Anti-aging Effects of Tirbanibulin 1% Ointment: A Real-Life Experience.

INTRODUCTION: Tirbanibulin 1% ointment has been licensed to treat non-hyperkeratotic actinic keratosis (AKs) on the face and scalp in adults to ensure excellent patient tolerability due to the mild side effects and the brief application time compared to other topical therapies on the market. A growing body of evidence suggests that, beyond their primary function, the treatments for AKs and the cancerization field may inadvertently confer substantial cosmetic benefits to patients. METHODS: We report a single-center retrospective case series of patients referred to the Dermatology Unit of the University Hospital of Messina, Italy, between February and December 2023 seeking treatment for AKs in the context of photodamaged areas in which the application of tirbanibulin 1% ointment induced, besides clearance of AKs, anti-aging effects on both skin texture and solar lentigos. RESULTS: Seven patients affected by Olsen grade 1-2 AKs experienced a powerful rejuvenating effect in the treated areas, with a marked efficacy in skin lightening and clearance of solar lentigo. CONCLUSIONS: Tirbanibulin 1% ointment seems able to improve skin aging as a desirable side effect at the site of application for AKs on chronic photodamaged skin. Such preliminary observation needs further confirmation in real-life studies on larger cohorts of patients, to explain the pathogenic mechanisms responsible for such aesthetically relevant results.

Photodynamic therapy for severe acne.

Acne is an inflammatory cutaneous disease affecting the pilosebaceous unit and hair follicles on the face, neck, back, and chest, with a typical onset in adolescence and, in some cases, persisting into adulthood. Systemic treatments with antibiotics or isotretinoin present many limitations, like antimicrobial resistance phenomena and teratogenicity, which appear more relevant in the pediatric population, both for the treatment-related risks and for the reticence of the parents. Photodynamic therapy (PDT) has already shown encouraging results in the treatment of acne in adult patients, with good aesthetic results compared to other therapies and few side effects. However, its use is still not standardized in the pediatric population. On this topic, we report our experience with PDT in a young patient affected by dorsal acne. After five sessions of ALA-PDT at monthly intervals, a remarkable improvement of the lesions was observed, with the healing of the inflamed nodules and pustules, resolution of the painful symptoms, and an acceptable cosmetic outcome. Our case is paradigmatic of the potentiality of PDT to treat difficult and resistant-to-treatment lesions. Despite being time-consuming, this procedure has been demonstrated to be safe and well-tolerated. Lastly, the therapy is also well accepted by parents, due to its minimal invasiveness and mild side effects, compared to the other therapeutic options.

Daylight photodynamic therapy for cutaneous leishmaniasis in a pediatric setting: A case report and literature review.

Cutaneous leishmaniasis (CL) is a vector-borne infection caused by the obligate intracellular parasites of the Leishmania genus. Children are more frequently affected due to increased exposure to sandflies and underdeveloped immune system. Currently, there is a lack of consensus on the most effective treatment approach for CL since most drugs are accompanied by numerous limitations, including adverse effects, toxicity, and onset of antimicrobial resistance phenomena. These limitations appear more relevant in the pediatric population, both for the treatment-related risks and for the reticence of the parents. Photodynamic therapy (PDT) has been increasingly employed in numerous inflammatory and infectious diseases, owing to its tissue selectivity and excellent cosmetic outcomes. On this topic, we report our experience with daylight-PDT (DL-PDT) therapy in a difficult-to-treat area like the facial region in a child with a six-month history of CL. Our case is paradigmatic of the potentiality of PDT to treat difficult lesions in a pediatric setting. However, its use has not yet been standardized either for the treatment of leishmania, with high variability in the number of sessions and time intervals. Specific protocols for pediatric patients should be better standardized in randomized clinical trials in order to provide clear indications for clinicians.

The Role of Nutraceuticals and Functional Foods in Skin Cancer: Mechanisms and Therapeutic Potential.

Skin cancer is a prevalent type of cancer worldwide and has a high growth rate compared to other diseases. Although modern targeted therapies have improved the management of cutaneous neoplasms, there is an urgent requirement for a safer, more affordable, and effective chemoprevention and treatment strategy for skin cancer. Nutraceuticals, which are natural substances derived from food, have emerged as a potential alternative or adjunctive treatment option. In this review, we explore the current evidence on the use of omega-3 fatty acids and polyphenols (curcumin, epigallocatechin gallate, apigenin, resveratrol, and genistein) for the treatment of melanoma and non-melanoma skin cancer (NMSC), as well as in their prevention. We discuss the mechanisms of action of the aforementioned nutraceuticals and their probable therapeutic benefits in skin cancer. Omega-3 fatty acids, curcumin, epigallocatechin gallate, apigenin, resveratrol, and genistein have several properties, among which are anti-inflammatory and anti-tumor, which can help to prevent and treat skin cancer. However, their effectiveness is limited due to poor bioavailability. Nanoparticles and other delivery systems can improve their absorption and targeting. More research is needed to evaluate their safety and effectiveness as a natural approach to skin cancer prevention and treatment. These compounds should not replace conventional cancer treatments, but may be used as complementary therapy under the guidance of a healthcare professional.

