Syphilis with HIV in Florence, 2003-2009: a 7-year epidemiological study.

SUMMARYThe aims of this study were to describe the trend of acquired syphilis in the city of Florence and its province over a 7-year period, to investigate sexual behaviours in the syphilis-infected population and to analyse syphilis/HIV co-infection. A total of 259 patients were classified according to age, sex and HIV infection. We estimated that from 2004 to 2008 cases increased by 248%. Most patients with concurrent HIV infection were male (31–45 years), but 40- to 60-year-old men who had sex with men predominated in both male and HIV-positive patients. Oral sex was identified as the most significant route of transmission, although most patients did not consider it so. Late-presenters with HIV accounted for 33% of HIV-positive patients: they were unaware of their HIV status and showed syphilis lesions only. In these cases, syphilis heralded the presence of HIV infection and allowed earlier diagnosis

Therapeutic Potential of Targeting the JAK/STAT Pathway in Psoriasis: Focus on TYK2 Inhibition

Psoriasis is an inflammatory skin disease with a chronic relapsing course and an often-detrimental impact on patients' quality of life. Thanks to incredible advances in research over the past few decades, the therapeutic armamentarium of psoriasis is now reasonably broad and structured, with several therapeutic agents that have demonstrated successful long-term control of this condition. However, there are still unfulfilled gaps resulting from the inherent limitations of existing therapies, which have paved the way for the identification of new therapeutic strategies or the improvement of existing ones. A great deal of attention has recently been paid to the JAK/STAT pathway, playing a crucial role in chronic inflammatory skin diseases, including psoriasis. Indeed, in a disease with such a complex pathogenesis, the possibility to antagonize multiple molecular pathways via JAK/STAT inhibition offers an undeniable therapeutic advantage. However, data from clinical trials evaluating the use of oral JAK inhibitors in immune-mediated disorders, such as RA, have arisen safety concerns, suggesting a potentially increased risk of class-specific AEs such as infections, venous thromboembolism, and malignancies. New molecules are currently under investigation for the treatment of psoriasis, such as deucravacitinib, an oral selective inhibitor that binds to the regulatory domain of TYK2, brepocitinib (PF-06700841) and PF-06826647 that bind to the active site in the catalytic domain. Due to the selective TYK2 blockade allowing the inhibition of key cytokine-mediated signals, such as those induced by IL-12 and IL-23, anti-TYK2 agents appear to be very promising as the safety profile seems to be superior compared with pan-JAK inhibitors. The aim of our review is to thoroughly explore the rationale behind the usage of JAK inhibitors in PsO, their efficacy and safety profiles, with a special focus on oral TYK2 inhibitors, as well as to provide a forward-looking update on novel therapeutic strategies targeting the TYK2 pathway in psoriasis

Signaling Pathways and Therapeutic Strategies in Advanced Basal Cell Carcinoma

Non-melanoma skin cancers (NMSCs) are the most common human neoplasms world-wide. In detail, basal cell carcinoma (BCC) is the most frequent malignancy in the fair-skinned population. The incidence of BCC remains difficult to assess due to the poor registration practice; however, it has been increasing in the last few years. Approximately, 85% of sporadic BCCs carry mutations in Hedgehog pathway genes, especially in PTCH, SUFU and SMO genes, which lead to the aberrant activation of GLI transcriptional factors, typically silent in cells of adult individuals. The management of advanced BCC (aBCC), both metastatic (mBCC) and locally advanced BCC (laBCC), not candidates for surgical excision or radiotherapy, remains challenging. The discovery of mutations in the Hh signaling pathway has paved the way for the development of Hh pathway inhibiting agents, such as vismodegib and sonidegib, which have represented a breakthrough in the aBCC management. However, the use of these agents is limited by the frequent occurrence of adverse events or the development of drug resistance. In this review, we thoroughly describe the current knowledge regarding the available options for the pharmacological management of aBCCs and provide a forward-looking update on novel therapeutic strategies that could enrich the therapeutic armamentarium of BCC in the near future

Clinical and laboratory characterization of patients with localized scleroderma and response to UVA-1 phototherapy: In vivo and in vitro skin models

Background/Purpose Localized scleroderma (LS) is a rare disease leading to progressive hardening and induration of the skin and subcutaneous tissues. LS is responsive to UVA-1 phototherapy, though its exact mechanism of action dermal fibrosis is yet to be fully elucidated. We aimed to investigate the molecular changes induced by UVA-1 rays in human primary fibroblasts cultures. Methods A total of 16 LS patients were treated with medium-dose UVA-1 phototherapy. At baseline, during and after therapy, Localized Scleroderma Assessment Tool, Dermatology Life Quality Index and lesions' staging and mapping were performed along with high-frequency ultrasound (HFUS) examination for dermal thickness assessment. Gene expression analysis for 23 mRNA transcripts, in vitro UVA-1 irradiation and viability tests were realized on lesional fibroblasts' primary cultures, before and 3 months after therapy. Results The dermal thickness, the LoSCAT and the DLQI progressively decreased starting from the last phototherapy session up to the 6 and 9 month follow-ups (-57% and -60%, respectively). Molecular gene analysis (rt-PCR) revealed that UVA-1 phototherapy exerts multiple effects: the activation of specific anti-fibrotic pathways (e.g., overexpression of CTHRC1 and metalloproteases 1, 2, 7, 8, 9, 12, suppression of TIMP-1), the downregulation of peculiar pro-fibrotic pathways (e.g., downregulation of TGF-ss, TGF-ssrII, Grb2, SMAD 2/3, TNRSF12A, CTGF) through a significant overexpression of IL-1ss; the stabilization of collagen synthesis acting on genes COL1A1, COL3A1, COL8A1, COL10A1, COL12A1. Conclusion UVA-1 phototherapy adds significant benefits in local tissue remodeling, rebalancing the alteration between pro-fibrotic and anti-fibrotic pathways; these changes can be well monitored by HFUS. © 2022 The Authors

