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Psoriasis is a chronic, immune-mediated, inflammatory skin disease, associated with multiple comorbidities and psychological and psychiatric disorders. The quality of life of patients with this disease is severely compromised, especially in moderate-to-severe plaque psoriasis. Secukinumab, a fully humanized monoclonal antibody, was the first anti-interleukin (IL)-17 biologic approved for treating psoriasis. Secukinumab demonstrated long-lasting efficacy and a good safety profile in individuals with plaque psoriasis, and it is associated with an improvement in health-related quality of life. While there is evidence that early treatment with systemic therapy can affect disease progression and improve long-term outcomes in other autoimmune diseases, evidence is limited in psoriasis, especially in real-world settings. This review provides an overview of studies describing the effectiveness of secukinumab in the treatment of psoriasis summarizing the literature and focusing on real-world evidence and early intervention. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a chronic inflammatory skin condition that affects millions of individuals worldwide, impacting their physical and emotional well-being. The management of psoriasis requires effective communication and a strong physician–patient relationship. Objective: We aim to develop a novel algorithm to enhance patient well-being and care in moderate-to-severe psoriasis, considering the time constraints that dermatologists have in public hospitals. Methods: This project employed a multidisciplinary approach, involving collaboration between 14 experienced dermatologists (referred to as Key Opinion Leaders: KOLs) and a psychologist. During three separate meetings (an initial virtual session, a face-to-face meeting, and a final virtual meeting), an algorithm (Embracing Patients' Well-being in their Journey of Moderate-to-Severe psoriasis: EMPATHY), describing the patient's reception through the entire first visit and follow-up visits, was developed and refined. Results: The EMPATHY algorithm provides a step-by-step approach from the moment the patient arrives at reception, through the first visit and on to subsequent visits. This algorithm fills a critical gap in the existing guidelines by specifically addressing how to foster empathy during psoriasis patient visits within time-limited consultations. The algorithm outlines patient-centered strategies at each visit. Key aspects include creating a welcoming environment, active listening, respecting privacy, tailoring communication styles, and managing patient expectations. Conclusions: The EMPATHY algorithm represents a novel and promising approach to improving patient care and well-being in moderate-to-severe psoriasis. Developed together by dermatologists and a psychologist, this algorithm offers healthcare providers practical guidance for managing both initial and follow-up patient visits. While further validation is necessary, the potential for adapting the EMPATHY algorithm to diverse healthcare settings and patient populations holds promise for improving patient outcomes across various chronic conditions. [ABSTRACT FROM AUTHOR]

Objectives: Atopic dermatitis (AD) is a chronic inflammatory skin disease often associated with non-atopic comorbidities. Recently, a severity-dependent relationship between AD and sleep/mental health diseases has been proposed. However, few studies investigated these comorbidities and their association with AD severity through validated questionnaires. This study aimed to use a set of validated instruments to assess the impact of AD on sleep and psychological disorders and estimate the association of itch and AD severity with sleep disorders and psychological symptoms, distinguishing between clinical-oriented and patient-oriented measures. Methods: We conducted a case-control study, recruiting 57 adult AD patients (mean age ± std. dev. 34.28 years ± 13.07; 27 males) matched for age and sex with 57 healthy adults (34.39 years ± 13.09; 27 males). To investigate the differences in sleep quality, insomnia, depression, and anxiety between the two groups, we performed independent sample t-Tests. Moreover, we conducted univariate linear regression analyses to examine the relationship between itch and objective/subjective severity of AD and sleep quality, insomnia, and psychological symptoms. Results: AD patients reported lower sleep quality (p = 0.002), more severe insomnia (p = 0.006) and depression (p = 0.013), and higher stress levels than healthy adults (p = 0.049). Itch intensity was linked to sleep disturbances and psychological symptoms (R2range = 0.13–0.19, prange = 0.02–<0.001). Objective and subjective AD severity were similarly associated with worse sleep quality (R2 = 0.26, p < 0.001; R2 = 0.24, p < 0.001; respectively), anxiety (R2 = 0.15, p = 0.04; R2 = 0.17, p = 0.001; respectively), and self-perceived stress (R2 = 0.10, p = 0.02; R2 = 0.07, p = 0.049; respectively). However, subjective AD severity was more strongly associated with insomnia (R2 = 0.31, p < 0.001) and depression (R2 = 0.20, p < 0.001) than clinical-oriented AD severity (R2 = 0.19, p < 0.001; R2 = 0.05, p = 0.098; respectively). Conclusions: The study demonstrated poor sleep quality and high levels of insomnia, depression, and stress in AD patients, with an aggravated psychological status for adults with more severe skin disease. We suggest implementing a multidisciplinary approach to AD management/treatment that considers objective and subjective measures of disease severity. [ABSTRACT FROM AUTHOR]

Background: The differential diagnosis of atypical melanocytic skin lesions localized on palms and soles represents a diagnostic challenge: indeed, this spectrum encompasses atypical nevi (AN) and early-stage melanomas (EN) displaying overlapping clinical and dermoscopic features. This often generates unnecessary excisions or delayed diagnosis. Investigations to date were mostly carried out in specific populations, focusing either on acrolentiginous melanomas or morphologically typical acquired nevi. Aims: To investigate the dermoscopic features of atypical melanocytic palmoplantar skin lesions (aMPPLs) as evaluated by variously skilled dermatologists and assess their concordance; to investigate the variations in dermoscopic appearance according to precise location on palms and soles; to detect the features with the strongest association with malignancy/benignity in each specific site. Methods: A dataset of 471 aMPPLs—excised in the suspect of malignancy—was collected from 10 European Centers, including a standardized dermoscopic picture (17×) and lesion/patient metadata. An anatomical classification into 17 subareas was considered, along with an anatomo-functional classification considering pressure/friction, (4 macroareas). A total of 156 participants (95 with less than 5 years of experience in dermoscopy and 61 with ≥than 5 years) from 17 countries performed a blinded tele-dermoscopic pattern analysis over 20 cases through a specifically realized web platform. Results: A total of 37,440 dermoscopic evaluations were obtained over 94 (20%) EM and 377 (80%) AN. The areas with the highest density of EM compared to AN were the heel (40.3% EM/aMPPLs) of the sole and the "fingers area" (33%EM/aMPPLs) of the palm, both characterized by intense/chronic traumatism/friction. Globally, the recognition rates of 12 dermoscopic patterns were non statistically different between 95 dermatology residents and 61 specialists: aMPPLs in the plantar arch appeared to be the most "difficult" to diagnose, the parallel ridge pattern was poorly recognized and irregular/regular fibrillar patterns often misinterpreted. Regarding the aMPPL of the "heel area", the parallel furrow pattern (p = 0.014) and lattice-like pattern (p = 0.001) significantly discriminated benign cases, while asymmetry of colors (p = 0.002) and regression structures (p = 0.025) malignant ones. In aMPPLs of the "plantar arch", the lattice-like pattern (p = 0.012) was significant for benignity and asymmetry of structures, asymmetry of colors, regression structures, or blue-white veil for malignancy. In palmar lesions, no data were significant in the discrimination between malignant and benign aMPPLs. Conclusions: This study highlights that (i) the pattern analysis of aMPPLs is challenging for both experienced and novice dermoscopists; (ii) the histological distribution varies according to the anatomo-functional classification; and (iii) different dermoscopic patterns are able to discriminate malignant from benign aMPPLs within specific plantar and palmar areas. [ABSTRACT FROM AUTHOR]

A collaboration of multidisciplinary experts from the European Association of Dermato‐Oncology, the European Dermatology Forum, the European Academy of Dermatology and Venereology, and the European Union of Medical Specialists was formed to develop European recommendations on AK diagnosis and treatment, based on current literature and expert consensus. This guideline addresses the epidemiology, diagnostics, risk stratification and treatments in immunocompetent as well as immunosuppressed patients. Actinic keratoses (AK) are potential precursors of cutaneous squamous cell carcinoma (cSCC) and display typical histopathologic and immunohistochemical features of this malignancy in an early stage. They can develop into cSSC in situ and become invasive in a low percentage of cases. AK is the most frequent neoplasia in white populations, frequently occurring within a cancerous field induced by ultraviolet radiation. Since it cannot be predicted, which lesion will progress to cSCC and when treatment is usually recommended. The diagnosis of AK and field cancerization is made by clinical examination. Dermatoscopy, confocal microscopy, optical coherence tomography or line‐field confocal‐OCT can help in the differential diagnosis of AK and other skin neoplasms. A biopsy is indicated in clinically and/or dermatoscopically suspicious and/or treatment‐refractory lesions. The choice of treatment depends on patients' and lesion characteristics. For single non‐hyperkeratotic lesions, the treatment can be started upon patient's request with destructive treatments or topical treatments. For multiple lesions, field cancerization treatment is advised with topical treatments and photodynamic therapy. Preventive measures such as sun protection, self‐examination and repeated field cancerization treatments of previously affected skin areas in high‐risk patients are advised. [ABSTRACT FROM AUTHOR]

