatment of cutaneous diseases: A retrospective study.

BACKGROUND: 5-Aminolaevulinic acid photodynamic therapy (ALA-PDT) is an effective therapy for cutaneous diseases, such as precancers, superficial non melanoma skin cancers and certain inflammatory or viral conditions. However, the absence of a complete picture of adverse reactions limits the promotion of ALA-PDT. OBJECTIVE: To systemically investigate the detailed evidence of adverse reactions relating to ALA-PDT for skin diseases. METHODS: A retrospective study performed at the Shanghai Skin Disease Hospital. RESULTS: In the retrospective study, 439 patients were included. Incidences of adverse reactions, including in-treatment pain (98.8%), erythema (92.4%), edema (35.0%), exudation (23.0%), hyperpigmentation (27.3%) were clarified. Edema was more common in female patients (P<0.05). Patients with HPV-related skin diseases were more likely to suffer erythema, edema or exudation (P<0.05). Hyperpigmentation was more likely to occur in skin appendage disorders (P<0.05). Fever (2.4%) and hypopigmentation (1.9%) are two neglected adverse reactions analyzed in detail. Fever is more prevalent in female patients. Hypopigmentation occurred predominantly in elderly with skin cancer or precancerosis lesions. CONCLUSION: The results outline detailed information about the adverse reactions, including systemic reactions following ALA-PDT, assisting dermatologists in predicting and managing adverse reactions for greater efficacy and higher patient satisfaction.

A case of palmar hypopigmentation induced by capecitabine in a gastrointestinal cancer patient.

INTRODUCTION: Capecitabine is an antimetabolite antineoplastic agent widely used in the treatment gastrointestinal cancers. The common frequently reported cutaneous adverse drug reaction associated with capecitabin are a palmar-plantar erythrodysesthesia syndrome, rash and hyperpigmentation. This case reports a capecitabine-induced palmar hypopigmentation. CASE REPORT: We report the case of a 74-years old patient with jejunum adenocarcinoma treated by capecitabine. The patient developed a pseudo-vitiligo after 2 cycles capecitabine and without history of cutaneous disorders. The skin lesions were characterized with skin hypopigmentation on both hands.Management and outcome: The hypopigmentation slowly recovered after capecitabine discontinuation. CONCLUSION: This is the first described case of pseudo-vitiligo induced by capecitabine. This impressive but non-severe adverse effect should be known by oncologists and oncology pharmacists to reassure the patients in particular about the possible recovery after discontinuation of capecitabine.