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T cell autoreactivity against the autoantigens LL37 and ADAMTSL5 contributes to inflammation in a subset of psoriatic patients. The immunological mechanisms underlying the treatment response in patients showing autoreactivity remain incompletely understood in clinical settings. This study investigated the impact of tildrakizumab on circulating immune populations and on autoantigen-specific T cell reactivity. Patients with moderate-to-severe psoriasis were enrolled and treated with tildrakizumab according to clinical practice. T cells autoreactivity to LL37 and ADAMTSL5 was assessed at baseline using a stimulation index (SI>2). Longitudinal changes in circulating T cell subsets were analyzed using multiparametric flow cytometry. Twenty of 38 psoriatic patients (52.6%) displayed circulating autoreactive T cells (SI>2) to LL37 and/or ADAMTSL5, compared with 5 of 33 healthy donors (15.2%). Baseline frequencies of Ki67 CD4 /CD8 , and IL-17 CD4 /CD8 T cell populations positively correlated with PASI. Stimulation of PBMCs with LL37 or ADAMTSL5 induced Th17- and Th1-related cytokines, but not Th2-related cytokines. During treatment, tildrakizumab significantly modulated multiple circulating T cell subsets, including Ki67 CD4 , Ki67 CD8 , Ki67 Th17, Th17, and Ki67 Tregs, and markedly reduced autoreactivity to both autoantigens. Notably, clinical improvement strongly correlated with reductions in Ki67 CD4 and Ki67 CD8 T cell frequencies. LL37-reactive patients exhibited a poorer clinical response at weeks 40 and 52. In autoreactive patients, tildrakizumab effectively modulated circulating T cell proliferation and reduced autoantigen-specific responses over time. LL37-reactive patients showed distinct long-term responses, suggesting that autoantigen-reactive subjects may represent a more treatment-challenging subgroup within the psoriatic population.

Scleromyxedema (SMX), the generalized and sclerodermic form of lichen myxedematous (LM), is a chronic mucinosis characterized by cutaneous manifestation and several systemic comorbidities. Treatment options are limited and there are no definitive therapeutic guidelines. We report a case of a 48-year-old man with scleromyxedema, associated with monoclonal gammopathy and arthritis, who has been successfully treated with intravenous immunoglobulins (IVIg), oral corticosteroids, and methotrexate (MTX). IVIg is the most used first-line therapy for SMX based on its efficacy and well-tolerated nature and has been used for a growing number of skin disorders. In our case, combining IVIg with oral prednisone and MTX allowed better control of skin disease and extra-cutaneous manifestations. To the best of our knowledge, this is the first case of a successful treatment for SMX with a combination of therapeutic strategies and a good safety profile.

Upadacitinib is a selective Janus kinase inhibitor approved for the treatment of severe atopic dermatitis (AD). This systematic review aims to summarize the most recent data in terms of effectiveness and safety of upadacitinib in the treatment of severe AD in a real-world setting. The review included a comprehensive search of databases, including PubMed, Google Scholar and Web of Science, according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The literature search initially identified 242 studies. Of these, 214 were excluded after reviewing their titles and abstracts. We then conducted a full-text review of 25 studies, of which 17 met our inclusion criteria and were therefore included in our systematic review. The analysis of real-world studies showed high effectiveness of upadacitinib, in terms of both clinical signs and subjective symptoms, in different patient populations, including those resistant to other treatments. No new significant safety concerns have emerged as compared to randomized clinical trials.

Chronic hand eczema (CHE) is a common and challenging skin condition, characterized by persistent hand dermatitis which lasts over 3 months or recurs at least twice a year. This condition is often multifactorial, involving genetic predispositions, environmental factors and triggers, such as irritants and allergens. Studies show a higher incidence in women, though prevalence estimates vary across different age groups. The pathogenesis involves complex immune mechanisms, particularly Th1/Th2 cell responses. Clinically, CHE presents in various forms, with symptoms such as redness, scaling and itching that significantly impact patients’ quality of life. Treatment approaches are diverse. While emollients and topical corticosteroids have historically been the mainstay, new systemic therapies like JAK inhibitors and biologics are progressively being used for severe cases. Key molecular targets comprise interleukin (IL)-4 and IL-13, the JAK-STAT pathway, phosphodiesterase 4 (PDE4) and chemoattractant chemokines. Managing CHE effectively remains a challenge because of its chronicity and the variability in individual responses to treatment. However, emerging therapeutic strategies will help clinicians to offer more patient-centred approaches.

Psoriasis is a chronic immune-mediated disease primarily affecting the skin. The most common subtype is plaque psoriasis, which can affect any body area, with a predilection for the knees, elbows, scalp, lumbosacral region, and genitalia. The European guidelines adopted in Italy recommend systemic therapies for moderate-to-severe psoriasis, defined by a Psoriasis Area and Severity Index (PASI) ≥10, Dermatology Life Quality Index (DLQI) ≥10, and/or Body Surface Area (BSA) ≥10. Over the past two decades, the development of biological agents has revolutionized psoriasis management, targeting specific cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-23, and IL-17. Among these, ixekizumab, secukinumab, brodalumab, and bimekizumab are approved for the treatment of moderate-to-severe plaque psoriasis. However, some patients require switching therapy because of primary/secondary ineffectiveness or side effects. We retrospectively analyzed 20 patients who had switched from one anti-IL-17 drug to another, assessing both safety and effectiveness. At baseline, the median PASI score was 10 (interquartile range [IQR] 4.5). After 16 weeks, it decreased to 2 (IQR 5.5), and after one year, it decreased further to 1 (IQR 2). Eight (40%) and six patients (30%) achieved PASI 90 and PASI 100 at 16 weeks, respectively. After one year, sustained effectiveness was observed, with PASI 90 (57.1%), PASI 100 (35.7%), and PASI≤2 (78.6%). No serious adverse events (AEs) or discontinuations due to AEs were observed during the study period. Our study confirms the safety and effectiveness of intra-class switching among IL-17 antagonists within the same class and highlights that switching between different classes of IL-17 inhibitors can be a valid option when patients fail to respond or lose effectiveness with a particular inhibitor. However, a deeper understanding requires further large-scale and long-term studies.

