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Introduction: Tildrakizumab, a humanized monoclonal antibody targeting the p19 subunit of interleukin 23 (IL-23), has shown promise in the management of moderate-to-severe plaque psoriasis, offering potential improvements in clinical outcomes and quality of life., Objectives: The study aimed to identify patient characteristics that indicate the initiation of a 200 mg dosage of tildrakizumab in a real-world setting, focusing on factors that enhance treatment effectiveness and safety., Methods: This prospective study included 54 adult patients with moderate-to-severe plaque psoriasis treated with tildrakizumab 200 mg from March 2023 to March 2024 across 13 Italian Dermatology Units. Data collected included demographics, disease duration, comorbidities, and previous treatments. PASI, BSA, and DLQI scores were recorded at baseline and at weeks 4, 16, and 28. Safety was assessed through adverse event reporting. Univariate analysis was performed to identify baseline characteristics significantly associated with achieving PASI ≤ 5 at week 16., Results: Significant reductions in PASI scores were observed at week 4 (9 ± 6.9, P < 0.001), with further improvements at weeks 16 (3.9 ± 4.2, P < 0.001) and 28 (2.9 ± 4.4, P < 0.001). Univariate analysis showed that obese patients (BMI > 30) had higher odds (OR = 4.333, P < 0.05) of achieving PASI ≤ 5. Longer disease duration and starting with a 100 mg dosage also correlated with better outcomes. The safety profile was favorable, with minimal adverse events reported., Conclusions: Tildrakizumab 200 mg is effective and safe for moderate-to-severe psoriasis, particularly in obese patients. These findings support its use as a long-term treatment option.

Objective: The present study evaluated the oral tissue expression of micro-RNA (miRNAs) linked to the potential malignant evolution of oral lichen planus (OLP). Furthermore, the correlation between OLP severity and miRNAs expression was assessed, and possible predictors of miRNAs in OLP patients were identified., Methods: The present study enrolled 41 patients with OLP (median age 58 years) and 42 healthy controls (median age 59 years). In each patient, miRNA levels (miR-7a-3p,-7a2-3p,-7a-5p,-21-3p,-21-5p,-100-3p,-100-5p,-125b-2-3p,-125b-5p,-200b-3p,-200b-5p) were assessed and analyzed through reverse transcription polymerase chain reaction. Clinical parameters and the eventual presence of OLP symptoms, signs, and disease severity scores in each patient were reported using an anamnestic questionnaire., Results: In comparison with healthy controls, OLP patients showed significantly higher miR-7a-3p,-7a-2-3p,-21-3p, miR-21-5p and miR-100-5p levels (p < 0.05) and significantly lower miR-125b-2-3p,-125b-5p,-200b-3p, and -200b-5p levels (p < 0.05). Furthermore, OLP symptoms and signs and disease severity scores were significantly correlated and were also predictors of all analyzed miRNAs (p < 0.05)., Conclusions: In comparison with healthy subjects, OLP patients exhibited unbalanced oral miRNAs expression linked to the risk of potential malignant evolution of OLP. Furthermore, some miRNAs were correlated with OLP extent and were significant predictors of OLP symptoms, signs, and disease severity scores., (© 2023 The Authors. Oral Diseases published by Wiley Periodicals LLC.)

A nationwide cross-sectional online survey was administered to dermatologists managing patients with moderate-to-severe plaque psoriasis across Italy to obtain real-world dermatologists' perspectives on the impact of psoriasis and its treatment on patients' daily lives and quality of life (QoL). A total of 91 dermatologists (aged 39.1 ± 11.2 years) completed a 31-question survey and workshop sessions were undertaken in order to identify the best management approach to achieve patient wellbeing. Social (4.2 ± 0.1), physical (4.26 ± 0.2) and mental components (4.1 ± 0.3) were rated by dermatologists as contributing to patient wellbeing to similar extents. While a high proportion (85.4%; rating of 4.3 out of 5) of dermatologists felt that they considered the QoL of patients, a lower proportion (69.6%; rating of 3.7 out of 5) felt that patients were satisfied in this regard. The psoriasis area and severity index and body surface area were the instruments most frequently used to assess the physical domain, while interviews/questions and the dermatology life quality index were used to assess social and mental domains, with only 60% of dermatologists following up on these aspects. The importance of investigating the presence of comorbidities was recognized but not always carried out by many dermatologists, (>70%), particularly for obesity and anxiety/depression. This survey identified key components contributing to barriers impacting on the QoL of patients with moderate-to-severe psoriasis from the perspective of the dermatologist.

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.

