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.

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.

Cumulative incidence and risk factors for cutaneous squamous cell carcinoma metastases in organ transplant recipients: The Skin Care in Organ Transplant Patients in Europe-International Transplant Skin Cancer Collaborative metastases study, a prospective multicenter study.

INTRODUCTION: Solid organ transplant recipients (SOTRs) are believed to have an increased risk of metastatic cutaneous squamous cell carcinoma (cSCC), but reliable data are lacking regarding the precise incidence and associated risk factors. METHODS: In a prospective cohort study, including 19 specialist dermatology outpatient clinics in 15 countries, patient and tumor characteristics were collected using standardized questionnaires when SOTRs presented with a new cSCC. After a minimum of 2 years of follow-up, relevant data for all SOTRs were collected. Cumulative incidence of metastases was calculated by the Aalen-Johansen estimator. Fine and Gray models were used to assess multiple risk factors for metastases. RESULTS: Of 514 SOTRs who presented with 623 primary cSCCs, metastases developed in 37 with a 2-year patient-based cumulative incidence of 6.2%. Risk factors for metastases included location in the head and neck area, local recurrence, size > 2 cm, clinical ulceration, poor differentiation grade, perineural invasion, and deep invasion. A high-stage tumor that is also ulcerated showed the highest risk of metastasis, with a 2-year cumulative incidence of 46.2% (31.9%-68.4%). CONCLUSIONS: SOTRs have a high risk of cSCC metastases and well-established clinical and histologic risk factors have been confirmed. High-stage, ulcerated cSCCs have the highest risk of metastasis.

Burden of Disease in the Real-Life Setting of Patients with Atopic Dermatitis: Italian Data From the MEASURE-AD Study.

INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disease that negatively impacts the quality of life and work productivity of patients. OBJECTIVES: We sought to evaluate the real-world burden of AD patients in Italy. METHODS: This sub-analysis of the MEASURE-AD multicountry study conducted between December 2019-2020 included patients diagnosed with moderate-to-severe AD eligible for or receiving systemic therapy in the previous 6 months. During a single visit, physician and patient-reported questionnaires were used. RESULTS: A total of 118 adult patients were enrolled and 57.6% (N = 68) of patients had moderate-to-severe AD at the time of enrolment according to the Eczema Area and Severity Index. Sleep disorders interfered with daily function in the previous week in 58.5% (N = 69) of patients, pruritus was severe in 50% (N = 59) and 42.4% (N = 50) reported a flare lasting >7 days in the previous 6 months. According to the Dermatology Quality of Life Index, 37.3% (N = 44) of patients reported a severe impact of AD and approximately 10% had clinical depression/anxiety. Current drug therapy was considered inadequate in controlling AD in 26.3% (N=31) of patients. Work activity impairment was 38.6±31.7% and monthly AD-related expenses were 148.6±134.6 Euros per patient. CONCLUSIONS: This real-life study documents a high burden of disease in patients with moderate-severe AD in Italy.

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.

Aquaporin 1, Aquaporin 8, and Aquaporin 9 Expressions in Malignant Melanoma: A Possible Correlation with Prognosis and Clinical Outcome.

Aquaporins (AQPs) are small transmembrane proteins able to facilitate the passive transport of water and small molecules throughout cells. Several studies have demonstrated that modulation of AQPs' expression contributes to cancer development and progression. However, to date, very little is known about their involvement in malignant melanoma (MM) progression. In this retrospective observational study, we evaluated the correlation between AQP1, -8, and -9 expression and the clinical outcomes of 58 patients diagnosed with MM from 2014 to 2016, of which 14 were diagnosed as nodular melanoma (NM) and 44 as superficial spreading melanoma (SSM). In general, we found that AQPs were more highly expressed in SSM than NM, suggesting a potential correlation with prognosis. While analyzing the expression of each AQP, we discovered that AQP1 was associated with a specific body site and low mitotic index, AQP8 with a negative sentinel lymph node, and AQP9 with the Breslow thickness and lack of ulcerations. Together with the survival analysis performed in this study, our results suggest that the expression of AQP1, -8, and -9 could be correlated with a better prognosis for malignant melanoma.

Exploring the Effects of Probiotic Treatment on Urinary and Serum Metabolic Profiles in Healthy Individuals.

Probiotics are live microorganisms that confer health benefits when administered in adequate amounts. They are used to promote gut health and alleviate various disorders. Recently, there has been an increasing interest in the potential effects of probiotics on human physiology. In the presented study, the effects of probiotic treatment on the metabolic profiles of human urine and serum using a nuclear magnetic resonance (NMR)-based metabonomic approach were investigated. Twenty-one healthy volunteers were enrolled in the study, and they received two different dosages of probiotics for 8 weeks. During the study, urine and serum samples were collected from volunteers before and during probiotic supplementation. The results showed that probiotics had a significant impact on the urinary and serum metabolic profiles without altering their phenotypes. This study demonstrated the effects of probiotics in terms of variations of metabolite levels resulting also from the different probiotic posology. Overall, the results suggest that probiotic administration may affect both urine and serum metabolomes, although more research is needed to understand the mechanisms and clinical implications of these effects. NMR-based metabonomic analysis of biofluids is a powerful tool for monitoring host-gut microflora dynamic interaction as well as for assessing the individual response to probiotic treatment.

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.

Role of the Microbiota in Skin Neoplasms: New Therapeutic Horizons.

