Short-, mid- and long-term efficacy of dupilumab in moderate to severe atopic dermatitis: a real life multicenter Italian study on 2576 patients.

BACKGROUND: The efficacy and safety of dupilumab in atopic dermatitis (AD) have been defined in clinical trials but limited real-world evidence on long term treatment outcomes are currently available to inform clinical decisions. OBJECTIVES: to describe long-term effectiveness and safety of dupilumab up to 48 months in patients with moderate-to-severe AD. METHODS: a multicenter, retrospective, dynamic cohort study was conducted to assess long term effectiveness and safety of dupilumab in patients with moderate to severe AD in a real-world setting. Predictors of minimal disease activity (MDA) optimal treatment target criteria (defined as the simultaneous achievement of EASI90, itch NRS score ≤1, sleep NRS score ≤1 and DLQI ≤1) were investigated. RESULTS: 2576 patients were enrolled from June 2018 to July 2022. MDA optimal treatment target criteria were achieved by 506 (21.91%), 769 (40.63%), 628 (50.36%), 330 (55.37%) and 58 (54.72%) of those that reached 4, 12, 24, 36 and 48 months of follow-up, respectively. Logistic regression revealed a negative effect on MDA achievement for conjunctivitis and food allergy at all timepoints. Adverse events (AE) were mild and were observed in 373 (15.78%), 166 (7.02%), 83 (6.43%), 27 (4.50%) and 5 (4.55%) of those that reached 4, 12, 24, 36 and 48 months of follow-up. Conjunctivitis was the most frequently reported AE during the available follow-up. AE led to treatment discontinuation in <1% of patients during the evaluated time periods. CONCLUSION: High long-term effectiveness and safety of dupilumab were confirmed in this dynamic cohort of patients with moderate to severe AD, regardless of clinical phenotype and course at baseline. Further research will be needed to investigate the effect of Th2 comorbidities and disease duration on the response to dupilumab and other newer therapeutics for AD.

Ex Vivo Analysis of Cell Differentiation, Oxidative Stress, Inflammation, and DNA Damage on Cutaneous Field Cancerization.

Cutaneous field cancerization (CFC) refers to a skin region containing mutated cells' clones, predominantly arising from chronic exposure to ultraviolet radiation (UVR), which exhibits an elevated risk of developing precancerous and neoplastic lesions. Despite extensive research, many molecular aspects of CFC still need to be better understood. In this study, we conducted ex vivo assessment of cell differentiation, oxidative stress, inflammation, and DNA damage in CFC samples. We collected perilesional skin from 41 patients with skin cancer and non-photoexposed skin from 25 healthy control individuals. These biopsies were either paraffin-embedded for indirect immunofluorescence and immunohistochemistry stain or processed for proteins and mRNA extraction from the epidermidis. Our findings indicate a downregulation of p53 expression and an upregulation of Ki67 and p16 in CFC tissues. Additionally, there were alterations in keratinocyte differentiation markers, disrupted cell differentiation, increased expression of iNOS and proinflammatory cytokines IL-6 and IL-8, along with evidence of oxidative DNA damage. Collectively, our results suggest that despite its outwardly normal appearance, CFC tissue shows early signs of DNA damage, an active inflammatory state, oxidative stress, abnormal cell proliferation and differentiation.

Trichophyton erinacei infection in humans: a case report and a literature review.

BACKGROUND: Trichophyton (T.) erinacei is a rare but emerging zoonotic dermatophyte that is rarely isolated as a human pathogen, with only a few cases extensively described in the literature. PATIENTS AND METHODS: We conducted a systematic search to identify eligible articles reporting demographics, clinical characteristics, and the therapeutic approach regarding T. erinacei infection in humans. RESULTS: 168 patients affected by T. erinacei were reported in the international literature between inception and November 2023. Only 56 cases (32.1%) were fully described. The median age at diagnosis was 26 years, the female/male ratio was around 2:1. The main source of the disease was the hedgehog. The infection presented with a combination of erythema, scaly plaques, pustules, papules, vesicles, oedema, and erosion; the most common locations were the hands and the head. The most frequently conducted examination was fungal culture, but gene sequencing and mass spectrometry improved both speed and precision in the most recent diagnostic course. Topical clotrimazole and systemic terbinafine were the most chosen treatment. CONCLUSIONS: Trichophyton erinacei should be considered in patients with erythematous scaly patches and recent contact with hedgehogs. Terbinafine should be considered as a first-line effective treatment, griseofulvin and azoles could be considered valid alternatives.