Introduction: Tildrakizumab is a humanized IgG1κ monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, approved in 2018 for the treatment of patients with moderate-to-severe chronic plaque psoriasis., Objectives: This study aimed to evaluate the effectiveness, safety and survival of tildrakizumab in the medium term (48 weeks) in psoriatic patients failure to previous biologic treatment in a real world setting., Methods: This was a retrospective, multicenter observational study that included adult patients with moderate-to-severe plaque psoriasis, failure to previous biologic therapy, consecutively treated with tildrakizumab. Psoriasis Area Severity Index (PASI) and Body Surface Area (BSA) values were recorded at baseline, at 12 and 48 weeks of treatment. Safety and tolerability of tildrakizumab were investigated by examining the presence of any adverse events., Results: Overall 51 patients were enrolled. Baseline disease severity was moderate to severe with a mean PASI score of 19.2 ± 8.5, mean BSA of 16 ± 10.4, and mean Dermatology Life Quality Index (DLQI) of 18.2 ± 6.8. A significant reduction in the mean PASI score was detected at 12 weeks of tildrakizumab therapy (3.5 ± 2.7, P < 0.001), with a further improvement at week 48 (0.6 ± 1.5, P < 0.001). At week 12, there was a great improvement in BSA score for all groups (P <0.001) with further increase at week 48. The effectiveness was confirmed also by DLQI assessment, with a significant decrease at week 12 and even more at week 48 (P <0.001)., Conclusions: This study confirms the effectiveness of tildrakizumab in daily clinical practice in patients with moderate-to-severe plaque psoriasis.

The skin fungal infection diagnostic workflow currently includes microscopic and culture-based methods as the gold standard. Recent published data described the possible limitations of these conventional techniques documenting the possibility of reducing response time intervals. The present study reports an evaluation of the DermaGenius® (DG) multiplex kit (PathoNostics) for rapid C. albicans and dermatophytes identification directly from skin samples. The investigations involved 90 specimens that underwent DNA extraction and amplification simultaneously to microscopic and culture methods. According to current guidelines, we defined a dermatophytic skin infection as the simultaneous presence of clinical evidence of skin lesions and positive results for dermatophyte elements from microscopy and/or cultures. The collected data remarked on the advantages of the molecular assay, especially in terms of sensitivity and rapidity. A statistical evaluation analysed a comparison between conventional and innovative diagnostic methods. The sensitivity, specificity, positive predictive value, and negative predictive value of DG-PCR in the cutaneous dermatophytosis were, respectively, 94.7%, 78.8%, 88.5%, and 89.6%. Based on our experience, the molecular technique could represent a diagnostic confirmation in the case of previous antifungal treatment, little biological material available, or urgent clinical conditions., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Discoid lupus erythematosus (DLE) is a chronic autoimmune disease that primarily affects the skin, causing red, scaly patches that may be disfiguring and can cause permanent scarring. This study aimed to investigate the potential clinical and therapeutic applications of heme oxygenase-1 (HMOX1) in the context of DLE. Immunohistochemical staining and bioinformatics analysis were performed on skin biopsy samples from DLE patients to examine the levels of HMOX1 and to correlate with markers of inflammation. Our study revealed a negative correlation between HMOX1 levels and the inflammatory status of DLE lesions, as well as an inverse correlation between HMOX1 levels and the infiltration of M1 macrophages and activated mastocytes. These findings suggest that HMOX1 plays a crucial role in the regulation of inflammation in DLE and could be a potential therapeutic target and biomarker for DLE.

Objective: To evaluate the effectiveness of two different therapies on oral lichen planus (OLP) treatment through the analysis of OLP symptoms and signs and to analyze the risk of side effects related to the adopted protocols., Methods: Thirty-eight patients with OLP were selected according to van der Meij and van der Waal clinical and histopathological criteria. Through a randomized design, 19 patients received Tacrolimus 0.1% ointment (T group) and 19 an anti-inflammatory mouthwash (M group) composed of calcium hydroxide 10%, hyaluronic acid 0.3%, umbelliferone, and oligomeric proanthocyanidins. The patients were examined on a regular basis for OLP symptoms, signs, and disease severity score changes over a 3-month follow-up period., Results: Both treatments were effective in the reduction of OLP signs and symptoms. However, at 3 months (T3), in comparison with the M group, T group patients showed significantly lower mean values of OLP signs (p = 0.035), symptoms (p = 0.045), and disease severity scores (p = 0.041). Moreover, the Spearman test showed that there was a significant correlation between OLP signs and symptoms at each follow-up session in all patients., Conclusions: Both treatments demonstrated a significant approach to control OLP. However, tacrolimus determined a more effective improvement in OLP signs and symptoms compared to anti-inflammatory mouthwash at 3-month follow-up., (© 2021 Wiley Periodicals LLC.)

