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Background: The complexity, high prevalence, and substantial personal and socioeconomic burden collectively render atopic dermatitis (AD) a major public health concern. Using crowdsourced Internet data has the potential to provide unique insights into this concern, as demonstrated by several previous studies. However, a comprehensive comparison across European countries remains lacking. Objectives: The study aimed to investigate AD‐related web searches across Europe to assess spatiotemporal variations and associations between disease‐related and external factors. Methods: AD‐related web search data were extracted for 21 European countries between February 2019 and January 2023. Descriptive analysis and autocorrelation functions were performed to examine spatiotemporal patterns. Correlations (r) were used to evaluate the associations between web searches and disease‐related, socioeconomic and meteorological data. Results: Over 241 million AD‐related web searches were identified, with search volume varying substantially among European countries (p < 0.001) and correlating with AD prevalence and disease burden (both r = 0.51, p = 0.019). Search volume increased between 2019 and 2023 in all countries and seasonally peaked in January and March. Negative correlations with median population age (r = −0.46, p = 0.039), number of general practitioners (r = −0.29, p = 0.226) and specialists (r = −0.27, p = 0.270) were observed. Moderate to strong correlations were found between search volume and cold, humid and windy weather with fewer sunshine hours, while higher online interest typically occurred 1–3 months after such weather conditions. Conclusion: The study highlights the great potential of online crowdsourced data analysis, for example, to investigate the impact of climate change or to identify unmet needs at a population level. Furthermore, the growing online interest in AD and the corresponding seasonal peaks emphasize the necessity of adapting treatment plans, intensifying public health campaigns, and disseminating reliable online information by governments and healthcare providers, especially during these periods. [ABSTRACT FROM AUTHOR]

In the past decade, our understanding of psoriasis pathogenesis has made significant steps forward, leading to the development of multiple game-changing therapies. While psoriasis primarily affects the skin, it is increasingly recognized as a systemic disease that can have effects beyond the skin. Obesity is associated with more severe forms of psoriasis and can potentially worsen the systemic inflammation and metabolic dysfunction seen in psoriatic patients. The exact mechanisms underlying the link between these two conditions are not fully understood, but it is believed that chronic inflammation and immune dysregulation play a role. In this review, we examine the existing body of knowledge regarding the intersection of pathogenic processes responsible for psoriasis and obesity. The ability of biological therapies to reduce systemic and obesity-related inflammation in patients with psoriasis will be also discussed. [ABSTRACT FROM AUTHOR]

This article discusses the nomenclature dilemma surrounding atopic dermatitis (AD) or atopic eczema (AE), a chronic inflammatory skin disease. The study analyzes web search data from 21 European countries to investigate the use of different terms and their impact on disease-related information access. The findings reveal that lay terms are preferred by the general population, indicating a need for standardized terminology and language in health information and patient communication. The study emphasizes the importance of adapting information to specific country needs and addressing confusion and perception differences in patient communication. [Extracted from the article]