Bowen's disease represents the in situ form of cutaneous squamous cell carcinoma; although it has an excellent prognosis, 3–5% of lesions progress to invasive cutaneous squamous cell carcinoma, with a higher risk in immunocompromised patients. Treatment is therefore always necessary, and conventional photodynamic therapy is a first-line option. The aim of this review is to provide an overview of the clinical response, recurrence rates, safety, and cosmetic outcome of photodynamic therapy in the treatment of Bowen's disease, considering different protocols in terms of photosensitizers, light source, and combination treatments. Photodynamic therapy is a valuable option for tumors at sites where wound healing is poor/delayed, in the case of multiple and/or large tumors, and where surgery would be difficult or invasive. Dermoscopy and reflectance confocal microscopy can be used as valuable tools for monitoring the therapeutic response. The treatment is generally well tolerated, with mild side effects, and is associated with a good/excellent cosmetic outcome. Periodic follow-up after photodynamic therapy is essential because of the risk of recurrence and progression to cSCC. As the incidence of keratinocyte tumors increases, the therapeutic space for photodynamic therapy will further increase. [ABSTRACT FROM AUTHOR]

Background: The differential diagnosis of atypical melanocytic palmoplantar skin lesions (aMPLs) represents a diagnostic challenge, including atypical nevi (AN) and early melanomas (MMs) that display overlapping clinical and dermoscopic features. We aimed to set up a multicentric dataset of aMPL dermoscopic cases paired with multiple anamnestic risk factors and demographic and morphologic data. Methods: Each aMPL case was paired with a dermoscopic and clinical picture and a series of lesion-related data (maximum diameter value; location on the palm/sole in 17 areas; histologic diagnosis; and patient-related data (age, sex, family history of melanoma/sunburns, phototype, pheomelanin, eye/hair color, multiple/dysplastic body nevi, and traumatism on palms/soles). Results: A total of 542 aMPL cases—113 MM and 429 AN—were collected from 195 males and 347 females. No sex prevalence was found for melanomas, while women were found to have relatively more nevi. Melanomas were prevalent on the heel, plantar arch, and fingers in patients aged 65.3 on average, with an average diameter of 17 mm. Atypical nevi were prevalent on the plantar arch and palmar area of patients aged 41.33 on average, with an average diameter of 7 mm. Conclusions: Keeping in mind the risk profile of an aMPL patient can help obtain a timely differentiation between malignant/benign cases, thus avoiding delayed and inappropriate excision, respectively, with the latter often causing discomfort/dysfunctional scarring, especially at acral sites. [ABSTRACT FROM AUTHOR]

Background and Objective: AtopyReg® is a multicenter, prospective, observational, non-profit cohort study on moderate-to-severe atopic dermatitis in adults promoted in 2018 by the Italian Society of Dermatology and Venereology (SIDeMaST). We aimed to describe baseline demographics, disease characteristics, comorbidities, and therapeutic data of adult patients affected by moderate-to-severe atopic dermatitis. Methods: Patients were selected based on the following inclusion criteria: age ≥ 18 years; Eczema Area and Severity Index score ≥ 16 or localization in visible or sensitive areas (face, neck, hands, or genitalia), or a Numeric Rating Scale itch score ≥ 7 or a Numeric Rating Scale sleep loss score ≥ 7, or a Dermatology Life Quality Index score ≥ 10. Demographic and clinical data at baseline were recorded and analyzed. Results: A total of 1170 patients (male 51.1%; mean age: 44.7 years; range 18–90 years) were enrolled by 12 Italian Dermatology Units between January 2019 and November 2022. Skin lesions were eczematous in 83.2% of patients, the most involved site were the flexures (53.9%), face (50.9%), and neck (48.0%). Mean Eczema Area and Severity Index score was 22.3, mean Dermatology Life Quality Index value was 17.6, mean Patient Oriented Eczema Measure score was 13.1, and mean Numeric Rating Scale itch and sleep loss scores were 7.6 and 5.9, respectively. Previous systemic therapies were corticosteroids in 77.7% of patients, antihistamines in 50.3% of patients, and cyclosporine A in 42.6% of patients. Conclusions: This baseline data analysis deriving from AtopyReg® provides real-life evidence on patients with moderate-to-severe atopic dermatitis in Italy confirming the high burden of atopic dermatitis with a significant impact on patients' quality of life. [ABSTRACT FROM AUTHOR]

Background: Subungual melanoma (SM) is an unusual type of melanocytic tumor affecting the nail apparatus. The mutational prevalence of the most prominently mutated genes in melanoma has been reported in small cohorts of SM, with unclear conclusions on whether SM is different from the rest of melanomas arising in acral locations or not. Hence, the molecular profile of a large series of SM is yet to be described. Objectives: The aim of this study was to describe the molecular characteristics of a large series of SM and their association with demographic and histopathological features. Methods: Patients diagnosed with SM between 2001 and 2021 were identified from six Spanish and Italian healthcare centers. The mutational status for BRAF, NRAS, KIT, and the promoter region of TERT (TERTp) were determined either by Sanger sequencing or next-generation sequencing. Clinical data were retrieved from the hospital databases to elucidate potential associations. Results: A total of 68 SM cases were included. Mutations were most common in BRAF (10.3%) and KIT (10%), followed by NRAS (7.6%), and TERTp (3.8%). Their prevalence was similar to that of non-subungual acral melanoma but higher in SM located on the hand than on the foot. Conclusions: To date, this study represents the largest cohort of SM patients with data on the known driver gene mutations. The low mutation rate supports a different etiopathogenic mechanism for SM in comparison of non-acral cutaneous melanoma, particularly for SM of the foot. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS) is a chronic-relapsing inflammatory skin disease. It usually appears in the second and third decades, but a smaller proportion of patients develop late-onset HS. Geriatric HS, defined as the persistence or the development of HS after the age of 65 years, has been poorly explored. This study aimed to investigate the clinical features, treatment management and response to therapies of HS elderly subjects (≥65 years old). We designed a multicentric observational study, gathering data from seven Italian university hospitals. Demographic and clinical data of HS patients aged over 65 years were collected at baseline, week 12 and week 24. Overall, 57 elderly subjects suffering from HS were enrolled. At baseline, disease severity was predominantly moderate-to-severe, with 45.6% of patients classified as Hurley III. The gluteal phenotype was the most frequently observed; it also appeared to affect patients' quality of life more than other phenotypes. Gluteal involvement was detected in about half (49.1%) of cases and associated with severe stages of the disease. In terms of therapeutic response, Hurley III patients showed the persistency of higher values of mean IHS4, DLQI, itch- and pain-NRS scores compared to Hurley I/II. In conclusion, disease severity in this subpopulation appears high and treatment is often challenging. [ABSTRACT FROM AUTHOR]

Background: Janus kinase (JAK) inhibitors, including upadacitinib, have been recently approved for the treatment of moderate-severe atopic dermatitis (AD) and real-world data on upadacitinib effectiveness and safety are limited. This interim analysis aimed to assess effectiveness and safety of upadacitinib throughout 48 weeks of observation in a real-world adult AD population. Methods: This prospective study collected data on adult patients affected by moderate-to-severe AD and treated with upadacitinib at the dosage of either 15 mg or 30 mg daily based on the physician decision. Upadacitinib was prescribed in the context of a national compassionate use programme. In this interim analysis, within patient comparisons of continuous scores of different scales (namely Eczema Area and Severity Index [EASI], body surface area [BSA], Dermatology Life Quality Index [DLQI], Patient Oriented Eczema Measure [POEM], Numeric Rating Scale [NRS] subtests) were performed. The percentage of patients achieving EASI 75, EASI 90 and EASI 100 at Week 16, 32 and 48 was also evaluated. Results: One hundred and forty-six patients were included in the analysis. Upadacitinib 15 mg or 30 mg daily was prescribed as monotherapy in most cases (127/146, 87.0%). Upadacitinib was initially prescribed at the dosage of 30 mg daily in 118 of 146 (80.8%) patients and 15 mg daily in 28/146 (19.2%) patients. A significant improvement in the clinical signs and symptoms of AD was detected by Week 16 and throughout the study period. EASI 75, EASI 90 and EASI 100 responses were achieved by 87.6%, 69.1% and 44.3% at Week 48, associated with a sustained reduction in the mean values of all physician-reported (EASI and BSA) and patient-reported (Itch- Sleep- and Pain-NRS, DLQI, and POEM) disease severity outcomes, up to 48 weeks of treatment. Treatment response observed in 15 mg upadacitinib-treated patients was comparable with that detected in 30 mg upadacitinib-treated patients, revealing no statistical difference between the two patient sub-cohorts. Through the observation period, dose reduction or escalation was observed in 38/146 (26%) of treated cases. Overall, 26 of 146 (17.8%) patients experienced at least one adverse event (AE) during the treatment period. In total, 29 AEs were recorded and most of them were evaluated as mild to moderate, while in 4 cases the occurrence of AE led to drug discontinuation, for a total of 7/146 (4.8%) dropouts. Conclusion: This study provides strong evidence of a sustained response obtained by upadacitinib in AD patients, who had failed to respond to conventional or biological systemic agents, through 48 weeks of observation. Upadacitinib was also demonstrated to be advantageous in terms of flexibility in dose reduction or escalation as upadacitinib dose was shaped on clinical needs that, in a real-world setting, might frequently change. [ABSTRACT FROM AUTHOR]

