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Eczema (atopic dermatitis, AD) is a skin disease characterized by skin barrier dysfunction due to various factors, including genetics, immune system abnormalities, and environmental triggers. Application of emollients and topical drugs such as corticosteroids and calcineurin inhibitors form the mainstay of treatments for this challenging condition. This review aims to summarize the recent advances made in phytochemical-based topical applications to treat AD and the different carriers that are being used. In this review, the clinical efficacy of several plant extracts and bioactive phytochemical compounds in treating AD are discussed. The anti-atopic effects of the herbs are evident through improvements in the Scoring Atopic Dermatitis (SCORAD) index, reduced epidermal thickness, decreased transepidermal water loss, and alleviated itching and dryness in individuals affected by AD as well as in AD mouse models. Histopathological studies and serum analyses conducted in AD mouse models demonstrated a reduction in key inflammatory factors, including thymic stromal lymphopoietin (TSLP), serum immunoglobulin E (IgE), and interleukins (IL). Additionally, there was an observed upregulation of the filaggrin (FLG) gene, which regulates the proteins constituting the stratum corneum, the outermost layer of the epidermis. Carriers play a crucial role in topical drug applications, influencing dose delivery, retention, and bioavailability. This discussion delves into the efficacy of various nanocarriers, including liposomes, ethosomes, nanoemulsions, micelles, nanocrystals, solid-lipid nanoparticles, and polymeric nanoparticles. Consequently, the potential long-term side effects such as atrophy, eruptions, lymphoma, pain, and allergic reactions that are associated with current topical treatments, including emollients, topical corticosteroids, topical calcineurin inhibitors, and crisaborole, can potentially be mitigated through the use of phytochemical-based natural topical treatments. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disorder influenced by genetic predisposition, environmental factors, immune dysregulation, and skin barrier dysfunction. The skin microbiome and metabolome play crucial roles in modulating the skin's immune environment and integrity. However, their specific contributions to AD remain unclear. We aimed to investigate the distinct skin microbial communities and skin metabolic compounds in AD patients compared to healthy controls (HCs). Seven patients with AD patients and seven HCs were enrolled, from whom skin samples were obtained for examination. The study involved 16S rRNA metagenomic sequencing and bioinformatics analysis as well as the use of gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) to detect metabolites associated with AD in the skin. We observed significant differences in microbial diversity between lesional and non-lesional skin of AD patients and HCs. Staphylococcus overgrowth was prominent in AD lesions, while Cutibacterium levels were decreased. Metabolomic analysis revealed elevated levels of several metabolites, including hypoxanthine and glycerol-3-phosphate in AD lesions, indicating perturbations in purine metabolism and energy production pathways. Moreover, we found a positive correlation between hypoxanthine and glycerol-3-phosphate and clinical severity of AD and Staphylococcus overgrowth. These findings suggest potential biomarkers for monitoring AD severity. Further research is needed to elucidate the causal relationships between microbial dysbiosis, metabolic alterations, and AD progression, paving the way for targeted therapeutic interventions. [ABSTRACT FROM AUTHOR]

Gut bacterial alterations have been previously linked to several non-communicable diseases in adults, while the association of mycobiome is not well understood in these diseases, especially in infants and children. Few studies have been conducted on the association between gut mycobiome and non-communicable diseases in children. We investigated gut mycobiome composition using 194 faecal samples collected at birth, 6 months after birth, and 18 months after birth in relation to atopic dermatitis (AD) and overweight diagnoses at the age of 18 or 36 months. The mycobiome exhibited distinct patterns, with Truncatella prevalent in the meconium samples of both overweight and non-overweight groups. Saccharomyces took precedence in overweight cases at 6 and 18 months, while Malassezia dominated non-overweight samples at 6 months. Saccharomyces emerged as a consistent high-abundance taxon across groups that had dermatitis and were overweight. We found a weak association between gut mycobiome and AD at birth and overweight at 18 months when using machine learning (ML) analyses. In ML, unidentified fungi, Alternaria, Rhodotorula, and Saccharomyces, were important for classifying AD, while Saccharomyces, Thelebolus, and Dothideomycetes were important for classifying overweight. Gut mycobiome might be associated with the development of AD and overweight in children. [ABSTRACT FROM AUTHOR]

Derangement of the epidermal barrier lipids and dysregulated immune responses are key pathogenic features of atopic dermatitis (AD). The Th2-type cytokines interleukin IL-4 and IL-13 play a prominent role in AD by activating the Janus Kinase/Signal Transduction and Activator of Transcription (JAK/STAT) intracellular signaling axis. This study aimed to investigate the role of JAK/STAT in the lipid perturbations induced by Th2 signaling in 3D epidermal equivalents. Tofacitinib, a low-molecular-mass JAK inhibitor, was used to screen for JAK/STAT-mediated deregulation of lipid metabolism. Th2 cytokines decreased the expression of elongases 1, 3, and 4 and serine-palmitoyl-transferase and increased that of sphingolipid delta(4)-desaturase and carbonic anhydrase 2. Th2 cytokines inhibited the synthesis of palmitoleic acid and caused depletion of triglycerides, in association with altered phosphatidylcholine profiles and fatty acid (FA) metabolism. Overall, the ceramide profiles were minimally affected. Except for most sphingolipids and very-long-chain FAs, the effects of Th2 on lipid pathways were reversed by co-treatment with tofacitinib. An increase in the mRNA levels of CPT1A and ACAT1, reduced by tofacitinib, suggests that Th2 cytokines promote FA beta-oxidation. In conclusion, pharmacological inhibition of JAK/STAT activation prevents the lipid disruption caused by the halted homeostasis of FA metabolism. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin condition with a considerable impact on patients' quality of life. Its etiology is multifactorial and, among the predisposing factors, a role is played by oxidative stress. Pollution, recurrent infections, and psychological stress contribute to oxidative stress, amplifying the production of proinflammatory cytokines and worsening barrier damage. There are various oxidative stress mechanisms involved in the pathogenesis of AD. Moreover, AD often appears to be associated with psychological disorders such as alexithymia, depression, and anxiety due to severe itching and related insomnia, as well as social distress and isolation. The increasing incidence of AD requires the evaluation of additional therapeutic approaches in order to reduce the psychological burden of this condition. Our review aims to evaluate the role of some nutraceuticals in AD treatment and its related psychological comorbidities. The combination of some natural compounds (flavonoids, alkaloids, terpenes, isothiocyanates) with traditional AD treatments might be useful in improving the effectiveness of therapy, by reducing chronic inflammation and preventing flare-ups, and in promoting corticosteroid sparing. In addition, some of these nutraceuticals also appear to have a role in the treatment of psychological disorders, although the underlying oxidative stress mechanisms are different from those already known for AD. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a condition with a multifactorial aetiology that affects the skin. It most often begins at preschool age and involves the skin. The disease's main symptom is intense itching, which occurs especially at night and affects the child's sleep, negatively impacting the quality of life of affected children and, consequently, their families. The difficulty in resting during the night leads to many problems during the day, particularly behavioural disorders and difficulties in paying attention at school, which results in learning impairment. The unexpected symptoms of AD are caused by pathophysiological processes that include many molecular pathways and inflammatory cytokines such as IL-31, IL-1, IL-2, TNF-a, and IL-6. Drawing on a comprehensive review of the literature in PubMed/MedLine, our review offers an in-depth exploration of both the psychosocial impacts of AD and the molecular processes that contribute to this disorder. [ABSTRACT FROM AUTHOR]