Background and Objectives: Janus kinase inhibitors (JAKi) have significantly advanced the treatment of various dermatological conditions by modulating the JAK-STAT signalling pathway. While these inhibitors have proven effective, they also pose challenges due to associated increase in serum lipid levels and relative potential cardiovascular risks. This perspective work aims to discuss the implications of these lipid alterations proposing management strategies for patients with dermatological disorders under JAKi treatments. Materials and Methods: This manuscript reviews existing and recent literature on the metabolic effects of JAKi, particularly focusing on their impact on lipid profiles in patients treated for dermatological diseases. Results: JAK inhibitors are consistently associated with an increase in both LDL and HDL levels shortly after treatment initiation, which tend to stabilise over time. Despite these changes, there is no clear evidence linking these alterations to an increased risk of major adverse cardiovascular events (MACE), indicating a complex interaction between lipid metabolism and JAK-STAT signalling. Conclusions: Although JAKi may induce lipid changes in patients, raising concerns, especially in ones with existing cardiovascular risks, currently there is no proven link to increased MACE in this population. Monitoring lipid levels, alongside lifestyle modifications and possible statin use, can manage these effects without the need to stopping treatment.

Klebsiella pneumoniae is a gram-negative bacterium rarely responsible for skin infections that are often difficult to diagnose. We present the case of an atypical presentation of this particular disease by site, absence of predisposing factors and duration of the condition.

The development of flares or new-onset of immune-mediated dermatologic diseases, including psoriasis, has occurred with the worldwide spreading of the COVID-19 pandemic. We report the case of a 38-year-old woman who came to our department with a severe flare of plaque psoriasis four weeks after SARS-CoV-2 infection. Her Psoriasis Area Severity Index was 25, and her Dermatology Life Quality Index was 18. Our initial decision was to prescribe acitretin, but the patients reported adverse events. For this reason, we started risankizumab with complete skin clearance after 16 weeks. The patient is still on treatment, and no adverse events have been reported to date.

Prurigo nodularis (PN) is a chronic dermatological condition characterized by intensely pruritic nodules resulting from repeated scratching. Its pathogenesis involves neuroimmune dysregulation, inflammatory cytokines, and neural proliferation. Conventional treatments often provide limited relief, necessitating novel therapeutic approaches. This narrative review explores emerging biologics and small molecules for PN treatment, assessing their mechanisms, efficacy, and safety. A comprehensive literature search was conducted using PubMed, Google Scholar, and Web of Science for relevant studies up to February 2025. Additionally, ongoing clinical trials were identified through a verified international website. The search terms included “prurigo nodularis”, “biologic treatments”, “monoclonal antibodies”, “small molecules”, and “JAK inhibitors”. Among new treatment options, dupilumab, an IL-4 receptor antagonist, and nemolizumab, an IL-31 receptor inhibitor, demonstrated significant efficacy in reducing pruritus and lesion severity in PN patients. Other promising monoclonal antibodies include vixarelimab (OSMRβ inhibitor) and barzolvolimab (KIT inhibitor). Small molecules such as JAK inhibitors (upadacitinib, povorcitinib) also show potential by modulating inflammatory pathways. Clinical trials highlight their efficacy, safety, and long-term benefits. Emerging biologics and small molecules represent a transformative approach for PN management, offering targeted therapies that address underlying immunological and neurological mechanisms. Ongoing research and long-term studies are crucial to optimizing treatment strategies and improving patient outcomes.

Background and Objectives: Amelanotic/hypomelanotic melanomas (AHMs) account for 2–8% of all cutaneous melanomas. Due to their clinical appearance and the lack of specific dermoscopic indicators, AHMs are challenging to diagnose, particularly in thinner cutaneous lesions. The aim of our study was to evaluate the clinicopathological and dermoscopic features of thin AHMs. Identifying the baseline clinical–pathological features and dermoscopic aspects of thin AHMs is crucial to better understand this entity. Materials and Methods: We divided the AHM cohort into two groups based on Breslow thickness: thin (≤1.00 mm) and thick (>1.00 mm). This stratification helped identify any significant clinicopathological differences between the groups. For dermoscopic analysis, we employed the “pattern analysis” approach, which involves a simultaneous and subjective assessment of different criteria. Results: Out of the 2.800 melanomas analyzed for Breslow thickness, 153 were identified as AHMs. Among these, 65 patients presented with thin AHMs and 88 with thick AHMs. Red hair color and phototype II were more prevalent in patients with thin AHMs. The trunk was the most common anatomic site for thin AHMs. Patients with thin AHMs showed a higher number of multiple melanomas. Dermoscopic analysis revealed no significant difference between thin AHMs and thick AHMs, except for a more frequent occurrence of residual reticulum in thin AHMs. Conclusions: Thin AHMs typically affect individuals with lower phototypes and red hair color. These aspects can be related to the higher presence of pheomelanin, which provides limited protection against sun damage. This also correlates with the fact that the trunk, a site commonly exposed to intermittent sun exposure, is the primary anatomical location for thin AHMs. Multiple primary melanomas are more common in patients with thin AHMs, likely due to an intrinsic predisposition as well as greater periodic dermatologic follow-ups in this class of patients. Apart from the presence of residual reticulum, no other significant dermoscopic differences were observed, complicating the differential diagnosis between thin and thick AHMs based on dermoscopy alone.