Nuovi meccanismi infiammatori nella patogenesi della psoriasi: effetti dell'IL-17A nel rilascio e cargo delle vescicole extracellulari in cheratinociti umani - New pathogenetic inflammatory mechanisms in psoriasis: Interleukin-17A affects extracellular vesicles release and cargo in human keratinocytes

La psoriasi è riconosciuta come uno dei più comuni disordini immuno-mediati, dove sia l'immunità acquisita che quella innata giocano un ruolo fondamentale nello sviluppo e nel mantenimento della patologia. Per tale ragione la psoriasi viene considerata un vero e proprio modello di studio dei meccanismi di infiammazione cronica Nella psoriasi si assiste alla disregolazione dell'asse citochinico IL-23/IL-17 da cui ne consegue da una parte l'attivazione del subset linfocitario Th-17 e dall'altra una risposta proliferative cheratinocitaria. Questo induce la secrezione di differenti citochine, chemochine e peptidi antimicrobici da parte dei cheratinociti stessi. L'induzione di specifici fattori chemiotattici richiama, nel sito dell'infiammazione, cellule dendritiche mieloidi, linfociti Th17 e neutrofili. Il processo infiammatorio psoriasico, oltre alle interazioni cellulari, coinvolge anche le strutture vascolari con il rilascio di citochine, ormoni e secondi messaggeri. È stato, inoltre, dimostrato che le cellule comunicano anche attraverso il rilascio di vescicole contenenti DNA, RNA, microRNA e proteine. Sebbene siano state riportate alterazioni del traffico micro-vescicolare in disturbi ematologici ed infettivi, vi sono poche evidenze di tali alterazioni nella patogenesi della psoriasi. I risultati preliminari ottenuti nei nostri laboratori indicano come l'IL-17 sia in grado di modificare, sia qualitativamente che quantitativamente, il carico e il rilascio extracellulare di vescicole. L'obiettivo del nostro studio, basato su un gruppo di ricerca multidisciplinare, è identificare nuovi biomarkers della psoriasi

Clinical utility of ingenol mebutate in the management of actinic keratosis. Perspectives from clinical practice

Actinic keratoses (AKs) are epidermal cutaneous neoplasia observed predominantly in middle-aged and older subjects with mainly photo type I and photo type II on sun-exposed surfaces as a result of DNA damage. AKs have historically been characterized as being "precancerous"; however, now it is considered by many authors a carcinoma in situ that can persist or progress to invasive squamous cell carcinoma (SCC) with metastatic potential. Despite the advances in the recognition of typical clinic, dermoscopic and histologic patterns, currently it is not yet possible to predict which AKs will progress to SCC. For this reason, early diagnosis and effective therapy are recommended based on cost/risk/benefit analysis. Current treatment consists of lesion-directed or field-directed therapies or a combination of both. Among the topical field therapies, ingenol mebutate stands out for its therapeutic efficacy, both as directed lesion therapy and as field directed therapy. The aim of this review is to demonstrate the utility of ingenol mebutate in the management of AK in daily clinical practice and to highlight data from real world in order to confirm evidence from pivotal studies. In order to explore clinical data from real world, PubMed searches were performed with the search terms "clinical data ingenol mebutate" and "real world ingenol mebutate". The hits were examined for relevant articles using defaults criteria. The timeframe for the sample search started from the first publication on this topic in 2008 up to now. A total of 23 articles were found using the keywords specified above. The overview points out a low number of real-life studies on the effectiveness and tolerability of this novel treatment due to short period of clinical experience for its recent approval. Further real-life studies are required in order to better identify the efficacy, safety and adherence of the drug on a larger population

The Mediterranean Region: between terrorism, tourism and security

Tourism remains a very vulnerable sector and sensitive to both internal and external impacts, such as economic and social crises, natural disasters, epidemics and diseases, national and international conflicts. Among these, the most alarming threat in the 21st century remains terrorism. In this sense, this paper aims to study the effects of the increasingly frequent terrorist attacks by the extremist factions of Al-Qaeda and ISIL on the tourism industry in the MediterraneanRegion. The contribution, after having discussed in general the tourism market in the Mediterranean Region, intends to highlight the impacts and repercussions of the terrorist attacks on tourism, presenting the example of Egypt and one of its best-known tourist destinations, Sharm el-Sheikh. In this sense, it is shown how, in a few years, the political instability of the country and the attacks of 2005 and 2016 have significantly reduced the influx of tourists, transforming it from one of the most visited destinations in the world in a place of increasing abandonment

Globalisation, migration flows and sustainability

The mobility of people is an important theme of geographical research because immigrant currents profoundly transform regional models, mainly urban areas, configuring themselves as a factor of social destabilization, as they change the composition of the population, triggering processes of mutual cultural contamination that are projected on the territory, differentiating it from its geographical surroundings. The contribution, starting from a look at international migration, intends to analyze different aspects related t o the phenomenon of mobility such as globalization, sustainability and the role of International Cooperation in the light of the objectives of Agenda 2030 for sustainable development, challenges that concern not only the present, but especially the future