The scientific article focuses on the role of azulene and its derivatives in the therapy of dermatological diseases, presenting the latest laboratory and clinical research as well as prospects for further studies. In a synthetic literature review, various databases such as PubMed, Scopus, Web of Science, and the Database of Polish Scientific Journals were queried to select relevant articles concerning azulene. The conclusions drawn from the thematic analysis of the studies emphasize the multifaceted pharmacological actions of azulene and its derivatives including their anti-inflammatory properties, potential anticancer effects, photoprotective abilities, alleviation of itching, management of atopic dermatitis, and treatment of erectile dysfunction. However, there are certain limitations associated with the application of unmodified azulene on the skin, particularly related to photodecomposition and the generation of reactive oxygen species under UV radiation. These effects, in turn, necessitate further research on the safety of azulene and azulene-derived substances, especially regarding their long-term use and potential application in phototherapy. The authors of this work emphasize the necessity of conducting further preclinical and clinical studies to fully understand the mechanisms of action. Incorporating azulene and its derivatives into the therapy of dermatological disorders may represent an innovative approach, thereby opening new treatment avenues for patients. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD), a prevalent chronic inflammatory skin disorder, is marked by impaired skin barrier function and persistent pruritus. It significantly deteriorates patients' quality of life, making it one of the most burdensome non-lethal skin disorders. Filaggrin plays a crucial role in the pathophysiology of barrier disruption in AD, interacting with inflammatory mediators. It is an integral part of the extracellular matrix architecture, serving to protect the skin barrier and attenuate the inflammatory cascade. In this study, we engineered a novel recombinant human filaggrin (rhFLA-10) expression vector, which was subsequently synthesized and purified. In vitro and ex vivo efficacy experiments were conducted for AD. rhFLA-10, at low concentrations (5 to 20 μg/mL), was non-toxic to HACaT cells, significantly inhibited the degranulation of P815 mast cells, and was readily absorbed by cells, thereby exerting a soothing therapeutic effect. Furthermore, rhFLA-10 demonstrated anti-inflammatory properties (p < 0.05). In vivo, efficacy experiments further substantiated that rhFLA-10 could effectively ameliorate AD in mice and facilitate the repair of damaged skin (p < 0.001). These findings underscore the considerable potential of rhFLA-10 in the treatment of AD. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common inflammatory skin condition found worldwide. It impacts patient quality of life (QoL) and is thought to arise as an inflammatory response to epidermal barrier dysfunction and hypersensitivity. AD can lead to large out-of-pocket costs and increased healthcare expenses over a lifetime. An analysis of all randomized control trials conducted since 1990 on topical therapies for AD were reviewed, including 207 trials in the final analysis. It was found that an average of 226 patients were enrolled over 2.43 arms. Common topical treatments included corticosteroids, calcineurin inhibitors, JAK inhibitors, and phosphodiesterase inhibitors. The most utilized tools to identify treatment efficacy were the EASI, IGA, SCORAD, and PGA. There was a paucity of data on trials that evaluated efficacy, QoL, and cost of treatment simultaneously. This review highlights the need for comprehensive trials that evaluate multiple aspects of treatment, including financial cost and QoL impact, to ensure each patient has the best treatment modality for the management of their AD. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD), a chronic inflammatory skin disease, is exacerbated by obesity, yet the precise linking mechanism remains elusive. This study aimed to elucidate how obesity amplifies AD symptoms. We studied skin samples from three mouse groups: sham control, AD, and high-fat (HF) + AD. The HF + AD mice exhibited more severe AD symptoms than the AD or sham control mice. Skin lipidome analysis revealed noteworthy changes in arachidonic acid (AA) metabolism, including increased expression of pla2g4, a key enzyme in AA generation. Genes for phospholipid transport (Scarb1) and acyltransferase utilizing AA as the acyl donor (Agpat3) were upregulated in HF + AD skin. Associations were observed between AA-containing phospholipids and skin lipids containing AA and its metabolites. Furthermore, imbalanced phospholipid metabolism was identified in the HF + AD mice, marked by excessive activation of the AA and phosphatidic acid (PA)-mediated pathway. This imbalance featured increased expression of Plcb1, Plcg1, and Dgk involved in PA generation, along with a decrease in genes converting PA into diglycerol (DG) and CDP-DG (Lpin1 and cds1). This investigation revealed imbalanced phospholipid metabolism in the skin of HF + AD mice, contributing to the heightened inflammatory response observed in HF + AD, shedding light on potential mechanisms linking obesity to the exacerbation of AD symptoms. [ABSTRACT FROM AUTHOR]

Background: Atopic Dermatitis (AD) is a prevalent inflammatory skin disease whose course is often complicated by the presence of concomitant anxiety and depressive disorders. Dupilumab has been demonstrated to be largely effective in AD. The aims of the present study were to (1) to verify the effectiveness of 2-year dupilumab treatment on the depressive and anxiety symptoms of patients affected by AD and (2) to identify predictors of the persistence of psychiatric symptoms despite maintenance treatment with dupilumab. Methods: A total of 331 patients with severe AD were assessed at baseline and at different times over 2 years by a large set of rating scales, including the Eczema Area and Severity Index (EASI), the Hospital Anxiety and Depression Scale (HADS), and the Dermatology Life Quality Index (DLQI). Paired sample t-tests were performed to verify the effectiveness of dupilumab on the severity of AD and mental health items. Two binary logistic regression models were then used to identify the predictors of the persistence of clinically significant depression and anxiety, defined by a score ≥ 8 on each sub-scale of the HADS. Results: After 2 years of treatment with dupilumab, the patients benefited, showing a significant improvement in both the dermatological disease and comorbid depression/anxiety (p < 0.001 for all scales). Overall, 17.5% and 13% of patients, respectively, reported residual depressive and anxiety symptoms after the 2-year treatment with dupilumab. The baseline predictors of the persistence of clinically significant depressive symptoms after the 2-year treatment with dupilumab were found to be a higher body mass index (BMI) (p = 0.012), a lower impact of dermatological disease on quality of life (p = 0.015), and more severe depressive symptoms (p < 0.01), while for anxiety, the only predictor was found to be female gender (p = 0.03). Conclusions: Using a multidisciplinary approach, at baseline, dermatologists should more closely monitor patients who are at a greater risk of maintaining residual psychiatric symptoms despite therapy, such as those with more severe depressive symptoms and those who are overweight. [ABSTRACT FROM AUTHOR]

Background: Hand eczema (HE) is a prevalent chronic condition that exerts a substantial and enduring adverse effect on quality of life (QoL) and imposes an economic burden on society. Managing HE poses challenges due to the limited effectiveness and potential adverse effects associated with many currently available topical and systemic treatments. Methods: This article examines twenty-one patients affected by HE treated with dupilumab, a fully human monoclonal antibody targeting interleukin IL-4 and IL-13 signaling. This involves a retrospective descriptive statistical analysis. Results: At week 6, HECSI-75 was achieved by 12 patients (57.9%). The proportion of patients meeting the HECSI-75 criteria steadily increased over the observation weeks, reaching 90% at week 16 and 100% at week 104. Furthermore, HECSI-90 and HECSI-100 were achieved by 75% and 60% of patients at week 16 and by 100% and 85% of patients at week 68, respectively. All patients who reached week 104 maintained complete disease remission according to HECSI 100. Conclusions: In all patients, dupilumab was shown to be an effective drug in achieving disease clearance, as indicated by all the parameters considered at each evaluation point (Week 6, Week 16, Week 32, Week 52, Week 68, Week 84, and Week 104), in comparison to the initial baseline. [ABSTRACT FROM AUTHOR]