Several comprehensive and updated guidelines are available on the management of psoriasis with systemic treatments. However, there is a lack of updates in recommendations and guidelines on topical treatments, particularly regarding the latest evidence and developments in treatment formulations. Consequently, a comprehensive literature review on this topic, considering the continuous evolution of knowledge and evaluation of the relevance of the available literature evidence, represents a current need to improve the topical management of psoriasis. This study critically appraises the available literature on all topical treatments of psoriasis from the past 20 years to address some relevant issues, such as the vehicle associated with the highest effectiveness, the best vehicle for improving patient adherence, and the best strategy in terms of efficacy and safety for long-term treatment. The greater effectiveness of the foam formulation was demonstrated for calcipotriene/betamethasone dipropionate (Cal/BD) administration compared with the gel and ointment. Without a direct comparison, matching-adjusted indirect comparison analyses support the superiority of the foam versus the cream overall. In addition, the reduced treatment period required by the Cal/BD foam (4 weeks) may favor this formulation over cream (8 weeks). The literature evidence, supported by a broad clinical experience, reported high rates of acceptability and adherence for the foam vehicle. A growing consensus is shared among dermatologists sustaining the proactive approach as the best option for the long-term topical treatment of psoriasis in adults. The Cal/BD foam is the only treatment for which the approved label allows biweekly maintenance use (proactive management), thus representing the first option for long-term topical treatment. [ABSTRACT FROM AUTHOR]

Background: Advanced basal cell carcinoma (aBCC) represents a complex and clinically heterogeneous group of lesions for which curative surgery and/or radiotherapy is unlikely. Systemic therapy with hedgehog pathway inhibitors (HHIs) changed the treatment landscape for this complex patient population. Objectives: The aims of the present study are to describe the clinical characteristics of a real-life Italian cohort diagnosed with aBCC and to investigate effectiveness and safety of HHI. Methods: A multicenter observational study was performed by twelve Italian centers in the period January 1, 2016 – October 15, 2022. Patients aged ≥18 years and diagnosed with aBCC (locally advanced [laBCC] and metastatic BCC [mBCC]) were eligible for the study. Methods for investigating tumor response to HHI included clinical and dermatoscopic evaluation, radiological imaging, and histopathology. For HHI safety assessment, therapy-related adverse events (AEs) were reported and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: We enrolled 178 patients under treatment with HHI: 126 (70.8%) and 52 patients (29.2%) received sonidegib and vismodegib, respectively. Comprehensive data on HHI effectiveness and disease outcome were available for 132 (74.1%) of 178 patients: 129 patients had a diagnosis of laBCC (n = 84, sonidegib; n = 45, vismodegib) and 3 patients of mBCC (n = 2, vismodegib; n = 1, sonidegib, off-label). Objective response rate was 76.7% (95% confidence interval [CI]: 82.3–68.7) and 33.3% (95% CI: 88.2–1.7) for laBCC (complete response [CR]: 43/129; PR: 56/129) and mBCC (CR: 0/3; PR: 1/3), respectively. High-risk aBCC histopathological subtypes and occurrence of >2 therapy-related AEs were significantly associated with nonresponse to HHI therapy ([OR: 2.61; 95% CI: 1.09–6.05; p: 0.03] and [OR: 2.74; 95% CI: 1.03–7.9; p: 0.04]), respectively. Majority of our cohort (54.5%) developed at least 1 therapy-related AE, most of which were mild-moderate in severity. Conclusions: Our results demonstrate the effectiveness and safety profile of HHI and confirm the reproducibility of pivotal trial results in real-life clinical setting. [ABSTRACT FROM AUTHOR]

Despite the introduction of targeted (BRAFi/MEKi) and immune checkpoint inhibitors (ICIs) has significantly reduced the recurrence rate and improved the overall survival (OS) of patients with Stage III and IV melanoma, only a percentage will benefit of durable disease control. The aim of this study was to examine whether the levels of circulating tumour DNA (ctDNA) in plasma of advanced melanoma patients undergoing BRAFi/MEKi or ICIs vary according to the patients' survival outcomes (i.e. progression‐free survival (PFS) and OS) and disease progression. Plasma samples of Stage III‐IV melanoma patients were collected at baseline (treatment initiation) and thereafter every 3 months. Circulating BRAFV600E/K and NRASQ61R/K mutations were analysed through droplet digital PCR (ddPCR, Bio‐Rad) in a total of 177 plasma samples from 48 melanoma patients (19 Stage III, 29 Stage IV). Baseline ctDNA concentration was significantly associated with OS (HR = 1.003, 95% CI = 1.000–1.006, p = 0.043) and PFS (HR = 1.004, 95% CI = 1.000–1.007, p = 0.029) independent of clinical‐prognostic confounders. For each unit increase in the ∆ctDNA (concentration difference between the last follow‐up and baseline) there was a 24% increased risk of disease progression, irrespective of treatment type and stage at diagnosis (OR = 1.24, 95% CI = 1.03–1.49, p = 0.020, AUC = 0.93). Patients with reduction of ctDNA level from baseline to the last follow‐up had longer OS (HR = 0.14; 95% CI = 0.05–0.44, p = 0.001) and PFS (HR = 0.08; 95% CI = 0.03–0.27, p < 0.0001) compared to patients with increased ctDNA, including adjustment for confounding factors. Our findings suggest that variation of ctDNA over time during melanoma treatment reflects the clinical outcome and tumour response to therapy and might be helpful in clinical monitoring. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common inflammatory chronic skin disease typically associated with atopic comorbidities and other non-atopic conditions such as sleep disturbances, and mood/anxiety disorders. A growing literature proposed a crucial role of sleep disturbances in the development of mental health problems in AD. We tested this assumption by mediation model analyses in adult AD patients. A total of 57 patients (mean age ± std. dev., 34.28 ± 13.07 years; 27 males; range 18–67 years) diagnosed with AD participated in a cross-sectional study. We evaluated self-perceived severity of AD, insomnia, depression, and anxiety symptoms using validated questionnaires: the Patient-Oriented Eczema Measure (POEM), the Insomnia Severity Index (ISI), the Beck Depression Inventory-second edition (BDI-II), and the Generalized Anxiety Disorder-7 scale (GAD-7), respectively. Two mediation models were performed, testing the mediation effect of insomnia symptoms on the relationship between AD severity and depression (model 1) and anxiety (model 2). AD symptoms, as expressed by POEM, were positively associated with insomnia, depression, and anxiety severity. Insomnia fully mediated the effect of AD severity on depression and anxiety. Specifically, insomnia accounted for 81.64% of the relationship between atopic eczema severity and depression, and for 81.84% of the effect of AD severity on anxiety symptoms. The present study proposed a critical role of insomnia in predisposing adult AD patients to experience depression and anxiety. Early interventions focused on treating sleep disturbances could indirectly be beneficial on mental health of patients with AD, counteracting the onset and exacerbation of anxiety and depression disorders. [ABSTRACT FROM AUTHOR]

Background: The idea of psoriatic disease continuum has been progressively prompted based on the advances of the knowledge about the pathogenic steps underpinning the occurrence of psoriasis (PSO) and psoriatic arthritis (PSA). To evaluate biomolecules (inflammatory cytokines, inflammatory chemokines, cell adhesion and cellular mediators) in naïve patients with PSO, PSA with PSO, and PSA sine PSO. To stratify the results considering the presence of psoriatic nail involvement, extensive skin disease and obesity evaluating all involved patients. Methods: By multiplex technology, 20 serum biomolecules were assessed with the inclusion of pro-inflammatory cytokines (GM-CSF, IFN-γ, IL-1α, IL-1β, IL-6, IL-8, IL-12p70, IL-17A, IL-23, TNF), anti-inflammatory cytokines (IFN-α, IL-4, IL-10, IL-13), inflammatory chemokines (IP-10, MCP-1, MIP-1α, MIP-1β), cell adhesion and cellular mediators (ICAM-1, E-selectin, P-selectin). The assessment of possible statistical differences between the means of the three groups was performed by One-Way ANOVA. In addition, by non-parametric T-tests, we stratified the results according to selected clinical characteristics (psoriatic nail involvement, PASI ≥ 10, BMI ≥ 30). Results: In 80 assessed naïve patients, patients with PSO showed significant increases of E-selectin (p=0.021) and IL-8 (0.041) than other groups. In patients with PSA with PSO, significant higher levels of ICAM-1 were observed (p=0.009) than other groups. We did not observe further differences comparing pro-inflammatory and anti-inflammatory cytokines, inflammatory chemokines, and cell adhesion and cellular mediators in patients with PSO, PSA with PSO, and PSA sine PSO. Patients with psoriatic onychopathy showed significant increased levels of ICAM-1 (p=0.010) and IP-10 (0.030) than others. In patients with PASI ≥ 10, significantly enhanced values of IL-8 (p=0.004), TNF (p=0.013), E-selectin (p=0.004), MIP-1α (p=0.003), and MIP-1β (p=0.039). In patients with BMI ≥ 30, significantly higher levels of E-selectin were pointed out (p=0.035) than others. Conclusion: Our findings may suggest that a similar cytokine profile may characterize naïve patients with PSO, PSA with PSO, and PSA sine PSO, reinforcing the concept of psoriatic disease continuum. However, some differences may be also shown, underlying possible pathogenic differences and leading to the clinical heterogeneity of these patients. [ABSTRACT FROM AUTHOR]

