Giulio Gualdi

Background: Circulating extracellular vesicle (EV)-associated particle profiles may differ between patients with melanoma and those with benign lesions. Methods: Preoperative citrated whole blood from 77 patients with clinically suspicious lesions was assessed by direct fluorescence-based flow cytometry; histopathology identified 20 CMM cases (12 primary and 8 metastatic) and 57 benign-lesion controls. Results: The reported total particle concentration was higher in CMM than controls (3299.86 ± 456.61 vs. 2873.40 ± 427.74 events/µL). CD45+, PD-L1+, and CD45+/PD-L1+ populations were also increased. CD45+/VISTA+ particles were higher in the reduced subset of 9 CMM cases and 48 controls. Conclusions: These exploratory observations require analytical validation and independent clinical confirmation before diagnostic or prognostic utility can be established.

Background: Psoriasis is a chronic inflammatory disease frequently associated with obesity and type 2 diabetes mellitus (T2DM). Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used for T2DM and obesity, have demonstrated anti-inflammatory and immunomodulatory properties that may be relevant in psoriasis. However, individual GLP-1RAs differ substantially in their pharmacological characteristics and clinical effects. Our objective was to systematically review the available evidence on the effects of individual GLP-1RAs in patients with psoriasis. Methods: A systematic review was conducted according to PRISMA 2020 guidelines. PubMed and Scopus were searched up to April 2026 for studies evaluating GLP-1RAs in psoriasis. Case reports, case series, observational studies, and randomized controlled trials were included. Preclinical, clinical and safety outcomes were extracted and narratively synthesized. Results: Twenty-six studies met the inclusion criteria. Most involved patients with concomitant obesity and/or T2DM. Overall, semaglutide, liraglutide, exenatide, and tirzepatide were associated with improvements in psoriasis severity, often accompanied by reductions in body weight, glycated haemoglobin, inflammatory markers, and cardiometabolic risk factors. Semaglutide and liraglutide showed the most consistent evidence of benefit. Experimental and clinical data also suggested direct immunomodulatory effects on pathways involved in psoriasis pathogenesis. However, paradoxical psoriasiform eruptions and psoriasis exacerbations were reported with some agents. The evidence base was limited by the predominance of case reports and small observational studies, substantial heterogeneity, and the limited availability of randomized controlled trials. Conclusions: Current evidence suggests that GLP-1RAs may improve both psoriatic disease activity and cardiometabolic outcomes, particularly in patients with obesity or T2DM. Nevertheless, potential differences among individual agents warrant further investigation in larger controlled studies.

Background: Actinic keratoses are common keratinocytic precursor lesions arising within chronically ultraviolet-damaged skin and are associated with an increased risk of progression to cutaneous squamous cell carcinoma. The concept of field cancerization has shifted therapeutic strategies from the treatment of isolated visible lesions toward broader field-directed approaches targeting both clinical and subclinical disease. Methods: This narrative review summarizes the rationale, mechanisms of action, efficacy profile, tolerability, and practical limitations of currently available field-directed therapies for actinic keratosis, including 5-fluorouracil, imiquimod, diclofenac, photodynamic therapy, and tirbanibulin. Based on their distinct biological targets, we propose a mechanism-based framework for sequential treatment strategies. Results: Available therapies act through partially non-overlapping mechanisms, including cytotoxic activity, immune activation, cyclooxygenase-2 inhibition, photodynamic oxidative damage, and tubulin/Src pathway inhibition. These complementary effects provide a biological rationale for sequential regimens aimed at addressing the heterogeneity of field cancerization. However, direct clinical evidence supporting specific treatment sequences remains limited, and proposed regimens should be interpreted as hypothesis-generating rather than as validated therapeutic protocols. Conclusions: Mechanism-based sequential field therapy may represent a rational strategy to optimize long-term control of actinic keratosis and field cancerization. Prospective comparative studies are needed to define optimal sequences, treatment intervals, patient selection criteria, and clinically meaningful endpoints, including sustained field clearance, recurrence reduction, tolerability, adherence, and prevention of progression to invasive cutaneous squamous cell carcinoma.