Impact of artificial intelligence-based color constancy on dermoscopical assessment of skin lesions: A comparative study.

BACKGROUND: The quality of dermoscopic images is affected by lighting conditions, operator experience, and device calibration. Color constancy algorithms reduce this variability by making images appear as if they were acquired under the same conditions, allowing artificial intelligence (AI)-based methods to achieve better results. The impact of color constancy algorithms has not yet been evaluated from a clinical dermatologist's workflow point of view. Here we propose an in-depth investigation of the impact of an AI-based color constancy algorithm, called DermoCC-GAN, on the skin lesion diagnostic routine. METHODS: Three dermatologists, with different experience levels, carried out two assignments. The clinical experts evaluated key parameters such as perceived image quality, lesion diagnosis, and diagnosis confidence. RESULTS: When the DermoCC-GAN color constancy algorithm was applied, the dermoscopic images were perceived to be of better quality overall. An increase in classification performance was observed, reaching a maximum accuracy of 74.67% for a six-class classification task. Finally, the use of normalized images results in an increase in the level of self-confidence in the qualitative diagnostic routine. CONCLUSIONS: From the conducted analysis, it is evident that the impact of AI-based color constancy algorithms, such as DermoCC-GAN, is positive and brings qualitative benefits to the clinical practitioner.

Prevalence of Self-Reported Hand Eczema Signs among Healthcare Workers after the Third Wave of COVID-19 Pandemic: A Survey in a Northern Italy Hospital.

Background: Proper hand hygiene is one of the enhanced preventive measures immediately proposed to avoid the spreading of the severe acute respiratory syndrome coronavirus-2, also known as COVID-19. Objectives: The objective of this study was to estimate the prevalence of self-reported hand eczema signs and symptoms among healthcare workers in a Northern Italy University Hospital after the third wave of the COVID-19 pandemic. Materials and methods: A cross-sectional study was conducted in June 2021. The hospital workers were invited to complete an online questionnaire through a link sent via institutional e-mail to both health personnel and support staff. Results: Eight-hundred and sixty-three subjects completed the questionnaire; 51.1% of them self-reported suffering from at least one hand skin lesion. One-hundred thirty-seven responders declared that they changed their hand hygiene habits, and 88.9% of them carried out these modifications both in occupational and domestic environments. In detail, a change in terms of daily hand washing frequency is reported as follows: before the COVID-19 pandemic, only 27.8% and 10.1% of responders washed their hands 10-20 and 20+ times per day, respectively, while after the pandemic, the percentage increased to 37.8% and 45.8%, respectively. When comparing the health care workers with the administrative staff, we observed a statistically significative difference (p = 0.0001) in the daily hand washing frequency among the two groups, with a higher value in health care personnel. Accordingly, a higher prevalence of hand eczema signs (52.8% versus 45.6%) was detected in the healthcare group. Conclusions: We underline the potential role of the pandemic in the spread of hand eczema as an occupational disease and the need to implement its prevention.

Rapid and exceptional response to Sonidegib in a patient with multiple locally advanced basal cell carcinomas.