Methyl aminolevulinate (MAL) is a topical compound approved for use with photodynamic therapy (PDT) for the treatment of actinic keratosis (AK) and field cancerization in certain countries. There exists a high burden of disease for patients with AK: repeated treatments are required, there is a known risk of progression to keratinocyte carcinoma, and cosmetic appearance is affected. Delivery of PDT using MAL is a flexible treatment strategy available in many forms; red light, daylight, or artificial daylight can be used for illumination, all of which result in high AK clearance rates and low recurrence. MAL-PDT protocols continue to evolve to further improve adherence and treatment outcomes. Here, we used PubMed to search MEDLINE to identify guidelines, consensus recommendations, and studies describing the use of MAL for the treatment of AK. The aim of this targeted review is to consider various MAL-PDT treatment strategies on the basis of published literature, with a focus on personalizing treatment for the heterogeneous AK population. [ABSTRACT FROM AUTHOR]

Brodalumab is a recombinant, fully human immunoglobulin IgG2 monoclonal antibody specifically targeted against interleukin-17RA that has been approved for the treatment of moderate-to-severe psoriasis in Europe. We developed a Delphi consensus document focused on brodalumab for the treatment of moderate-to-severe psoriasis. Based on published literature and their clinical experience a steering committee drafted 17 statements covering 7 domains specific to the treatment of moderate-to-severe psoriasis with brodalumab. A panel of 32 Italian dermatologists indicated their level of agreement using a 5-point Likert scale (from 1 = "strongly disagree" to 5 = "strongly agree") using an online modified Delphi method. After the first round of voting (32 participants), positive consensus was reached for 15/17 (88.2%) of the proposed statements. Following a face-to-face virtual meeting, the steering committee decided that 5 statements would form "main principles" and 10 statements formed the final list. After a second round of voting, consensus was reached in 4/5 (80%) of the main principles and 8/10 (80%) for consensus statements. The final list of 5 main principles and 10 consensus statements identify key indications specific to the use of brodalumab in the treatment of moderate-to-severe psoriasis in Italy. These statements aid dermatologists in the management of patients with moderate-to-severe psoriasis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Advanced cutaneous squamous cell carcinoma (aCSCC) represents an area of unmet clinical need, with no standardized treatments until the recent approval of immune checkpoint inhibitors (ICIs). Objectives: The aim of the study was to describe clinical characteristics and therapeutic strategies of a real-life Italian cohort of aCSCC patients managed at the beginning of cemiplimab approval as compassionate use in Italy. Methods: A multicenter retrospective study was performed by 10 Italian centers in the period January 1, 2018–May 31, 2020. Patients aged ≥18 years and diagnosed with aCSCC (locally aCSCC and metastatic CSCC) were eligible for the study. Analysis of patients' characteristics and treatment strategies was performed. Results: 239 patients were initially recruited in the study: 19 patients were excluded due to incomplete data collection, yielding a final cohort of 220 patients, of which 191 and 220 were included for patients' clinical characteristics and therapeutic intervention analysis, respectively. Median age at the time of diagnosis was 81 years (range: 72–86); nodal metastases were detected in 64/220 (29%) patients, and distant metastatic spread was reported in 33/220 (15%) patients. Most of our patients referred chronic occupational and/or recreational sun exposure, experienced ≥1 sunburn during their lifetime, never wore hats or used photoprotective filters, and presented with signs of cumulative sun damage (solar lentigines and/or actinic keratosis). Majority of our cohort received at least one intervention directed to the primary tumor (n = 212, 96.3%); surgery and radiotherapy were the most common therapeutic choices. Immunotherapy was administered to a small number of patients as compassionate use, especially in the metastatic setting. Conclusions: Our study outlines the complex and heterogeneous clinical and therapeutic landscape of aCSCC patients at the beginning of ICI era, highlighting the need of a standardized care for this fragile and high-need patient population. [ABSTRACT FROM AUTHOR]

Purpose: Secukinumab is a fully human monoclonal antibody that inhibits interleukin (IL)-17A approved for the treatment of moderate to severe plaque psoriasis in adults and children. We compared the efficacy and safety of secukinumab in patients aged < 65 years (adult patients) versus patients aged ≥ 65 years (elderly patients) in a post-hoc analysis of the SUPREME study. Patients and Methods: Patients with moderate to severe plaque psoriasis received subcutaneous secukinumab 300 mg per week for the first 5 weeks, then 300 mg per month. We compared the following outcomes in patients aged ≥ 65 years vs < 65 years: baseline characteristics; PASI50/75/90/100 response rates (improvements ≥ 50%/75%/90%/100% in Psoriasis Area and Severity Index (PASI) from baseline); changes in Dermatology Life Quality Index (DLQI); Hospital Anxiety and Depression Scale (HAD-A, HAD-D) score changes; treatment-emergent adverse events (TEAEs). Results: Secukinumab was slightly less effective in elderly patients than in adult patients (response rates at week 16: PASI90, 69.4% vs 80.9%, p = 0.4528; PASI100, 44.4% vs 56.7%, p = 0.8973). Elderly and adult patients showed a similar time course of changes in absolute PASI scores. Patients aged ≥ 65 years had a statistically significantly lower improvement in quality of life (mean DLQI reduction) than patients aged < 65 years at week 16 [− 5.4 (± 4.3) vs − 8.8 (± 6.9), p = 0.0065] and at week 24 [− 5.3 (± 4.4) vs − 9.2 (± 7.1), p = 0.0038]. Secukinumab treatment resulted in comparable mean reductions in anxiety and depression scores in both cohorts at 24 weeks [HAD-A, − 1.3 (± 3.3) vs − 2.1 (± 3.8), p = 0.9004; HAD-D, − 1.0 (± 3.3) vs − 1.5 (± 3.1), p = 0.4598]. The frequency of TEAEs in the two cohorts was similar (16.7% vs 14.6%, p = 0.7391). Conclusion: Secukinumab is a valid option for the management of moderate to severe psoriasis in elderly patients. [ABSTRACT FROM AUTHOR]

Simple Summary: T cell immunoglobulin and mucin domain 3 (TIM-3) is an inhibitory immunocheckpoint expressed on cytotoxic CD8+ T lymphocytes, NK cells, and myeloid lineage cells in addition to Th1 lymphocytes. Various studies have investigated its role within the tumour microenvironment of melanoma, but also within the melanocytic component, with sometimes conflicting results. In this review, we address the most up-to-date knowledge about this molecule in the context of melanoma, attempting to outline future prospects and potential applications. T cell immunoglobulin and mucin domain 3 (TIM-3) is an inhibitory immunocheckpoint that belongs to the TIM gene family. Monney et al. first discovered it about 20 years ago and linked it to some autoimmune diseases; subsequent studies have revealed that some tumours, including melanoma, have the capacity to produce inhibitory ligands that bind to these receptor checkpoints on tumour-specific immune cells. We conducted a literature search using PubMed, Web of Science (WoS), Scopus, Google Scholar, and Cochrane, searching for the following keywords: "T cell immunoglobulin and mucin-domain containing-3", "TIM-3" and/or "Immunocheckpoint inhibitors" in combination with "malignant melanoma" or "human malignant melanoma" or "cutaneous melanoma". The literature search initially turned up 117 documents, 23 of which were duplicates. After verifying eligibility and inclusion criteria, 17 publications were ultimately included. A growing body of scientific evidence considers TIM-3 a valid inhibitory immuno-checkpoint with a very interesting potential in the field of melanoma. However, other recent studies have discovered new roles for TIM-3 that seem almost to contradict previous findings in this regard. All this demonstrates how common and valid the concept of 'pleiotropism' is in the TME field, in that the same molecule can behave completely or partially differently depending on the cell type considered or on temporary conditions. Further studies, large case series, and a special focus on the immunophenotype of TIM-3 are absolutely necessary in order to explore this highly promising topic in the near future. [ABSTRACT FROM AUTHOR]

Clinically and dermoscopically, trichoepithelioma (TE) often mimics basal cell carcinoma (BCC).[[1], [3]] In this multicentre case-control study, we sought to determine the clinical and dermoscopic features associated with TE as compared to BCC. Dermoscopic features of trichoepithelioma: A multicentre observational case-control study conducted by the International Dermoscopy Society These criteria were significant predictors of TE over BCC on univariate logistic regression and multivariate analysis (Figure 1). 1 TABLE Frequencies of dermoscopic features among trichoepithelioma (TE) and basal cell carcinoma (BCC). [Extracted from the article]

