Angela Filoni

Introduction: Interleukin-6 (IL-6) is a pleiotropic cytokine produced by several immunologic cells during inflammatory processes, showing an increased serum value in several autoimmune diseases and infections. Recently, it has been used to evaluate lung involvement in COVID-19 infection, and a specific laboratory test has been developed for such a purpose. We used IL-6 to monitor the evolution of Stevens Johnson Syndrome/Toxic Epidermal Necrolysis in two patients. Case Summary: We observed two cases of generalized allopurinol-induced adverse cutaneous reactions, including severe hypersensitivity. Serum IL-6 measurement allowed us to evaluate the magnitude of the immune and inflammatory status of patients better than C Reactive Protein (CRP) or White Blood Cell (WBC) count and to evaluate the response to the treatment. Conclusion: Although different cytokines and serum markers have been proposed for the diagnosis of severe cutaneous adverse reactions (SCAR) like SJS/TEN, they are still experimental. We were the first to use IL-6 measurement as a helpful biomarker in the diagnosis and therapeutic management.

Lichen sclerosus (LS) is a chronic inflammatory dermatosis that primarily affects the genital mucosa in both sexes. Although most prevalent in women and characterized by distinct age peaks, its clinical presentation, marked by ivory-white atrophic patches and plaques, often overlaps with other conditions. Delayed diagnosis, frequently due to asymptomatic progression, poses a significant risk of malignant transformation. The etiology of LS is multifactorial, involving a complex interplay of genetic, epigenetic, environmental, and autoimmune factors. Pathogenetically, the disease is characterized by several co-occurring features, including an immune imbalance with elevated pro-inflammatory cytokines, impaired T-regulatory (Treg) cell activity, a persistent local inflammatory state, and dysregulated collagen metabolism with associated fibrosis and scarring. Furthermore, the production of autoantibodies against extracellular matrix protein 1 (ECM1) disrupts skin integrity, while the generation of reactive oxygen species (ROS) further exacerbates tissue damage, autoimmunity, and tumorigenesis. Despite its severe impact on patient quality of life, current diagnostic and therapeutic strategies remain limited. While potent topical corticosteroids represent the gold standard first-line treatment—with topical calcineurin inhibitors serving as a second-line alternative—the lack of a fully elucidated etiopathogenesis continues to restrict curative options. However, recent translational research is paving the way for innovative regenerative therapies. This review provides an updated comprehensive overview of the latest advancements in LS pathogenesis and explores emerging therapeutic landscapes.

Vitiligo is a chronic autoimmune disease characterized by the destruction of epidermal melanocyte, resulting in well-demarcated white patches on the skin. Despite the established use of corticosteroids and calcineurin inhibitors and the recent introduction of Janus kinase (JAK) inhibitors, a breakthrough targeted therapy that interrupts the IFN-γ signaling pathway, stable repigmentation remains a major clinical challenge, necessitating deeper investigation into its pathogenesis. Among the factors contributing to vitiligo, including genetic predisposition and autoimmunity, oxidative stress is a central driver of melanocyte damage and the subsequent autoimmune response. Chronic oxidative disequilibrium (high ROS level and impaired mitochondrial activity) and reduced antioxidant capacity (Nrf2/ARE pathway and catalase deficiency) function as triggering factors upstream of most other pathogenic pathways. Consequently, targeting oxidative stress, either as a monotherapy or in synergy with emerging targeted treatments, remains a pivotal area of therapeutic interest even in the current era of targeted therapies. Still, a significant gap remains the lack of standardized oxidative biomarkers to monitor disease activity and therapeutic response. Identifying these indicators is essential for personalized clinical management in vitiligo. This review examines how chronic oxidative disequilibrium and a reduced antioxidant capacity initiate and sustain the autoimmune cascade, leading to disease onset and progression.