Photodynamic therapy for intergluteal warts in a child affected by Rett syndrome.

Genital warts (GWs) are the most common sexually transmitted infections worldwide, caused by the human papillomavirus (HPV). The increasing prevalence of GWs in children has renewed the interest in therapeutic management which still presents a unique challenge, being influenced by many variables including size, quantity, and location of warts, as well as the presence of comorbidities. Conventional photodynamic therapy (C-PDT) has already shown encouraging results in the treatment of viral warts in adult patients, but its use is still not standardized in the pediatric population. On this topic, we report our experience with C-PDT in a difficult-to-treat area like the perianal region in a 12-year-old girl affected by Rett syndrome, an X-linked dominant neurological disorder, with a 10-month history of florid genital condylomatosis. After the third session of C-PDT, complete clearance of the lesions was achieved. Our case is paradigmatic of the potentiality of PDT to treat difficult lesions in difficult patients. Despite being expensive and time-consuming, this procedure has been demonstrated to be safe and well-tolerated. Lastly, the therapy is also well accepted by parents, due to its minimal invasiveness and the few side effects, compared to the other therapeutic options.

Alopecia Areata: A Review of the Role of Oxidative Stress, Possible Biomarkers, and Potential Novel Therapeutic Approaches.

Alopecia areata (AA) is a dermatological condition characterized by non-scarring hair loss. Exact etiopathogenesis of AA is still unknown although it is known that several factors contribute to the collapse of the hair-follicle (HF)-immune-privileged (IP) site. Oxidative stress (OS) plays an important role in skin diseases. The aim of this review was to clarify the role of OS in AA pathogenesis and diagnosis, and to discuss potential treatment options. Oxidative-stress markers are altered in serum and skin samples of patients with AA, confirming a general pro-oxidative status in patients with AA. OS induces MHC class I chain-related A (MICA) expression in HF keratinocytes that activates the receptor NKG2D, expressed in NK cells and CD8+ T cytotoxic cells leading to destabilization of the HF immune-privileged site through the production of IFN-γ that stimulates JAK1 and JAK2 pathways. OS also activates the KEAP1-NRF2 pathway, an antioxidant system that contributes to skin homeostasis. In addition, a decrease of ATG5 and LC3B in the hair matrix and an increase in p62 levels indicates a reduction of intrafollicular autophagy during the evolution of AA. Potential biomarkers of OS in AA could be: malondialdehyde (MDA), advanced glycation end-products (AGEs), and ischemic-modified albumin (IMA). JAK inhibitors are the new frontier in treatment of AA and the use of nutraceuticals that modulate the OS balance, in combination with standard treatments, represent promising therapeutic tools.

Vitiligo-like Lesions and COVID-19: Case Report and Review of Vaccination- and Infection-Associated Vitiligo.

Several cutaneous manifestations in patients undergoing COVID-19 vaccination have been described in the literature. Herein, we presented a case of new-onset vitiligo that occurred after the second dose of the Comirnaty vaccine. An updated literature search revealed the occurrence of a total of 16 cases, including new-onset or worsening of preexisting vitiligo. Given the autoimmune pathogenesis of the disease, we reviewed and discussed the potential role of the vaccine prophylaxis as a trigger for the development of such hypopigmented skin lesions.

Efficacy of Systemic Biologic Drugs in Pediatric Psoriasis: Evidence From Five Selected Randomized Clinical Trials.

