IGF1 synthesis after CO2 fractional laser resurfacing (FLR): New insights in the treatment of scalp actinic keratoses

ObjectivesActinic keratosis have a high risk of progression to a squamous cell carcinoma. Insulin-like growth factor 1 and its receptor play a relevant role in restoring repair of ultraviolet-induced cell damage. This pathway is reduced in patients older than 65 years. Ablative fractional laser resurfacing could normalize insulin-like growth factor 1 (IGF-1) secretion in elderly by recruiting new fibroblasts. The aim of the study is to evaluate restoration of IGF1 values by PCR in senescent fibroblasts after ablative fractional laser resurfacing. MethodsWe enrolled 30 male patients with multiple actinic keratosis on the scalp, equally divided into two mirror areas of up to 50 cm(2), treating only the right one. We performed one skin biopsy for each area 30 days after treatment. Real-time PCR in fibroblasts was performed to assess the change in IGF1. At baseline and after 6 months, in vivo reflectance confocal microscopy examination was performed in all patients. ResultsIGF1 values were increased in the treated side by about 60%. The right areas had fairly complete resolution of actinic keratosis at the last follow-up visit after 6 months with no appearance of new lesions. The mean number of actinic keratosis in the right area was reduced by more than 75% at four- and six-follow-up visits compared to the left area. The improvement in the right area was also evidenced by lower values of the mean AKASI (actinic keratosis area and severity index) score. Reflectance confocal microscopy showed a reduction of keratinocytic disarray and scales after treatment. DiscussionTaken together, all the clinical, laboratory, and in vivo results of our study allowed us to confirm that ablative fractional laser resurfacing is a valuable tool for the treatment of actinic keratosis and cancerization field, both for the management of clinically evident lesions and for preventing the occurrence of squamous cell carcinoma

Blocking the IL-4/IL-13 Axis versus the JAK/STAT Pathway in Atopic Dermatitis: How Can We Choose?

Atopic dermatitis (AD) is an immune-mediated skin disorder with a chronic-relapsing course and a multifactorial pathogenesis. In contrast to the traditional concept of AD as solely a type 2 immune-activated disease, new findings highlight the disease as highly heterogeneous, as it can be classified into variable phenotypes based on clinical/epidemiological or molecular parameters. For many years, the only therapeutic option for moderate-severe AD was traditional immunosuppressive drugs. Recently, the area of systemic therapy of AD has significantly flourished, and many new substances are now marketed, licensed, or in the last step of clinical development. Biological agents and small molecules have enriched the therapeutic armamentarium of moderate-to-severe AD, such as dupilumab, tralokinumab, lebrikizumab (monoclonal antibodies targeting the IL-4/13 pathway), abrocitinib, upadacitinib, and baricitinib (JAK inhibitors). Indeed, the AD treatment paradigm is now split into two main approaches: targeting the IL-4/13 axis or the JAK/STAT pathway. Both approaches are valid and have strong evidence of preclinical and clinical efficacy. Therefore, the choice between the two can often be difficult and represents a major challenge for dermatologists. Indeed, several important factors must be taken into account, such as the heterogeneity of AD and its classification in phenotypes, patients' comorbidities, age, and personal preferences. The aim of our review is to provide an overview of the clinical and molecular heterogeneities of AD and to explore the factors and parameters that, in clinical practice, may help inform clinical decision-making

Dermoscopic and reflectance confocal microscopy features of two cases of vulvar basal cell carcinoma

Basal cell carcinoma (BCC) is the most common malignant skin cancer. Its genital localization is rare, and the diagnosis in this site could be challenging. Here, we report two patients with vulvar BCC and describe their clinical, dermoscopic and in vivo and ex vivo reflectance confocal microscopic (RCM) features. Dermoscopy and RCM can be useful tools for helping the clinical diagnosis of vulvar BCC and for identifying the correct surgical margins

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

Reflectance confocal microscopy and optical coherence tomography for the diagnosis of bullous pemphigoid and pemphigus

Introduction & Objectives: Bullous pemphigoid (BP) and pemphigus (P) are autoimmune diseases characterized by the presence of blisters on the skin and/or the mucous membranes. The diagnosis of these bullous diseases is based on a combination of criteria encompassing clinical features, histology, immunofluorescence and laboratory data. The aim of this study was to evaluate features of BP and P at reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) in order to provide a rapid non-invasive bed-side diagnosis. Secondary objective was to evaluate the detectability of clinically non-visible lesions. Material & Methods: This was an observational, retrospective, multicentre study (University of Modena, Italy and University of Saint-Etienne, France) in which patients with suspicious lesions for BP or P underwent clinical assessment, RCM, OCT, blood tests and skin biopsy for histological and direct immunofluorescence examinations. A total of 72 lesions in 24 patients (16 with PB and 8 with P) were evaluated. Apparently unaffected skin was examined in order to test sub-clinical lesion detectability in all patients. Data analysis was performed from January 2014 to December 2015. Results: RCM was able to detect sub-epidermal and intra-epidermal blisters respectively in 75% and 50% of the patients affected by BP and P. At OCT the exact blister level was identified in all BP and P cases’. Acantholytic cells were observed only at RCM in P (62.5%). Fibrin deposition inside the blisters was only found in PB, evidenced both at RCM and OCT. Subclinical bullae were revealed on clinically healthy skin at OCT in some cases of BP and P. Conclusions: RCM and/or OCT can assist the clinician in providing rapid information through a non-invasive procedure for a rapid diagnosis of BP and P. Combined use of RCM and OCT for a real-time examination of the skin lesions associates the higher resolution of RCM with the greater penetration depth in cross-sectional view of OCT, providing in vivo quasi-histologic information

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