Psoriasis (PSO) and Atopic dermatitis (AD) are common inflammatory skin diseases that affect people of all ages globally. They negatively impact the quality of life (QoL) of patients in health-related aspects such as physical, psychological and mental functioning. Here, we conducted a review of studies relating to candidate biomarkers and indicators associated with QoL impairment in PSO and AD. Data research was performed using PUBMED and SCOPUS databases from inception to September 2022. Most of the included studies reported genomic or proteomic biomarkers associated with disease activity and QoL outcomes. Sociodemographic, clinical and therapeutic factors have also been implicated in deterioration of life quality in these patients. The inclusion of clinical characteristics, QoL impairment and co-diagnosis should be considered in drug development programs, since processing biomarkers based on an increased number of features in addition to drug class and disease will intensify the value of the biomarker itself, thereby maximizing the future clinical utility as a stratification tool. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory skin disease showing a high burden due to its aesthetic, social, psychological, and quality of life (QoL) implications which also affect patient‐physician relationship and, consequently, the adherence to treatments. Limited data on the natural history of psoriasis and factors predicting its prognosis are available. The aim of this study was to investigate patients' global characteristics, including treatments, associated with QoL impairment in psoriasis. Questionnaires evaluating sociodemographic features and Dermatology Life Quality Index (DLQI) were administered to patients. Multiple regression analysis was performed to evaluate factors associated with a large effect on patient's life (DLQI > 10), moderate effect on patient's life (DLQI ≥ 6 ≤ 10), small effect on patient's life (DLQI ≥ 2 < 6), and no effect on patient's life (DLQI < 2). Overall, 1052 consecutive patients affected by mild‐to‐severe psoriasis were recruited. Our logistic regression analysis showed that the influencing factors for a large effect on QoL were living in Southern Italy, depression, psoriatic arthritis, and psoriasis localization on facial, intertriginous, palmoplantar, trunk and scalp regions. For a moderate effect on patient's life, phototherapy and non‐biological systemic therapies resulted to be the predictive factors. Mild psoriasis, living in social housing and the isolated involvement of scalp psoriasis had a small effect on QoL. Lastly, mild psoriasis and current biological therapies including anti‐IL‐12/23, anti‐IL‐17, and anti‐TNF‐α were positively associated with no life quality impairment. Perceived quality of life impairment in psoriasis not only depends on the skin disease but rather on patients' global characteristics. Therefore, the individual background of these patients should be respected in the selection of treatment options. [ABSTRACT FROM AUTHOR]

The toxicity of malathion to Solea senegalensis was studied in a static renewal bioassay during its first month of larval life (between 4 and 30 dph). Through the use of different biomarkers and biochemical, cellular and molecular approaches (inhibition of cholinesterases [ChEs], changes in cytochrome P450‐1A [CYP1A] and the study of histopathological alterations), the effects of three concentrations of malathion (1.56, 3.12, and 6.25 μg/L) have been analyzed. In subacute exposure, malathion inhibited cholinesterase activities (AChE, BChE, CbE) in a dose‐ and time‐dependent manner, ranging the inhibition percentage from 20% to 90%. However, the expression levels of CYP1A and AChE transcripts or proteins were not modified. Additionally, exposure to malathion provoked histopathological alterations in several organ systems of Senegalese sole in a time‐ and dose dependent way, namely disruption of parenchymal architecture in the liver, epithelial desquamation, pyknotic nuclei and steatosis in the intestine, disorganization of supporting cartilage, and sings of hyperplasia and hypertrophy in the gills and degeneration of the epithelial cells from the renal tubules. Malathion exposure also provoked strong disorganization of cardiac fibers from the heart. The findings provide evidence that exposure to sublethal concentrations of malathion that provoked serious injury to the fish S. senegalensis, were below the expected environmental concentrations reported in many other ecosystems and different fish species,revealing a higher sensitivity for Solea senegalensis to malathion exposure, thus reinforcing its use as sentinel species for environmental pollution in coastal and estuarine environments. [ABSTRACT FROM AUTHOR]

Background: Knowledge regarding differences in care for psoriatic patients is limited. The aim of this study was to investigate factors influencing prescription of systemic treatments for patients with psoriasis with a special focus on socioeconomic factors. Methods and findings: This was a non-interventional, cross-sectional study, conducted in 18 Italian University and/or hospital centers with psoriasis-specialized units. Questionnaires evaluating demographic and socioeconomic characteristics were administered to participants. Overall, 1880 consecutive patients affected by mild-to-severe psoriasis were recruited. Univariate and multivariable logistic regression analyses of systemic therapy prescription, with a special focus on biologics, accounting for the above mentioned characteristics were performed. Our analysis showed that all analyzed patients' characteristics were significantly associated with biological therapy compared to non-biological systemic one. Particularly, women were less likely to receive biologics than men (OR = 0.66; 95% CI, 0.57–0.77). Elderly patients (≥65 years) and subjects with a BMI ≥30 had lower odds to receive biologics respect to adults (≥35–64 years) (OR = 0.33; 95% CI, 0.25–0.40), and subjects with BMI≥25<30 (OR = 0.64; 95% CI, 0.53–0.77), respectively. Northern and Southern patients were both less likely to receive biologics than Central patients (OR = 0.75; 95% CI, 0.63–0.89, and OR = 0.56; 95% CI,0.47–0.68, respectively). Lower economic profile and never reading books were both associated with decreased odds of receiving biological therapy. Conclusions: This study shows that sex, age, comorbidities, and socioeconomic characteristics influence the prescription of systemic treatments in psoriasis, highlighting that there are still unmet needs influencing the therapeutic decision-making process that have to be addressed. [ABSTRACT FROM AUTHOR]