The transmembrane glycoprotein OX40 receptor (OX40) and its ligand, OX40L, are instrumental modulators of the adaptive immune response in humans. OX40 functions as a costimulatory molecule that promotes T cell activation, differentiation, and survival through ligation with OX40L. T cells play an integral role in the pathogenesis of several inflammatory skin conditions, including atopic dermatitis (AD). In particular, T helper 2 (TH2) cells strongly contribute to AD pathogenesis via the production of cytokines associated with type 2 inflammation (e.g., IL-4, IL-5, IL-13, and IL-31) that lead to skin barrier dysfunction and pruritus. The OX40-OX40L interaction also promotes the activation and proliferation of other T helper cell populations (e.g., TH1, TH22, and TH17), and AD patients have demonstrated higher levels of OX40 expression on peripheral blood mononuclear cells than healthy controls. As such, the OX40-OX40L pathway is a potential target for AD treatment. Novel therapies targeting the OX40 pathway are currently in development, several of which have demonstrated promising safety and efficacy results in patients with moderate-to-severe AD. Herein, we review the function of OX40 and the OX40-OX40L signaling pathway, their role in AD pathogenesis, and emerging therapies targeting OX40-OX40L that may offer insights into the future of AD management. [ABSTRACT FROM AUTHOR]

Immuno-correlated dermatological pathologies refer to skin disorders that are closely associated with immune system dysfunction or abnormal immune responses. Advancements in the field of artificial intelligence (AI) have shown promise in enhancing the diagnosis, management, and assessment of immuno-correlated dermatological pathologies. This intersection of dermatology and immunology plays a pivotal role in comprehending and addressing complex skin disorders with immune system involvement. The paper explores the knowledge known so far and the evolution and achievements of AI in diagnosis; discusses segmentation and the classification of medical images; and reviews existing challenges, in immunological-related skin diseases. From our review, the role of AI has emerged, especially in the analysis of images for both diagnostic and severity assessment purposes. Furthermore, the possibility of predicting patients' response to therapies is emerging, in order to create tailored therapies. [ABSTRACT FROM AUTHOR]

Skin conditions are numerous and often have a major impact on patients' quality of life, and effective and safe treatment is very important. The conventional drugs used for skin diseases are usually corticosteroids and antimicrobial products that can induce various side effects, especially with long-term use, which is why researchers are studying alternatives, especially biologically active natural products. Three products caught our attention: bee venom (BV), due to reported experimental results showing anti-inflammatory, antibacterial, antiviral, antioxidant, antimycotic, and anticancer effects, Ficus carica (FC) due to its demonstrated antioxidant, antibacterial, and anti-inflammatory action, and finally Geranium essential oil (GEO), with proven antifungal, antibacterial, anti-inflammatory, and antioxidant effects. Following a review of the literature, we produced this paper, which presents a review of the potential therapeutic applications of the three products in combating various skin conditions and for skin care, because BV, FC, and GEO have common pharmacological actions (anti-inflammatory, antibacterial, and antioxidant). We also focused on studying the safety of the topical use of BV, FC, and GEO, and new approaches to this. This paper presents the use of these natural therapeutic agents to treat patients with conditions such as vitiligo, melasma, and melanoma, as well as their use in treating dermatological conditions in patients with diabetes. [ABSTRACT FROM AUTHOR]

(1) Background: Although the association between psoriasis and atopic dermatitis (AD) is reported in the literature, scarce data are known about the efficacy of biologic therapy (including TNF and IL-17 inhibitors) in patients with psoriatic arthritis (PsA) and concomitant AD. (2) Objective: We aimed to explore AD in patients with PsA undergoing biologics for their active disease, focusing on prevalence and clinical and potential therapeutic implications. (3) Material and methods: We performed a retrospective analysis of 64 patients with PsA receiving various biological agents, followed-up in an academic outpatient rheumatology department up to 10 years. (4) Results: Atopic diseases were reported in about one third of cases, with a higher incidence of AD (10 cases; 52.6%) vs. atopic rhinitis (6 cases; 31.6%) and allergic asthma (3 cases; 15.8%). Three morphological patterns of AD were recognized including chronic prurigo (3 cases), a chronic lichen simplex (1 case), and eczemas (6 cases). All PsA with concomitant AD displayed a late onset of skin atopy (in their adult life) and demonstrated a specific profile (younger), from urban settings, equally distributed among genders, and requiring switching to a higher number of biologics to achieve disease control. (5) Conclusion: PsA and AD may coexist, requiring special attention when selecting the optimal biologic agent. [ABSTRACT FROM AUTHOR]

Clinical trials and real-world studies have shown the effectiveness of upadacitinib for treating rash and pruritus in patients with atopic dermatitis (AD). This study aimed to determine whether the early reduction in rash or pruritus at week 12 of upadacitinib treatment could be maintained at later treatment stages. This retrospective study involved 227 and 73 patients with moderate-to-severe AD treated with 15 and 30 mg upadacitinib daily, respectively. The eczema area and severity index (EASI) scores, peak pruritus numerical rating scale (PP-NRS), and investigator's global assessment (IGA) were analyzed. At week 12, patients were divided into achievers and non-achievers of EASI 75, 90, 100, absolute EASI ≤ 2, IGA0/1, PP-NRS4, or absolute PP-NRS ≤ 1. Achievement rates for each endpoint were assessed at later time points (weeks 24, 36, and 48) in both groups. Week 12 achievers largely maintained their endpoint achievements until week 48, regardless of dosage (15 mg or 30 mg). Week 12 non-achievers saw an increasing achievement rate of EASI 75 until week 48. The initial reduction in rash and pruritus at week 12 persisted until week 48 with upadacitinib treatment, suggesting potential benefits for patients requiring prolonged treatment despite not achieving EASI 75 at week 12. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a heterogenous inflammatory disease with high variety in terms of clinical symptoms and etiopathogenesis, occurring both in pediatric and adult populations. The clinical manifestation of atopic dermatitis varies depending on the age of patients, but all age groups share certain common features, such as a chronic and recurrent course of disease, pruritus, and a co-occurrence of atopic diseases in personal or family medical history. Treating pruritus is a high priority due to its incidence rate in atopic dermatitis and substantial impact on quality of life. In recent years, treatments with biological drugs have increased the range of therapeutic possibilities in atopic dermatitis. The aim of the study is to present the safety profile, efficacy, and effectiveness of various biological treatment methods for the therapy of pruritus in the course of atopic dermatitis. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with pruritus, an impaired cutaneous barrier function and a disrupted water holding capacity. Levels of ceramides, which are major components of intercellular lipids and are crucial for their functions, are decreased in the stratum corneum of patients with AD. Treatments to increase ceramide levels are effective for AD care. Synthetic pseudo-ceramide (cetyl PG hydroxyethyl palmitamide (SLE66)), which has a structure developed via molecular designs, and a eucalyptus leaf extract (ELE) enhance ceramide synthesis in the epidermis. The topical application of a skin moisturizer containing SLE66 and ELE improves the barrier functions and water holding capacity of AD skin accompanied by an improvement in skin symptoms. This is a multifaceted review that summarizes the efficacy of the topical application of a skin moisturizer containing SLE66 and ELE on atopic dermatitis. [ABSTRACT FROM AUTHOR]