Introduction: Early psoriatic arthritis (PsA) diagnosis is critical to prescribe timely treatment to prevent the irreversible joint damage and the many other problems that patients with PsA experience. This retrospective study aimed to highlight the benefits of a Rheuma-Derma Clinic focused on the early diagnosis and prompt treatment of PsA with a shared approach among Italian psoriasis patients. Diagnosing PsA early is the main goal to reduce joint damage and disability in the patients affected. Studies describing the results of rheuma-derma clinics aimed to reach this goal emerged in the last decade. This study presents limitations and advantages typical of retrospective designs., Methods: A Rheuma-Derma Clinic was created in 2017 at the Rheumatology Department of the Hospital Policlinico Gaspare Rodolico of the University of Catania in San Marco, Italy. This study compared the number of patients under disease-modifying antirheumatic treatment 5 years before and after the joint clinic was created. A rheumatologist and dermatologist simultaneously assessed patients with psoriasis and/or PsA to obtain a rapid multidisciplinary diagnostic approach and a shared therapeutic strategy. In addition, demographic, clinical, and clinimetrics data were collected., Results: The number of patients with PsA receiving biological disease-modifying antirheumatic drugs increased 47% (from 255 to 374 patients) before and after the joint clinic was implemented. Likewise, those receiving conventional synthetic disease-modifying antirheumatic drugs increased by 47% (from 367 to 539) as well. Additionally, for all the clinimetrics evaluated (DAS28, HAQ, BASDAI, DAPSA, PASI, PGA), there was an improvement over the 12 months under the Rheuma-Derma Clinic care. The measures that improved the most were DAPSA, PGA, PASI, and BASDAI., Conclusion: The implementation of the Rheuma-Derma Clinic was associated with an increase in the number of patients diagnosed, the number of patients with PsA receiving DMARD treatments, and improvements in clinimetrics among the study participants., (© 2022. The Author(s).)

Background: The management of paediatric atopic dermatitis (AD) is challenging, mostly relying on emollients and topical corticosteroids. Dupilumab, a fully human monoclonal antibody, has been recently approved for the treatment of children aged 6-11 years with moderate-to-severe AD not adequately controlled with topical therapies or when those therapies are not advisable., Objectives: The aim of this study was to evaluate in real life the effectiveness and safety of dupilumab in the treatment of children aged from 6 to 11 years., Methods: Demographic and clinical data of children aged 6-11 years, affected by moderate-to-severe AD and treated with dupilumab, were retrospectively collected from 24 dermatological and paediatric referral centres. Dupilumab was administered subcutaneously at an induction dose of 300 mg on day (D) 1, followed by 300 mg on D15 and 300 mg every 4 weeks. Disease severity was assessed at baseline and after week 2 (W2), W4 and W16 of dupilumab therapy using Eczema Area Severity Index (EASI), Pruritus Numerical Rating Scale (P-NRS) and Sleep NRS (S-NRS) and Children's Dermatology Life Quality Index (c-DLQI) score., Results: A total of 55 AD children (24 males [43.64%], 31 females [56.36%]; mean age 9.35 ± 1.75 years) were included. A significant improvement in EASI score, P-NRS, S-NRS and c-DLQI was observed from baseline to W16 of treatment with dupilumab. In particular, at W16 the proportion of patients achieving EASI75 was 74.54%. Moreover, at the same timepoint a significant mean percentage reduction for P-NRS, S-NRS and c-DLQI was also observed (68.39%, 70.22% and 79.03%, respectively)., Conclusions: Our real-life data seem to confirm the effectiveness of dupilumab in paediatric patients on all disease aspects, including extent and severity of signs, intensity of symptoms, sleep and QoL, with a good safety profile., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Psoriasis is a complex disease often needing a multidisciplinary approach. In particular, the collaboration between dermatologist and rheumatologist is crucial for the management of patients suffering from both psoriasis (PSO) and psoriatic arthritis (PsA). Here we report a series of recommendations from a group of experts, as a result of a Consensus Conference, defining the circumstances in which it is preferable or even mandatory, depending on the available settings, to rely on the opinion of the two specialists, jointly or in a deferred manner. Indications are given on how to organize a 3 rd level joint Dermatology- Rheumatology care unit, in connection with 1 st and 2 nd level clinicians of both specialties, GPs, and other specialists involved in the management of psoriasis. A potential patient journey is suggested, that can be used as a basis for future design and validation of national and/or local diagnostic therapeutic and assistance pathways., (©Copyright: the Author(s).)

