Search Results (47)

Background/Objectives: Long-term real-world data on dupilumab effectiveness and response trajectories in paediatric atopic dermatitis (AD) remain limited. This study evaluated long-term effectiveness, safety, response durability, and treatment trajectories in paediatric patients with moderate-to-severe AD treated with dupilumab. Methods: This retrospective single-centre cohort study included 55 paediatric patients with moderate-to-severe AD treated with dupilumab. Clinical outcomes, including Eczema Area and Severity Index (EASI), body surface area (BSA), and Children’s Dermatology Life Quality Index (CDLQI), were assessed longitudinally throughout treatment. The primary endpoint was the achievement of EASI-75 over the course of treatment, including timing of response onset. Secondary endpoints included EASI-90 achievement, longitudinal changes in disease severity and quality of life, treatment durability, safety, and response trajectory analyses. Patients were additionally classified into mutually exclusive trajectory groups based on timing and durability of EASI-75 achievement. Results: Dupilumab treatment was associated with rapid and sustained clinical improvement. Some patients achieved EASI-75 as early as week 4, highlighting interindividual variability in response kinetics. At week 16, EASI-75 was achieved in 85.5% of patients and EASI-90 in 47.3%. Clinical effectiveness further improved during long-term follow-up, with EASI-75 achieved in 96.2% and EASI-90 in 86.5% of patients at the last available follow-up. Median CDLQI decreased from 22.0 at baseline to 3.0 during follow-up, indicating marked improvement in quality of life. Most patients (83.6%) were classified as early responders, while 10.9% demonstrated delayed but clinically meaningful improvement during continued treatment. Loss of response after initial EASI-75 achievement was uncommon (3.7%). Adverse events were predominantly mild, with eosinophilia and conjunctivitis representing the most frequently observed findings. Conclusions: Overall, dupilumab demonstrated high long-term effectiveness and favourable tolerability in paediatric patients with moderate-to-severe AD. Trajectory analyses revealed clinically meaningful heterogeneity in response kinetics despite favourable long-term outcomes, highlighting that delayed responders may still achieve substantial benefit during continued therapy. Full article

Background: Patient-perceived seasonality of psoriasis is frequently reported, yet the independent contribution of objectively quantified, individualized ultraviolet (UV) exposure remains insufficiently characterized. We evaluated seasonal variation in plaque psoriasis and its association with geocoded, phototype-adjusted ambient antipsoriatic radiant exposures (ARE) using mixed-effects modeling. Methods: This cross-sectional study included 119 adults with plaque psoriasis (476 seasonal observations). Participants rated seasonal disease courses using a 7-point scale. Ambient ARE was geocoded to residential postal codes and quantified as a behaviorally weighted dose normalized to individual minimal erythema dose (MED). Mixed-effects logistic regression models, adjusted for relevant confounders, estimated associations with seasonal improvement and worsening. Results: Seasonality was reported by 89.9% of participants (p < 0.001). Summer was the most favorable season, whereas winter was the most detrimental. The highest ARE quartile was independently associated with increased odds of improvement (OR 4.65, 95% CI 2.04–10.58, p < 0.001) and reduced odds of worsening (OR 0.16, 95% CI 0.08–0.33, p < 0.001). Crucially, continuous quadratic modeling revealed a significant inverted U-shaped relationship between UV exposure and improvement, with an estimated turning point of 3.85 (95% CI 1.88–5.82, p < 0.001) for the declared daily ARE (UV_decl) normalized by MED. Beyond this threshold, the probability of improvement attenuated. The protective effect against seasonal worsening remained linear. Conclusions: Psoriasis seasonality demonstrates a robust exposure–response association relationship with ambient UV. The estimated turning point (UV_decl/MED = 3.85) within our modeled exposure metric is exploratory and hypothesis-generating. It suggests an association where moderate UV exposure correlates with patient-perceived benefits, but these diminish at very high levels. This threshold requires external prospective validation before being considered a clinically actionable recommendation. Full article

Children with skin color (SOC) are underrepresented in dermatologic research, despite structural and functional differences that shape disease presentation. Atopic dermatitis (AD), one of the most common pediatric dermatoses, often appears differently in SOC than in white children. This study compared dermatologic conditions prompting Pediatric Emergency Department (PED) referral in SOC and white children, and described clinical features of AD in SOC. A retrospective study was performed at IRCCS AOUBO Policlinico di Sant’Orsola, Bologna, Italy, analyzing records and photographs from 2019. Patients presenting with dermatologic conditions and evaluated by a pediatric dermatologist were included. Of 411 patients, 109 (26.5%) had SOC. In SOC, common diagnoses were scabies (22%), AD (17.4%), viral infections (12.8%), burns (9.2%), and contact dermatitis (7.3%). In white children, viral infections (16.9%), burns (14.2%), contact dermatitis (13.9%), AD (12.9%), and insect bites (5.6%) predominated. Scabies and pruritus were significantly more frequent in SOC (p < 0.05). Among 38 SOC patients with AD, lichenoid (31.6%), pityriasis alba (29.0%), prurigo nodularis (26.3%), and classic AD (13.2%) were the most frequent variants. Erythema was often subtle or absent. Dermatologic conditions and AD morphology differ between SOC and white children, highlighting the need for tailored diagnostic approaches and equitable care. Full article