(1) Background: Atopic dermatitis (AD) is one of the most common inflammatory skin conditions, thus having a significant impact on the quality of life (QoL) of patients and their families. We performed a survey to gather more data to help describe the burden of AD in Lithuania and to help expand the treatment plan to this important aspect of the disease. (2) Methods: A cross-sectional study was conducted involving healthy and AD pediatric patients. The assessment instruments used were the Patient-Oriented Eczema Measure (POEM), QoL, and original questionnaires (the original questionnaire was designed by the authors to determine the demographics, medical history, and treatment methods of the respondents). (3) Results: This study included 302 participants in total: 247 AD patients (51% boys) and 55 non-AD patients (51% boys). The mean age for AD patients was 6.8 ± 4.4. years, and this was 10.5 ± 3.1 years for the control patients. A significant difference was found between the QoL questionnaire scores and the Family Dermatology Life Quality Index (FDLQI) score for the atopic dermatitis group (QoL: 6.3 ± 5.6; FDLQI: 7.1 ± 6.9) and controls (QoL 0.5 ± 1.1; FDLQI 2.1 ± 5.9) (p = 0.000). The mean QoL questionnaire score for severe AD was 14.3 ± 6.2 (very large effect), that for moderate AD was 6.9 ± 4.4 (moderate effect), and that for mild AD was 4.4 ± 4.2 (small effect) (p = 0.000). (4) Conclusions: Our study revealed a moderate effect of AD on dermatology-related QoL in patients and their families. It has been shown that increased disease severity was associated with a greater impairment of QoL in both patients and patient's parents. The burden of AD in children and their parents is considerable and should be taken into account in the management of atopic dermatitis. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common chronic inflammatory skin condition characterised by pruritus and recurrent eczematous patches and plaques. It impacts sleep and its visibility can lead to stigmatisation, low self-esteem, social withdrawal, reduced quality of life (QOL), and psychological burden. This study explores the relationship between AD and mental health, including possible causation pathways. A literature review was conducted in PubMed without using limiters. AD carries higher odds of suicidality and an increased risk of depression, anxiety, alexithymia, and obsessive–compulsive disorder (OCD) across all severities. While some studies report an association of AD with attention deficit hyperactivity disorder (ADHD), and possibly autism spectrum disorder (ASD), others do not. There is increasing evidence that AD contributes to chronic low-grade inflammation and cognitive impairment (CI). Causative factors for mental health complications of AD likely include both psychosocial and biological variables. AD is associated with higher levels of cutaneous and circulating proinflammatory cytokines; these can breach the blood–brain barrier and trigger central nervous system events, including oxidative stress, neurotransmitter breakdown, altered serotonin metabolism, and reduced neurogenesis in several brain regions. Excessive inflammation in AD may thus contribute to CI, depression, and suicidality. AD providers should be vigilant about mental health. [ABSTRACT FROM AUTHOR]

Inflammatory skin diseases include a series of disorders characterized by a strong activation of the innate and adaptive immune system in which proinflammatory cytokines play a fundamental role in supporting inflammation. Skin inflammation is a complex process influenced by various factors, including genetic and environmental factors, characterized by the dysfunction of both immune and non-immune cells. Psoriasis (PS) and atopic dermatitis (AD) are the most common chronic inflammatory conditions of the skin whose pathogeneses are very complex and multifactorial. Both diseases are characterized by an immunological dysfunction involving a predominance of Th1 and Th17 cells in PS and of Th2 cells in AD. Suppressor of cytokine signaling (SOCS) proteins are intracellular proteins that control inflammatory responses by regulating various signaling pathways activated by proinflammatory cytokines. SOCS signaling is involved in the regulation and progression of inflammatory responses in skin-resident and non-resident immune cells, and recent data suggest that these negative modulators are dysregulated in inflammatory skin diseases such as PS and AD. This review focuses on the current understanding about the role of SOCS proteins in modulating the activity of inflammatory mediators implicated in the pathogenesis of inflammatory skin diseases such as PS and AD. [ABSTRACT FROM AUTHOR]

This study investigates the roles of mucosal-associated invariant T (MAIT) cells and Vα7.2+/CD161− T cells in skin diseases, focusing on atopic dermatitis. MAIT cells, crucial for bridging innate and adaptive immunity, were analyzed alongside Vα7.2+/CD161− T cells in peripheral blood samples from 14 atopic dermatitis patients and 10 healthy controls. Flow cytometry and machine learning algorithms were employed for a comprehensive analysis. The results indicate a significant decrease in MAIT cells and CD69 subsets in atopic dermatitis, coupled with elevated CD38 and polyfunctional MAIT cells producing TNFα and Granzyme B (TNFα+/GzB+). Vα7.2+/CD161− T cells in atopic dermatitis exhibited a decrease in CD8 and IFNγ-producing subsets but an increase in CD38 activated and IL-22-producing subsets. These results highlight the distinctive features of MAIT cells and Vα7.2+/CD161− T cells and their different roles in the pathogenesis of atopic dermatitis and provide insights into their potential roles in immune-mediated skin diseases. [ABSTRACT FROM AUTHOR]

Mitochondria are eukaryotic cellular organelles that function in energy metabolism, ROS production, and programmed cell death. Cutaneous epithelial and hair follicle dermal papilla cells are energy-rich cells that thereby may be affected by mitochondrial dysfunction and DNA mutation accumulation. In this review, we aimed to summarize the medical literature assessing dermatologic conditions and outcomes associated with mitochondrial dysfunction. A search of PubMed and Embase was performed with subsequent handsearching to retrieve additional relevant articles. Mitochondrial DNA (mtDNA) deletions, mutation accumulation, and damage are associated with phenotypic signs of cutaneous aging, hair loss, and impaired wound healing. In addition, several dermatologic conditions are associated with aberrant mitochondrial activity, such as systemic lupus erythematosus, psoriasis, vitiligo, and atopic dermatitis. Mouse model studies have better established causality between mitochondrial damage and dermatologic outcomes, with some depicting reversibility upon restoration of mitochondrial function. Mitochondrial function mediates a variety of dermatologic conditions, and mitochondrial components may be a promising target for therapeutic strategies. [ABSTRACT FROM AUTHOR]

Atopic dermatitis, or eczema, is the most common chronic skin disorder, characterized by red and pruritic lesions. Its etiology is multifaceted, involving an interplay of factors, such as the allergic immune response, skin barrier dysfunction, and dysbiosis of the skin microbiota. Recent studies have explored the role of extracellular vesicles (EVs), which are lipid bilayer-delimitated particles released by all cells, in atopic dermatitis. Examination of the available literature identified that most studies investigated EVs released by Staphylococcus aureus, which were found to impact the skin barrier and promote the release of cytokines that contribute to atopic dermatitis development. In addition, EVs released by the skin fungus, Malassezia sympodialis, were found to contain allergens, suggesting a potential contribution to allergic sensitization via the skin. The final major finding was the role of EVs released by mast cells, which were capable of activating various immune cells and attenuating the allergic response. While research in this area is still in its infancy, the studies examined in this review provide encouraging insights into how EVs released from a variety of cells play a role in both contributing to and protecting against atopic dermatitis. [ABSTRACT FROM AUTHOR]