Hidradenitis suppurativa (HS) is a chronic autoinflammatory follicular disease, affecting body areas that are rich in apocrine glands. Moderate-to-severe HS may severely impair patients' quality of life also because the available therapies are often unsatisfactory. Several lines of evidence suggest that inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-17 play a pivotal role in the physiopathology of HS. TNF-α inhibitors have long been used with benefit in moderate-severe forms of HS. However, several monoclonal antibodies against IL-17 isoforms are currently being investigated for HS. We report the case of a 50-year-old man with long-standing HS and concomitant palmo-plantar psoriasis treated with brodalumab after failure of various TNF-α inhibitors. The HS lesions and the patient's quality of life improved steadily over time until week-136. Interestingly, the clinical benefit was confirmed by radiological improvement with MRI evaluation. Our case report demonstrates the long-term efficacy and safety of brodalumab in HS encouraging the use of drugs to inhibit the T helper-type 17 immune axis, especially in cases of HS refractory to therapy with TNF-α inhibitors. [ABSTRACT FROM AUTHOR]

Coupled with its rarity in non-endemic areas, the clinical heterogeneity of leprosy makes diagnosis very challenging. We report a diagnosis of multibacillary leprosy in a 22-year-old Indian woman, adopted at the age of 10 and living in Italy. The patient presented with painful skin lesions on the face, trunk, and lower and upper extremities, associated with dysesthesia and a motor deficit in her left leg following corticosteroid therapy interruption. Histopathology results from the skin lesions suggested leprosy, but no acid-fast bacilli were identified. Molecular biology in a center specializing in tropical diseases confirmed the diagnosis, allowing prompt and adequate treatment. Genotype analysis allowed the identification of a genotype 1D of M. leprae, facilitating the epidemiological investigation of the plausible infection origin. No resistances to rifampicin, dapsone, or ofloxacin were detected. Leprosy will continue to exist in high-income nations, and the incidence may rise over time due to increasing migration and globalization. CARE guidelines were followed. [ABSTRACT FROM AUTHOR]

Post-therapeutic relapse, poor survival rates and increasing incidence justify the search for novel therapeutic targets and strategies in cutaneous malignant melanoma (CMM). Within this context, a potential oncogenic role for TrkA in CMM is suggested by reports of NTRK1 amplification, enhanced TrkA expression and intracellular TrkA activation associated with poor prognosis. TrkA, however, exhibits tumour-suppressing properties in melanoma cell lines and has recently been reported not to be associated with CMM progression. To better understand these contradictions, we present the first analysis of potential oncogenic alternative TrkA mRNA splicing, associated with TrkA immunoreactivity, in CMMs, and compare the behaviour of fully spliced TrkA and the alternative TrkAIII splice variant in BRAF(V600E)-mutated A375 melanoma cells. Alternative TrkA splicing in CMMs was associated with unfolded protein response (UPR) activation. Of the several alternative TrkA mRNA splice variants detected, TrkAIII was the only variant with an open reading frame and, therefore, oncogenic potential. TrkAIII expression was more frequent in metastatic CMMs, predominated over fully spliced TrkA mRNA expression in ≈50% and was invariably linked to intracellular phosphorylated TrkA immunoreactivity. Phosphorylated TrkA species resembling TrkAIII were also detected in metastatic CMM extracts. In A375 cells, reductive stress induced UPR activation and promoted TrkAIII expression and, in transient transfectants, promoted TrkAIII and Akt phosphorylation, enhancing resistance to reductive stress-induced death, which was prevented by lestaurtinib and entrectinib. In contrast, fully spliced TrkA was dysfunctional in A375 cells. The data identify fully spliced TrkA dysfunction as a novel mechanism for reducing melanoma suppression, support a causal relationship between reductive stress, UPR activation, alternative TrkAIII splicing and TrkAIII activation and characterise a targetable oncogenic pro-survival role for TrkAIII in CMM. [ABSTRACT FROM AUTHOR]

Purpose: To characterize nail and enthesis abnormalities using high frequency ultrasound (HFUS) in patients with psoriasis (PSO), psoriatic arthritis (PSA) with PSO, and PSA sine PSO. Material and Methods: Patients with PSO, PSA with PSO, and PSA sine PSO were evaluated and compared in a cross-sectional single centre study. Nail and enthesis abnormalities were evaluated by HFUS using high frequency probes (27 MHz). After a descriptive assessment, Brown University Nail Enthesis Scale (BUNES) and Madrid Sonography Enthesitis Index (MASEI) were used to assess nail and enthesis, respectively. Results: Fifty-nine patients were enrolled (19 PSO, 22 PSA with PSO, 18 PSA sine PSO). In patients with PSO and in those with PSA and PSO, HFUS evaluation identified the following nail alterations characterised by thickened matrix, inhomogeneous echogenicity of the nail bed, and increased blood flow by power Doppler. In 38.9% patients with PSA sine PSO, a subclinical nail involvement was described. No difference was observed comparing BUNES values in three groups. In PSA patients with PSO and in those with PSA sine PSO, HFUS assessment of entheses mainly showed a hypoechoic aspect and thickness of the tendon, focal cortical erosion, and ossification. A subclinical enthesis involvement in 47.4% patients with PSO was observed. No difference was reported comparing MASEI values in three groups. Conclusion: Qualitative and quantitative abnormalities of nail and enthesis were demonstrated by HFUS in patients with PSO, PSA with PSO, and PSA sine PSO, suggesting a practical additional tool to be used in clinical settings. Furthermore, HFUS highlighted a subclinical nail involvement in patients with PSA sine PSO and enthesis subclinical alterations in patients with PSO. [ABSTRACT FROM AUTHOR]

Introduction: There is limited evidence to guide clinicians on the treatment of psoriasis with biologics in patients with a history of malignancy who are often excluded from clinical trials investigating biologics. The aim of this work is to report a multicenter real-life experience of secukinumab treatment in patients with psoriasis and a personal history of cancer. Methods: This retrospective observational study included adult patients with moderate-to-severe plaque psoriasis treated with secukinumab for at least 24 weeks and a previous diagnosis of cancer at 15 Italian referral centers. The primary endpoint of the study was tumor recurrence or progression and new cancer diagnosis during treatment. Secondary outcome assessment of secukinumab effectiveness (reduction of Psoriasis Area and Severity Index [PASI] score, improvement of Dermatology Life Quality Index [DLQI], itch and pain). Results: Forty-two patients (27 male) were included. Malignancy was diagnosed in the previous 5 years in 21 (56.8%) and in the previous 10 years in 37 (88.1%). The mean interval between cancer diagnosis and the start of secukinumab treatment was 3.5 ± 3.3 years. No tumor recurrence nor progression occurred over a mean of 56 ± 31.7 weeks of treatment. Three patients developed a new malignancy not related to the previous cancer. At week 48, PASI 90 was reached by 64.7% of patients and PASI 100 by 38.2%. Mean DLQI, itch, and pain VAS scores significantly improved during treatment. Conclusions: Our multicenter real-life experience is the largest reported to date focusing on a specific biologic and adds evidence to the safety of secukinumab in psoriatic patients with a personal history of cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Merkel cell carcinoma is rarely suspected and often misdiagnosed in the clinical setting. Robust epidemiological data are missing, contributing to a lack of knowledge of this type of tumor among clinicians. We aimed to demographically and clinically characterize Merkel cell carcinoma patients and the tumor's features through a multicenter real-world analysis of patients from Central Italy from 2015 to 2020. Our study revealed a higher incidence rate compared to the one estimated for the Italian population, with the lower limbs as the anatomical site affected the most. We also report that several specialists are involved in the first-line management of the pathology. In this light, a deeper knowledge of this tumor is advised. Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer that usually occurs in elderly people on sun-exposed areas, with a predisposition to local recurrence. Evidence suggests a growing incidence over the past decade; however, robust epidemiologic data are still lacking. We describe the MCC population in clinical practice in a retrospective analysis of demographic, clinical, and tumor characteristics from medical records of primary MCC patients, between 2015 and 2020, at six dermatology clinics in Central Italy. Ninety-four patients were included (57.4% male; mean age 78.2 ± 10.1 years, range 47–99 years). The estimated incidence rate of MCC was 0.93 per 100,000 inhabitants/year. Lower limbs were the most frequently affected site (31.5%), and 54% of patients for whom information was available were immunosuppressed. Lymph node involvement was reported in 42.5% of patients, and distant metastases in almost 20%. Most patients underwent surgery for tumor excision and were mainly referred to specialized dermatology clinics by dermatologists (47.9%) and general surgeons (28.7%). Apart from the relatively balanced prevalence of MCC in men and women, the predominant location on lower limbs, and the higher incidence rate compared with previous reports in Italy, this population is, overall, similar to the populations described in other observational studies. MCC management requires the involvement of several specialties. Increased awareness of MCC and standardization of its management are urgently needed. [ABSTRACT FROM AUTHOR]

This study aimed to compare adalimumab originator vs. biosimilar in HS patients, and to evaluate the effect of a switch to a biosimilar, or a switch back to the originator, in terms of treatment ineffectiveness. Patients with a diagnosis of HS were enrolled from 14 Italian sites. Treatment ineffectiveness was measured using Hurley score. The major analyses were 1) comparison between the two treatment groups (non-switcher analysis), and 2) the cross-over trend of Hurley score between treatment switchers (switcher analysis). Cox and Poisson regression models were used to compare the treatment ineffectiveness between groups. A total of 326 patients were divided into four groups: 171 (52.5%) taking originator; 61 (18.7%) patients taking biosimilar; 66 (20.2%) switchers; 28 (8.6%) switchers from originator to biosimilar and switched. A greater loss of efficacy was observed in the group allocated to the biosimilar than the originator group. The switcher analysis showed an effectiveness loss in the biosimilar compared to the originator. These results seem to indicate that a switch from one drug to the other may lead to a greater risk of inefficacy. A return to the previous treatment also does not ensure efficaciousness. [ABSTRACT FROM AUTHOR]