Purpose: Epidermal hyperplasia and the involvement of immune cells characterize the clinical picture of psoriasis. Among the several factors involved, attention has been focused on sirtuin 1 (SIRT1) - a deacetylase endowed with a variety of functions including the control of metabolic and inflammatory processes-, and on nicotinamide phosphoribosyltransferase (NAMPT), important for SIRT1 activation and involved in inflammatory events. The aim of the study was to analyze changes of SIRT1 and NAMPT expression in psoriatic skin., Patients and Methods: Samples from healthy controls and psoriatic patients were subjected to immunohistochemical analysis., Results: A strong downregulation of SIRT1 expression was observed in skin samples from psoriatic patients compared to healthy controls. This was accompanied by a parallel reduction of adenosine monophosphate-activated kinase (AMPK) expression and, more strikingly, by the disappearance of cells immunolabeled for its active, phosphorylated form (pAMPK). In both cases, analysis of the distribution of immunopositive cells revealed a shift towards reduced intensity of staining. In contrast, NAMPT expression was upregulated in psoriatic samples in line with its pro-inflammatory role. This was again more visible with an intensity-based distribution analysis that evidenced a shift towards more intensely immunostained cell populations., Conclusions: The present data correlate in the same samples the expression of SIRT1, pAMPK/AMPK and NAMPT in psoriasis and open the way for novel pharmacological targets in the treatment of the disease., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2022 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Diabetes is characterized by an increased rate of serum glucose due to defects in insulin secretion, insulin action or both conditions. Glucose excesses can lead to extended cellular damage, with the consequence of several infectious and non-infectious skin disorders. The aim of the present study was to evaluate the toenail onychomycosis incidence in diabetic patients and healthy ones. The non-interventional, retrospective study was performed at the mycology laboratory of the University hospital "Policlinico-San Marco" in Catania, Italy, for over one year. Nail clippings were collected to perform microscopic and cultural exams, which allowed for the identification of fungal aetiological agents. A total of 715 patients (47 diabetic and 668 non-diabetic patients) were enrolled. In diabetic patients, dermatophytes were the most common cultural isolates (50%), followed by yeasts and moulds in 30.8% and 19.2%, respectively. In non-diabetic patients, the distribution of dermatophytes, yeasts and non-dermatophytic moulds was 67.4%, 5.3% and 27.3%, respectively. According to our results, diabetic patients are more predisposed to nail fungal infection. Our data suggest that dermatological follow-ups should always be performed for diabetic patients. All skin and nail disorders should be carefully monitored to perform a diagnostic confirmation and correct management of diabetic patients.

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.

Background: Onychomycosis is a nail fungal infection mainly caused by dermatophytes. Diagnostic confirmation is conventionally made by direct microscopy and culture, which suffer from low or moderate sensitivity. Several molecular methods have been used for dermatophytes detection and identification directly from nail samples. The aim of this study was the evaluation of the DermaGenius®(DG) multiplex kit in detecting and identifying dermatophytes from nail samples of untreated and treated patients with a clinical suspicion of onychomycosis., Methods: All the patients underwent a nail scarification, performed with a sterile scalpel to collect small nail fragments from the suspected site of infection. All nail clippings were first analysed by microscopic and culture methods to define a diagnostic confirmation. DG PCR assays were retrospectively applied to the same samples., Results: A total of 109 toenails were collected for the microscopic, culture and DG PCR assays. The sensitivity, specificity, positive and negative predictive values of DG in the onychomycosis diagnosis in all 109 patients were respectively 78.5%, 100%, 100%, and 75.9%. Only for cultural exams the rate of positive results was significantly different in the two groups of patients with a percentage of 73.7% in untreated patients versus a 40.7% value in treated patients (P < 0.05)., Conclusions: Our results suggest that the use of DG kit could be useful to confirm the diagnosis of onychomycosis, implementing sensitivity especially in patients who underwent antifungal treatments without any clinical improvement., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Scleroderma-like disorders include a set of entities involving cutis, subcutis and, sometimes, even muscular tissue, caused by several pathogenetic mechanisms responsible for different clinical-pathological pictures. The absence of antinuclear antibodies (ANA), Raynaud's phenomenon and capillaroscopic anomalies constitutes an important element of differential diagnosis with systemic sclerosis. When scleroderma can be excluded, on the basis of the main body sites, clinical evolution, any associated pathological conditions and specific histological features, it is possible to make a correct diagnosis.

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., Competing Interests: Giuseppe Argenziano has no conflict of interest to declare. Paolo Amerio has served as a consultant or Speaker for Abbvie, Celgene, Pfizer, Sanofi-Genzyme, Eli Lilly, and Jannsen, Galderma. Maria Grazia Aragone has served on advisory boards for Novartis, AbbVie, LeoPharma. Ginevra Baggini has no conflict of interest to declare. Manuela Baldari has no conflict of interest to declare. Gianpiero Castelli has no conflict of interest to declare. Simmaco Coppola is IQVIA employee. Antonio Costanzo has served as an advisory board member and consultant, and has received fees and speaker’s honoraria or has participated in clinical trials for Abbvie, Almirall, Biogen, LEO Pharma, Lilly, Janssen, Novartis, Pfizer, Sanofi Genzyme, and UCB-Pharma. De Pasquale has no conflict of interest to declare. Maria Concetta Fargnoli has served on advisory boards, received honoraria for lectures and research grants from Mylan, Medac Pharma, Pierre Fabre, Sanofi-Genzyme, Sunpharma, MSD. Caterina Foti advisory board and speaker for Novartis, Sanofi, Abbvie, Lillie. Claudia Giofrè has been a member of scientific board/speaker/clinical study investigator for AbbVie, Celgene, Janssen, Novartis, Sanofi. Serena Lembo has no conflict of interest to declare. Claudia Leporati has served on advisory boards for Novartis, AbbVie, Leo Pharma, Almirall. Francesco Loconsole served on advisory boards and/or received honoraria for lectures from Abbvie, Jansen-Cilag, Novartis, Lilly, Sanofi. Giovanna Malara has been a member of scientific board/speaker/clinical study investigator for AbbVie, Celgene, Janssen, Eli-Lilly, Novartis, Sanofi. Ketty Peris reports personal fees from Abbvie, personal fees from Almirall, personal fees from Lilly, personal fees from Galderma, personal fees from Leo Pharma, personal fees from Pierre Fabre, personal fees from Novartis, personal fees from Sanofi, personal fees from Sun Pharma, personal fees from Janssen, outside the submitted work. Antonio Giovanni Richetta has been a member of scientific board/speaker/clinical study investigator for AbbVie, Celgene, Janssen, Eli-Lilly, Novartis. Paola Savoia has no conflict of interest to declare. Rossana Tiberio has no conflict of interest to declare. Massimo Travaglini has no conflict of interest to declare. Maria Teresa Uzzauto has no conflict of interest to declare. Luca Bianchi has been speaker or board member for Abbie, Novartis, Eli Lilly, Biogen, Sanofi, Leo Pharma, Janssen. The authors report no other conflicts of interest in this work., (© 2021 Argenziano et al.)