Children’s skin is uniquely vulnerable, requiring specialised design solutions that transcend traditional aesthetics. This exploratory study investigates the importance of paediatric dermatology in informing functional fashion design through expert medical perspectives. Using a qualitative approach, data were gathered from a purposive cohort of paediatric dermatologists and immunoallergologists and analysed through inductive thematic analysis. Findings identify four core themes: the physiological immaturity of children’s skin (notably the prevalence of atopic dermatitis), clothing’s role as a symptomatic aggravator rather than a primary aetiology, the clinical risks posed by chemical additives in synthetic textile processes, and the therapeutic potential of natural fibres and biofunctional agents. The data also highlights significant diagnostic constraints in paediatric patch testing, emphasising the necessity of proactive material safety. The findings suggest that integrating healthcare expertise into human-centred design may support the development of safer paediatric clothing solutions, ensuring that fashion industry innovation meets the physiological requirements of children. By transitioning from hazardous synthetic processes to biocompatible textiles, such as undyed natural fibres and medicinal plant-derived dyes, the industry can transform apparel from a potential irritant into a secondary protective barrier. This provides initial insights for developing clothing that safeguards the skin barrier and improves the overall wellbeing of vulnerable populations. Full article

Biopsies are only performed in less than 1% of all consultations dedicated to paediatric genital dermatology. The objectives of this paper are to review and clarify the histopathological features of the conditions most often biopsied: first, lichen sclerosus, which has a peak incidence in childhood and progresses over years; secondly, pigmented lesions, including atypical genital naevi and common naevi in the context of lichen sclerosus, both histologically differential diagnoses of melanoma, which probably does not present in childhood. And finally, Crohn’s disease, which is a cause of vulval oedema or genital ulceration. Full article

Background: Parasitic skin-related conditions represent a frequent and evolving challenge in human dermatology, as they often mimic other dermatoses, and are increasingly complicated by therapeutic resistance. With this study, we aimed to provide a practical, clinician-oriented overview of our experience, contextualising it within the current literature. Materials and Methods: We conducted a retrospective, single-centre observational study, reporting a case series of 88 patients diagnosed with parasitic or arthropod-related skin infestations at the San Raffaele Hospital Dermatology Unit (Milan) between 2019 and 2024, and integrated a concise narrative review of contemporary evidence on diagnosis, non-invasive imaging and management. For each case, we documented clinical presentation, dermoscopic or reflectance confocal microscopy (RCM) findings, and treatment response. Non-invasive tools (dermoscopy, videodermoscopy, RCM) were used when appropriate. Results: The spectrum of conditions included flea bites, bed bug bites, cutaneous larva migrans, subcutaneous dirofilariasis, Dermanyssus gallinae dermatitis, pediculosis, tick bites (including Lyme disease), myiasis, scabies, and cutaneous leishmaniasis. One case of eosinophilic dermatosis of haematologic malignancy was also considered due to its possible association with arthropod bites. Non-invasive imaging was critical in confirming suspected infestations, particularly in ambiguous cases or when invasive testing was not feasible. Several cases highlighted suspected therapeutic resistance: a paediatric pediculosis and three adult scabies cases required systemic therapy after standard regimens failed, raising concerns over putative resistance to permethrin and pyrethroids. In dirofilariasis, the persistence of filarial elements visualised by RCM justified the extension of antiparasitic therapy despite prior surgical removal. Conclusions: Our findings underline that accurate diagnosis, early intervention, and tailored treatment remain essential for the effective management of cutaneous infestations. The observed vast spectrum of isolated parasites reflects broader health and ecological dynamics, including zoonotic transmission, international mobility, and changing environmental conditions. At the same time, diagnostic delays, inappropriate treatments, and neglected parasitic diseases continue to pose significant risks. To address these challenges, clinicians should remain alert to atypical presentations, and consider a multidisciplinary approach including the consultation with parasitologists and veterinarians, as well as the incorporation of high-resolution imaging and alternative therapeutic strategies into their routine practice. Full article