Background: Cutaneous melanoma accounts for the majority of skin cancer-related deaths. Readily identifiable phenotypic characteristics and total body nevus count (TBNC) >50 are among the most important risk factors for cutaneous melanoma. Implementation of nevus self-count procedures and self-assessment of phenotypic traits as part of skin self-examination could be an excellent screening tool for identifying an at-risk target population. Objectives: Objectives of the study were to assess the skills of a central Italian and eastern Spanish population sample to recognize their skin lesions via the submission of a self-assessment questionnaire and to explore which self-assessment questionnaire item combination best predicts the high-risk condition of TBNC >50. Methods: Patients aged ≥18 years filled a self-assessment questionnaire, autonomously and prior to the dermatological visit. Subsequently, dermatologists performed total body skin examination and reported patients' skin lesions on a separate questionnaire. Results: We reported fair to moderate patient-dermatologist agreement for skin lesion self-assessment. The item number of nevi on the back was the single questionnaire item most accurately predicting TBNC >50. The high-sensitivity and high-specificity classification and regression tree models for the prediction of TBNC >50 displayed different items combinations; the item nevus on the back was always the first and most important predictor in both our models. Conclusions: Patients were partially able to provide correct estimation of their whole-body nevus self-count. The item nevi on the back seems to be the first and most important predictor of TBNC >50 across our models. Delivery of high-sensitivity and high-specificity prediction models based on our questionnaire item combination may help defining a high-risk target population. [ABSTRACT FROM AUTHOR]

Background: The efficacy and safety of upadacitinib in atopic dermatitis (AD) have been defined in clinical trials, but no real-world data are currently available. We aimed to assess the safety and effectiveness of upadacitinib in a real-world AD patient cohort that mostly included patients who failed the available systemic therapies, including dupilumab. Methods: Prospective cohort study collecting data on upadacitinib-treated AD adult patients completing at least 16 weeks of therapy. Results: Forty-three patients showed rapid and marked response to upadacitinib with significant reduction of all disease severity scores since the first follow-up visit. At week 16, Eczema Area and Severity Index (EASI) 75, EASI 90, and EASI 100 response was observed in 97.5%, 82.1%, and 69.2% of patients, respectively. EASI 90 response reflected the achievement of a clear or almost clear condition (POEM 0-2), self-evaluated by 79.5% of patients. Patients' quality of life improved as suggested by the achievement of DLQI 0/1 by 38.5% of patients at week 4, and by 76.9% at week 16. Conclusion: Elevated effectiveness and favorable safety of upadacitinib were confirmed in patients unresponsive to dupilumab, who were not included in upadacitinib trials. [ABSTRACT FROM AUTHOR]

This document provides a list of criteria that are considered essential for determining which patients with cutaneous squamous cell carcinoma (cSCC) may benefit from adjuvant radiotherapy. The criteria include perineural invasion, invasion beyond subcutaneous fat, bone invasion, poor differentiation, tumor diameter ≥2 cm, recurrent tumor, initial surgical approach, life expectation, primary site nonhair-bearing lip, age of the patient, Breslow thickness exceeding 2 mm, Clark level of IV or higher, primary site ear, and the number of criteria met. Perineural invasion and bone invasion are particularly important risk factors for local, regional, and distant metastasis in cSCC. Standardizing these criteria will improve patient management and reduce the risk of recurrence and metastasis. The research received no specific funding and the authors declare no conflicts of interest. The data underlying the article will be shared upon request. [Extracted from the article]

Introduction: Psoriasis affects children with a considerable burden in early life. Treating pediatric psoriasis is challenging also because of the lack of updated specific guidelines. With the recent approval of several biologics for pediatric psoriasis and the ongoing COVID-19 pandemic, the management of young psoriatic patients is facing major changes. A revision of treatment recommendations is therefore needed. Methods: In September 2021, a board of six Italian dermatologists convened to update treatment recommendations. The board issued evidence- and consensus-based statements covering relevant areas of pediatric psoriasis, namely: assessment of psoriasis severity, management of children with psoriasis, and treatment of pediatric psoriasis. To reach consensus, the statements were submitted to a panel of 24 experts in a Delphi process performed entirely via videoconference. A treatment algorithm was produced. Results: There was full consensus that psoriasis severity is determined by the extension/severity of skin lesions, site of lesions, and impact on patient quality of life. Agreement was reached on the need for a multidisciplinary approach to pediatric psoriasis and the importance of patient/parents education. The relevance of vaccinations, including COVID-19 vaccination, for psoriatic children was acknowledged by all participants. Management issues that initially failed to reach consensus included the screening for psoriasis comorbidities and early treatment with biologics to prevent them and the use of telemedicine to facilitate patient follow-up. There was full consensus that topical corticosteroids are the first choice for the treatment of mild pediatric psoriasis, while phototherapy and systemic therapy are used in children with moderate-severe psoriasis. According to the proposed treatment algorithm, biologics are the first line of systemic therapy. Conclusions: Targeted systemic therapies are changing the treatment of moderate-severe pediatric psoriasis, while topical corticosteroids continue to be the first choice for mild disease. Children-centered research is needed to further improve the treatment of pediatric psoriasis. [ABSTRACT FROM AUTHOR]

While several high-penetrance melanoma risk genes are known, variation in these genes fail to explain melanoma susceptibility in a large proportion of high-risk families. As part of a melanoma family sequencing study, including 435 families from Mediterranean populations we identified a novel NRAS variant (c.170A > C, p.D57A) in an Italian melanoma-prone family. This variant is absent in exomes in gnomAD, ESP, UKBiobank, and the 1000 Genomes Project, as well as in 11,273 Mediterranean individuals and 109 melanoma-prone families from the US and Australia. This variant occurs in the GTP-binding pocket of NRAS. Differently from other RAS activating alterations, NRAS D57A expression is unable to activate MAPK-pathway both constitutively and after stimulation but enhances EGF-induced PI3K-pathway signaling in serum starved conditions in vitro. Consistent with in vitro data demonstrating that NRAS D57A does not enrich GTP binding, molecular modeling suggests that the D57A substitution would be expected to impair Mg2 + binding and decrease nucleotide-binding and GTPase activity of NRAS. While we cannot firmly establish NRAS c.170A > C (p.D57A) as a melanoma susceptibility variant, further investigation of NRAS as a familial melanoma gene is warranted. [ABSTRACT FROM AUTHOR]

A nationwide survey was conducted in adult patients with psoriasis (PsO) across Italy to obtain their real-world perspective of the impact of PsO on their wellbeing. Patients completed a 26-question survey (based on the patient benefit index; PBI, The Dermatology Life Quality Index; DLQI and the World Health Organization-five; WHO-5 wellbeing index) and workshop discussion sessions were undertaken by dermatologists to interpret results from the survey. 392 patients with PsO completed the survey. Analysis of results was restricted to patients who had moderate-to-severe plaque psoriasis (assessed by patients; n = 252; 64.3%). Dermatologists (n = 32) completed one question from the survey related to wellbeing and rated social, physical and mental domains as contributing to a similar extent, with comparable scores also observed by patients. For treatment, biologics yielded higher scores on average, whereas little difference was observed between topical and conventional systemic treatments. Only 23.8% of patients felt that their dermatologist was taking into consideration their wellbeing and 32.6% of the patients considered their therapy as inadequate in improving signs and symptoms of the disease. This survey identified key factors contributing to barriers impacting on patient wellbeing. Simple, but comprehensive questionnaires can provide important insight to patients' needs that may significantly increase clinician awareness during visits leading to tailored treatment. [ABSTRACT FROM AUTHOR]