Simple Summary: Oclacitinib is a tablet-based therapy given for itching that is caused by allergic or atopic dermatitis in dogs. The objective of this study was to understand pet owners' perceptions of the conventional film-coated form of oclacitinib and the chewable form of oclacitinib in terms of convenience and value. Firstly, an interview phase with pet owners and veterinarians was used to develop detailed written profiles of these treatment options. Then, pet owners were invited to participate in a survey about their experiences and preferences. Overall, 1590 pet owners provided survey responses. Most respondents (62%) reported having experienced challenges giving tablet-based therapies to their dog(s), and half of the respondents (52%) had experience giving flavoured or chewable tablets to their dog. Comparing oclacitinib and chewable oclacitinib (with or without associated costs), the majority of the respondents preferred the chewable formulation in all countries for both short-term and long-term itch (≥58%; all p < 0.05). Chewable and/or palatable treatment options may be welcomed by pet owners and may have potential positive impacts on convenience, compliance, outcomes, quality of life, and the human–animal bond. Oclacitinib is an oral therapy indicated for pruritus associated with allergic or atopic dermatitis in dogs. This study sought to assess pet owners' perceptions of the relative convenience and value of the conventional film-coated formulation and the chewable formulation. A quantitative discrete-choice experimental methodology was applied, comparing (conventional, film-coated) oclacitinib versus chewable oclacitinib using unbranded treatment profiles. Initially, a qualitative interview phase with pet owners and veterinarians was conducted to develop detailed treatment profiles. Subsequently, pet owners participated in a quantitative survey. Overall, 1590 pet owners provided survey responses. Most respondents (62%) reported having experienced challenges administering tablet-based therapies to their dog(s). Half of all respondents (52%) had experience administering flavoured or chewable tablets to their dog. Comparing oclacitinib and chewable oclacitinib (with or without associated costs), the majority of the respondents preferred the chewable formulation in all regions across short-term and long-term scenarios (≥58%; all p < 0.05). The current research is one of few survey-driven studies for treatment preferences in companion animal medicine. Veterinarians may offer chewable or palatable treatment options where available, with potential positive impacts on convenience, compliance, outcomes, quality of life, and the human–animal bond. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is increasingly prevalent globally. However, the frequent and prolonged use of corticosteroids, which are commonly employed for AD treatment, carries potential side effects. Korean mistletoe (Viscum album L. var. coloratum), a perennial parasitic plant, has demonstrated various biological effects. In this study, we conducted in vivo investigations to determine whether Korean mistletoe possesses anti-inflammatory effects that play pivotal roles in regulating the pathological mechanisms of AD. BALB/c mice with AD-like skin lesions induced by 2,4-dinitrochlorobenzene (DNCB) were utilized to explore the therapeutic effects of 1% and 2% Korean mistletoe extract (KME) ointments. The KME ointment was topically applied to the dorsal surface of the BALB/c mice, and they were categorized into four distinct groups: normal, DNCB-induced, DNCB-induced with 1% KME ointment, and DNCB-induced with 2% KME ointment. Each assessment parameter employed to evaluate the curative impact of the KME ointment displayed improvement with the application of the 1% KME ointment. While the effects observed were less pronounced than those of the 1% KME ointment, the overall therapeutic outcomes were also evident with the utilization of the 2% KME ointment. The results suggest the potential of Korean mistletoe as a viable therapeutic agent for AD. Further investigations are warranted to elucidate the underlying mechanisms of action. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a chronic inflammatory skin disease. The treatment plays an important role in influencing the patients' quality of life. The basic management consists of appropriate skin cleansing, including bathing and eventually using bathing additives. Recommendations regarding frequency and duration of bathing, water temperature and usefulness of bathing additives are widely different, often leading to confusion among patients. This review aims to give insights into the best bathing practices and the use of bathing additives in atopic dermatitis in children. Several bathing additives, including bleach baths, commercial baby cleansers, bath baby oils and bath salt, appear to be promising adjunctive therapies for atopic dermatitis due to their anti-inflammatory, anti-bacterial, anti-pruritus and skin barrier repair properties through different mechanisms of action. However, their efficacy and safety are not fully understood in some cases. The usefulness of other bath additives, such as acidic and more natural substances (green tea extracts, pine tar, sodium bicarbonate), is still under investigation. Further studies are needed to determine their optimal use to achieve clinical benefit safely. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is an inflammatory skin condition that frequently develops before the onset of allergic rhinitis or asthma. More than 10% of children are affected by this serious skin condition, which is painful for the sufferers. Recent research has connected the environment, genetics, the skin barrier, drugs, psychological factors, and the immune system to the onset and severity of AD. The causes and consequences of AD and its cellular and molecular origins are reviewed in this paper. The exploration of interleukins and their influence on the immunological pathway in AD has been facilitated by using relevant biomarkers in clinical trials. This approach enables the identification of novel therapeutic modalities, fostering the potential for targeted translational research within the realm of personalized medicine. This review focuses on AD's pathophysiology and the ever-changing therapeutic landscape. Beyond the plethora of biologic medications in various stages of approval or development, a range of non-biologic targeted therapies, specifically small molecules, have emerged. These include Janus kinase (JAK) inhibitors like Baricitinib, Upadacitinib, and Abrocitinib, thus expanding the spectrum of therapeutic options. This review also addresses the latest clinical efficacy data and elucidates the scientific rationale behind each targeted treatment for atopic dermatitis. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus, a bacterium found on human skin, produces toxins and various virulence factors that can lead to skin infections such as atopic dermatitis. These toxins and virulence factors are carried in membrane vesicles (MVs), composed of the bacterium's own cell membranes, and are expected to reach host target cells in a concentrated form, inducing inflammation. This study investigated the effects of two polyphenols, (–)-epigallocatechin gallate (EGCG) and nobiletin (NOL), on the expression of S. aureus virulence factors and the inflammation induced by MVs. The study found that EGCG alone decreased the production of Staphylococcal Enterotoxin A (SEA), while both EGCG and NOL reduced biofilm formation and the expression of virulence factor-related genes. When S. aureus was cultured in a broth supplemented with these polyphenols, the resulting MVs showed a reduction in SEA content and several cargo proteins. These MVs also exhibited decreased levels of inflammation-related gene expression in immortalized human keratinocytes. These results suggest that EGCG and NOL are expected to inhibit inflammation in the skin by altering the properties of MVs derived from S. aureus. [ABSTRACT FROM AUTHOR]

Extracorporeal photopheresis (ECP) is an apheresis procedure that is conventionally used as a first-line treatment for cutaneous and leukemic subtypes of T-cell lymphoma, such as Sezary's syndrome and mycosis fungoides. Over the past three decades, its immunotherapeutic properties have been tested on a variety of autoimmune conditions, including many dermatologic diseases. There is ample evidence of ECP's ability to modify leukocytes and alter cytokine production for certain dermatologic diseases that have been refractory to first-line treatments, such as atopic dermatitis. However, the evidence on the efficacy of ECP for the treatment of these dermatologic diseases is unclear and/or lacks sufficient evidence. The purpose of this paper is to review the literature on the utilization and clinical efficacy of ECP in the treatment of several [autoimmune] dermatologic diseases and discuss its applications, guidelines, recommendations, and future implementation for dermatologic diseases. [ABSTRACT FROM AUTHOR]

Nucleotides, glycosaminoglycans, and omega-3 essential fatty acids (O3s) could be used for improving skin health, although their modes of action, alone or in combination, are not yet fully understood. To gain some insight into these mechanisms, we performed two in vitro tests and one in vivo pilot trial. The effects on human dermal fibroblast proliferation and migration were evaluated with the following compounds and combinations: 0.156 mg/mL O3s, 0.0017 mg/mL hyaluronic acid (HA), 0.0004 mg/mL dermatan sulfate (DS), 0.0818 mg/mL nucleotides, and [O3s + HA + DS] and [O3s + HA + DS + nucleotides] at the same concentrations. In both in vitro assays, adding nucleotides to [O3s + HA + DS] provided significant improvements. The resulting combination [O3s + HA + DS + nucleotides] was then tested in vivo in dogs with atopic dermatitis by oral administration of a supplement providing a daily amount of 40 mg/kg nucleotides, 0.9 mg/kg HA, 0.18 mg/kg DS, 53.4 mg/kg EPA, and 7.6 mg/kg DHA. After 30 days, the pruritus visual analog scale (pVAS) score was significantly reduced, and no adverse effects were observed. In conclusion, the combination of nucleotides plus glycosaminoglycans and O3s could serve as a useful therapeutic alternative in skin health applications. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests a link between atopic dermatitis (AD) and gastrointestinal disorders, particularly in relation to gut microbial dysbiosis. This study explored the potential exacerbation of AD by gut inflammation and microbial imbalances using an irritable bowel syndrome (IBS) mouse model. Chronic gut inflammation was induced in the model by intrarectal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS), followed by a 4-week development period. We noted significant upregulation of proinflammatory cytokines in the colon and evident gut microbial dysbiosis in the IBS mice. Additionally, these mice exhibited impaired gut barrier function, increased permeability, and elevated systemic inflammation markers such as IL-6 and LPS. A subsequent MC903 challenge on the right cheek lasting for 7 days revealed more severe AD symptoms in IBS mice compared to controls. Further, fecal microbial transplantation (FMT) from IBS mice resulted in aggravated AD symptoms, a result similarly observed with FMT from an IBS patient. Notably, an increased abundance of Alistipes in the feces of IBS mice correlated with heightened systemic and localized inflammation in both the gut and skin. These findings collectively indicate that chronic gut inflammation and microbial dysbiosis in IBS are critical factors exacerbating AD, highlighting the integral relationship between gut and skin health. [ABSTRACT FROM AUTHOR]