Actinic keratosis (AK) is considered the early phase of a squamous cell carcinoma (SCC) and represents one of the most common epithelial skin lesions, with an estimated global prevalence of approximately 14%. An estimated annual risk of progression has been reported with a range from 0 to 0.53%. Although spontaneous regression of individual AK lesions has been described in approximately 23% of cases, the frequent presence of multiple lesions, usually in the broader context of field cancerization, significantly diminishes the likelihood of regression and contributes to a higher cumulative risk of progression to SCC. The aim of the present narrative review was to provide an overview of the current evidence of the most effective available lesion-directed and field-directed treatments for actinic keratoses, on the personalized, combined, or sequential approach, as well as on the emerging therapeutic options.

The relationship between psoriasis, immunomodulatory therapies, and the risk of malignancies is complex and still debated. The scarcity of evidence in this field makes clinicians hesitate to prescribe biological therapies for 'difficult-to-treat' patients. Based on a comprehensive MEDLINE/PUBMED search of articles published up to November 2024, this review synthesizes the current evidence on the association between psoriasis and cancer. This review specifically addresses four key aspects: the overall cancer risk in psoriatic patients, the potential role of cytokines involved in psoriasis pathogenesis in tumor development, the association between biological therapies and the incidence of new malignancies in this population, and the risk of cancer recurrence or progression in patients with a history of malignancy who are treated with biologics. Biological therapies do not significantly elevate malignancy risk compared to non-biological treatments or the general population. Evidence is also reassuring for patients with prior malignancy, showing no tumor progression or recurrence. These findings support the timely use of biological treatments in 'difficult-to-treat' patients. Regular cancer screenings and risk-factor minimization should always be recommended for psoriatic patients undergoing immunomodulatory therapies. Multidisciplinary management involving oncologists is suggested, particularly for patients with active and advanced oncological disease.

Objective. Psoriatic arthritis (PsA) can be treated with biological drugs targeting IL-17A, such as secukinumab, with good responses and long-term positive outcomes in clinical studies. Methods. An observational study was conducted on adult subjects with PsA and comorbidities treated with secukinumab after prior therapy with conventional disease-modifying anti-rheumatic drugs or biological agents that were discontinued due to lack of efficacy or adverse drug reactions. Patients were followed up with clinical visits at 3, 6, 9, and 12 months and evaluated for disease activity, pain, and quality of life compared to baseline. Moreover, a narrative review of the literature was performed on secukinumab’s use for PsA in real life. Results. Fifteen patients completed 6 months of follow-up, eleven patients completed 9 months, and six patients were followed for 12 months. The major comorbidities recorded were fibromyalgia (33% of patients), recurrent bilateral anterior uveitis, and autoimmune thyroiditis with hypothyroidism (both 13% of the patients). A significant improvement in Disease Activity Score-28 was recorded at 6 and 9 months, while a significant difference vs. baseline was seen at 3, 6, and 9 months for the Psoriasis Area Severity Index. The Bath Ankylosing Spondylitis Disease Activity Index showed significant differences vs. baseline at 9 and 12 months. There was an improving trend at 9 and 12 months for pain scores and a significant improvement at 6 and 9 months for the physical component and at 12 months for the social component (Short Form 36 Health Survey quality of life scores). For the review of the literature, 35 articles were identified, but only 17 papers were eventually considered. Conclusions. Secukinumab has demonstrated effectiveness for PsA treatment in several real-world studies. Both patient-oriented and clinician-oriented outcomes showed a significant improvement with this treatment. The present real-world evaluation adds further evidence on the use of secukinumab for PsA treatment, showing the rapid, safe, clinically significant, and sustained responses of PsA patients affected by co-morbidities.

Skin lesions are frequently observed in children with rheumatic diseases, particularly in conditions such as IgA vasculitis (IgAV) and Kawasaki disease (KD). In paediatric vasculitis, the presence of skin lesions serves as an early indicator, emphasising the importance of timely diagnosis to prevent complications, such as cardiac or renal involvement. Conversely, autoinflammatory disorders like juvenile systemic lupus erythematosus (SLE) and juvenile dermatomyositis (DM) may manifest with cutaneous manifestations either at the onset of disease or during its progression. Identifying these skin lesions prior to the appearance of systemic symptoms offers an opportunity for early diagnosis and treatment, which has a positive influence on the outcomes. Additionally, it is noteworthy that specific rheumatological conditions, such as acute rheumatic fever (ARF) or oligoarticular or polyarticular forms of juvenile idiopathic arthritis (JIA), may exhibit occasional, but significant skin involvement, which is strongly correlated with an unfavourable prognosis. The assessment of skin is important in the holist approach to assessing patients for potentially systemic/multisystem disorder and helps distinguish discrete conditions.