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Enrico Matteini,1,* Laura Diluvio,1,* Sara Lambiase,1 Arnaldo Cioni,1 Ruslana Gaeta Shumak,1 Gaetana Costanza,2 Caterina Lanna,1 Giacomo Caldarola,3,4 Luca Bianchi,1 Elena Campione1 1Dermatology Unit, Department of Systems Medicine, University of Rome “Tor Vergata”, Rome, Italy; 2Department of Experimental Medicine, University of Rome ”Tor Vergata”, Rome, Italy; 3UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome, Italy; 4Dermatologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy*These authors contributed equally to this workCorrespondence: Laura Diluvio, Dermatology Unit, Department of Systems Medicine, University of Rome “Tor Vergata”, Viale Oxford 81, Rome, 00133, Italy, Tel +39 06 20902743, Fax +39 06 20902742, Email lauradiluvio@yahoo.itAbstract: Alopecia areata represents an autoimmune disease that specifically damages growing hair follicles on the scalp and/or around the body. Janus kinase inhibitors have been identified as an effective therapy in adult patients and topical formulations, such as Brevilin-A, might represent a well-tolerated treatment for mild-moderate disease in children and adolescents. The mechanism of action of Brevilin-A, a sesquiterpene lactone isolated from Centipeda minima, could consist in blocking STAT3 and STAT1 signaling as well as the JAKs activity by inhibiting the JAKs tyrosine kinase domain JH1. We report our cases of successful application of Brevilin-A in pediatric patients, suggesting this treatment as a safe and effective therapeutic option also for recalcitrant alopecia areata in pediatric population.Keywords: alopecia areata, brevelin A, pediatric, topical JAK inhibitors

This article discusses the use of baricitinib, a medication that modulates the JAK-STAT signaling pathway, in the treatment of alopecia areata (AA). The study evaluated five patients with AA who were treated with oral baricitinib for 24 weeks. Trichoscopy, a method of examining the scalp and hair, was used to assess the patients' response to treatment. The findings showed that trichoscopic evaluation can provide valuable information about disease activity and treatment response in patients with AA. The study also identified specific trichoscopic features that correlated with clinical improvement. Overall, the research suggests that trichoscopy can be a useful tool in assessing the effectiveness of baricitinib treatment for AA. [Extracted from the article]

Purpose of the article: Interleukin-23 inhibitors, such as tildrakizumab, have emerged as safe and effective options for the management of psoriasis. Yet their efficacy in elderly patients (aged 65 years or more), particularly in those with difficult-to-treat areas involvement, remains insufficiently explored. We conducted this real-life retrospective multicentric observational study to assess the effectiveness of tildrakizumab in elderly patients with moderate-to-severe psoriasis, with involvement of difficult-to-treat areas. Materials and methods: We enrolled forty-nine patients aged 65 years old or more (mean age 73.1 ± 6.0), all treated with tildrakizumab for at least 28 weeks. The effectiveness of tildrakizumab was assessed by Static Physician's Global Assessment of Genitalia (sPGA-G), fingernail-PGA (f-PGA), palmoplantar PGA (pp-PGA), scalp-specific PGA (sc-PGA), and Psoriasis Area and Severity Index (PASI) scores. Results: Significant improvements in PASI scores were observed within 28 weeks of treatment, with 77.5%, 60%, and 45.2% of patients achieving PASI75, PASI90, and PASI100, respectively. The mean PASI decreased significantly from baseline (13.6 ± 9.9) to 1.3 ± 1.7 at week 28. More than 90% of patients had clear sPGA-G and pp-PGA scores and over 70% had clear f-PGA and sc-PGA scores after 28 weeks. Conclusions: Our findings suggest that tildrakizumab could be a valuable option for the treatment of elderly patients, including those with difficult-to-treat areas involvement.

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 cm 2 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.

