Topical CCL3 Is Well-Tolerated and Improves Liver Function in Diabetic Mice: Evidence from a 14-Day Toxicity Study
Deepa Dehari, Rajalekshmy Padmakumari, Getnet Tesfaw
et al.
Diabetic wounds exhibit impaired immune function, delayed neutrophils recruitment, and heightened infection risk which compromises early infection control and delays healing. We have demonstrated that topical CCL3 treatment restores neutrophil influx, reduces bacterial infection by ~99%, and accelerates wound healing in diabetic mice. As per Food and Drug Administration (FDA) Guidelines for Investigational New Drug (IND), we conducted a 14-day acute toxicity study in diabetic mice following a single topical administration of CCL3 at effective low dose (1 µg) and high dose (10 µg) per wound. Mice were monitored for clinical signs, body weight, and food intake throughout the study period. On day 14, serum biochemistry (ALT, AST, BUN, creatinine, metabolic markers) and histopathology of major organs (liver, kidney, heart, lungs, spleen) were assessed. CCL3-treated diabetic mice exhibited no adverse clinical effects. Hematological and biochemical parameters remained within normal limits, and histopathological analyses revealed no additional organ injury in CCL3-treated groups compared to diabetic control mice. Intriguingly, CCL3-treated mice showed improved ALT levels and reduced hepatic pathology, suggesting hepatoprotective effects and reduced serum IgG, indicating reduced systemic inflammation. Overall, our study demonstrates that diabetic mice tolerate topical CCL3 at doses up to 10 times the effective therapeutic concentration without evidence of systemic organ toxicity. These findings provide strong preclinical support for the translational development of CCL3 as a novel therapy for diabetic wound care.
Arginine Metabolic Disruption Impairs Hair Regeneration via ROS‐Mediated Inactivation of mTOR Signaling in Androgenetic Alopecia
Shixin Duan, Guo Li, Yanji Chu
et al.
Abstract Androgenetic alopecia (AGA), a pervasive hair loss disorder, lacks effective therapies due to incomplete pathogenic understanding. Growing evidence suggests a connection between AGA and metabolic disorders. Leveraging unbiased serum metabolomics, a strikingly differentiated metabolic signature in AGA patients compared to healthy controls is identified, with arginine deficiency exhibiting the most pronounced reduction among all amino acids. Concomitant downregulation of the arginine transporter SLC7A1 and upregulation of arginine catabolic enzyme ARG2 in balding HFs are further identified, collectively driving localized arginine scarcity through impaired uptake and accelerated catabolism. This metabolic perturbation triggers pathological reactive oxygen species (ROS) accumulation in hair follicles (HFs), which, in turn, inhibits mTOR signaling and impairs HF regeneration. Conversely, arginine restoration via exogenous supplementation or inhibiting arginine‐to‐ornithine conversion with ARG2 siRNA rescues hair growth in both murine AGA model and cultured human HFs. Most importantly, a microneedle‐based delivery system for targeted dermal arginine replenishment demonstrates robust therapeutic efficacy in humanized AGA models. This work establishes arginine insufficiency as a core pathogenic driver in AGA and validates localized metabolic correction as a promising clinical strategy.
Predictors of Patient Satisfaction in Atopic Dermatitis
Bruno Halioua, Charles Taieb, Stéphanie Merhand
et al.
