Pincelli, Thaís

Abstract Lichen Planopilaris (LPP) is a lymphocyte-mediated scarring alopecia characterized by progressive follicular destruction and fibrosis. In this clinical trial, patients with biopsy proven LPP were treated with deucravacitinib (an oral inhibitor of tyrosine kinase 2 (TYK2)) 6 mg BID for 24 weeks (NCT-06091956). Bulk and single-cell RNA sequencing was performed on paired pre- and post-treatment scalp biopsies from baseline and week 4. Patients (N=10) demonstrated improvements in PGA (88.9%, p=0.008), LPPAI (−2.3 points, SD 1.1, p=0.002) and Skindex-16 (−21.0 points, SD 22.1, p=0.014) scores at week 24. Bulk transcriptomic analysis of untreated LPP revealed upregulation of type I Interferon (IFN)-stimulated genes and pathways related to inflammation, immune activation, keratinization, and extracellular matrix remodelling, with downregulation of immune and inflammatory pathways following treatment. Single-cell RNA-seq of LPP was characterized by enrichment of CD8+GZMK+ T cells which showed downregulation of T-cell receptor signaling as well as antiviral pathways with treatment. Basal keratinocytes exhibited reduced cytokine and interferon signaling and decreased communication with NK cells following treatment. CCL19+ fibroblasts were prominent in untreated disease was attenuated after treatment, with downregulation of type I IFN signaling. Selective TYK2 inhibition with deucravacitinib effectively suppresses these inflammatory circuits in LPP and represents a promising therapeutic strategy.

Phosphodiesterase type 5 (PDE5) inhibitors are the first-line treatment for erectile dysfunction, with modest adverse effects. Since 2011, concerns have arisen about increased melanoma risk in PDE5 inhibitor users. PDE5 inhibitors affect the rat sarcoma virus oncogene–rapidly accelerated fibrosarcoma–mitogen‐activated protein kinase–extracellular signal‐regulated kinase signaling cascade, which is involved in melanoma formation. This systematic review and meta-analysis investigates melanoma risk in PDE5 inhibitor users. PubMed, Cochrane, and Embase were searched to examine the relationship between PDE5 inhibitors and melanoma. A random-effects model estimated pooled odds ratios (ORs) and hazard ratios (HRs), with the I² statistic assessing heterogeneity. RStudio v4.4.2 was used for the meta-analysis, and a P value less than 0.05 was deemed significant. Eight studies including 7 620 765 patients were analyzed, with 2 123 165 (27.86%) comprising the PDE5 inhibitor-exposed group. The meta-analysis found a relationship between PDE5 inhibitor use and increased melanoma risk [OR: 1.60, 95% confidence interval (CI): 1.13–2.27, P = 0.009, I² = 98%] and [HR: 1.10, 95% CI: 1.03–1.17, P = 0.005, I² = 43%]. When each PDE5 inhibitor was examined separately, increased melanoma incidence was observed, though not statistically significant. The OR for sildenafil was 1.85 (95% CI: 0.97–3.51, P = 0.059, I² = 99%), tadalafil 1.54 (95% CI: 0.79–3.00, P = 0.203, I² = 96%), and vardenafil 1.16 (95% CI: 0.82–1.64, P = 0.391, I² = 89%). This study suggests PDE5 inhibitor users have a higher chance of developing potentially fatal melanoma. Patients with a history of skin cancer, a family history of melanoma, or other risk factors should avoid these medications.

ABSTRACTBackgroundCellulite is a localized skin condition that affects many women, particularly after puberty. It results from a complex interplay of several factors that lead to the characteristic dimpled appearance of the skin. Cellulite may cause psychological stress and negatively impact quality of life. Additionally, body skin laxity may further exacerbate cosmetic concerns in these patients. Consequently, multiple therapeutic options, including topical treatments, have been explored to address both cellulite and skin laxity.ObjectivesTo review the pathophysiology of cellulite and skin laxity, as well as topical skincare options for their management.MethodsA literature search from 2000 to 2024 was conducted using the databases PubMed, EBSCOhost, Scopus, and Google Scholar, with the key terms “cellulite,” “cellulite management,” “cellulite topical treatment,” “skin sagging,” “skin laxity,” and “loose skin.” The search included clinical trials, observational studies, book chapters, and review articles in English and Spanish.ResultsThe pathophysiologic mechanisms underlying cellulite involve a combination of histological, hormonal, genetic, and lifestyle factors. Several topical agents, including retinoids and methylxanthines, have shown potential in improving the cosmetic appearance of cellulite and may contribute to localized fat reduction. Emerging botanical extracts hold promise as topical treatments for cellulite and skin tightening.ConclusionsCellulite and skin laxity are prevalent cosmetic concerns with multifactorial and complex pathophysiologic origins. Topical treatments for cellulite and skin tightening require further investigation. Although some studies have demonstrated positive outcomes with skincare products and topicals, robust evidence and studies with extended follow‐up are still lacking. Additional research is necessary to evaluate the long‐term efficacy of topical treatments as standalone therapies for cellulite and skin tightening.

Alopecia is prevalent among females, categorised as either scarring or non-scarring, depending on the potential for hair follicle regeneration. Various aetiologic factors are implicated in non-scarring alopecia, including genetic predisposition, loss of immune privilege, oxidative damage, and hormonal fluctuations. Telogen effluvium, alopecia areata, and female pattern hair loss are the main causes of non-scarring alopecia in females of all ages. This review covers the aetiology, pathophysiology, and treatment of the most common non-scarring alopecias in females.

Background: The regenerative properties of platelet growth factors make platelet-rich-plasma (PRP) an attractive modality for treatment of aging skin. The main objective of this study was to determine efficacy and safety of PRP injections and microneedling compared with saline injections in women with aging skin of the face. Methods: In this prospective, randomized clinical trial, 18 women with facial aging were randomized to receive either PRP injections to the unilateral face and saline injections to the contralateral side, or vice versa. Microneedling was performed after injections on the entire face. Physician assessment, photographs, and treatment satisfaction questionnaires were used for outcome assessment at baseline and 16- and 24-week follow-ups. Results: There was no evidence of improvement and suggestion of worsening in skin laxity and rhytides from baseline to weeks 4, 16, and 24 for PRP and saline (all P ≤ 0.004) and no notable difference in skin roughness between baseline and follow-up time points for PRP or saline (all P ≥ 0.19). The degree of change in skin laxity, rhytides, and skin roughness from baseline to follow-up time points was similar for PRP and saline. All patients experienced some degree of pain/discomfort and burning/stinging sensation at treatment weeks 4, 8, and 12 for both saline and PRP. Conclusions: PRP injections did not seem to be effective for treatment of aging skin of the face in women, with no notable macroscopic improvement in appearance when compared with baseline or saline injections. Advanced age of study participants (>45 years) and less-sensitive methods of evaluation may be potential contributing factors to the lack of detected response.