The Diagnosis and Management of Cutaneous Metastases from Melanoma

Melanoma is one of the deadliest skin tumors, accounting for almost 90% of skin cancer mortality. Although immune therapy and targeted therapy have dramatically changed the prognosis of metastatic melanoma, many patients experience disease progression despite the currently available new treatments. Skin metastases from melanoma represent a relatively common event as first sign of advanced disease or a sign of recurrence. Skin metastases are usually asymptomatic, although in advanced stages, they can present with ulceration, bleeding, and superinfection; furthermore, they can cause symptoms related to compression on nearby tissues. Treatments vary from simple surgery resections to topical or intralesional local injections, or a combination of these techniques with the most recent systemic immune or target therapies. New research and studies should focus on the pathogenesis and molecular mechanisms of the cutaneous metastases of melanoma in order to shed light on the mechanisms underlying the different behavior and prognoses of different patients

Green Nail Syndrome Treated with Ozenoxacin: Two Case Reports

Green nail syndrome (GNS) is a persistent greenish pigmentation of the nail plate, originally described in 1944 by Goldman and Fox, due to Pseudomonas aeruginosa infection. Recently, pulmonary co-infection of P. aeruginosa and Achromobacter spp. has been described in patients with cystic fibrosis. Achromobacter xylosoxidans is a multidrug-resistant (MDR) pathogen involved in lung and soft tissue skin infections. Both Achromobacter xylosoxidans and P. aeruginosa are mainly found in humid environments or in water. There are no recognized co-infections due to P. aeruginosa and A. xylosoxidans in the skin and appendages. We describe two cases of GNS, the first due to P. aeruginosa associated with Achromobacter xylosoxidans; the other due to MDR P. aeruginosa, both successfully treated with topical ozenoxacin 1% cream daily for 12 weeks. The clinical management of GNS can be confusing, especially when the bacterial culture result is inconsistent or when non-Pseudomonas bacteria are isolated. In our case, due to the co-infection of P. aeruginosa and Achromobacter spp., local treatment with ozenoxacin - the first nonfluorinated quinolone - could be a safe and effective treatment in case of MDR nail infections. Further studies are required to evaluate clinical isolation from nail infections and the co-presence of P. aeruginosa and A. xylosoxidans

Preliminary Evidence of Efficacy, Safety, and Treatment Satisfaction with Tirbanibulin 1% Ointment: A Clinical Perspective on Actinic Keratoses

background: actinic keratosis is a common precancerous skin lesion that can progress into invasive squamous cell carcinomas. many topical treatments for actinic keratoses often have poor tolerability and prolonged duration. Tirbanibulin is a novel synthetic drug with potent antitumor and antiproliferative activities. methods: we conducted a single-center, prospective and observational study using tirbanibulin ointment on a 25 cm2 area for 5 consecutive days on 30 participants with AKs on the face or scalp. They were followed for at least 57 days to assess the safety profile and efficacy of the drug as well as treatment satisfaction. we evaluated six signs of local skin reaction (LSR): erythema, scaling, crusting, swelling, blisters/pustules, and erosions/ulcerations, grading the severity as mild, moderate, or severe. The effectiveness was evaluated both clinically and dermoscopically. the treatment satisfaction was assessed using the treatment satisfaction questionnaire for medication (TSQM 1.4). results: on day 57, 70% of the patients showed a complete clinical and dermoscopic response. The highest scores obtained from the TSQM 1.4 were more evident in the convenience and side effects domains. most LSRs, including erythema (83.3%), scaling (30%), and swelling (3.3%), occurred on day 8 but resolved spontaneously. Conclusion: Tirbanibulin is a viable therapeutic option with a short regimen treatment and good tolerability, which favors therapy adherence