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, with incidence steadily increasing due to cumulative ultraviolet (UV) exposure, impaired immune surveillance, and chronic tissue damage. While most cases are effectively managed with surgical excision, a subset progress to locally advanced or metastatic disease, associated with high recurrence rates, limited curative options, and poor prognosis. The introduction of immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis has significantly altered the management of advanced cSCC. Cemiplimab and pembrolizumab are now established systemic therapies, producing durable responses in a proportion of patients. These outcomes reflect the typically high tumor mutational burden and immunogenic microenvironment of cSCC. However, therapeutic decision-making remains particularly complex in several high-risk populations, including solid organ transplant recipients at risk of allograft rejection, patients with chronic dermatologic disorders or non-healing wounds that predispose to carcinogenesis, and individuals with rare hereditary syndromes such as recessive dystrophic epidermolysis bullosa. These so-called challenging populations are frequently excluded from pivotal trials, resulting in limited evidence regarding efficacy, safety, and optimal treatment strategies. This review summarizes current evidence on the management of advanced cSCC in high-risk and underserved patient groups, integrating trial data, real-world evidence, and contemporary guidelines. It also highlights key gaps in knowledge and outlines future directions, with particular focus on the interplay between host immune status, tumor biology, and therapeutic response. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin condition that affects up to 25% of children and impairs both skin barrier function and quality of life. This study examined the effectiveness of an emulgel containing hyaluronic acid, glycerol, grape seed oil, Calendula officinalis, aloe vera and sh-oligopeptide-1 (a synthetic Epidermal Growth Factor) for treating paediatric AD. In a randomised, self-controlled trial, 57 children (aged 2–14) applied the emulgel twice daily for 10 days to one forearm and left the other forearm as a control. Skin barrier parameters such as transepidermal water loss (TEWL), stratum corneum hydration (SCH), erythema and pH were measured. After applying the emulgel, lesional skin showed reduced erythema (p = 0.007), lower TEWL (p = 0.002) and higher SCH (p < 0.001). Non-lesional skin showed improved SCH (p < 0.001). SCORing Atopic Dermatitis (SCORAD) and Eczema Area and Severity Index (EASI) scores indicated milder disease post-treatment (mild cases: 64.9% to 80.7% SCORAD; 82.5% to 93.0%EASI). The Dermatology Life Quality Index improved by ~3.5 points, and patients reported high satisfaction with no adverse effects. This emulgel is an effective and well-tolerated adjunctive therapy for paediatric AD, enhancing barrier function and clinical outcomes. Full article

Background/Objectives: Psoriasis is an immune-mediated disease influenced by genetic predisposition, environmental triggers, and metabolic comorbidities. Biologic therapies have markedly improved disease control; however, variability in patient response remains insufficiently understood. The aim of the study is to evaluate whether CARD14 mutations and the season of treatment initiation influence the efficacy of biologic therapy in psoriasis. We also examined the potential interactions between CARD14 status, seasonality, drug class, and nutrition status on short-term clinical outcomes. Methods: This retrospective study included 72 patients receiving biologic therapy within the Polish NHF B.47 program. Clinical endpoints (PASI, BSA, DLQI) were assessed at baseline and after 1, 4, 7, and 10 months. CARD14 genotyping was performed using Sanger sequencing. Patients were stratified according to mutation status, season of therapy initiation (warm vs. cold), drug class, and BMI category. Statistical analyses included t-tests, chi-square, ANOVA, and MANOVA. Results: The CARD14 rs34367357 mutation was associated with earlier disease onset (15.6 vs. 22.7 years, p = 0.0134) and higher DLQI baseline (p = 0.0265) but did not significantly impact treatment response. Therapy initiated during the warm season (April–September) led to greater PASI improvement (p < 0.0001). Obesity was associated with reduced response (p = 0.02385). Drug class and interaction effects were not statistically significant. Conclusions: Our findings suggest that seasonal timing, nutritional status, and genetic background may modulate the efficacy of biologic therapies in psoriasis. Although not statistically conclusive, the potential interaction between CARD14 rs34367357 and seasonality warrants further investigation. Full article

The hydroxycarboxylic acid receptor (HCAR) family belongs to G-protein-coupled receptors (GPCRs) implicated in a diverse array of physiological and pathological mechanisms. Kynurenic acid, a metabolite of the tryptophan catabolic pathway, has been proposed as a putative ligand of HCAR3. This receptor, among other HCARs, has garnered particular attention due to its exclusive expression in humans and closely related primates, and its emerging role in immunometabolic regulation. This review focuses on the potential role of HCAR3 in cancer initiation, progression, and metastasis. Moreover, it presents a comprehensive analysis of the potential functional and molecular interactions between kynurenic acid and HCAR3 in the context of cancer pathophysiology, which may have significant implications for tumor immunomodulation and the development of new therapeutic strategies. Full article