Background: Ixekizumab (anti-IL-17A) is a biological agent used for the treatment of moderate-to-severe psoriasis. Real-life data on the effectiveness and safety of ixekizumab are currently scarce. Objective: The objective of this study was to evaluate the effectiveness and safety of ixekizumab in a cohort of psoriatic and psoriatic arthritis patients. Methods: We conducted a retrospective study involving 201 patients affected by moderate-to-severe psoriasis and treated with ixekizumab at seven Italian University centers. Data analysis focused on 110 patients who started ixekizumab at baseline and completed at least 24 weeks of treatment. Results: Significant reduction of mean (± standard deviation) baseline Psoriasis Area Severity Index (PASI) score (14.3 ± 5.8) was detected at 4 weeks of ixekizumab therapy (4.9 ± 4.2, p < 0.001), with a further significant improvement at weeks 12 and 24 (1.9 ± 2.9 and 0.9 ± 1.6, respectively) (p < 0.001). Our analysis showed 90%, 72%, and 57% of patients achieving PASI 75, 90, and 100 responses (75%, 90%, and 100% reduction in PASI score), respectively, after 24 weeks' therapy. For patients with arthritis (28%), a significant reduction in the mean (± standard deviation) baseline Disease Activity Score (DAS)-28 score (4.6 ± 5.1) was detected at week 4 (2.5 ± 3.9, p < 0.01), with a further significant improvement at weeks 12 and 24 (2.1 ± 1.2 and 1.4 ± 0.9, respectively) (p < 0.001). The bio-naïve group showed significantly higher PASI 90 and 100 response rates at week 12 than the bio-exposed one (p < 0.05). This trend in terms of PASI 100 response was also maintained at week 24 (p < 0.05). Furthermore, PASI 90 responses were significantly higher in anti-interleukin (IL)-17A-naïve patients at week 24 than in anti-IL-17A-experienced ones (p < 0.05). The dropout rate for adverse events (AEs) was as low as 2% (2/110), while AEs that did not cause treatment interruption were observed in 6% (7/110). Patients withdrawing from the study were defined as non-responders according to the non-responder imputation method. The retrospective design of the study does not allow missing data to be retrieved or homogeneous patient selection. Conclusions: The present study illustrates ixekizumab in real-world clinical practice, confirming its usefulness and safety in the management of psoriasis and psoriatic arthritis. [ABSTRACT FROM AUTHOR]

Psoriasis over-expresses several inflammatory mediators, which impacts the activity of melanocytes. Tyrosinase (Tyr) and microphthalmia-associated transcription factor (MITF) are the primary regulators of melanogenesis. Furthermore, bone morphogenetic proteins (BMPs) modulate various pathobiologic processes including inflammation, melanogenesis and melanomagenesis. To determine the association between psoriasis and melanogenesis, psoriatic lesional skin was screened through gene expression, immunohistochemistry, immunogold staining and melanin content assays. The present study detected a decreased expression of Tyr, MITF and BMP-4 in psoriatic lesional skin compared with healthy skin. Tyr, BMP-4 and melanin content were also evaluated in the psoriatic lesional skin of patients receiving adalimumab therapy, before and after 16 weeks of treatment. TNF-α blockade modulated the Tyr, BMP-4 and melanin content of the patient skin lesions, which supported the hypothesis that hyper-pigmentation may occur in areas of psoriatic plaque after biological treatment. The present study confirmed the influence of the psoriatic pro-inflammatory network on melanogenesis, exerting an inhibitory effect mediated by TNF-α. Furthermore, the results regarding BMP-4 in the present study add another important element to the mechanism of psoriasis. [ABSTRACT FROM AUTHOR]