Long-term oral ingestion of unheated yuzu seed oil in humans reduces lipid peroxides in the blood. Moreover, yuzu seed oil contains limonin, which can induce antioxidant and anti-inflammatory effects by activating the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). Previously, Nrf2 has been shown to reduce atopic dermatitis (AD). Therefore, we hypothesized that ingesting unheated yuzu seed oil can regulate AD through Nrf2. An AD model was established using NC/Nga mice through repeated local exposure to mite antigens. Unheated and purified yuzu seed oil (100 µL/mice) or water (control, 100 µL/mice) was administered orally once a day using a gastric cannula for rodents for 28 days. On day 28, mice in the unheated yuzu seed oil group exhibited significantly lower clinical skin severity scores and ear thickness than those in the purified yuzu seed oil and water groups. Serum histamine levels remained unaltered among the three AD-induced groups. Serum Dermatophagoides farina body (Dfb)-specific immunoglobulin E (IgE) levels were significantly lower in the unheated yuzu seed oil group. Oral ingestion of yuzu seed oil in NC/Nga AD model mice significantly suppressed dermatitis deterioration and decreased serum IgE levels. Clinical trials (n = 41) have already confirmed that unheated yuzu oil is safe for long-term intake, further suggesting its potential use in improving AD symptoms. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a persistent inflammatory skin condition that impacts individuals of various age groups, including both children and adults. Its pathophysiology involves allergens penetrating a disrupted epidermal barrier, triggering the dermal cells to produce pro-inflammatory cytokines and eliciting a T-cell-mediated immune response. Notably, interleukins (ILs), particularly interleukin 4 (IL-4) and interleukin 13 (IL-13), play a key role in AD pathogenesis. Therapies directed at inflammatory mechanisms, including Dupilumab, have demonstrated notable effectiveness in enhancing skin lesions, alleviating subjective symptoms, and improving the overall quality of life for individuals with AD. Despite therapeutic advances, assessing AD severity remains challenging. The commonly used tools, such as the SCORAD and DLQI scores, rely on subjective patient responses. Paraclinically, the search for universal biomarkers continues, with efforts to identify reliable indicators reflecting disease severity and treatment response. Various biomarkers, including Th2-related chemokines and cytokines, have been explored, but none have gained universal recognition for routine clinical use. This study aims to investigate the dynamics of the plasma levels of IL-4 and IL-13 during Dupilumab treatment and establish correlations between these ILs and disease severity, as measured using the SCORAD and DLQI scores. The ultimate endpoint is to determine whether IL-4 and IL-13 can serve as reliable biomarkers, assessing their correlation with patient-reported feelings and disease activity and potentially influencing their inclusion or exclusion as diagnostic elements in routine clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: It is an international standard to recommend patients with atopic dermatitis (AD) to use moisturizers; however, little is known about their effect on lipids in the stratum corneum (SC). Methods: In this randomized clinical experiment of 30 Caucasian participants (15 with AD and 15 healthy controls), the superficial SC lipid profile was assessed through tape stripping non-lesional skin following treatment thrice daily for seven days with a moisturizer, and subsequently compared with untreated skin. Results: No discernible disparity in superficial SC lipid quantity was evident between the AD group and the control group. However, the SC lipid composition diverged significantly, with the AD group exhibiting diminished levels of long-chain EO CERs (p = 0.024) and elevated levels of short-chain C34 CERs (p = 0.025) compared to healthy skin. Moisturizer application significantly reduced the total SC lipids and all lipid subgroups in both groups. Within the AD group, a non-significant inclination towards an augmentation in EO CERs (p = 0.053) and reduction in C34 CERs (p = 0.073) was observed. Conclusion: The recent identification of distinctions in SC lipid composition between AD and healthy skin was substantiated by our findings. Topical moisturizer application, despite reducing overall total lipids, indicated a potential tendency towards a healthier lipid constitution in AD skin. [ABSTRACT FROM AUTHOR]

In traditional Korean medicines, Magnolia officinalis is commonly included for the remedy of atopic dermatitis, and magnolol is a major constituent of Magnolia officinalis. Its pharmacological effects include anti-inflammatory, hepatoprotective, and antioxidant effects. Using BALB/c mice repeatedly exposed to 1-chloro-2,4-dinitrobenzene (DNCB), magnolol was evaluated in atopic dermatitis-like lesions. Administration of magnolol (10 mg/kg, intraperitoneal injection) markedly relieved the skin lesion severity including cracking, edema, erythema, and excoriation, and significantly inhibited the increase in IgE levels in the peripheral blood. A DNCB-induced increase in mast cell accumulation in atopic dermatitis skin lesions was reversed by magnolol administration, as well as a rise in expression levels of pro-inflammatory Th2/Th17/Th1 cytokines' (IL-4, IL-13, IL-17A, IFN-γ, IL-12A, TARC, IL-8, and IL-6) mRNAs in the lymph nodes and skin (n = 5 per group). In lymph nodes, magnolol reversed DNCB's increase in CD4+RORγt+ Th17 cell fraction and decrease in CD4+FoxP3+ regulatory T cell fraction. The results also showed that magnolol suppressed T cell differentiation into Th17 and Th2 cells, but not Th1 cells. Magnolol suppresses atopic dermatitis-like responses in the lymph nodes and skin, suggesting that it may be feasible to use it as a treatment for atopic dermatitis through its suppression of Th2/Th17 differentiation. [ABSTRACT FROM AUTHOR]

Scutellaria baicalensis Georgi and Raphanus Sativus Linne herbal mixture (SRE) is a Chinese herbal medicine. In this study, we aimed to evaluate the therapeutic efficacy of SRE as an active ingredient for 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) and to predict the underlying therapeutic mechanisms and involved pathways using network pharmacological analysis. Treatment with SRE accelerated the development of AD-like lesions, improving thickness and edema of the epidermis. Moreover, administering the SRE to AD-like mice suppressed immunoglobulin E and interleukin-4 cytokine and reduced T lymphocyte differentiation. In silico, network analysis was used to predict the exact genes, proteins, and pathways responsible for the therapeutic effect of the SRE against DNCB-induced AD. These results indicated that the SRE exerted protective effects on the DNCB-induced AD-like model by attenuating histopathological changes and suppressing the levels of inflammatory mediators. Therefore, the SRE can potentially be a new remedy for improving AD and other inflammatory diseases and predicting the intracellular signaling pathways and target genes involved. This therapeutic effect of the SRE on AD can be used to treat DNCB-induced AD and its associated symptoms. [ABSTRACT FROM AUTHOR]