Different viral agents, such as herpesviruses, human papillomavirus, and Coxsackie virus, are responsible for primary oral lesions, while other viruses, such as human immunodeficiency virus, affect the oral cavity due to immune system weakness. Interestingly, it has been reported that coronavirus disease 2019 (COVID-19) patients can show cutaneous manifestations, including the oral cavity. However, the association between oral injuries and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still unclear. This narrative review aimed to summarize the available literature and provide an overview of oral lesions associated with COVID-19. An online literature search was conducted to select relevant studies published up to November 2020. The results of 17 studies showed variability in oral lesions associated with COVID-19, including ulcerations, aphthous-like lesions, and macules. The tongue, lips, and palate were the most frequent anatomical locations. According to current knowledge, the etiopathogenesis of multiple COVID-19-associated lesions seems to be multifactorial. The appearance of such lesions could be related to the direct or indirect action of SARS-CoV-2 over the oral mucosa cells, coinfections, immunity impairment, and adverse drug reactions. Nevertheless, COVID-19-associated oral lesions may be underreported, mainly due to lockdown periods and the lack of mandatory dispositive protection. Consequently, further research is necessary to determine the diagnostic and pathological significance of oral manifestations of COVID-19. All medical doctors, dentists, and dermatologists are encouraged to perform an accurate and thorough oral examination of all suspected and confirmed COVID-19 cases to recognize the disease's possible early manifestations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 La Rosa, Libra, De Pasquale, Ferlito and Pedullà.)

Discoid Lupus Erythematosus (DLE) is a chronic cutaneous disease of unknown etiology and of immunoinflammatory origin that is characterized by inflammatory plaques and may lead to disfiguring scarring and skin atrophy. Current treatments are limited, with a large proportion of patients either poorly or not responsive, which makes DLE an unmet medical need. Macrophage migration inhibitory factor (MIF) is the prototype of a pleiotropic family of cytokine that also includes the recently discovered homologue D-dopachrome tautomerase (DDT) or MIF2. MIF and DDT/MIF-2 exert several biological properties, primarily, but not exclusively of a proinflammatory nature. MIF and DDT have been suggested to play a key role in the pathogenesis of several autoimmune diseases, such as multiple sclerosis and type 1 diabetes, as well as in the development and progression of certain forms of cancers. In the present study, we have performed an immunohistochemistry analysis for the evaluation of MIF in DLE lesions and normal skin. We found high levels of MIF in the basal layer of the epidermis as well as in the cutaneous appendage (eccrine glands and sebocytes) of normal skin. In DLE lesions, we observed a significant negative correlation between the expression of MIF and the severity of inflammation. In addition, we performed an analysis of MIF and DDT expression levels in the skin of DLE patients in a publicly available microarray dataset. Interestingly, while these in silico data only evidenced a trend toward reduced levels of MIF, they demonstrated a significant pattern of expression and correlation of DDT with inflammatory infiltrates in DLE skins. Overall, our data support a protective role for endogenous MIF and possibly DDT in the regulation of homeostasis and inflammation in the skin and open up novel avenues for the treatment of DLE.

Oral lichen planus (OLP) is a chronic, inflammatory, immune-mediated disease, which can alter the quality of life of patients. The aim of this randomized clinical trial was to compare the therapeutic efficacy of clobetasol oral gel 0.05% versus an anti-inflammatory in oral solution (mouthwash) in the management of patients suffering from symptomatic OLP. The secondary objective was to analyze which one of the two treatments induced a greater risk of developing side effects. Forty patients were assigned (20 patients for group), through a randomized design, to receive clobetasol gel 0.05% or an anti-inflammatory mouthwash, which contains calcium hydroxide, hyaluronic acid, umbelliferone and oligomeric pro-anthocyanidins) for three months. At baseline (T0) and after 3 months (T1), patients underwent dental and dermatological examinations to assess their symptoms (Numerical Pain Scale (NRS) score) and signs (Thongprasom score). Data were calculated using T -test for the dependent variable, Wilcoxon test and Mann-Whitney u test. Both clobetasol and anti-inflammatory resulted in a statistically significant reduction of signs, ( p < 0.001 and p = 0.02, respectively) and symptoms ( p < 0.001 for clobetasol and p = 0.02 for anti-inflammatory). In conclusion, the results evidenced that, compared to clobetasol, the anti-inflammatory was less effective in determining the reduction of signs and symptom in OLP patients.