Background: Psoriasis is a chronic, immune-mediated skin disease that may occur at any age. Prevalence in children ranges between 0.5 and 1.0% across Europe. Approximately 10-20% of paediatric psoriasis patients are moderate-to-severe in severity and may require the use of systemic therapy. Objective: Recently, newer targeted, systemic therapies have been licensed for treatment of moderate-to-severe paediatric psoriasis. The objective of this study was to evaluate the short-term efficacy of available antipsoriatic systemic drugs in children with a narrative synthesis of key efficacy from randomized clinical trials. Methods: A systematic review of literature was performed on Medline and embase databases and the Cochrane Central Register of Controlled Trials. Randomized clinical trials investigating the efficacy of treatments licensed by the US Food and Drug Administration and/or the European Medicines Agency for paediatric and adolescent psoriatic population were retrieved and analyzed. Data from this literature review was assessed in line with GRADE (grading of recommendations, assessment, development and evaluations). The short-term (12-16 weeks) clinical efficacy from baseline was evaluated according to the Psoriasis Area and Severity Index (PASI) 75 and 90 compared to baseline. Illustrative comparative risks, relative risk (RR) and the number needed to treat (NNT) for response on PASI 75 and PASI 90 were extracted. Results: A total of five relevant studies were identified on two TNF-alpha blockers (etanercept and adalimumab), the IL12/23 inhibitor ustekinumab and two IL-17 inhibitors (ixekizumab, secukinumab). Comparators were placebo (3 studies), placebo and etanercept (1 study) methotrexate (1 study). All examined drugs resulted efficacious. The probability to achieve PASI 75 and PASI 90 was higher for the IL-12/23 and IL-17 inhibitors. Overall, the anti-IL17s and the anti-IL12/23 antibodies showed a more favourable NNT for PASI 75, whereas IL-17 inhibitors for PASI 90. Conclusion: The approved biological therapies may be beneficial for the treatment of moderate to severe plaque psoriasis in children and adolescents. Since psoriasis is a chronic and often challenging condition with no definitive solution, systematic evaluations of long-term efficacy, drug survival and adverse effects may help careful, individualized, patient-centered clinical decision making.

MicroRNA Cross-Involvement in Acne Vulgaris and Hidradenitis Suppurativa: A Literature Review.

Acne Vulgaris (AV) and Hidradenitis suppurativa (HS) are common chronic inflammatory skin conditions that affect the follicular units that often coexist or are involved in differential diagnoses. Inflammation in both these diseases may result from shared pathways, which may partially explain their frequent coexistence. MicroRNAs (miRNAs) are a class of endogenous, short, non-protein coding, gene-silencing or promoting RNAs that may promote various inflammatory diseases. This narrative review investigates the current knowledge regarding miRNAs and their link to AV and HS. The aim is to examine the role of these molecules in the pathogenesis of AV and HS and to identify possible common miRNAs that could explain the similar characteristics of these two diseases. Five miRNA (miR-155 miR-223-, miR-21, and miRNA-146a) levels were found to be altered in both HS and AV. These miRNAs are related to pathogenetic aspects common to both pathologies, such as the regulation of the innate immune response, regulation of the Th1/Th17 axis, and fibrosis processes that induce scar formation. This review provides a starting point for further studies aimed at investigating the role of miRNAs in AV and HS for their possible use as diagnostic-therapeutic targets.

Role of Epithelium-Derived Cytokines in Atopic Dermatitis and Psoriasis: Evidence and Therapeutic Perspectives.

Atopic dermatitis and psoriasis are two of the most common chronic skin conditions. Current target therapies represent viable and safe solutions for the most severe cases of these two dermatoses but, presently, several limitations exist in terms of efficacy and side effects. A new class of products, epithelium-derived cytokines (TSLP, IL-25, IL-33), show an increasing potential for use in target therapy for these patients, and demonstrate a direct link between a generalized inflammatory and oxidative stress status and the human skin. A review was conducted to better understand their role in the aforementioned conditions. Of these three molecules, TSLP led has been most often considered in studies regarding target therapies, and most of the results in the literature are related to this cytokine. These three cytokines share common stimuli and are linked to each other in both acute and chronic phases of these diseases, and have been challenged as target therapies or biomarkers of disease activity. The results lead to the conclusion that epithelium-derived cytokines could represent a therapeutic opportunity for these patients, especially in itch control. Furthermore, they might work better when paired together with currently available therapies or in combination with in-development treatments. Further studies are needed in order to verify the efficacy and safety of the biologic treatments currently under development.

Involvement of microRNAs as a Response to Phototherapy and Photodynamic Therapy: A Literature Review.

The current knowledge about the mechanisms of action of light-based treatments (chiefly photodynamic therapy and phototherapy) in skin diseases leans to the possible involvement of epigenetic and oxidative stress mechanisms. To better understand and exploit, to the fullest, these relatively safe and reproducible treatments, several studies have focused on miRNAs, small non-encoding RNAs (22-24 nucleotides), after light-based treatments. The current narrative review focused on 25 articles. A meta-analysis was not deemed appropriate. The results gather the most recurrent skin-related miRNAs up- or downregulated after light treatment. Five of these, miR-21, -29, -125, -145 and -155, are either the most consistently related to efficacy/resistance to treatment or identified as helpful diagnostic tools. A specific class of miRNAs (angioMIRs) requires further studies. Future treatments and imaging techniques could benefit greatly from the use of antagomirs as a possible co-adjuvant therapy along with light-based treatments.