"Your Skin Tells You" Campaign for Keratinocyte Cancers: When Individuals' Selection Makes the Difference.

BACKGROUND: Prevention campaigns for skin cancers have focused primarily on melanoma, and over time there has been increasing awareness of the need to select the population to be screened to maximize program effectiveness. OBJECTIVES: The objective of the study was to report the results of a free dermatological initiative, as part of an awareness campaign dedicated to keratinocyte cancers, targeting individuals pre-selected through a short questionnaire. METHODS: One day of dermatological consultations was held at 15 dermato-oncology referral centers during May 22-June 30, 2021. For selection, individuals answered a telephone interview consisting of 7 yes/no questions on risk factors. Demographics, clinical characteristics of suspicious tumors, and histopathologic diagnosis of excised lesions were collected. Suspicion rate, detection rate, and positive predictive values (PPVs) for any skin cancer, basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and melanoma were calculated. RESULTS: A total of 320 individuals (56.9% males; 43.1% females) with a median age of 69.6 (range 21-91) years qualified for the screening initiative. Overall, skin cancers and precancerous lesions were diagnosed in 65.9% of the patients. Suspicion rate was 28.7% for any skin cancer (92/320), 22.8% for BCC (73/320), 4.7% for cSCC (15/320), and 1.2% for melanoma (4/320). Detection rate was 23.4% for any skin cancer (PPV 93.7%), 18.1% for BCC (PPV 95.1%), 4.4% for cSCC (PPV 93.3%), and 0.9% for melanoma (PPV 75%). CONCLUSIONS: Selection of individuals at high risk is a cost-effective approach for early detection campaigns for keratinocyte cancers.

Efficacy of Dupilumab in two patients with severe and recalcitrant atopic dermatitis previously treated with extracorporeal photopheresis.

Atopic dermatitis (AD) is a complex disease and can often be a clinical challenge for dermatologists. When standard immunosuppressive therapies fail, extracorporeal phototherapy (ECP) can be considered as a therapeutic option. In recent years, better understanding of the pathogenesis of AD allowed to improve treatment strategies with many emerging therapeutic options. Currently, Dupilumab, a monoclonal antibody that selectively inhibits IL-4 and IL-13, is the only biological drug authorized for the treatment of severe adult atopic dermatitis, refractory to traditional firstline and secondline therapies. ECP, compared to biological therapy, is associated with some disadvantages: it is costly and time-consuming for patients and personnel to administer. Moreover, it should be noted that the completion of the entire procedure takes about 3 hr and must be done in a hospital, while the administration of Dupilumab can be carried out by patients themselves at home. For these reasons and on the basis of our experience, it would be necessary to evaluate whether all patients with refractory atopic dermatitis in treatment with ECP with unsatisfactory clinical response should be switched to recent available target therapies.

Exploring the Relationship Between Dermatology Life Quality Index, Eczema Area and Severity Index, and Sleep Numerical Rating Scale and Pruritus Numerical Rating Scale in Patients with Atopic Dermatitis Treated with Dupilumab.

Objective: Patients with atopic dermatitis (AD) experience decreased quality of life (QoL). Here we describe the relationship between severity and QoL-related scores in patients with moderate-to-severe AD treated with dupilumab. Patients and Methods: This was a real-life, retrospective, and observational study involving patients with AD treated with dupilumab. Treatment effectiveness was evaluated based on the changes in the eczema area and severity index (EASI), sleep quality numerical rating scale ,and pruritus numerical rating scale (PNRS), as well as the dermatology life quality index (DLQI). The relationship between each of them was analyzed. After the first data collection at baseline, patients were re-evaluated at 3 subsequent follow-ups (4, 8, and 12 months). Results: A total of 52 patients were enrolled in the study. At 4 months, the change in DLQI is more correlated with PNRSs (r = 0.643, P < 0.001) than the other scores considered. At 8 months, however, the change in DLQIs correlates similarly both with PNRSs (r = 0.644, P < 0.001) and with the change in EASIs (r = 0.633, P < 0.001). At 12 months of treatments, however, the trend reverses and the correlation with EASIs becomes higher (r = 0.735, P < 0.001) than PNRSs (r = 0.0.659, P < 0.001). Conclusions: The results of our study show that the reduction in the impact on QoL for AD patients in the first months of therapy with dupilumab correlates more with the control of pruritus than with the disappearance of skin lesions.