Tildrakizumab is a humanized IgG1κ monoclonal antibody that selectively targets the p19 subunit of interleukin IL-23, thereby inhibiting the IL-23/IL-17 axis, which is primarily implicated in the immunopathogenesis of psoriasis. Tildrakizumab is approved for the treatment of moderate-to-severe plaque-type psoriasis in adults based on the evidence of two randomized and controlled phase-III clinical trials (reSURFACE 1 and reSURFACE 2). Here, we report our real-life experience treating 53 psoriatic patients (19 female and 34 male) who were administered tildrakizumab every 12 weeks and received follow-ups over 52 weeks. Descriptive and inferential statistical analyses were performed, in particular the Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI) and, if applicable, the Nail Psoriasis Severity Index (NAPSI) and Palmoplantar Psoriasis Physician Global Assessment (PPPGA). These were assessed at baseline and after different timepoints (weeks) during the follow-up period. We described and evaluated demographical and epidemiological characteristics in our cohort group, focusing on comorbidities. In this group, 35.9% of patients were female and 64.1% were male, with 47.1% being smokers and with a mean age of 51.2 years. A total of 37.7% of these patients was affected by scalp psoriasis; regarding comorbidities, hypertension was the most frequent (32.5%), followed by psoriatic arthritis (PsA) (18.60%) and diabetes (13.9%). At week 52, 93%, 90.2% and 77% of patients achieved a PASI reduction ≥75% (PASI 75), PASI 90 and PASI 100, respectively. In addition, NAPSI, PPPGA and DLQI scores were significantly reduced by week 52. In our cohort of complex psoriasis patients, disease remission began at the end of the fourth week of treatment and remained constant from week 16 to week 52.

Introduction: Psoriasis is an inflammatory, chronic and immune-mediated disease that can affect the skin and joints. Pro-inflammatory cytokines have a dominant role in the pathogenesis of this heterogeneous disease in which the IL-23/IL-17 axis plays a crucial role. The IL-17 family is involved in numerous processes such as immune defense, intestinal disorders and diseases of the central nervous system. In psoriasis, in particular, many cytokines belonging to the IL-17 family are involved in the inflammatory cascade underlying the disease., Areas Covered: The knowledge of the mechanisms and pathways behind psoriasis is crucial for the development of new target therapies. We focused on IL-17 biology in order to understand why biological drugs against this cytokine are an effective treatment for moderate to severe psoriasis. Clinical trials results of ixekizumab, brodalumab, secukinumab and bimekizumab have been presented., Expert Opinion: Il-17 inhibitors are a very fast and effective treatment against psoriasis; however, fungal infections can occur during their use, due to IL-17 biological functions. Therefore, it should be mandatory to choose the right patients to treat with these monoclonal antibodies in order to have a tailored target therapy for each patient.

Background: Actinic keratosis is one of the most common dermatological disorders. A new topical solution, constituted by 0.5% 5-fluorouracil and 10% salicylic acid (Actikerall, Almirall) has been introduced in the treatment pipeline of hyperkeratotic actinic keratoses of the head and neck., Patients and Methods: We analyzed in an observational prospective clinical study the short-term treatment effectiveness of 5-fluorouracil and salicylic acid on face and scalp actinic keratoses of grade 1 and 2 of 40 patients. Efficacy assessment was performed by clinical dermatological examination, collecting color photographs, calculating AKASI score, and by means of dermoscopy for each target lesion at every visit., Results: AKASI score decreased from an initial score of 3.3 to a final score of 0.9. At week 4, we were able to record a complete clearance of 50% of the treated lesions and a partial clearance of 28%. At the end of 12 weeks, 84% of the total lesions showed complete clearance, while 8% had partial clearance., Conclusions: 5-fluorouracil and salicylic acid topical solution is effective in the treatment of mild to moderate actinic keratoses. In the future, further studies are needed to evaluate the chance of adjusting drug dosage according to patients' and actinic keratoses features.

Purpose:  Psoriasis is a chronic, immune-mediated inflammatory skin condition marked by erythematous, scaly plaques. This retrospective observational study evaluated the long-term efficacy and safety of bimekizumab, a dual IL-17A and IL-17F inhibitor, in treating moderate to severe plaque psoriasis in 56 patients across two dermatology clinics in Italy., Materials and Methods:  Adult participants with a baseline Psoriasis Area and Severity Index (PASI) >10, or <10 with sensitive area involvement, were followed for 16 to 52 weeks. Clinical outcomes were measured by PASI 75, 90, and 100 responses and Dermatology Life Quality Index (DLQI) scores at 4, 16, 36, and 52 weeks., Results:  At week 16, 97.5% of patients achieved PASI 75, 76.7% reached PASI 90, and 66% attained PASI 100. By week 52, 91.5% achieved PASI 90 and 85.1% reached PASI 100, with 95.7% reporting a Dermatology Life Quality Index (DLQI) score of 0 or 1, indicating minimal impact on daily life. The study found similar efficacy across bio-naïve and bio-experienced groups, and between normal-weight and obese patients, without statistically significant differences. The safety profile was consistent with previous trials, with oral candidiasis as the most frequent adverse event (21%)., Conclusions:  These findings support the efficacy and tolerability of bimekizumab for long-term psoriasis management.