Nail lesions in red squamous lichen planus: a review of the literature
R. V. Saranyk, T. A. Gosteva
Background. Lichen planus is a chronic inflammatory disease affecting the mucous membranes, skin and its appendages. Nail lesions in lichen planus are quite common, which leads to a negative psychological and physical impact on patients. In addition to nail lesions against the background of the underlying disease, there are also isolated forms in which only the nail plates are affected in patients with lichen planus without involving the skin and mucous membranes. Changes in the nail plates in lichen planus can be irreversible, destroying the nail plate itself and the entire nail apparatus.Objective. The aim of this article was to study the most common nail lesions in lichen planus.Materials and methods. In the period from April to July 2024, we analyzed publications from the PubMed and eLibrary databases devoted to nail lesions in lichen planus. The search queries included "Nail lichen planus", "Lichen planus", "Nail lichen planus", "Trachionychia", "Twenty nail dystrophy", "Dermoscopy nail lichen planus".Results. The study revealed that the most common nail lesions in lichen planus are longitudinal grooves, general dystrophic changes in the nails in the form of their fragility, onychorrhexis and trachyonychia. It was also noted that lichen planus is characterized by severe irreversible changes in the nails, such as anonychia and pterygium. In the course of this work, we noted the evolution of pathological changes in the nails in lichen planus. This observation can be useful in the diagnostic search and choice of treatment tactics in the early stages of the lesion.Conclusion. Timely diagnosis of pathological changes in the nails in lichen planus is crucial in choosing patient management tactics. The development of irreversible lesions of the nail plates in lichen planus should be prevented by treating earlier pathological changes.
Change of guard
B M Shashikumar
Ectoparasitic infestations among patients attending the dermatology OPD: A hospital-based study
Harihar Adhikari, Uttara Gautam, Prabhat Singh Rajput
et al.
Background: Ectoparasites are organisms that live in the skin for varying lengths of time and can cause disease. These infestations are highly prevalent in poor and underdeveloped areas. There is a paucity of studies regarding their prevalence in rural areas like the upper Karnali region of Nepal. We conducted a hospital-based study to know the burden of these infestations in the area.
Methods: A hospital-based descriptive study was done from March 2023 to February 2024. Data were collected from medical records of the dermatology outpatient department (OPD) and all the clinically diagnosed cases of ectoparasitic infestation were studied. Data were presented as frequency and percentage; seasonal pattern of the diseases was also reported.
Results: A total of 6,698 patients attended dermatology OPD during the study period, among whom 1340 had ectoparasitic infestations, resulting in a proportion of 20.01% in this group. Two infestations were found, namely, scabies and pediculosis capitis, with a proportion of 18.36% and 1.65%, respectively. Females represented almost half of the patients with ectoparasitic infestations (49.63%), but about 98% with pediculosis. Ectoparasitic infestation was most common in children aged 0–9 years, i.e., 31.31% and pediculosis was most common in children of 10–19 years (31.81%). Ectoparasitic infestations (41.94%), both scabies (41.7%) and pediculosis (44.55%) were most common during the monsoon season.
Conclusion: The ectoparasitic infestations were common the patients presenting to the hospital. Scabies was the most common ectoparasitic infestation and a major public health problem.
A Systematic Review on Clinical Evidence for Topical Metformin: Old Medication With New Application
Kimia Afshar, Sara Adibfard, Mohammad Hossein Nikbakht
et al.
ABSTRACT Background and Aims Metformin is a widely used oral agent for controlling diabetes mellitus, but it also has other therapeutic benefits for various conditions. In addition, conventional oral metformin, and topical metformin have been used in, in‐vitro studies in the treatment of acne, psoriasis, wound healing, and and so forth. While topical metformin has shown promising results in animal studies, there is limited data on its effectiveness in humans. Our study aims to summarize the clinical findings of human studies on the efficacy of topical metformin. Methods This review followed the PRISMA standards and systematically searched multiple databases using specific keywords. The relevant articles were selected according to the inclusions and exclusions criteria. Results Our search strategy yielded 1831 articles, after screening, 27 articles met our inclusion criteria which were: human studies, articles published before the start of the search, and topical forms of metformin. We also identified three additional relevant articles through reference checking. Therefore, our systematic review included a total of 30 articles. Conclusion Most commonly, topical metformin has been studied in dentistry and dermatology. In dentistry, it has been found effective in treating periodontitis when used with scaling and root planning. Combining metformin with platelet‐rich fibrin can provide better benefits for furcation‐involved teeth, and coating dental implants with metformin improves osseointegration. In dermatology, studies on melasma have had inconsistent results. Topical metformin has also shown promising results in promoting hair regrowth, wound healing, and acne vulgaris, suggesting it could be a potential treatment option for these conditions.