Introduction: Dimethyl fumarate (DMF) is approved as oral systemic treatment for moderate-to-severe psoriasis. Scarce evidence is available for DMF treatment in psoriatic patients at the time of COVID-19 pandemic. The objective of this study was to assess the long-term effectiveness and safety of DMF monotherapy in moderate-to-severe psoriasis during the COVID-19 pandemic period. Methods: This multicenter, retrospective study included patients with moderate-to-severe psoriasis who had received a 48-week DMF treatment during the COVID-19 pandemic. Selected outcomes were: variation of mean PASI, proportion of patients achieving PASI50 and PASI75, variation of mean PGA and face PGA, genital PGA, scalp PGA, mean itch VAS and mean DLQI. Results: Forty-four patients were enrolled, and four patients became COVID-19 positive during the observation period but did not discontinue DMF therapy. DMF produced a significant improvement of signs and symptoms of psoriasis as expressed by mean PASI variation from 13.07 at baseline to 6.11 at week 48 (p < 0.0001), itch VAS from 3.22 at baseline to 1.18 at week 48 (p < 0.001), PGA from 2.84 at baseline to 1.30 at week 48 (p < 0.0001) and DLQI from 13.09 at baseline to 6.07 at week 48 (p < 0.0001). The percentage of patients who achieved PASI50 and PASI75 was 4.55% at week 4 and 59.09% at week 48 and 0% at week 4 and 22.73% at week 48, respectively. A clinical important decrease of mean PGA score was observed in all subgroups, face psoriasis, genital psoriasis and scalp psoriasis. Adverse events were predictable and manageable. Conclusions: DMF monotherapy is an effective and safe treatment option in moderate-to-severe psoriasis also in patients who develop SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Background: Skin toxicity in patients affected by metastatic colorectal cancer (mCRC) treated with epidermal growth factor receptor (EGFR) inhibitors is well known. However, ad hoc ESMO guidelines have only recently been published. Aim and methods: To describe the management (pre-emptive or reactive) of anti-EGFR-related cutaneous adverse events (AEs), in a real-life clinical context, in a selected population of patients with left-sided, metastatic RAS/BRAF wild-type mCRC treated with doublet chemotherapy plus anti-EGFR monoclonal antibody (i.e., panitumumab or cetuximab) as first-line regimen at 22 Institutions. The measured clinical outcomes were treatment-related adverse events, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: Of 515 patients included in the analysis, 173 (33.6%) received a pre-emptive and 342 (66.4%) a reactive treatment. The median follow-up period for the overall population was 30.0 months. A significantly lower incidence of any grade acneiform rash was found in the pre-emptive compared to the reactive cohort both in the overall population (78.6% vs 94.4%, p < 0.001) and in patients treated with panitumumab (76.1% vs 93.7%, p < 0.001) or cetuximab (83.3% vs 95.4%, p = 0.004), respectively. A lower incidence of any grade (41.6% vs 50.9%, p = 0.047) but a higher incidence of G3-G4 (9.2% vs 4.7%, p = 0.042) paronychia/nail disorders were found in the pre-emptive compared to the reactive cohort. Nevertheless, a lower rate of patients within the reactive compared to the pre-emptive cohort was referred to dermatological counseling (21.4% vs 15.3%, respectively, p = 0.001). A higher rate of anti-EGFR therapy modification was needed in the pre-emptive compared to the reactive cohort (35.9% vs 41.6%, respectively, p < 0.001). The pre-emptive approach did not reduce the efficacy of antineoplastic therapy compared to the reactive in terms of ORR (69.2% vs 72.8%), median PFS (12.3 vs 13.0 months), and median OS (28.8 vs 33.5 months). Conclusion: Although recommended by international guidelines, the pre-emptive approach of anti-EGFR-related skin toxicity in mCRC patients still appears less adopted in daily clinical practice, compared to the reactive one. A wider reception and application of this indication is desirable to improve patients' quality of life without compromising the continuity and efficacy of antineoplastic therapy. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disorder that is associated with higher rates of psychological disorders, but limited evidence supported the association with alexithymia, a psychoaffective dysfunction.Objectives: This study was aimed to investigate the occurrence of alexithymia in AD patients, compared to healthy subjects.Methods: This cross-sectional study assessed AD severity by the Eczema Area and Severity Index (EASI) score, sleeplessness and itch by a numeric rating scale (NRS), and alexithymia by the 20-item Toronto Alexithymia Scale (TAS-20) score. The association between disease characteristics and alexithymia was evaluated through several logistic regression models.Results: 202 AD patients and 240 healthy subjects were included in this study. The alexithymic personality trait (TAS-20 ≥51) was more frequently observed among AD patients compared to the control group (62.4% [126/202] vs. 29.2% [70/240], p < 0.0001). In particular, alexithymia (TAS-20 score ≥61) was detected in a significantly higher number of AD patients than in the controls (27.7% [56/202] vs. 7.5% [18/240]; p < 0.0001), whereas borderline alexithymia was detected in 34.6% (70/202) of AD patients compared to 21.7% of healthy controls. Alexithymia was more common among severe AD patients (43.6%) compared to mild AD patients (15.6%) and correlated with itch intensity and sleep disturbances. Among clinical variables, ordered logistic regression analyses revealed disease severity as predictor of alexithymia. Indeed, univariate analysis showed EASI score, sleep NRS, and itch NRS being significantly associated with alexithymia, while a multivariate model identified increased EASI score values as predicting factor.Conclusion: This study described alexithymia in AD patients correlating its occurrence with clinical AD severity markers (EASI score, itch, and sleeplessness) and identifying the increase in EASI score as predicting factor. [ABSTRACT FROM AUTHOR]

Cutaneous squamous cell carcinoma (CSCC) is the second most common skin malignancy in white-skinned populations. Only a minority of patients (<5%) develop advanced disease, but this is often difficult to treat and characterised by a poor prognosis. Cemiplimab, a fully human IgG4 monoclonal antibody against programmed cell death-1 receptor, is indicated for advanced (i.e. locally advanced or metastatic) CSCC. Although the definition of metastatic CSCC is clear, there is currently no agreed definition of locally advanced CSCC. In recent guidelines, locally advanced CSCC was described as non-metastatic CSCC that is unlikely to be cured with surgery, radiotherapy or combination treatment. A multi-disciplinary advisory group of Italian CSCC experts was convened to develop criteria to assist in identifying appropriate candidates for cemiplimab therapy in advanced CSCC, based on the literature and clinical experience. In locally advanced CSCC, absolute, or mandatory, criteria for the use of cemiplimab are deep invasion, multiple lesions without defined margins, inadequate surgical excision margins and multiple recurrences, whereas relative criteria include large lesions, in critical or functionally significant areas and that are surgically complex. In addition, physicians should consider patient willingness/preferences (an absolute criterion), and their age and health status/comorbidities (relative criteria). It is hoped that these proposed absolute and relative criteria will help guide rational identification of patients who will receive maximum benefit from immunotherapy, while more clinical data accumulate. [ABSTRACT FROM AUTHOR]

EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: An obserVAtional (CANOVA) study was aimed at providing real‐world evidence of the effectiveness of biologics in Italian patients with moderate–severe psoriasis. It was an observational, retro‐prospective cohort study conducted in 17 Italian dermatology clinics. Adult patients with moderate–severe plaque psoriasis, who started a biologic treatment between 24 weeks and 24 months before enrolment, were included. With a follow‐up visit at 6 months after enrolment, each patient had at least 12 months of observation. The primary objective was to describe the clinical response rates (PASI 75) after 16/24/52 weeks from biologic treatment start. Secondary outcomes were sustained response, quality of life, and treatment satisfaction. Of the 669 eligible patients (64% males), 52% were naïve to biologics, though a mean duration of psoriasis since first diagnosis of 18.6 years (SD 13.2). The most frequently prescribed biologics were secukinumab (41%), ustekinumab (25%), TNF‐inhibitors (22%) and ixekizumab (12%). PASI 75 was achieved by 86% of patients (95% CI: 82%–89%) at 16 weeks, 90% (87%–93%) at 24 weeks, and 91% (89%–94%) at 52 weeks. Patients achieving PASI 90 and PASI 100 at 52 weeks were 75% (71%–79%) and 53% (49%–57%), respectively. Sustained PASI 75 response after 1 year from treatment start was achieved by 78% (74%–82%) of patients. Mean DLQI total score was 2.3 (SD 3.9) at enrollment and decreased at the final visit to 1.8 (3.6). A high level of treatment satisfaction was expressed by patients over the study period. This large real‐world study confirms in the clinical practice the good effectiveness and acceptability of biologics in psoriasis patients. [ABSTRACT FROM AUTHOR]

Purpose: For patients with psoriasis, treatment adherence and persistence are fundamental if therapeutic goals are to be met. Patient Support Programs (PSPs) may be used as a support tool to assist patients and health care professionals optimize treatment and improve disease management. Patients and Methods: In Italy, the PSP PSOLife CARE, which began on the 9th of February 2017 and is ongoing, aimed to support patients with psoriasis under therapy with secukinumab (Cosentyx®). A team of medical professionals including Dermatologists, Psychologists, Nutritionists, and field Nurses provided outpatient treatment as well as remote support via phone calls. Patients had a standard duration in the Program of 6 months. This report analyzes the data of patients who benefited from the Program from February 2017 to August 2020, for a total observation of 42 months. Results: We provide here a descriptive report on the benefits of participation in the PSOLife CARE Program for patients with psoriasis and medical professionals involved in their care. Throughout their time in the PSOLife CARE Program, patient satisfaction remained consistently high with sustained improvements observed in all aspects of quality of life (ie emotional, social, physical, and economic). Despite exiting from the Program, most patients continued to adhere to secukinumab. Medical professionals also reported positive outcomes on their interactions with patients, with more than half of those surveyed rating the overall quality of the Program as "Outstanding". Conclusion: By supporting treatment adherence, the PSOLife CARE Program may have empowered patients to better manage their psoriasis, increasing their satisfaction with treatment and quality of life. [ABSTRACT FROM AUTHOR]