Searching Novel Therapeutic Targets for Scleroderma: P2X7-Receptor Is Up-regulated and Promotes a Fibrogenic Phenotype in Systemic Sclerosis Fibroblasts.

Objectives: Systemic sclerosis (SSc) is a connective tissue disorder presenting fibrosis of the skin and internal organs, for which no effective treatments are currently available. Increasing evidence indicates that the P2X7 receptor (P2X7R), a nucleotide-gated ionotropic channel primarily involved in the inflammatory response, may also have a key role in the development of tissue fibrosis in different body districts. This study was aimed at investigating P2X7R expression and function in promoting a fibrogenic phenotype in dermal fibroblasts from SSc patients, also analyzing putative underlying mechanistic pathways. Methods: Fibroblasts were isolated by skin biopsy from 9 SSc patients and 8 healthy controls. P2X7R expression, and function (cytosolic free Ca2+ fluxes, α-smooth muscle actin [α-SMA] expression, cell migration, and collagen release) were studied. Moreover, the role of cytokine (interleukin-1ß, interleukin-6) and connective tissue growth factor (CTGF) production, and extracellular signal-regulated kinases (ERK) activation in mediating P2X7R-dependent pro-fibrotic effects in SSc fibroblasts was evaluated. Results: P2X7R expression and Ca2+ permeability induced by the selective P2X7R agonist 2'-3'-O-(4-benzoylbenzoyl)ATP (BzATP) were markedly higher in SSc than control fibroblasts. Moreover, increased αSMA expression, cell migration, CTGF, and collagen release were observed in lipopolysaccharides-primed SSc fibroblasts after BzATP stimulation. While P2X7-induced cytokine changes did not affect collagen production, it was completely abrogated by inhibition of the ERK pathway. Conclusion: In SSc fibroblasts, P2X7R is overexpressed and its stimulation induces Ca2+-signaling activation and a fibrogenic phenotype characterized by increased migration and collagen production. These data point to the P2X7R as a potential, novel therapeutic target for controlling exaggerated collagen deposition and tissue fibrosis in patients with SSc.

Computer-assisted melanoma diagnosis: a new integrated system.

In dermatology, attempts at synergy between man and machine have mainly been made to improve melanoma diagnosis. The aim of the present study was to test an 'integrated digital dermoscopy analysis' (i-DDA) system with a series of melanocytic lesions that were benign and malignant in nature, and to evaluate its discriminating power with respect to histological diagnosis. In a retrospective study we used an i-DDA system to evaluate a series of 856 excised, clinically atypical pigmented skin lesions (584 benign and 272 malignant). The system evaluated 48 parameters to be studied as possible discriminant variables, grouped into four categories (geometries, colours, textures and islands of colour) integrated with three personal metadata items (sex, age and site of lesion) and presence/absence of three dermoscopic patterns (regression structures, blue-white veil and polymorphic vascular structures). Stepwise multivariate logistic regression of i-DDA data selected nine variables with the highest possible discriminant power. At the end of the stepwise procedure the percentage of cases correctly classified by i-DDA was 89.2% (100% sensitivity and 40.8% specificity). The limitations of the study included those associated with a retrospective design and the 'a priori' exclusion of nonmelanocytic skin lesions. By incorporating numerical digital features with personal data and some dermoscopic patterns into the learning process, the proposed i-DDA improved the performance of assisted melanoma diagnosis, with the advantage that our results can be objectively repeated in any other clinical setting.