Genodermatoses Picture: Difficulties Faced And Way Forward in Nepal
Niraj Parajuli, Rabindra Baskota, Ritu Jain
Genodermatoses are group of genetic disorders that present with cutaneous manifestations. The exact prevalence on many of these conditions are unknown due to its rarity, need of specialized tests for diagnosis and lack of proper reporting system. Most of the patients are faced with life-long disability and associated stigma. There is a need for specialized centers for proper diagnosis of these conditions and a very elaborated yet simple reporting system in Nepal. These rare conditions should be kept in priority by the government in align with the sustainable development goals to ensure healthy-lives and promote well-being for all. A wider engagement of patient-led support groups might be useful in providing necessary information on the disease to the general population and alleviate the stigma associated with these diseases.
Keywords: Epidermolysis bullosa; genodermatoses; rare diseases; Nepal
Identification of anoikis-related subtypes and development of risk stratification system in skin cutaneous melanoma
Jun Tian, Zi-jian Cao, Yuan Zhang
et al.
Background: Anoikis, a form of apoptosis induced by cell detachment, plays a key role in cancer metastasis. However, the potential roles of anoikis-related genes (ARGs) in assessing the prognosis of skin cutaneous melanoma (SKCM) and the tumor microenvironment (TME) remain unclear. Methods: The data from TCGA corresponding to transcriptomic expression patterns for patients with SKCM were downloaded and utilized to screen distinct molecular subtypes by a non-negative matrix factorization algorithm. The prognostic signature was constructed by least absolute shrinkage and selection operator (LASSO) Cox regression and was validated in SKCM patients from the GEO cohort. Moreover, the relationship of the ARG_score with prognosis, tumor-infiltrating immune cells, gene mutation, microsatellite instability (MSI), and immunotherapy efficacy. Results: We screened 100 anoikis-related differentially expressed genes between SKCM tissues and normal skin tissues, which could divide all patients into three different subtypes with significantly distinct prognosis and immune cell infiltration. Then, an anoikis-related signature was developed based on subtype-related DEGs, which could classify all SKCM patients into low and high ARG_score groups with differing overall survival (OS) rates. ARG_score was confirmed to be a strong independent prognostic indicator for SKCM patients. By combining ARG_score with clinicopathological features, a nomogram was constructed, which could accurately predict the individual OS of patients with SKCM. Moreover, low ARG_score patients presented with higher levels of immune cell infiltration, TME score, higher tumor mutation burden, and better immunotherapy responses. Conclusions: Our comprehensive analysis of ARGs in SKCM provides important insights into the immunological microenvironment within the tumor of SKCM patients and helps to forecast prognosis and the response to immunotherapy in SKCM patients, thereby making it easier to tailor more effective treatment strategies to individual patients.
Science (General), Social sciences (General)
Evaluation of the adverse dermatological effects due to frequent handwashing accompanying the COVID-19 pandemic: A cross-sectional study
Fawwaz F Alshammarie, Asma A Aloufi, Laila M Alshammari
et al.