Background: Actinic keratoses (AKs) are common pre-neoplastic lesions that may progress to cutaneous squamous cell carcinoma (cSCC). Photodynamic therapy (PDT) is an effective field-directed treatment for AK, but its impact on key biomarkers remains unclear. This study evaluates the clinical, dermatoscopic, and immunohistochemical effects of PDT on AK, with a focus on proliferation (Ki67, p53) and inflammation (COX-2) markers, to assess its efficacy in delaying carcinogenesis. Methods: In our prospective one-center study, we enrolled 31 patients with AK, with no history of previous AK treatment. They underwent three PDT sessions at four-week intervals, with follow-up eight weeks after the final session. Clinical, dermatoscopic, and immunohistochemical analyses of Ki67, p53, and COX-2 expression were performed before and after treatment. Results: Clinically, 54.8% of patients achieved complete lesion clearance, with no residual severe AK lesions. Ki67 and p53 immunoexpression significantly decreased post-PDT (p < 0.05), confirming its antiproliferative effect. COX-2 expression also declined significantly (p < 0.05), supporting PDT’s anti-inflammatory role. However, COX-2 remained stable or increased in 35.48% of cases, possibly due to inflammation-induced regeneration. There is a positive correlation between the reduction in Ki67, p53, and COX-2 immunoexpression and the decrease in AK severity (both according to Olsen grade and dermatoscopic grade). Conclusions: PDT effectively reduces AK severity, proliferation, and inflammation markers, potentially delaying carcinogenesis. However, residual biomarker expression suggests that additional treatment sessions or combination therapies may be necessary for complete lesion clearance. Further studies are required to optimize PDT protocols. Full article

Resistance to anti-PD-1 therapy in melanoma remains a major obstacle in achieving effective and durable treatment outcomes, highlighting the need to understand and address the underlying mechanisms. The first key factor is innate anti-PD-1 resistance signature (IPRES), an expression of a group of genes associated with tumor plasticity and immune evasion. IPRES promotes epithelial-to-mesenchymal transition (EMT), increasing melanoma cells’ invasiveness and survival. Overexpressed AXL, TWIST2, and WNT5a induce phenotypic changes. The upregulation of pro-inflammatory cytokines frequently coincides with EMT-related changes, further promoting a resistant and aggressive tumor phenotype. Inflamed tumor microenvironment may also drive the expression of resistance. The complexity of immune resistance development suggests that combination therapies are necessary to overcome it. Furthermore, targeting epigenetic regulation and exploring novel approaches such as miR-146a modulation may provide new strategies to counter resistance in melanoma. Full article

Psoriasis is a multifactorial, chronic, and inflammatory disease that severely impacts patients’ quality of life. The disease is caused by genetic irregularities affected by epigenetic and environmental factors. Some of these factors may include seasonal changes, such as solar radiation, air pollution, and humidity, and changes in circadian rhythm, especially in the temporal and polar zones. Thus, some psoriasis patients report seasonal variability of symptoms. Through a comprehensive review, we aim to delve deeper into the intricate interplay between seasonality, environmental factors, and the genetic and epigenetic landscape of psoriasis. By elucidating these complex relationships, we strive to provide insights that may inform targeted interventions and personalized management strategies for individuals living with psoriasis. Full article

Background: Psoriasis is a chronic, multisystemic, inflammatory disease affecting approximately 1% of children and significantly reducing their health-related quality of life. Etanercept is a biologic fusion protein-blocking TNF-α and belongs to one of the biologics used among the children population. The purpose of this study was to assess the effectiveness and safety profile of etanercept in paediatric patients with plaque-type psoriasis. Material and methods: The outcome of the treatment was evaluated based on Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA), and Children’s Dermatology Life Quality Index (CDLQI). Achievement of at least PASI75 at week 16 was assessed as an adequate response to therapy, which was the primary endpoint. Results: Forty-three paediatric patients were included in the study, 24 females and 19 males. The average age at inclusion into our study was 13 years. At baseline, the mean PASI score, BSA, and CDLQI were 16.3 ± 6.5, 22.3 ± 12.2%, and 17.4 ± 5.3, respectively. At week 16, 90.7% of patients achieved PASI 50, 79.1% achieved PASI 75, and 46.5% attained PASI 90. There was also a decrease in mean BSA and CDLQI values to 3.5 ± 3.8 and 5.4 ± 5.7, respectively. Conclusions: Etanercept proved to be effective, safe, and well-tolerated among the paediatric population with psoriasis. Full article