Cutaneous melanoma is one of the most aggressive skin cancers, and early diagnosis remains essential to reduce mortality. Reflectance Confocal Microscopy (RCM) provides non-invasive, quasi-histological images of the epidermis, dermoepidermal junction (DEJ), and dermis, enabling real-time assessment of melanocytic lesions. However, interpretation still relies on expert visual evaluation, which is time-consuming and subjective. In this context, Artificial Intelligence (AI) and Computer-Assisted Detection (CAD) systems are emerging as valuable tools to improve diagnostic accuracy and reproducibility. This review summarizes research on AI applications in RCM imaging for melanoma, focusing on three major areas: delineation of skin strata, segmentation of tissues and morphological patterns, and classification of benign versus malignant lesions. Early approaches included Bayesian classifiers, wavelet-based decision trees, and logistic regression, while recent studies have employed support vector machines, random forests, and increasingly deep learning architectures such as convolutional and recurrent neural networks. The results demonstrate encouraging accuracy in DEJ localization, the segmentation of diagnostically relevant patterns, and the discrimination of melanoma from benign nevi. We distinguish the maturity of dermoscopy-based AI (AUC (ROC) > 0.80 on large multicenter cohorts) from the still-exploratory evidence for RCM-based AI. Nonetheless, current studies are often limited by small datasets, heterogeneous protocols, and a lack of multicenter validation. Overall, progress in AI applied to RCM supports the development of CAD systems that could assist clinicians during acquisition and diagnosis, reducing unnecessary biopsies and improving early melanoma detection. Future work should address standardization, dataset expansion, and the integration of advanced AI methods to move closer to clinical implementation.

Article: Generalized morphea treated with secukinumab - Italian Journal of Dermatology and Venereology 2023 August;158(4):368-9 - Minerva Medica - Journals

Background: In recent years, great research interest has been directed to the diagnostic, therapeutic and marker role of Preferentially expressed Antigen in Melanoma (PRAME) in the setting of various human neoplasms. Although it has been extensively studied mainly in the differential diagnosis setting of melanocytic pigmented lesions, still very few papers have analyzed the usefulness or otherwise of PRAME in the context of other non-melanoma skin cancers (NMSC). (2) Methods: In this paper, we report the data of our experience of 21 cases of sebaceous carcinoma (SC) classified in the three WHO grade and collected in the period between January 2005 and 31 October 2022, on which immunostaining for PRAME was performed; Non-parametric Mann–Whitney test for non-normally distributed values was performed. A comparison was made of the means between the three study groups (grade I, II and III). A value of p ≤ 0.05 was set as statistically significant (3) Results: Only seven cases (33.3%) were positive with an immunoscore of 2+/3+ for intensity and 1+/2+ for percentage cells positivity, while 14 cases (66.6%) were totally or nearly totally negative for PRAME with a few of sebaceous-like cells positive with an immunoscore of 1+. Eight cases of SC grade I were immunostaining for PRAME, a level of the cytoplasm of foci of sebaceous differentiation with a significant statical value (p < 0.0001) with respect to ten cases of SC grade II; furthermore, the eight cases of grade I were positive for PRAME in the same areas respect the 3 cases of SC grade III (p = 0.0303). There were no statistical significance between the 10 cases of grade II and 3 cases of grade III (p = 0.2028); (4) Conclusions: PRAME not seems to add particular information in the case of histopathological diagnostics of SC where other markers, including adipophylline, can be quite indicative. It seems, on the other hand, that PRAME can be useful in the subclassification setting of sebaceous carcinoma in grades I–II–III according to the directives of the latest WHO 2018, highlighting the foci of mature sebaceous differentiation most present in grades 1–2 and almost completely absent in grade 3 of the SC.

Article: Nutritional impairment of neonates with epidermolysis bullosa: a retrospective study - Italian Journal of Dermatology and Venereology 2022 Apr 07 - Minerva Medica - Journals

Epidermolysis bullosa (EB) is a group of rare congenital diseases caused by mutations in structural proteins of the dermal/epidermal junction that are characterized by extreme epithelial fragility, which determines the formation of bullae and erosions either spontaneously or after local mechanical traumas. In EB patients, skin fragility leads to many possible complications and comorbidities. One of the most feared complications is the development of cutaneous squamous cell carcinomas (SCCs) that particularly in the dystrophic recessive EB subtype can be extremely aggressive and often metastatic. SCCs in EB patients generally arise more often in the extremities, where chronic blisters and scars are generally located. SCCs represent a big therapeutic challenge in the EB population. No standard of care exists for the treatment of SCC in these patients, and therapy is based on small case studies. Moreover, the pathogenesis of cSCC in EB patients is still unclear. Many theories have been indeed postulated in order to explain why cSCC behaves so much more aggressively in EB patients compared to the general population. cSCC in EB seems to be the result of many complex interactions among cancer cells, skin microenvironment, susceptibility to DNA mutations and host immune response. In this review, we analyze the different pathogenetic mechanisms of cSCC in EB patients, as well as new therapies for this condition.