Locally advanced basal cell carcinoma (laBCC) represents a rare but possible occurrence in the vast scenario of dermatological diseases. It is well known that most BCC has a pathological activation of the hedgehog pathway, making them susceptible to targeted therapy with selective inhibitors. Sonidegib, approved for the treatment of laBCC on the basis of the results of the basal cell carcinoma outcomes with LDE225 treatment study, demonstrated rapid efficacy and a manageable safety profile. Here, we describe the case of a patient affected by multiple laBCC treated with Sonidegib. The patient experienced an important regression of tumors after only 2 months of therapy, with few side effects. This result confirms the role of Sonidegib as a valid and well-tolerated therapeutic option for laBCC.

Non-Invasive Analysis of Actinic Keratosis before and after Topical Treatment Using a Cold Stimulation and Near-Infrared Spectroscopy.

Background and objectives: The possible evolution of actinic keratoses (AKs) into invasive squamous cell carcinomas (SCC) makes their treatment and monitoring essential. AKs are typically monitored before and after treatment only through a visual analysis, lacking a quantitative measure to determine treatment effectiveness. Near-infrared spectroscopy (NIRS) is a non-invasive measure of the relative change of oxy-hemoglobin and deoxy-hemoglobin (O2Hb and HHb) in tissues. The aim of our study is to determine if a time and frequency analysis of the NIRS signals acquired from the skin lesion before and after a topical treatment can highlight quantitative differences between the AK skin lesion area. Materials and Methods: The NIRS signals were acquired from the skin lesions of twenty-two patients, with the same acquisition protocol: baseline signals, application of an ice pack near the lesion, removal of ice pack and acquisition of vascular recovery. We calculated 18 features from the NIRS signals, and we applied multivariate analysis of variance (MANOVA) to compare differences between the NIRS signals acquired before and after the therapy. Results: The MANOVA showed that the features computed on the NIRS signals before and after treatment could be considered as two statistically separate groups, after the ice pack removal. Conclusions: Overall, the NIRS technique with the cold stimulation may be useful to support non-invasive and quantitative lesion analysis and regression after a treatment. The results provide a baseline from which to further study skin lesions and the effects of various treatments.

The Diagnostic-Therapeutic Care Pathway in Psoriasis: Towards ISO 9001:2015 Certification.

Background and objectives: Psoriasis (Pso) is a common skin condition characterized by a strong psychosocial impact, and is nowadays accepted as a systemic immune-mediated inflammatory disease. Diagnostic-Therapeutic Care Pathways (DTCPs) represent a predefined sequence of diagnostic, therapeutic, and assistance activities that integrate the participation of several specialists to obtain, for each patient, the correct diagnosis and thus the most appropriate therapy. A DTCP was validated in our dermatology clinic (AOU Maggiore della Carità, Novara, Italy). The validation process included the detailed elaboration of a protocol of diagnosis, staging of care, therapies, and follow-up of the patient with Pso. The formalization and adaptation of our DTCP resulted in ISO 9001: 2015 certification in May 2019. Materials and methods: This process involved several stages, including analysis of context and the identification of (i) targets, (ii) indicators, and (iii) service providers. The evaluation was based on a cohort of over 200 patients affected by moderate to severe Pso, who were treated and followed-up at our institution from September 2017 to April 2019. Results: The ISO 9001:2015 quality certification process allowed us to identify our weaknesses, i.e., the long waiting times for the first visit and the reduced physician-patient ratio, but also our strengths, such as the commitment to clinical research, effective collaboration with other specialists, the efficient use of technological and human resources, and attention to ensuring patient follow-up. Conclusions: In qualifying for and achieving the ISO Quality Management System (QMS) certification we were heartened to realize that our basic methodology and approach were fit for purpose. The implementation of the ISO QMS helped us to reorganize our priorities by placing the patient at the center of the process and raising awareness that Pso is not just a skin disease.

Primary trichodysplasia spinulosa polyomavirus infection in a kidney transplant child displaying virus-infected decoy cells in the urine.

We report a case of primary trichodysplasia spinulosa (TS) infection in a kidney transplant child and describe for the first time the presence of degenerated TS-associated polyomavirus (TSPyV)-infected cells in a TS patient's urine that are morphologically different from BK or JC polyomavirus-infected decoy cells.

