Multiplex real-time PCR for skin fungal infections: The diagnostic reliability in a one-year non-interventional study.

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.

Our study aims to evaluate innovative technologies in diagnosing skin dermatophytosis. The final purpose was to describe an added diagnostic value, aiming to improve patients' outcomes. High sensitivity rates and a restricted turn-around time represent the main advantages.

Analysis of the response to two pharmacological protocols in patients with oral lichen planus: A randomized clinical trial.

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.

Analysis of oral lichen planus severity on micro-RNA linked with malignant transformation risks.

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.

Macrophage Migration Inhibitory Factor (MIF) and Its Homologue d-Dopachrome Tautomerase (DDT) Inversely Correlate with Inflammation in Discoid Lupus Erythematosus.

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.

Clinical and Histopathological Features of Scleroderma-like Disorders: An Update.

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.

Juvenile elastoma without germline mutations in LEMD3 gene: A case of Buschke-Ollendorff syndrome?

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.

Vulvar Melanoma Associated with Lichen Sclerosus in a Child: Case Report and Literature Review.

The authors describe the sixth pediatric case to date of primary vulvar melanoma associated with lichen sclerosus and propose a practical management for such a rare cancer.

Evaluation of the Involvement of Heme Oxygenase-1 Expression in Discoid Lupus Erythematosus Lesions.

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.

Effectiveness and Safety After a Switch to Tildrakizumab: A Real World Multicenter Italian Study in Psoriasis.

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.

Understanding Barriers Impacting upon Patient Wellbeing: A Nationwide Italian Survey and Expert Opinion of Dermatologists Treating Patients with Moderate-to-Severe Psoriasis.

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.

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.

Nevus vascularis mixtus (cutaneous vascular twin nevi) associated with intracranial vascular malformation of the Dyke-Davidoff-Masson type in two patients.

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.

Prevalence of Onychomycosis in Diabetic Patients: A Case-Control Study Performed at University Hospital Policlinico in Catania.

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.

Use of real time multiplex PCR for the diagnosis of dermatophytes onychomycosis in patients with empirical antifungal treatments.

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.

Multidisciplinary Rheuma-Derma Clinics: 5 Years of Experience at the San Marco Hospital in Catania.

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.

Inverse correlation between the expression of AMPK/SIRT1 and NAMPT in psoriatic skin: A pilot study.

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.

Sharing Patient and Clinician Experiences of Moderate-to-Severe Psoriasis: A Nationwide Italian Survey and Expert Opinion to Explore Barriers Impacting upon Patient Wellbeing.

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.

Dupilumab Treatment in Children Aged 6-11 Years With Atopic Dermatitis: A Multicentre, Real-Life Study.

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.

A consensus-based approach on the management of patients with both psoriasis and psoriatic arthritis in the dermatological and rheumatological settings in Italy: The ADOI PSO-Amore Project.

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 3rd level joint Dermatology- Rheumatology care unit, in connection with 1st and 2nd 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.