Background: Washing hands regularly is among the key suggestions the World Health Organization (WHO) made for the general public. However, intensive handwashing can cause hand dermatitis and is associated with illnesses such as methicillin-resistant Staphylococcus aureus infection. Purpose: The purpose of this study was to assess the prevalence and consequences of handwashing during the COVID-19 pandemic. Methods: This descriptive cross-sectional study was carried out in a convenience sample of 5000 participants in Saudi Arabia and captured participant handwashing practices, glove use, and potential dermatological side effects from regular handwashing. Data were obtained using a pretested questionnaire and then analyzed using the Statistical Package for the Social Sciences (SPSS), version 24. Results: The majority of participants (80%) repeatedly washed their hands with sanitizers and disinfectants. Only 31% used moisturizing soap, and 19% used warm water. A quarter of participants washed their hands for 20–30 s, and roughly 26% washed their hands 1–5 times every day. Moreover, 27% of participants experienced contact dermatitis on their skin because of the use of gloves and sterilizers. Conclusion: The repeated use of alcohol-based sanitizers in handwashing is associated with a high risk of eczema in about 27%. Decreasing the number of times they wash their hands and the use of detergents while using more emollients and nonpowdered gloves, may be helpful for avoiding hand dermatitis.
Skin organoids: A new human model for developmental and translational research
Jiyoon Lee, Karl R. Koehler
Culturing skin cells outside of the body has been a cornerstone of dermatological investigation for many years; however, human skin equivalent systems typically lack the full complexity of native skin. Notably, skin appendages, such as hair follicles and sweat glands, remain a challenge to generate or maintain in cell cultures and reconstruct in damaged skin. Recent work from our lab has demonstrated methods for generating appendage‐bearing skin tissue—known as skin organoids—from pluripotent stem cells. Here, we will summarize this work and other related works, and then discuss the potential future applications of skin organoids in dermatological research.
Patrón de dermatitis de cabeza y cuello en pacientes tratados con dupilumab: diagnóstico diferencial y tratamiento
F.J. Navarro-Triviño, R. Ruiz-Villaverde
Dermatology, Internal medicine
Behçet Disease with Generalized Polymorphous Cutaneous Lesions: A Case Report
Li-Wei Wang, Ling-Ling Luo, Wei Zhang
et al.
Introduction:. Behçet disease is a chronic multisystem vasculitis disease, however generalized polymorphous cutaneous lesions are uncommon.
Here, we reported a case of Behçet disease with multiple parts of the body and complex lesions, which may lead to misjudging in clinical diagnosis.
Case report:. A 69-year-old man presented with a seven-year history of recurrent generalized polymorphous mucocutaneous lesions (erythematous papules, nodules, ulcers, and necrosis) over his entire body, and the lesions had been painful for the past three years. Based on the past medical history, clinical presentation, histological examination excluded other diseases, and the 2014-amended International Criteria for Behget disease, the patient had a score of 6 points and was diagnosed as Behçet disease.
Discussion:. The common clinical feature in patients with Behçet syndrome is the presence of recurrent and usually painful mucocutaneous ulcers. Other clinical manifestations of this disorder are more variable among different patients. A diagnosis of generalized polymorphous cutaneous lesions should remain on the list of differential diagnosis of Behçet disease after excluding other diseases.
Conclusion:. The mucocutaneous lesions of Behçet disease are often preceded by other manifestations, and timely diagnosis may benefit early treatment and prognosis.
The journey of CAR-T therapy in hematological malignancies
Junru Lu, Guan Jiang
Abstract Chimeric antigen receptor T (CAR-T) cells therapy has revolutionized the treatment paradigms for hematological malignancies, with multi-line therapy-refractory patients achieving durable complete remissions (CR) and relatively high objective response rate (ORR). So far, many CAR-T products, such as Kymriah, Yescarta and Tecartus, have been developed and got the unprecedented results. However, some patients may relapse afterwards, driving intense investigations into promoting the development of novel strategies to overcome resistance and mechanisms of relapse. Notable technical progress, such as nanobodies and CRISPR-Case9, has also taken place to ensure CAR-T cell therapy fully satisfies its medical potential. In this review, we outline the basic principles for the development and manufacturing processes of CAR-T cell therapy, summarize the similarities and differences in efficacy of different products as well as their corresponding clinical results, and discuss CAR-T immunotherapy combined with other clinical effects of drug therapy.