Nowadays, it is well established a link between psoriasis and cardiovascular (CV) diseases. A series of different overlapping mechanisms including inflammation, homeostasis dysregulation, and genetic susceptibility are thought to underlie this association. Advances in understanding the molecular patterns involved in the complex scenario of psoriasis have highlighted a tight correlation with atherosclerosis. Indeed, common profiles are shared in term of inflammatory cytokines and cell types. In the last decade, the management of psoriasis patients has been revolutionized with the introduction of biological therapies, such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-12/23, and IL-17 inhibitors. In clinical setting, the effectiveness of these therapies as well as the incidence of CV events is related to the type of biologics. In particular, anti-TNF-α agents seem to reduce these events in psoriasis patients whereas anti-IL-12/23 agents related CV events reduction still remain to clarify. It has to be taken into account that IL-12/23 inhibitors have a shorter post-marketing surveillance period. An even more restricted observational time is available for anti-IL-17 agents. IL-17 is associated with psoriasis, vascular disease, and inflammation. However, IL-17 role in atherosclerosis is still debated, exerting both pro-atherogenic and anti-atherogenic effects depending on the specific context. In this review, we will discuss the differences between the onset of CV events in psoriasis patients, referred to specific biological therapy and the underlying immunological mechanism. Given the development of new therapeutic strategies, the investigation of these inhibitors impact on heart failure outcome is extremely important. [ABSTRACT FROM AUTHOR]

Abstract: In this study, we investigated the role of IL‐26 in allergic contact dermatitis (ACD), highlighting its’ contribute in the cytotoxic mechanism responsible for the tissue injury. IL‐26 is a signature Th17 cytokine, and immune cells are its predominant sources. Recently, it has shown that Th17 cell‐derived‐IL‐26 functions like an antimicrobial peptide. Here, we hypothesized that IL‐26 could be involved in cytotoxicity mechanism that underlies ACD. Indeed, we have attributed a role to IL‐26 in this context, through PBMC cytotoxicity assays vs HaCat. To demonstrate that IL‐26 was effectively involved in this activity, we performed the assay using transfected ACD PBMCs by siRNA for IL‐26. Indeed, we demonstrated that these cells were less able to kill keratinocytes compared with ACD PBMCs (P < .01). In conclusion, our findings support the idea that this emergent cytokine, IL‐26, is implicated in the killing mechanisms of KC observed during ACD. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease primarily affecting apocrine gland-rich areas of the body. It is a multifactorial disease in which genetic and environmental factors play a key role. The primary defect in HS pathophysiology involves follicular occlusion of the folliculopilosebaceous unit, followed by follicular rupture and immune responses. Innate pro-inflammatory cytokines (e.g., IL-1β, and TNF-α); mediators of activated T helper (Th)1 and Th17 cells (e.g., IFN-γ, and IL-17); and effector mechanisms of neutrophilic granulocytes, macrophages, and plasma cells are involved. On the other hand, HS lesions contain anti-inflammatory mediators (e.g., IL-10) and show limited activity of Th22 cells. The inflammatory vicious circle finally results in pain, purulence, tissue destruction, and scarring. HS pathogenesis is still enigmatic, and a valid animal model for HS is currently not available. All these aspects represent a challenge for the development of therapeutic approaches, which are urgently needed for this debilitating disease. Available treatments are limited, mostly off-label, and surgical interventions are often required to achieve remission. In this paper, we provide an overview of the current knowledge surrounding HS, including the diagnosis, pathogenesis, treatments, and existing translational studies. [ABSTRACT FROM AUTHOR]