Chronic wounds often occur in patients with diabetes mellitus due to the impairment of wound healing. This has negative consequences for both the patient and the medical system and considering the growing prevalence of diabetes, it will be a significant medical, social, and economic burden in the near future. Hence, the need for therapeutic alternatives to the current available treatments that, although various, do not guarantee a rapid and definite reparative process, appears necessary. We here analyzed current treatments for wound healing, but mainly focused the attention on few classes of drugs that are already in the market with different indications, but that have shown in preclinical and few clinical trials the potentiality to be used in the treatment of impaired wound healing. In particular, repurposing of the antiglycemic agents dipeptidylpeptidase 4 (DPP4) inhibitors and metformin, but also, statins and phenyotin have been analyzed. All show encouraging results in the treatment of chronic wounds, but additional, well designed studies are needed to allow these drugs access to the clinics in the therapy of impaired wound healing.

Human autochthonous myiasis is uncommonly reported in Europe. This report describes a case of myiasis of a wound caused by Sarcophaga spp. Suffering from cutaneous lymphoma, the patient showed, at the level of his scalp lesions, the presence of larvae that were removed during curettage surgery; they were subsequently identified as belonging to the genus Sarcophaga. Preservation of these larvae in 10% formalin did not allow identification at the species level using molecular methods.

We report the case of a 6-year-old Caucasian girl with clinical and histopathologic features of Buschke-Ollendorff syndrome. Histologic examination of skin lesions showed thick, curly, elastic fibers in the derma. Bone lesions compatible with Buschke-Ollendorff syndrome were found in the girl's mother. Mutations in LEMD3 are pathogenic for Buschke-Ollendorff syndrome. Analysis of all exons and exon-intron junctions of LEMD3 did not reveal any germline mutations., (© 2017 Wiley Periodicals, Inc.)

P40 is a particulate fraction or fragment isolated from Corynebacterium granulosum , which exhibits a wide spectrum of pharmacological functions including antitumor, antibacterial, phagocytic, antiviral and cytokine induction effects. In the present study, the immunomodulatory potential of P40-conjugated with hyaluronic acid was assessed in a mouse model of dermatitis induced by oxazolone. Oxazolone-induced allergic contact dermatitis is a T cell-mediated Th2-like hypersensitivity reaction, which mimics the corresponding reaction in humans. Female cluster of differentiation-1 mice were sensitized on days 0 and 1 by the application of 2% oxazolone onto a shaved back. The disease was induced by re-challenge on day 7 using 15% oxazolone in the inner and outer of the left ears of the mice. Mice were topically treated with hyaluronic acid-P40 conjugate cream or with placebo to the inner and outer surface of the left ear for 7 consecutive days starting from 1 h after the sensitization. A significant reduction in ear thickness and weight and in edema and leukocyte recruitment were observed in the mice treated with hyaluronic-P40 conjugate cream compared with mice treated with the cream base alone (P<0.05). Thus, P40-conjugated with hyaluronic acid may constitute an innovative dermatitis treatment.

Melanoma of the uveal tract accounts for approximately 5% of all melanomas and represents the most common primary intraocular malignancy. Despite improvements in diagnosis and more effective local therapies for primary cancer, the rate of metastatic death has not changed in the past forty years. In the present study, we made use of bioinformatics to analyze the data obtained from three public available microarray datasets on uveal melanoma in an attempt to identify novel putative chemotherapeutic options for the liver metastatic disease. We have first carried out a meta-analysis of publicly available whole-genome datasets, that included data from 132 patients, comparing metastatic vs. non metastatic uveal melanomas, in order to identify the most relevant genes characterizing the spreading of tumor to the liver. Subsequently, the L1000CDS 2 web-based utility was used to predict small molecules and drugs targeting the metastatic uveal melanoma gene signature. The most promising drugs were found to be Cinnarizine, an anti-histaminic drug used for motion sickness, Digitoxigenin, a precursor of cardiac glycosides, and Clofazimine, a fat-soluble iminophenazine used in leprosy. In vitro and in vivo validation studies will be needed to confirm the efficacy of these molecules for the prevention and treatment of metastatic uveal melanoma.