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Cost Minimization Analysis of a Teledermatology Triage System in a Managed Care Setting.
Adam Zakaria, T. Miclau, T. Maurer
et al.
Importance Teledermatology (TD) enables remote triage and management of dermatology patients. Previous analyses of TD systems have demonstrated improved access to care but an inconsistent fiscal impact. Objective To compare the organizationwide cost of managing newly referred dermatology patients within a TD triage system vs a conventional dermatology care model at the Zuckerberg San Francisco General Hospital and Trauma Center (hereafter referred to as the ZSFG) in California. Design, Setting, and Participants A retrospective cost minimization analysis was conducted of 2098 patients referred to the dermatology department at the ZSFG between June 1 and December 31, 2017. Intervention Implementation of the TD triage system in January 2015. Main Outcomes and Measures The main outcome was mean cost to the health care organization to manage newly referred dermatology patients with or without TD triage. To estimate costs, decision-tree models were constructed to characterize possible care paths with TD triage and within a conventional dermatology care model. Costs associated with primary care visits, dermatology visits, and TD visits were then applied to the decision-tree models to estimate the mean cost of managing patients following each care path for 6 months. The mean cost for each visit type incorporated personnel costs, with the mean cost per TD consultation also incorporating software implementation and maintenance costs. Finally, ZSFG patient data were applied within the models to evaluate branch probabilities, enabling calculation of mean cost per patient within each model. Results The analysis captured 2098 patients (1154 men [55.0%]; mean [SD] age, 53.4 [16.8] years), with 1099 (52.4%) having Medi-Cal insurance and 879 (41.9%) identifying as non-White. In the decision-tree model with TD triage, the mean (SD) cost per patient to the health care organization was $559.84 ($319.29). In the decision-tree model for conventional dermatology care, the mean (SD) cost per patient was $699.96 ($390.24). Therefore, the TD model demonstrated a statistically significant mean (SE) cost savings of $140.12 ($11.01) per patient. Given an annual dermatology referral volume of 3150 patients, the analysis estimates an annual savings of $441 378. Conclusions and Relevance Implementation of a TD triage system within the dermatology department at the ZSFG was associated with cost savings, suggesting that managed health care settings may experience significant cost savings from using TD to triage and manage patients.
Case Report: Circulating Anti-SARS-CoV-2 Antibodies Do Not Cross-React With Pemphigus or Pemphigoid Autoantigens
Michael Kasperkiewicz, Marta Bednarek, Stefan Tukaj
It is hypothesized that SARS-CoV-2 has the potential to elicit autoimmunity due to molecular mimicry between immunogenic proteins of the virus and human extracellular molecules. While in silico and in vitro evaluation of such immune cross-reactivity of human antibodies to SARS-CoV-2 proteins with several different tissue antigens has been described, there is limited information specifically pertaining to the immunological effects of COVID-19 and vaccines against SARS-CoV-2 on the development of autoimmune bullous diseases (AIBDs). Twelve seropositive post-COVID-19 individuals and 12 seropositive healthy volunteers who received two doses of the mRNA COVID-19 vaccine from Pfizer-BioNTech have been included in this case series investigation. Serum samples of these blood donors were tested for autoantibodies to the main immunobullous autoantigens, i.e., desmoglein 1, desmoglein 3, envoplakin, BP180, BP230, and type VII collagen. Our study revealed that none of the 24 anti-SARS-CoV-2 IgG-positive subjects had concomitant antibody reactivity with any of the tested autoantigens. These results argue against a relationship between SARS-CoV-2 infection/vaccines and AIBDs with respect to disease-triggering antibody cross-reactivity.
The uses of naltrexone in dermatologic conditions.