In daily practice management of psoriasis, evaluation of risk factors for infections is having a growing influence. Indeed, in psoriatic patients, risk of infections may be due to psoriasis itself, immunomodulatory therapy, and comorbidities that may increase this risk and patient hospitalization. Given the greater understanding of psoriasis pathogenesis and the increasing number of treatment options, it is particularly important to customize therapy according to each, single patient; psoriasis features and comorbidities are also essential to tailor treatment goals. In this perspective, the current knowledge on the infectious risk in psoriatic patient, related to comorbidities, such as diabetes mellitus, cardiovascular disease, and chronic obstructive pulmonary, to 'special populations,' to chronic infections, such as latent tuberculosis, chronic hepatitis B and C, and HIV, and to the most recent Covid-19 pandemic scenario, is reviewed and discussed in order to suggest the most appropriate approach and achieve the best available therapeutic option. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a chronic immune-mediated inflammatory skin disease which can also involve joints. It is often associated with burdensome comorbidities which negatively impact prognosis and quality of life (QoL). Biologic agents have been shown to be effective in controlling disease progression, but their use is associated with higher costs compared with traditional systemic treatments. The economic analysis of the CANOVA (EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: an obserVAtional longitudinal study of real-life clinical practice) study aims to assess the costs and cost-effectiveness of biologics in a real-world context in Italy.Methods: The annualised overall direct costs of moderate-to-severe plaque psoriasis management, the annualised cost of biologic drugs and the cost per responder in the Italian National Health System perspective were assessed. More specifically, the cost per response and cost per sustained response of the most prescribed biologic therapies for the treatment of moderate-to-severe plaque psoriasis within the CANOVA study were assessed using the Psoriasis Area Severity Index (PASI) at several score levels (75, 90 and 100%).Results: The most frequently used biologic therapies for plaque psoriasis were secukinumab, ustekinumab, adalimumab originator, and ixekizumab. Cost of biologics was the driver of expenditure, accounting for about 98% of total costs. Adalimumab originator was the biologic with the lowest cost per responder ratio (range: €7848 - €31,378), followed by secukinumab (range: €9015 - €33,419). Ustekinumab (range: €11,689 - €39,280) and ixekizumab (range: €11,092 - €34,289) ranked respectively third and fourth, in terms of cost-effectiveness ratio. As concerns the cost per sustained response analysis, secukinumab showed the lowest value observed (€21,375) over the other options, because of its high response rate (86% vs. 60-80%), which was achieved early in time.Conclusion: Biologic therapy is a valuable asset for the treatment of moderate-to-severe plaque psoriasis. Concomitant assessment of treatment costs against the expected therapeutic response over time can provide physicians and payers additional insights which can complement the traditional risk-benefit profile assessment and drive treatment decisions. [ABSTRACT FROM AUTHOR]

Topical treatment is the mainstay for mild or moderate psoriasis, but patients are generally little satisfied. Calcipotriol/betamethasone dipropionate (Cal/BD) cutaneous foam has shown to improve signs and symptoms in plaque psoriasis patients. This study assessed patient's satisfaction with Cal/BD foam in a real‐life Italian dermatological clinical practice. A multicenter, 4‐week observational prospective cohort study enrolled, in 17 Italian dermatology clinics, adult patients with plaque psoriasis on the body and/or scalp. Treatment satisfaction was assessed by 9‐item Treatment Satisfaction Questionnaire for Medication (TSQM‐9), preference over previous treatments by Patient Preference Questionnaire (PPQ), and change in disease state by Psoriasis Area Severity Index (PASI). Overall 256 patients were eligible, with a mean (SD) age of 55.6 (15.4) years, 59.4% were males. Psoriasis severity was mild in 52.0% of patients, moderate in 43.3%, and severe in 4.7%. Scalp involvement was present in 36.7% of patients. Previous antipsoriatic treatments had been received by 80.5% of patients. TSQM‐9 median (25th–75th percentile) scores were 83.3 (66.7–88.9) for effectiveness, 77.8 (66.7–88.9) for convenience, and 78.6 (64.3–92.9) for global satisfaction. Mean (SD) PASI value decreased from 7.3 (4.8) to 2.1 (2.7) after 4 weeks. More than 90% of patients previously treated for psoriasis evaluated the Cal/BD foam more effective, easier to use and better tolerated compared to previous topical treatments at PPQ. This observational study provides real‐life evidence of a high level of satisfaction with effectiveness and convenience of the Cal/BD foam in a cohort of plaque psoriasis patients, with an objective improvement in PASI. [ABSTRACT FROM AUTHOR]

Dupilumab showed significant improvement of adolescent atopic dermatitis (AD) signs and symptoms in clinical trials, with a good safety profile. Herein we report the real‐word effectiveness and safety of dupilumab in adolescents with moderate to severe AD from January to October 2020, during the COVID‐19 pandemic in Italy. All patients had a diagnosis of AD for a mean [SD] 12.8 [3.1] years. Baseline demographics, AD characteristics (EASI, cDLQI, NRS itch score, NRS sleep loss score) at baseline and week 16, and safety data were collected. Nineteen patients (52.6% men; mean [SD] age, 15.6 [1.4] years [range, 13–17 years]) were included in the analysis. All patients reached EASI‐50 and 78.9% EASI‐75, especially in those with EASI≥30 and BMI < 25 at baseline, with marked reduction for cDLQI (77.4%), NRS itch score (5.9 point), and NRS sleep loss score (87.5%). One patient contracted asymptomatic SARS‐CoV‐2 infection and 1 developed mild conjuntivitis, without stopping dupilumab. In this real‐word experience the effectiveness of dupilumab was excellent and resulted higher than that observed in clinical trials, with a good safety profile during COVID‐19 pandemic. [ABSTRACT FROM AUTHOR]

Introduction: Dupilumab is approved as first-line systemic treatment for adults/adolescents with moderate-to-severe atopic dermatitis (AD) in Europe and elsewhere owing to its favourable benefit–risk profile. However, systemic non-steroidal immunosuppressants (NSISS) are often used as first-line therapy in clinical practice. Impact of prior therapy with NSISS on dupilumab's treatment effect vs. control has not been described previously. This study assessed dupilumab's efficacy vs. control in patients with moderate-to-severe AD, comparing treatment effect in patients with/without prior systemic NSISS therapy, in four phase 3 trials. Methods: This post hoc analysis included 1553 patients randomized to placebo or dupilumab (300 mg q2w) as monotherapy for 16 weeks, or with concomitant topical corticosteroids (TCS) for 16/52 weeks, from four randomized, double-blind, placebo-controlled, phase 3 trials. Patients were stratified by prior use of systemic NSISS and dupilumab-treated patients were analysed against control groups (treated with placebo or placebo + TCS). Results: Dupilumab-treated patients, regardless of prior treatment with NSISS, achieved a significantly higher percentage reduction from baseline in Eczema Area and Severity Index (EASI), SCORing Atopic Dermatitis (SCORAD), Dermatology life Quality Index (DLQI), and Patient-Oriented Eczema Measure (POEM) vs. control; significantly more achieved EASI score ≤ 7, Peak Pruritus Numerical Rating Scale ≤ 4, POEM ≤ 7, and DLQI ≤ 5 by week 4. These rapid, significant improvements were seen with or without concomitant TCS and sustained through end-of-treatment. Conclusions: Dupilumab treatment (monotherapy or + TCS) provides rapid, significant, sustained improvements in signs, symptoms, and quality of life in patients with moderate-to-severe AD compared with control, regardless of prior systemic NSISS use. Clinical Trial Registration: LIBERTY AD SOLO 1: ClinicalTrials.gov identifier NCT02277743, EudraCT 2014-001198-15. LIBERTY AD SOLO 2: ClinicalTrials.gov identifier NCT02277769, EudraCT 2014-002619-40. LIBERTY AD CHRONOS: ClinicalTrials.gov identifier NCT02260986, EudraCT 2013-003254-24. LIBERTY AD CAFÉ: ClinicalTrials.gov identifier NCT02755649, EudraCT 2015-002653-35. Plain Language Summary: Atopic dermatitis (AD), also known as eczema, is characterized by red, oozy, and dry skin that can become cracked and infected. Dupilumab is a drug that blocks key molecules that cause allergic conditions, such as AD. It has been shown to be effective in treating moderate-to-severe AD. Other drugs commonly used to treat AD include certain anti-inflammatory drugs, known as non-steroidal immunosuppressants (NSISS), such as cyclosporin. It is not known if patients treated in the past with NSISS get the same results from AD treatment with dupilumab. This analysis used data from four large studies that included patients with moderate-to-severe AD. The objective was to see if prior NSISS use impacted how dupilumab worked to control AD. The researchers looked at a range of measurements—including ones that were assessed by a patient's doctor such as measurements of AD skin lesions. Itching and how patients felt about their overall life quality were also analysed (which included items such as sleep, pain, ability to work or do normal leisure activities, etc.). The researchers found that if a patient had taken an NSISS for AD before taking dupilumab, it had no impact on the efficacy of dupilumab. All of the measurements evaluated improved significantly more in patients treated with dupilumab than in patients taking a placebo (dummy) medication. The benefits of treatment occurred within a few weeks of starting dupilumab treatment and remained until the end of the longest study included in this analysis, 1 year. [ABSTRACT FROM AUTHOR]