Gender matter in isotretinoin therapy for acne vulgaris? A retrospective study

Introduction: Gender differences have been recently highlighted for several aspects of acne vulgaris such as epidemiology, pathogenesis, clinical course, quality of life and treatment outcome. In particular a shorter but more severe clinical course has been reported in males than in females; nevertheless, usually men have their quality of life less affected. Aim: To determine if the response and the adverse events to 1 cycle of oral isotretinoin therapy can be influenced by gender. Methods: A retrospective study was conducted on consecutive patients affected by acne vulgaris and treated with oral isotretinoin. Global acne grading system (GAGS), acne-related quality of life (AQoL) and isotretinoin-related adverse events were considered as outcome measures and were evaluated before (T0), every month during administration and 4 weeks after the withdrawal (T1) of oral isotretinoin therapy. Mann-Whitney U test and Wilcoxon signed-rank test were used for quantitative parameters and Fisher exact test for qualitative ones. Results: Forty-nine acneic patients were retrospectively selected (33 males 67.3% and 16 females -32.7%; median age: 19 years). Patients had received a median dosage of isotretinoin of 0.4 mg/kg/die for a median period of 5 months; no differences in outcome measures among genders were reported. Limitations: The study is retrospective and the sample is small and not homogenously distributed among genders, as males are double in number than females. Conclusions: In our study population gender didn't influence neither the clinical and the quality of life outcome measures nor the occurrence of adverse events to oral isotretinoin therapy for acne

Factors influencing response to ingenol mebutate therapy for actinic keratosis of face and scalp

AIM To determine factors independently influencing response to ingenol mebutate therapy and assess efficacy on clinical setting of non-hypertrophic non-hyperkeratotic actinic keratosis (AK). METHODS Consecutive patients affected by non-hypertrophic non-hyperkeratotic AKs of the face or scalp were enrolled to receive ingenol mebutate 0.015% gel on a selected skin area of 25 cm2 for 3 consecutive days. Local skin reactions were calculated at each follow up visit using a validated composite score. Efficacy was evaluated by the comparison of clinical and dermoscopic pictures before the treatment and at day 57, and classified as complete, partial and poor response. RESULTS A number of 130 patients were enrolled, of which 101 (77.7%) were treated on the face, while 29 (22.3%) on the scalp. The great majority of our study population (n = 119, 91.5%) reached at least a 75% clearance of AKs and, in particular, 58 patients (44.6%) achieved a complete response while 61 (46.9%) a partial one. Logistic backward multivariate analysis showed that facial localization, level of local skin reaction (LSR) at day 2, the highest LSR values and level of crusts at day 8 were factors independently associated with the achievement of a complete response. CONCLUSION Ingenol mebutate 0.015% gel, when properly applied, is more effective on the face than on the scalp and efficacy is directly associated to LSR score

Efficacy of Cemiplimab in a patient affected by Cutaneous Squamous Cell Carcinoma and Myelodysplastic Syndrome

Cutaneous squamous cell carcinoma (cSCC) is a prevalent skin malignancy, often managed through surgical intervention. However, in certain cases, especially when complicated by concurrent hematologic disorders such as myelodysplastic syndrome (MDS), treatment options become more challenging. This abstract highlights a case study examining the efficacy of cemiplimab, a monoclonal antibody targeting programmed cell death protein 1 (PD-1), in a patient diagnosed with both cSCC and MDS. The patient, initially presenting with an advanced cSCC lesion and underlying MDS, underwent treatment with cemiplimab as a therapeutic approach. Monitoring of the patient's response included clinical evaluation, radiological assessments, and laboratory analyses. Results demonstrated a notable reduction in the size of the cSCC lesion and stabilization of hematologic parameters, suggesting a positive therapeutic effect of cemiplimab in this complex clinical scenario. This case underscores the potential utility of immunotherapeutic agents, specifically PD-1 inhibitors like cemiplimab, in the management of cutaneous malignancies coexisting with hematologic disorders. Further investigations and larger-scale studies are warranted to validate these findings and establish cemiplimab's role as a viable treatment option in similar clinical contexts

Dermatitis Artefacta in a Patient Affected by Impulse Control Disorder: Case Report

Dermatitis artefacta is a disease characterized by self-inflicted skin lesions in fully aware patients. Mechanical and chemical devices are most commonly used to produce such injuries. Several psychological disorders like depression, obsessive compulsive disorders, hysteria, etc. are associated with this kind of disease. Most of the patients are young females aged between 15 and 30, but the diagnosis of dermatitis artefacta may even be made in pediatric patients or elderly people. Because of its rarity and the polymorphism of lesions, dermatitis artefacta is often a challenge for the clinicians. More difficulties might be due to the lack of cooperation in these patients, who usually refuse the dialogue with doctors and deny their primary role in damaging their skin. We present a case of an elderly woman who showed a peculiar pattern of deep excoriating lesions disseminated on the upper part of her body, with an evident state of depression. Diagnostic and therapeutic procedure, that is often long lasting and difficult in such cases, was made by teamwork of dermatologists, psychiatrists and psychologists, leading to steady control of impulses and full remission of cutaneous symptoms

Erythrodermic Psoriasis Successfully Treated with Anti IL-17: A Case Series

Erythrodermic psoriasis (EP) is a very rare but extremely severe subtype of chronic plaque psoriasis, affecting 1.00-2.25% of patients with psoriasis (1). Its pathogenesis still remains unknown, and current therapeutic strategies frequently end in failure. In this condition, the skin becomes diffusely red, tending to purple, shiny, with marked desquamation and exudation. Erythema and edema are widespread, covering more than 90% of the body surface and can lead to high risk of multi-organ failure and death (2) due to fluid and protein loss. Predominance of the Th2 immune response and dysregulation of angiogenesis have been proposed to be implicated in the pathogenesis of EP, although this has not yet been fully elucidated (3). Nevertheless, Th17 has been shown to be the second-most predominant T-cell type after Th2 in EP lesions (4,5)