Background: Functional gastrointestinal disorders are very common condition. The aim of this study is to evaluate the implications of the mode of pregnancy termination and early infant feeding on the incidence of gastrointestinal disorders and atopic dermatitis at birth and 3, 6, and 12 months of age. Methods: This study included 82 pregnant women and their newborns born at term. All newborns were examined at birth and 3, 6, and 12 months of age according to the ROME IV criteria. Results: In children born after cesarean section, the incidence of regurgitation was significantly higher. In children fed mostly or exclusively with formula, dry skin with allergic features was observed more often compared to breastfed children, but this relation was statistically significant only at the age of 12 months. The use of antibiotic therapy increased the risk of allergic skin lesions by almost seven times at 3 months of life. Gastrointestinal disorders in the form of regurgitation, colic, and constipation occur within the period of up to 12 months of the child's life and may be related to the mode of the termination of pregnancy via cesarean section and the use of artificial feeding or antibiotic therapy. The occurrence of atopic dermatitis in infants at 12 months of life is correlated with the mode of the termination of pregnancy after cesarean section. Conclusions: One of the risk factors for the occurrence of atopic dermatitis and gastrointestinal disorders in the period up to 12 months of the child's life may be a cesarean section and the use of formula feeding or antibiotic therapy. [ABSTRACT FROM AUTHOR]

Dermatoses are an increasingly common problem, particularly in developed countries. The causes of this phenomenon include genetic factors and environmental elements. More and more scientific reports suggest that the gut microbiome, more specifically its dysbiosis, also plays an important role in the induction and progression of diseases, including dermatological diseases. The gut microbiome is recognised as the largest endocrine organ, and has a key function in maintaining human homeostasis. In this review, the authors will take a close look at the link between the gut–skin axis and the pathogenesis of dermatoses such as atopic dermatitis, psoriasis, alopecia areata, and acne. The authors will also focus on the role of probiotics in remodelling the microbiome and the alleviation of dermatoses. [ABSTRACT FROM AUTHOR]

(1) Background: Prurigo nodularis (PN) is a persistent and inflammatory dermatological condition characterized by chronic itching and the formation of hardened nodules, significantly impacting the affected individuals' quality of life and psychological well-being. The management of PN poses challenges due to the limited efficacy and undesirable side effects associated with current interventions. (2) Methods: This article examines sixteen patients affected by PN treated with dupilumab, a fully human monoclonal antibody targeting interleukin IL-4 and IL-13 signaling. This involves a retrospective descriptive statistical analysis. (3) Results and (4) Conclusions: In all patients, dupilumab proves to be an effective drug in achieving disease clearance, as indicated by all the parameters considered as assessed by both physicians and patients at each evaluation point (Week 6, Week 16, Week 32, Week 52, Week 68, and Week 84), in comparison to the initial baseline. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) is a chronic, pruritic skin disease with complex pathogenesis, which affects about 43 million children aged 1–4 years. One of the most known methods of alleviating symptoms of AD is emollient treatment, which varies depending on formulation and additional active ingredients. There is some evidence that emollients could be used in AD prevention in high-risk children. Materials and methods: A search of the literature from Cochrane Library, PubMed and Medline was conducted between August and September 2023 with the following keywords: "atopic dermatitis", "emollients", and "prevention". Only randomised clinical trials published in the last 5 years were included into the meta-analysis. Results: Considering the inclusion criteria only 11 randomized clinical trials were taken into account, and six of them proved lack of effect of emollients in the prevention of atopic dermatitis among neonates from AD risk groups. Conclusions: Emollient treatment has a good safety profile and most of the ingredients used in formulations are nonirritant for sensitive newborn and infant skin. There is some evidence of the positive effects of emollient treatment in prevention of AD in predisposed populations. The relatively high cost of emollient treatment (vs regular infant skin-care routine) would support the necessity for further evaluation of their effectiveness in nonpredisposed populations. [ABSTRACT FROM AUTHOR]

Erythroderma is a condition characterized by erythema affecting at least 90% of the skin surface area. It can be caused by various underlying conditions. Due to nonspecific clinical and laboratory findings, determining the cause may pose a challenge. In the retrospective study, we identified 212 patients hospitalized for erythroderma in the Department of Dermatology, Venereology, and Allergology at Wroclaw Medical University between January 2012 and March 2022. Clinical, laboratory, and histopathological features, as well as the management of patients, were studied. The median age of adults was 61 years (IQR = 47–68). The most common causes of erythroderma were psoriasis (n = 49, 24.01%), followed by atopic dermatitis (AD) (n = 27, 13.23%), and cutaneous T-cell lymphomas (CTCL) (n = 27, 13.23%). Despite laboratory tests and histopathological examination, the etiology of erythroderma remained undetermined in 39 cases (19.12%). In 70.59% of patients, it was the first episode of erythroderma, while 29.41% experienced a recurrent episode. Regardless of the etiology of erythroderma, patients were most frequently treated with systemic antihistamines (146 cases, 71.57%) and systemic steroids (132 cases, 64.71%). Patients with idiopathic erythroderma constitute the greatest diagnostic and therapeutic challenge, requiring particularly thorough evaluation. [ABSTRACT FROM AUTHOR]

Mast cells (MCs) are an important part of the immune system, responding both to pathogens and toxins, but they also play an important role in allergic diseases, where recent data show that non-IgE-mediated activation is also of relevance, especially in chronic urticaria (CU) and atopic dermatitis (AD). Skin MCs express Mas-related G-protein-coupled receptor X2 (MRGPRX2), a key protein in non-IgE-dependent MC degranulation, and its overactivity is one of the triggering factors for the above-mentioned diseases, making MRGPRX2 a potential therapeutic target. Reviewing the latest literature revealed our need to focus on the discovery of MRGPRX2 activators as well as the ongoing vast research towards finding specific MRGPRX2 inhibitors for potential therapeutic approaches. Most of these studies are in their preliminary stages, with one drug currently being investigated in a clinical trial. Future studies and improved model systems are needed to verify whether any of these inhibitors may have the potential to be the next therapeutic treatment for CU, AD, and other pseudo-allergic reactions. [ABSTRACT FROM AUTHOR]

The transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel expressed on sensory neurons and immune cells. We hypothesize that TRPV1 plays a role in human eosinophil function and is modulated by inflammatory conditions. TRPV1 expression on human eosinophils was examined by qPCR, flow cytometry, and immunohistochemistry, respectively. TRPV1 functionality was analyzed by investigating calcium flux, apoptosis, modulation by cytokines and acidic pH, and CD69 externalization using flow cytometry. Activation of TRPV1 induced calcium influx and prolonged survival. Although eosinophils were not directly activated by TRPV1 agonists, activation by IL-3 or GM-CSF was mainly restricted to TRPV1-positive eosinophils. TRPV1 surface content was increased by acidic pH, IL-3, IL-31, IL-33, TSLP, TNF-α, BDNF, and NGF-β. Interestingly, TRPV1 was also expressed by eosinophils located in proximity to peripheral nerves in atopic dermatitis (AD) skin. In conclusion, eosinophils express functional TRPV1 channels which are increased by extracellular acidification and AD-related cytokines. Since eosinophils also express TRPV1 in AD skin, our results indicate an important role of TRPV1 for neuroimmune interaction mechanisms in itchy, inflammatory skin diseases, like AD. [ABSTRACT FROM AUTHOR]

Bisphenol is a chemical substance widely used in plastic products and food containers. In this study, we observed a relationship between DNA methylation and atopic dermatitis (AD) in the peripheral blood mononuclear cells (PBMCs) of pregnant women exposed to bisphenol A (BPA) and its alternatives, bisphenol S (BPS) and bisphenol F (BPF). DNA methylation is an epigenetic mechanism that regulates gene expression, which can be altered by environmental factors, and affects the onset and progression of diseases. We found that genes belonging to the JAK-STAT and PI3K-AKT signaling pathways were hypomethylated in the blood of pregnant women exposed to bisphenols. These genes play important roles in skin barrier function and immune responses, and may influence AD. Therefore, we suggest that not only BPA, but also BPS and BPF, which are used as alternatives, can have a negative impact on AD through epigenetic mechanisms. [ABSTRACT FROM AUTHOR]