Deep Learning Techniques for the Dermoscopic Differential Diagnosis of Benign/Malignant Melanocytic Skin Lesions: From the Past to the Present

There has been growing scientific interest in the research field of deep learning techniques applied to skin cancer diagnosis in the last decade. Though encouraging data have been globally reported, several discrepancies have been observed in terms of study methodology, result presentations and validation in clinical settings. The present review aimed to screen the scientific literature on the application of DL techniques to dermoscopic melanoma/nevi differential diagnosis and extrapolate those original studies adequately by reporting on a DL model, comparing them among clinicians and/or another DL architecture. The second aim was to examine those studies together according to a standard set of statistical measures, and the third was to provide dermatologists with a comprehensive explanation and definition of the most used artificial intelligence (AI) terms to better/further understand the scientific literature on this topic and, in parallel, to be updated on the newest applications in the medical dermatologic field, along with a historical perspective. After screening nearly 2000 records, a subset of 54 was selected. Comparing the 20 studies reporting on convolutional neural network (CNN)/deep convolutional neural network (DCNN) models, we have a scenario of highly performant DL algorithms, especially in terms of low false positive results, with average values of accuracy (83.99%), sensitivity (77.74%), and specificity (80.61%). Looking at the comparison with diagnoses by clinicians (13 studies), the main difference relies on the specificity values, with a +15.63% increase for the CNN/DCNN models (average specificity of 84.87%) compared to humans (average specificity of 64.24%) with a 14,85% gap in average accuracy; the sensitivity values were comparable (79.77% for DL and 79.78% for humans). To obtain higher diagnostic accuracy and feasibility in clinical practice, rather than in experimental retrospective settings, future DL models should be based on a large dataset integrating dermoscopic images with relevant clinical and anamnestic data that is prospectively tested and adequately compared with physicians

Fibromyalgia and Skin Disorders: A Systematic Review

Background: Fibromyalgia is a complex multifaceted syndrome primarily characterised by chronic musculoskeletal pain, fatigue, and functional symptoms. Although FM is known to be associated with several comorbidities, the aim of this systematic review was to comprehensively examine the available evidence regarding the relationship between FM and dermatological manifestations. Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and MedLine and Web of Science (WOS) databases were searched up to June 2023. After removing duplicate records, 21 articles were deemed eligible for inclusion in the qualitative synthesis. Results: Overall, the included studies revealed an increased frequency of FM among patients with cutaneous diseases, including psoriasis, chronic urticaria, contact allergy, acneiform disorders, hidradenitis suppurativa, and vitiligo. Additionally, the presence of comorbid FM may intensify skin conditions, which has a negative impact on quality of life and vice versa. Conclusions: Although the causal mechanisms of FM are still far from being understood, this systematic review suggests a relationship between FM and skin disorders. However, further research is encouraged in this area

Syphilis Diagnosis and Treatment: State of The Art

The present review summarises the current knowledge in the field of syphilis diagnosis and treatment, along with epidemiologic and historical data. A literature search was conducted in PubMed and Google Scholar, using the search terms "syphilis", "diagnosis", "dermoscopy", "management AND treatment", "laboratory tests AND syphilis", and "primary OR secondary OR tertiary OR congenital syphilis". A total of 55 out of 100 papers were included in this review. An overview of the different clinical presentation of primary, secondary, tertiary, and congenital syphilis, with particular attention to dermatologic signs and dermoscopic examination, is provided. The panorama diagnostic procedures are illustrated, along with their accuracy and recommendation. Treatment and management options of patients at different syphilis stages are provided and discussed according to the referring guidelines. The dermatologist can play a key role in providing the early and correct diagnosis and setting up in the proper management of patients with syphilis infection

Line-Field Confocal Optical Coherence Tomography for the Diagnosis of Skin Carcinomas: Real-Life Data over Three Years

Line-field confocal optical coherence tomography (LC-OCT) can help the clinical diagnosis of skin diseases. The present study aimed to evaluate the sensitivity, specificity, and diagnostic accuracy of LC-OCT for the diagnosis of the most frequent non-melanoma skin cancers (NMSCs), i.e., basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Comparing LC-OCT diagnostic performances with those of dermoscopy, histopathological examination was used as a gold standard. For every study endpoint, the diagnostic ability of LC-OCT revealed superiority over the dermoscopic examination. In particular, a significant increase in specificity was observed. Sensitivity, specificity, and diagnostic accuracy of dermoscopy and LC-OCT for the diagnosis of malignancy were, respectively, 0.97 (CI 0.94–0.99), 0.43 (CI 0.36–0.51), and 0.77 (CI 0.72–0.81) for dermoscopy and 0.99 (CI 0.97–1.00), 0.90 (CI 0.84–0.94), and 0.96 (CI 0.93–0.97) for LC-OCT. The positive predictive value (PPV) resulted in 0.74 (CI 0.69–0.78) for dermoscopy and 0.94 (CI 0.91–0.97) for LC-OCT, and the negative predictive value (NPV) was 0.89 (CI 0.81–0.95) for dermoscopy and 0.98 (CI 0.95–1.00) for LC-OCT. Finally, our real-life study showed a potentially important role of LC-OCT in the non-invasive diagnosis of NMSCs, especially BCC. The real-time imaging technique could spare unnecessary biopsies with an increased sensitivity, a much higher specificity, and better accuracy than clinical assessment with dermoscopy alone