Whilst the importance of keratinocytes as a first-line defense has been widely investigated, little is known about their interactions with non-resident immune cells. In this study, the impact of human keratinocytes on T cell effector functions was analyzed in an antigen-specific in vitro model of allergic contact dermatitis (ACD) to nickel sulfate. Keratinocytes partially inhibited T cell proliferation and cytokine production. This effect was dependent on the keratinocyte/T cell ratio and was partially reversible by increasing the number of autologous dendritic cells. The inhibition of T cell proliferation by keratinocytes was independent of the T cell subtype and antigen presentation by different professional antigen-presenting cells. Autologous and heterologous keratinocytes showed comparable effects, while the fixation of keratinocytes with paraformaldehyde abrogated the immunosuppressive effect. The separation of keratinocytes and T cells by a transwell chamber, as well as a cell-free keratinocyte supernatant, inhibited T cell effector functions to the same amount as directly co-cultured keratinocytes, thus proving that soluble factor/s account for the observed suppressive effects. In conclusion, keratinocytes critically control the threshold of inflammatory processes in the skin by inhibiting T cell proliferation and cytokine production. [ABSTRACT FROM AUTHOR]

The benefits of thermal water in different diseases have been known since ancient times. Over the past decades, a re-assessment of the use of mineral water for the treatment of several pathologic conditions has taken place around the world. Today, water therapy is being practiced in many countries that have a variety of mineral springs considerably different in their hydrogeologic origin, temperature, and chemical composition. Thermal water and balneotherapy offer several advantages: this approach needs no chemicals or potentially harmful drugs; there are almost no side effects during and after treatment, and there is a low risk to the patient's general health and well-being. However, it is difficult to evaluate the efficacy of this therapeutic approach in clinical practice due to the complexity of molecular mechanisms underlying its efficacy. Here we review the current knowledge of the chemical, immunological, and microbiological basis for therapeutic effects of thermal water with a specific focus on chronic inflammatory skin diseases. We also describe recent evidence of the major dermatologic diseases that are frequently treated by balneotherapy with a remarkable rate of success. Moreover, we discuss the potential role of balneotherapy either alone or as a complement to conventional medical treatments. [ABSTRACT FROM AUTHOR]

This study aims to cast light on immunocytometric alterations in COVID-19, a potentially fatal viral infection with heterogeneous clinical expression and a not completely defined pathophysiology. We studied 35 COVID patients at hospital admission testing by cytofluorimetry a large panel of lymphocyte subpopulations and serum tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-17A and the soluble receptor of IL-17A (IL-17RA). At hospital admission, total lymphocytes and most T and B subpopulations were reduced in 50–80% of patients, with close relationship to disease severity. While activated T helper 1 (TH1) and TH17 cells resulted normal or higher. Serum IL-6 was increased in all patients, while TNF-α and IL-17A were higher in advanced stages. A patient subset with low severity had very high IL-17RA levels. Tocilizumab treatment caused an increase of IL-17A in 3/6 patients and a reduction in 3 others, while the lymphocyte number increased in 3 patients and did not change in the others. Cytofluorimetry revealed a functional exhaustion of most lymphocyte populations in COVID patients not involving activated TH1 and TH17. Consequently, there was a relevant cytokines production that contributes to impair the respiratory inflammation. The increase of TH17 and IL-17 in a subset of cases and the evidence of a significant increase of IL-17RA (that prevents the interaction of IL-17 with the cell receptor) in patients with low severity suggest that some patients could benefit from monoclonal antibodies treatment targeting IL-17 pathway. Immunocytofluorimetric markers may contribute to a personalized therapy in COVID patients. • Total lymphocytes and most T and B sub-clusters were reduced in COVID-19 patients. • Activated TH1 and TH17 cells resulted normal or higher in COVID-19 patients. • Serum IL-6 levels were increased in all patients. • Serum TNF-α and IL-17A were higher in advanced stages. • Evidence of a significant increase of serum IL-17RA in patients with low severity. [ABSTRACT FROM AUTHOR]