Identification of Risk Factors for Multiple Non-Melanoma Skin Cancers in Italian Kidney Transplant Recipients.

Background and objectives: Non-melanoma skin cancers (NMSCs) represent the most frequently encountered malignancy in organ transplant recipients and their incidence increases proportionally to the duration of immunosuppression. Furthermore, patients of this group often develop multiple and more aggressive cancers and, to date, risk factors for the development of multiple NMSCs have not been yet established. The present study aimed to identify risk factors for multiple NMSCs in a cohort of Italian kidney transplant recipients (KTRs). Materials and Methods: We consecutively included all KTRs referring to two post-transplant outpatient clinics of North-Western Italy between 2001 and 2017. In this cohort, we evaluated different clinical (endogenous and exogenous) risk factors in order to establish their correlation with NMSCs. Results: 518 KTRs were included, of which 148 (28.6%) developed keratinocyte cancers, with a single tumor in 77 subjects, two skin cancers in 31 patients, 3 in 21 patients, whereas at least 4 NMSCs developed in 19 KTRs. We observed an increased risk of the development of cutaneous neoplasms for the male gender, old age at transplantation (>50 years), light phototype, solar lentigo, history of sunburns, or chronic actinic damage. Considering patients affected by multiple keratinocyte neoplasms, we observed a significant association of actinic damage and solar lentigo with an increased risk of NMSCs; their significance was confirmed even at the multivariable model. Conclusions: Our results confirm the role played by chronic cutaneous actinic damage in carcinogenesis on KTRs and highlight the significance of individualized periodic dermatological screening.

Inflammatory Cutaneous Diseases in Renal Transplant Recipients.

Kidney transplant recipients frequently suffer from skin infections and malignancies, possibly due to the effects of long-term immunosuppressive therapy. While the relationships between immunosuppression and these pathological conditions have been widely investigated, little is known about the relative incidence and characteristics of inflammatory skin diseases in this type of patient. In this study, we analyze the incidence of a number of inflammatory cutaneous diseases in a cohort of patients who underwent kidney transplantation. Although our study shows a relatively low incidence of these pathologies in transplanted patients-in agreement with the general action of immunosuppressant therapies in reducing inflammation-we scored a different efficacy of the various immunosuppressive regimens on inflammatory and autoimmune skin diseases. This information can be key for designing immunosuppressive regimens and devising accurate follow-up protocols.

Vitis vinifera L. Leaf Extract, a Microbiota Green Ally against Infectious and Inflammatory Skin and Scalp Diseases: An In-Depth Update.

The skin microbiota, with its millions of bacteria, fungi, and viruses, plays a key role in balancing the health of the skin and scalp. Its continuous exposure to potentially harmful stressors can lead to abnormalities such as local dysbiosis, altered barrier function, pathobiont overabundance, and infections often sustained by multidrug-resistant bacteria. These factors contribute to skin impairment, deregulation of immune response, and chronic inflammation, with local and systemic consequences. In this scenario, according to the needs of the bio-circular-green economy model, novel harmless strategies, both for regulating the diverse epidermal infectious and inflammatory processes and for preserving or restoring the host skin eubiosis and barrier selectivity, are requested. Vitis vinifera L. leaves and their derived extracts are rich in plant secondary metabolites, such as polyphenols, with antioxidant, anti-inflammatory, antimicrobial, and immunomodulatory properties that can be further exploited through microbe-driven fermentation processes. On this premise, this literature review aims to provide an informative summary of the most updated evidence on their interactions with skin commensals and pathogens and on their ability to manage inflammatory conditions and restore microbial biodiversity. The emerging research showcases the potential novel beneficial ingredients for addressing various skincare concerns and advancing the cosmeceutics field as well.

Epidemiology and risk factors for multiple squamous cell carcinomas in a cohort of organ transplant recipients from northern Italy: a single center study.