The skin and the gut are regularly colonized by a variety of microorganisms capable of interacting with the immune system through their metabolites and influencing the balance between immune tolerance and inflammation. Alterations in the composition and diversity of the skin microbiota have been described in various cutaneous diseases, including skin cancer, and the actual function of the human microbiota in skin carcinogenesis, such as in progression and metastasis, is currently an active area of research. The role of Human Papilloma Virus (HPV) in the pathogenesis of squamous cell carcinoma is well consolidated, especially in chronically immunosuppressed patients. Furthermore, an imbalance between Staphylococcus spp., such as Staphylococcus epidermidis and aureus, has been found to be strongly related to the progression from actinic keratosis to squamous cell carcinoma and differently associated with various stages of the diseases in cutaneous T-cell lymphoma patients. Also, in melanoma patients, differences in microbiota have been related to dissimilar disease course and prognosis and may affect the effectiveness and tolerability of immune checkpoint inhibitors, which currently represent one of the best chances of a cure. From this point of view, acting on microbiota can be considered a possible therapeutic option for patients with advanced skin cancers, even if several issues are still open.

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.

Temporal correlation between the first melanoma and the first noncutaneous tumor in CKDN2A genotyped patients.

CDKN2A pathogenic variants are well known to be associated with cutaneous melanoma and noncutaneous tumors (NCTs). Herein, we investigated the temporal correlation between the first cutaneous melanoma and NCT both in CDKN2A mutation carriers (MUT) and in wild-type melanoma patients, a poorly explored issue to date. Two hundred forty-five cutaneous melanoma patients were genotyped for the CDKN2A gene and divided into 51 MUT and 189 wild-type; the remaining five variant carriers were excluded from the analyses. MUT developed a significantly higher number of cutaneous melanoma than wild-type, while 13.7% in both genotyped groups received a diagnosis of at least one malignant NCT, without statistically significant differences. The onset of the first cutaneous melanoma preceded that of the first malignant or benign NCT in both MUT and wild-type patients by an average of 4.5 and 3.02 years, respectively. Considering only malignant tumors, the diagnosis of melanoma preceded that of the first NCT on an average of 8 and 4.34 years, in MUT and wild-type patients respectively. We emphasize the relevance to adopt a global vision for the primary and secondary surveillance of patients affected by cutaneous melanoma, not only limited to high-risk for multiple primary skin cancers but also to NCT that may develop several years after the diagnosis of the first cutaneous melanoma.

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.

Decreased Gas6 and sAxl Plasma Levels Are Associated with Hair Loss in COVID-19 Survivors.

Post-acute conditions after coronavirus disease 2019 (COVID-19) are quite common, although the underlying pathogenetic mechanisms leading to these conditions are not yet completely understood. In this prospective observational study, we aimed to test the hypothesis that Growth Arrest-Specific 6 (Gas6) and its soluble receptors, Axl (sAxl) and MerTK (sMer), might be implicated. A total of 263 subjects underwent a structured clinical evaluation one year after their hospital discharge for COVID-19, and they consented to donate a blood sample to measure their circulating Gas6, sAxl, and sMer levels. A total of 98 (37.3%) post-COVID-19 subjects complained of at least one residual physical symptom one year after their hospital discharge. Univariate analysis revealed that sAxl was marginally associated with residual symptoms, but at the level of logistic regression analysis, only the diffusing capacity of the lungs for carbon monoxide (DLCO) (OR 0.98, CI 95%: 0.96-0.99; p = 0.007) and the female sex (OR 2.49, CI 95%: 1.45-4.28; p = 0.001) were independently associated with long-lasting symptoms. A total of 69 (26.2%) subjects had hair loss. At the level of univariate analysis, Gas6, sAxl, DLCO, and the female gender were associated with its development. In a logistic regression analysis model, Gas6 (OR 0.96, CI 95%: 0.92-0.99; p = 0.015) and sAxl (OR 0.98, CI 95%; 0.97-1.0; p = 0.014), along with the female sex (OR 6.58, CI 95%: 3.39-12.78; p = 0.0001), were independent predictors of hair loss. Decreased levels of Gas6 and sAxl were associated with a history of hair loss following COVID-19. This was resolved spontaneously in most patients, although 23.7% complained of persistent hair loss one year after hospital discharge.

Is There any Link between Madelung Disease and Ischemic Stroke? A Case Report.

A 70-year-old man presented to the Emergency Department with left hemiparesis, slurred speech, and elevated blood pressure. A brain computed tomography scan revealed an ischemic lesion in the right frontal and parietal lobes. At clinical examination bilateral pseudo gynecomastia was detected together with the presence of multiple elastic, adipose bulging masses on the neck, trunk, and upper limbs. A type I-II Lanois-Bensaude syndrome was diagnosed. Ultrasonography confirmed their adipose nature. Multiple symmetric lipomatosis, also known as Lanois-Bensaude syndrome or Madelung disease, is a very rare condition with extreme variability in its clinical presentation. The simultaneous occurrence of ischemic stroke and lipomatosis in the same patient might be due to a mitochondrial function impairment, which could lead to abnormal fat tissue distribution and defective cellular energy production, thus resulting in neuronal sufferance and death. The possibility that, in our case, lipomatosis could have represented a further risk factor in promoting the stroke occurrence is discussed. In our opinion, multiple symmetric lipomatosis must be carefully evaluated to improve the patients' quality of life.