Background: In order to improve the control of atopic diseases, it is important to clarify the pathogenesis of atopy and identify its various triggers. Single nucleotide polymorphisms (SNPs) of the vitamin D receptor gene (VDR) may impact atopy. The aim of this study was to investigate the possible associations between VDR SNPs and vitamin D, total IgE, and eosinophils in atopy. Methods: In total, 203 adults, including 122 patients with atopic diseases (45 with atopic dermatitis, 77 with allergic asthma) and 81 healthy controls, were involved in the study. The blood eosinophil count was determined with an automated hematology analyzer. Vitamin D and total immunoglobulin E (IgE) levels were evaluated using the ELISA method. Polymorphisms in the VDR gene were analyzed with real-time PCR using TaqMan probes. Results: We analyzed six VDR single nucleotide polymorphisms and found a significant association between VDR rs731236 GG genotype and normal vitamin D levels in atopic patients and healthy subjects (OR 11.33; 95% CI: 1.049–122.388 and OR 4.04; 95% CI: 1.117–14.588, respectively, p < 0.05). Additionally, the study results revealed a significant relationship between the VDR rs2228570 GG genotype and normal vitamin D levels in patients with atopy and healthy subjects (OR 3.80; 95% CI: 1.190–12.134 and OR 2.09; 95% CI: 1.044–4.194, respectively, p < 0.05). The rs2228570 allele A was associated with decreased vitamin D levels in patients with atopy and healthy subjects (OR 0.28; 95% CI: 0.098–0.804 and OR 0.229; 95% CI: 0.069–0.761, respectively, p < 0.05). The VDR rs3847987 genotypes AA and AC were significantly associated with normal vitamin D levels in healthy subjects (OR 35.99; 95% CI: 6.401–202.446 and OR 4.72; 95% CI: 1.489–15.007, respectively, p < 0.05). In addition, a decreased amount of vitamin D was associated with atopic diseases such as atopic dermatitis and allergic asthma (OR 0.49; 95% CI: 0.439–1.308 and OR 0.58; 95% CI: 0.372–0.908, respectively, p < 0.05). The rs11168293 allele T was associated with the normal range of total IgE in atopy (OR 2.366; 95% CI: 1.133–5.027; p < 0.05). Significant associations were found between VDR rs731263 allele G, rs11168293 allele G, and increased blood eosinophil levels in patients with atopy (OR 0.319; 95% CI: 0.163–0.934 and OR 0.323; 95% CI: 0.112–0.935, respectively, p < 0.05). Conclusions: A decreased vitamin D level showed a significant relationship with atopic diseases (atopic dermatitis and allergic asthma). The association between the VDR gene polymorphisms rs2228570, rs731236, and rs11168293 and vitamin D, total IgE, and blood eosinophils in patients with atopy suggested that VDR polymorphisms and the vitamin D level should be considered when examining the factors associated with atopy. [ABSTRACT FROM AUTHOR]

Simple Summary: In people, skin allergies to environmental factors have been linked to abnormalities in the skin itself. One of these abnormalities in people is a lower amount of a family of skin proteins called filaggrins. This decrease makes the skin more permeable to the absorption of environmental allergens such as dust mites. In our study, we wanted to use a dog model of skin allergies to study the impact of standardized and repeated dust mite exposures on the skin itself. More specifically, we wanted to see how these exposures would affect filaggrin proteins and compare the response of normal and allergic dogs. We found that the skin of allergic dogs overreacted to dust mite exposure by getting thicker and increasing the production of filaggrins compared to the normal dogs. Despite this extra production of filaggrin, the allergic skin showed more breakdown products of filaggrin. We conclude that allergic skin attempts to compensate for the allergic insult but it is not as efficient as normal skin. Filaggrin is important for the skin barrier and atopic dermatitis. Another filaggrin-like protein, filaggrin 2, has been described. We evaluated antibodies against both filaggrins in normal and atopic skin biopsies from dogs before and after allergen challenges (D0, D1, D3 and D10). Filaggrins expression was evaluated by immunohistochemistry and Western blot. We used PCR to investigate changes in filaggrin gene expression. Effects of group (p = 0.0134) and time (p = 0.0422) were shown for the intensity of filaggrin staining. Only an effect of group was found for filaggrin 2 (p = 0.0129). Atopic samples had higher intensity of staining than normal dogs [filaggrin on D3 (p = 0.0155) and filaggrin 2 on D3 (p = 0.0038) and D10 (p < 0.0001)]. Atopic samples showed increased epidermal thickness after allergen exposure (D3 vs. D0, p = 0.005), while normal dogs did not. In atopic samples, significant increased gene expression was found for filaggrin overtime but not for filaggrin 2. Western blot showed an increase in filaggrin 2 on D3. A small size band (15 kD) containing a filaggrin sequence was found in Western blots of atopic samples only. We conclude that atopic skin reacts to allergen exposure by proliferating and increasing filaggrin production but that it also has more extensive filaggrin degradation compared to normal skin. [ABSTRACT FROM AUTHOR]

Background: Limited real-world data are available on upadacitinib drug survival in patients with atopic dermatitis (AD). Objectives: To investigate upadacitinib drug survival, and the reasons and predictors of drug discontinuation in AD patients. Methods: All consecutive patients aged 18–75 years, affected by moderate-to-severe AD, and treated with upadacitinib for more than 1 month at dermatological clinics were included during November 2020–August 2023. Upadacitinib survival was investigated through Kaplan–Meier survival analysis and the predictors through multivariable logistic regression analysis. Results: Overall, 325 adult AD patients (mean (SD) age, 38.6(15.6) years) had a 1-year and 1.5-year upadacitinib drug survival of 91.5% and 80.2%, respectively. The main reasons for drug discontinuation (25/325, 7.7%) were adverse events (4.9%), including cutaneous or infectious diseases (1.5%), such as acne and herpes zoster; blood test changes (1.2%), including hypercholesterolemia, creatine phosphokinase or liver enzyme elevation, and lymphopenia; urinary or respiratory infections (0.9%); deep venous thrombosis (0.3%); malignancies (0.3%); loss of consciousness (0.3%); and arthralgias (0.3%); followed by ineffectiveness (0.6%). No specific characteristic was significantly associated with an increased risk of upadacitinib discontinuation. Conclusions: Our findings show that upadacitinib was effective in moderate-to-severe AD after more than 1 year of continuous treatment but point to the need for clinical and laboratory monitoring of patients. [ABSTRACT FROM AUTHOR]

Background: Isolated mast cell angioedema (MC-AE) can be divided into allergic and nonallergic (spontaneous) forms. The former is often associated with food, Hymenoptera venoms or drug allergies. This study aimed to evaluate the relationship between the occurrence of atopic diseases and the risk of angioedema. Methods: A retrospective study analyzed 304 patients with confirmed MC-AE and 1066 controls. All were analyzed for allergic asthma (AA), atopic dermatitis (AD) and allergic rhinitis (AR) based on ICD-10 codes. In addition, total IgE and peripheral eosinophilia were calculated. Results: The analyzed atopic diseases were more frequent in the group of patients diagnosed with MC-AE than in the controls: 78 (25.7%) vs. 173 (16.2%) for p < 0.01. Patients diagnosed with AD had a higher risk of MC-AE (hazard ratio (HR) = 1.48,) similar to those diagnosed with AR (HR = 1.51). However, in patients with two or three atopic comorbidities, the risk increased significantly to HR = 2.45 or HR = 4.1, respectively. There was a positive correlation between the serum total IgE concentration or eosinophilia and the risk of angioedema (p < 0.01). Conclusion: Patients with MC-AE had a more frequent occurrence of atopic diseases associated with inhalant allergies. This risk increased in patients with IgE-mediated polymorphic disease. [ABSTRACT FROM AUTHOR]