BACKGROUND: Keratinocyte cancers account for the most frequent oncological complication in organ transplant recipients. To date, many different risk factors have been reported, unless variability among the studies exist. We aimed to determine the incidence and risk factors for keratinocyte neoplasms in a cohort of kidney transplant and liver transplant recipients. METHODS: A cohort of 338 patients were included in this retrospective study and followed-up from transplantation until the end of December 2021, with a 2-year minimum transplant time. Each skin cancer was collected in a specific database, together with all the demographic data and dermatological history and feature of patients. RESULTS: In our cohort, liver transplant patients presented a higher keratinocyte cancer incidence compared to kidney transplant recipients. Regarding the risk factors for skin cancer in the entire group of patients, we observed a significant association with the detection of actinic keratosis and solar lentigo, and such relation was stronger when considering patients developing multiple skin cancers, in which fair skin types and occupational sun exposure were also associated. Furthermore, while actinic keratosis and a history of previous dialysis were significantly associated with the development of a least one squamous cell carcinoma, the presence of keratotic lesions and azathioprine intake resulted connected with the appearance of multiple squamous neoplasms. CONCLUSIONS: We report here that, in our cohort, factors potentially leading to immune dysfunction were found to play a causative role in the development of the more aggressive histotype of keratinocyte tumors, and such association seemed more convincing in case of multiple squamous cell carcinomas.

A prospective randomized controlled trial of Psychodermatology on the efficacy of Rilastil Difesa Sterile® cream in the hand eczema of healthcare workers during the COVID-19 pandemic.

Hand eczema is one of the most frequent dermatological diseases, with an incidence increased during the COVID-19 pandemic. The impact on life quality is considerable, giving rise to the need for a psycho-dermatological approach. This is a Randomized Control Trial (RCT) evaluating, either by the dermatological or psychological point of view, the effectiveness of an emollient and rehydrating topical product (Rilastil Difesa Sterile® cream) versus a standard treatment (i.e. moisturizing basic cream) in a group of 51 healthcare workers suffering from hand eczema during the COVID-19 pandemic. The enrolled subjects were randomized into a treatment or a control arm, treated for 8 weeks, and monitored through a clinical score (HECSI) and questionnaires evaluating the impact of the pathology and treatment on quality of life (DLQI and QOLHEQ). A psychometric evaluation was performed using the SCL-90 R, OCI-R, and CPDI scales. Our data, despite not reaching the statistical significance, demonstrated that both the clinical and psychological scores decreased mostly in patients treated with Rilastil Difesa Sterile® cream when compared to those treated with simple topical emollients. Moreover, we observed a high level of psychic suffering in dermatological patients and a parallel change in dermatological and psychological indicators, thus confirming their connection.

A 52-week multicenter retrospective real-world study on effectiveness and safety of dupilumab in children with atopic dermatitis aged from 6 to 11 years.

Background: Dupilumab has been shown to be a safe and effective drug for the treatment of atopic dermatitis (AD) in children from 6 months to 11 years in randomized clinical trials. Aim: The aim of this real-life study was to determine the effectiveness in disease control and safety of dupilumab at W52 in moderate-to-severe AD children aged 6-11 years.Methods: All data were collected from 36 Italian dermatological or paediatric referral centres. Dupilumab was administered at label dosage with an induction dose of 300 mg on day 1 (D1), followed by 300 mg on D15 and 300 mg every 4 weeks (Q4W). Treatment effect was determined as overall disease severity, using EASI, P-NRS, S-NRS and c-DLQI at baseline, W16, W24, and W52. Ninety-six AD children diagnosed with moderate-to-severe AD and treated with dupilumab were enrolled.Results: Ninety-one (94.8%) patients completed the 52-week treatment period and were included in the study. A significant improvement in EASI score, P-NRS, S-NRS and c-DLQI was observed from baseline to weeks 16, 24 and 52.Conclusions: Our real-life data seem to confirm dupilumab effectiveness and safety in paediatric patients. Moreover, our experience highlighted that patients achieving clinical improvement at W16 preserved this condition over time.