Dipeptidyl peptidase 4 (DPP4) is expressed in various tissues, including the skin, and DPP4 inhibitors, that are currently used for the treatment of diabetes, may be effective also for complications of diabetes that affect the skin. To assess the role of DPP4 in keratinocytes, after creating a scratch wound in a monolayer of NTCC 2544 cells, we evaluated DPP4 expression and monitored wound repair over time, after treatment with the DPP4 inhibitor 1(((1-(hydroxymethyl)cyclopentyl)amino)acetyl)2,5-cis-pyrrolidinedicarbonitrile (DPP4-In). Expression of DPP4 increased early and was maintained up to 48 h following the scratch as shown by western blot and immunostaining. Treatment with 10 μM DPP4-In reduced DPP4 expression and significantly accelerated wound repair. This effect did not involve enhanced cell proliferation as shown by MTT proliferation assay, the lack of changes of cell cycle profiles and the slight inhibition of ERK phosphorylation. Enhancement of wound repair by DPP4 inhibition was prevented by the non-specific MMPs inhibitor GM6100 (5 μM). Treatment with DPP4-In increased the expression of high mobility group box 1 (HMGB1), a substrate of this enzyme, and exposure of NCTC 2544 cells to DPP4-In and exogenous HMGB1 (10 nM) produced a non-additive effect. Finally the healing promoting effect of DPP4-In was prevented by pretreatment with a neutralizing anti-HMGB1 antibody. The present results suggest that DPP4 inhibition contributes to enhanced wound healing by inducing keratinocytes to migrate into a scratched area. This effect seems to be independent of cell proliferation and involves enhanced production of HMGB1.

The Gianotti-Crosti syndrome is a relatively common children dermatosis characterized by a monomorphous erythematous papular rash limited to the face and extensor surface of the arms and legs. Although the pathogenesis is still unclear, infections are considered as the most important factor. Human β-defensins are cationic antimicrobial peptides closely related to bacterial and viral infections of many epithelia. We herein report a case of Gianotti-Crosti syndrome in a 7-year-old Caucasian girl presented with prominent eruption consisting of dome-shaped lichenoid papules on her upper and lower extremities, with spontaneous resolution. Skin biopsy revealed a dense lichenoid lymphohistiocytic infiltrate and showed strong cytoplasmic immunopositivity for human β-defensin-4 in the stratum corneum, stratum granulosum, and stratum spinosum. Considering that β-defensins have been described to be induced by infections, we investigated the expression of human β-defensin-4 by immunohistochemistry in a case of Gianotti-Crosti syndrome, in order to demonstrate that it represents a cutaneous response to skin infections.

The term twin spotting refers to phenotypes characterized by the spatial and temporal co-occurrence of two (or more) different nevi arranged in variable cutaneous patterns, and can be associated with extra-cutaneous anomalies. Several examples of twin spotting have been described in humans including nevus vascularis mixtus, cutis tricolor, lesions of overgrowth, and deficient growth in Proteus and Elattoproteus syndromes, epidermolytic hyperkeratosis of Brocq, and the so-called phacomatoses pigmentovascularis and pigmentokeratotica. We report on a 28-year-old man and a 15-year-old girl, who presented with a previously unrecognized association of paired cutaneous vascular nevi of the telangiectaticus and anemicus types (naevus vascularis mixtus) distributed in a mosaic pattern on the face (in both patients) and over the entire body (in the man) and a complex brain malformation (in both patients) consisting of cerebral hemiatrophy, hypoplasia of the cerebral vessels and homolateral hypertrophy of the skull and sinuses (known as Dyke-Davidoff-Masson malformation). Both patients had facial asymmetry and the young man had facial dysmorphism, seizures with EEG anomalies, hemiplegia, insulin-dependent diabetes mellitus (IDDM), autoimmune thyroiditis, a large hepatic cavernous vascular malformation, and left Legg-Calvé-Perthes disease (LCPD) [LCPD-like presentation]. Array-CGH analysis and mutation analysis of the RASA1 gene were normal in both patients., (Copyright © 2012 Wiley Periodicals, Inc.)

We have recently shown that covalent attachment of the nitric oxide (NO) moiety to the HIV protease inhibitor Saquinavir (Saq) produced a qualitatively new chemical entity, named Saquinavir-NO (Saq-NO), with enhanced anticancer properties and reduced toxicity both in vitro and in vivo. The aim of this study was to address several unanswered questions both on the pharmacological profile of Saq-NO as well as on the in vivo role of NO in the oncogenesis of A375 human melanoma cells. To this end, we have evaluated here the impact of single and combined effects of Saq-NO, Saq, the NO-donor DETA NONOate and the iNOS inhibitor L-NAME on the in vitro as well as in vivo growth of the iNOS positive A375 cells. Our data confirm clear-cut evidence for a strong and powerful anti-melanoma action of Saq-NO that is not duplicable by the combined use of Saq and DETA NONOate. Surprisingly, but also in agreement with the complex and multifaceted role of endogenous NO in A375 cells, both DETA NONOate and L-NAME significantly suppressed the in vivo growth of xenotransplants.