Role of Neutrophil-to-Lymphocyte Ratio (NLR) in Patients with Mycosis Fungoides

background: the neutrophil/lymphocyte ratio (NLR) at baseline has been demonstrated to correlate with higher stages of disease and to be a prognostic factor in numerous cancers. however, its function as a prognostic factor for mycosis fungoides (MF) has not been yet clarified. objective: our work aimed to assess the association of the NLR with different stages of MF and to outline whether higher values of this marker are related to a more aggressive MF.methods: we retrospectively calculated the NLRs in 302 MF patients at the moment of diagnosis. the NLR was obtained using the complete blood count values.results: the median NLR among patients with early stage disease (low-grade IA-IB-IIA) was 1.88, while the median NLR for patients with high-grade MF (IIB-IIIA-IIIB) was 2.64. statistical analysis showed positive associations of advanced MF stages with NLRs higher than 2.3. conclusions: our analysis demonstrates that the NLR represents a cheap and easily available parameter functioning as a marker for advanced MF. this might guide physicians in recognizing patients with advanced stages of disease requiring a strict follow-up or an early treatment

Pharmacological inhibition of PDGF-C/neuropilin-1 interaction: A novel strategy to reduce melanoma metastatic potential

activation of neuropilin-1 (NRP-1) by platelet derived growth factor (PDGF)-C sustains melanoma invasiveness. therefore, in the search of novel agents capable of reducing melanoma spreading, PDGF-C/NRP-1 interaction was investigated as a potential druggable target. since the PDGF-C region involved in NRP-1 binding is not yet known, based on the sequence and structural homology between PDGF-C and vascular endothelial growth factor-A (VEGF-A), we hypothesized that the NRP-1 b1 domain region involved in the interaction with VEGF-A might also be required for PDGF-C binding. hence, this region was selected from the protein crystal structure and used as target in the molecular docking procedure. In the following virtual screening, compounds from a drug bank database were used as query ligands to identify agents potentially capable of disrupting NRP-1/PDGF-C interaction. among the top 45 candidates with the highest affinity, five drugs were selected based on the safety profile, lack of hormonal effects, and current availability in the market: the antipsychotic pimozide, antidiabetic gliclazide, antiallergic cromolyn sodium, anticancer tyrosine kinase inhibitor entrectinib, and antihistamine azelastine. analysis of drug influence on PDGF-C in vitro binding to NRP-1 and PDGF-C induced migration of human melanoma cells expressing NRP-1, indicated gliclazide and entrectinib as the most specific agents that were active at clinically achievable and non-toxic concentrations. both drugs also reverted PDGF-C ability to stimulate extracellular matrix invasion by melanoma cells resistant to BRAF inhibitors. the inhibitory effect on tumor cell motility involved a decrease of p130Cas phosphorylation, a signal transduction pathway activated by PDGF-C-mediated stimulation of NRP-1

Latest evidence regarding the effects of photosensitive drugs on the skin: pathogenetic mechanisms and clinical manifestations

Photosensitivity induced by drugs is a widely experienced problem, concerning both molecule design and clinical practice. Indeed, photo-induced cutaneous eruptions represent one of the most common drug adverse events and are frequently an important issue to consider in the therapeutic management of patients. Phototoxicity and photoallergy are the two different pathogenic mechanisms involved in photosensitization. Related cutaneous manifestations are heterogeneous, depending on the culprit drug and subject susceptibility. Here we report an updated review of the literature with respect to pathogenic mechanisms of photosensitivity, clinical manifestations, patient management, and prediction and evaluation of drug-induced photosensitivity. We present and discuss principal groups of photosensitizing drugs (antimicrobials, nonsteroidal anti-inflammatory drugs, anti-hypertensives, anti-arrhythmics, cholesterol, and glycemia-lowering agents, psychotropic drugs, chemotherapeutics, etc.) and their main damage mechanisms according to recent evidence. The link between the drug and the cutaneous manifestation is not always clear; more investigations would be helpful to better predict drug photosensitizing potential, prevent and manage cutaneous adverse events and find the most appropriate alternative therapeutic strategy