Brigette Lee, D. Elston
BACKGROUND Naltrexone in standard and reduced doses is efficacious in many inflammatory and acantholytic disorders. OBJECTIVE We summarized the current data of naltrexone that are relevant to dermatologic practice. METHODS An English language PubMed literature search was performed using the terms naltrexone, low-dose naltrexone, Hailey-Hailey, psoriasis, lichen planopilaris, alopecia, opioid, opioid receptor, treatment, dermatology, monitoring, side effect, skin, pruritus, cutaneous, acantholytic, and Darier. RESULTS Opioid receptors are found throughout the skin and affect cell proliferation, migration, and adhesion. μ Opioid receptors have been found in all layers of the epidermis, while δ receptors are concentrated at cell junctions and can reduce desmoglein expression. Typical doses of naltrexone result in continuous binding to receptors. Low doses result in intermittent blockade with increased ligand and receptor expression, potentiating their effect. LIMITATIONS Our review was restricted to the English language literature. CONCLUSION Naltrexone affects inflammation, cell adhesion, and keratinocyte proliferation and migration. While low-dose naltrexone has demonstrated efficacy in treating patients with Hailey-Hailey disease, further dose-ranging studies are needed. Data suggest that naltrexone could be helpful in the treatment of pruritus and a variety of inflammatory and acantholytic skin diseases that are refractory to other treatments. At higher doses, liver function tests should be monitored on a periodic basis.
S2k guidelines for the treatment of psoriasis in children and adolescents – Short version part 2
Lisa Eisert, M. Augustin, Sabine Bach
et al.
The present guidelines are aimed at residents and board‐certified physicians in the fields of dermatology, pediatrics, pediatric dermatology and pediatric rheumatology as well as policymakers and insurance funds. They were developed by dermatologists and pediatric dermatologists in collaboration with pediatric rheumatologists using a formal consensus process (S2k).
Corynebacterium tuberculostearicum, a human skin colonizer, induces the canonical nuclear factor‐κB inflammatory signaling pathway in human skin cells
Mohammed O. Altonsy, Habib A. Kurwa, Gilles J. Lauzon
et al.
Abstract Introduction Corynebacterium tuberculostearicum (C. t.) is a ubiquitous bacterium that colonizes human skin. In contrast to other members of the genus Corynebacterium, such as toxigenic Corynebacterium diphtheriae or the opportunistic pathogen Corynebacterium jeikeium, several studies suggest that C. t. may play a role in skin health and disease. However, the mechanisms underlying these effects remain poorly understood. Methods To investigate whether C. t. induces inflammatory pathways in primary human epidermal keratinocytes (HEKs) and human cutaneous squamous carcinoma cells (SCCs), cell culture, reverse transcription‐polymerase chain reaction (PCR), enzyme‐linked immunosorbent assay, immunofluorescence microscopy, Western blot, chromatin immunoprecipitation‐PCR, small interfering RNA knockdown and luciferase reporter expression system were used. Results Herein, we demonstrate that C. t. upregulates the messenger RNA (mRNA) and protein levels of inflammatory mediators in two human skin cell lines, HEKs and SCCs. We further show activation of the canonical nuclear factor‐κB (NF‐κB) pathway in response to C. t. infection, including phosphorylation of the inhibitor of κB (IκB), the nuclear translocation of NF‐κB subunit (NF‐κB‐P65) and the recruitment of NF‐κB‐P65 and RNA polymerase to the NF‐κB response elements at the promoter region of the inflammatory genes. Lastly, the data confirm that C. t.‐induced tumor necrosis factor mRNA expression in HEKs is toll‐like receptor 2 (TLR2) dependent. Conclusion Our results offer a mechanistic model for C. t.‐induced inflammation in human keratinocytes via TLR2 and activation of IκB kinase and downstream signaling through the canonical NF‐κB pathway. Relevance to chronic inflammatory diseases of the skin and cutaneous oncology is discussed.
Immunologic diseases. Allergy
Guidelines for the use of local anesthesia in office-based dermatologic surgery.
D. Kouba, Matteo C. LoPiccolo, Murad Alam
et al.