Aims: The Atrophodermas include a large group of disorders appearing as localized or widespread depressed skin areas and characterized by underlying dermal atrophy. The present study aims to report a peculiar form of previously unreported focal dermal atrophy., Methods: We studied over a period of 5 years a boy who manifested, since birth, multiple hypopigmented cutaneous atrophic lesions of the atrophoderma type in a mosaic distribution over the body and the legs., Results: This boy did no develop other cutaneous or systemic stigmata except for an idiopathic thrombocytopenic purpura (ITP) manifested at age 2 years. Full serum, metabolic and infective analyses; full ophthalmological examination; ultrasound examination of the heart and internal organs; skeletal x-rays; brain magnetic resonance imaging; and DNA analysis of the PORCN (Focal Dermal Hypoplasia - FDH) gene in this boy yielded normal results. Pathological analysis of multiple skin specimens from an affected area revealed slightly reduced dermal thickness; hyperpigmentation of the basal layer; homogenized and disarrayed collagen bundles; perivascular chronic infiltrates of lymphocytes and histiocytes; and normal skin appendages. Currently, the child is healthy; he has mildly improved skin status with less-evident skin depression throughout the lesion areas and no further complication has been recorded. The histological and clinical appearance of the skin lesions and the course were against any known disorder in the group of the atrophodermas., Conclusions: The cutaneous lesions seen in this boy represent a possibly new congenital skin disorder characterized by multiple, benign areas of focal dermal atrophy in a mosaic distribution.

We report a case of a 43-year-old uncircumcised Caucasian, diabetic man with a 4-year history of Zoon's balanitis unresponsive to topical steroids, in whom control of the disease was achieved with topical imiquimod. A histopathological examination of a biopsy specimen was performed before and after treatment with imiquimod 5% cream applied 3 times a week. A moderate to marked increased local skin reaction occurred several times throughout the treatment period, necessitating multiple rest periods of several days' duration. Clinical but not histological resolution was obtained after 4 months of treatment, with no relapses at an 18-month follow-up. This positive treatment outcome indicates that imiquimod may have a role in the management of Zoon's balanitis. However, the dose and duration of therapy required to achieve complete clinical response still needs to be established. Also, the question of whether normalization of histology can be achieved with topical imiquimod has yet to be answered.

A 61-year-old woman developed multiple and clustered eruptive epidermoid cysts at the site of treatment of a basal cell carcinoma located on her nose with imiquimod 5% cream (5 times/week for 6 weeks). Clearing was achieved after topical treatment with tretinoin 0.025% cream (1 application/day for 1 month)., (2007 S. Karger AG, Basel)

Imiquimod is an immune response-modifying agent with potent antiviral and antitumor activity effective in the treatment of various skin disorders, including in situ carcinoma of the skin (Bowen's disease). The case of a 64-year-old man affected by an in situ carcinoma of the glans mucosa, namely erythroplasia of Queyrat, successfully treated with imiquimod 5% cream is described. Because the results of tests for human papillomavirus infection were negative in this case, we suggest that imiquimod may have acted through an antitumor effect mediated by cytokine activation. This compound may represent an alternative treatment in patients with erythroplasia of Queyrat, although the dosing schedule and treatment duration require further evaluation.

We describe a 16-year-old boy with intestinal lymphangiectasia, lymphedema of the limbs and genitalia, mild mental retardation, and facial anomalies (Hennekam syndrome) and cutaneous lesions. Severe edema in the genital area created a gigantic mass that included the scrotum and penis. Numerous grouped red-violaceous pseudo-vesicular lesions and plaques, as well as verrucous brown papules, were present on the penis and scrotum. The prepuce was hypertrophic, with severe phimosis. Histologic analysis revealed dilated lymphatic vessels lined by a discontinuous layer of flat endothelial cells in the papillary dermis and extending down to the reticular dermis. Dilated blood vessels were also present but no cellular abnormalities were identified. A diagnosis of superficial cutaneous lymphatic malformations was made. To the best of our knowledge, this is the first detailed cutaneous histologic investigation in a patient with Hennekam syndrome. We assume that the onset of cutaneous lesions in our patient was likely triggered by a generalized worsening of his lymphedema.

A 69-year-old male presented with about 20 reddish, sharply circumscribed, smooth papules, 5-10 mm in diameter, sometimes with a peripheral scaling collarette, scattered on the legs, which appeared during the last 5 years. Videodermatoscopic examination showed a similar pattern in all lesions, consisting of symmetrical and homogeneous pinpoint-like vascular structures which tended to be arranged in a net-like pattern. At higher magnification each vascular structure appeared to have a bush-like aspect. On the basis of past medical history, clinical and dermatoscopic features, the diagnosis of multiple clear cell acanthoma (CCA) was considered. Histologic examination of a papular lesion confirmed the diagnosis. In conclusion, although the dermatoscopic pattern of CCA is not specific, videodermatoscopy may improve the clinical diagnosis of single or multiple CCA, ruling out clinically similar disorders that do not show the same dermatoscopic vascular pattern of CCA., (Copyright John Libbey Eurotext 2003)