Search Results (2,242)

Background and aims: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease among children. Our study aimed to evaluate the prevalence of hypogammaglobulinemia among pediatric patients with AD and to characterize the clinical and laboratory findings of patients diagnosed with AD and hypogammaglobulinemia. Method: The electronic files of 1850 patients aged 0–18 years diagnosed with AD between 2020 and 2022 in the Pediatric Immunology and Allergy Clinic of Bursa Medical Faculty City Hospital were retrospectively analyzed. During this period, all patients newly diagnosed with atopic dermatitis at our clinic were systematically screened for their serum immunoglobulin (Ig) levels (IgG, IgA, and IgM) at the time of initial presentation. We included 200 AD patients with hypogammaglobulinemia. Disease severity was classified using the Scoring Atopic Dermatitis (SCORAD) index. Multivariate logistic and linear regression analyses were performed to identify independent determinants of disease severity, considering age, sex, eosinophil counts, total IgE, food allergies, and baseline immunoglobulin levels. Results: The prevalence of hypogammaglobulinemia among the 1850 screened children with AD was 10.8% (200/1850). Of the 200 patients included in this study, 128 (64%) were male, and 72 (36%) were female. The median age at first clinic presentation was 8 months (interquartile range (IQR) 25–75%: 5–16). According to the Scoring Atopic Dermatitis (SCORAD) index, AD severity was mild in 150 (75%) patients and moderate-to-severe in 50 (25%). Food allergy sensitization was present in 72 (36%) patients. Patients with moderate-to-severe AD had significantly lower IgG (300 vs. 374 mg/dL; p < 0.001; r = −0.346), IgA (10 vs. 14 mg/dL; p = 0.004), and IgM (38 vs. 51 mg/dL; p = 0.001) levels when compared with those with mild disease. Multivariate logistic regression confirmed that lower IgG was the only immunoglobulin independently associated with moderate-to-severe AD (OR = 1.97 per 100 mg/dL decrease; 95% CI: 1.15–3.39; p = 0.013), while food allergy was the strongest independent predictor of the SCORAD index (β = +11.97; p < 0.001). None of the patients received intravenous immunoglobulin (IVIG) treatment. Of the 142 patients who underwent serial serum immunoglobulin measurements, 56 (39%) achieved age-appropriate normal IgG levels, while hypogammaglobulinemia persisted in 86 (61%). Conclusions: We found a higher frequency of hypogammaglobulinemia in patients with AD in our study, as compared with previously reported rates of THI in children from the general pediatric population. Although our study showed an increase in IgG levels during the follow-up period in many patients, it emphasizes the need for long-term immunological monitoring, especially in patients with moderate-to-severe AD. Full article

Background: Systemic sclerosis (SSc) is a systemic autoimmune disease leading to extensive fibrosis of the skin and many visceral organs, including the lungs. The need for effective treatments is urgent, as none exists today that can stop or reverse the progression of fibrosis. We examined the effect of restoring KLF4 levels in primary human lung fibroblasts of SSc patients with pulmonary fibrosis as a potential therapeutic strategy. Methods: We restored KLF4 levels in SSc lung fibroblasts by adenoviral infection and extracted total RNA for RNA sequencing. Genes and systems level analyses were performed, and selected genes of interest and markers of alveolar, inflammatory, and fibrotic fibroblasts were further validated at the mRNA and protein levels. Results: Our results showed that restoring KLF4 levels in SSc lung fibroblasts initiated dedifferentiation of αSMA and CTHRC1, expressing myofibroblasts by repressing markers of inflammatory and fibrotic fibroblasts while boosting markers of alveolar fibroblasts. Our data also revealed that restoring KLF4 levels prevented TGFβ1-induced fibrogenesis in normal lung fibroblasts, and reduced fibrosis in explanted human lungs in organ culture. Conclusions: Our results in human primary SSc lung fibroblasts showed that restoring KLF4 levels initiated dedifferentiation of fibrotic and inflammatory fibroblasts towards the phenotype of alveolar fibroblasts, their lineage precursors, highlighting the potential of KLF4 as a therapy to stop and reverse fibrosis. Full article

Psoriasis, a chronic inflammatory skin disease affecting men and women equally, presents distinct gender-based differences in severity and treatment response. While molecular mechanisms underlying psoriasis are well-studied, sex-specific differences remain largely unexplored. To address this, we conducted a comprehensive analysis of transcriptomic data from lesional psoriasis skin and healthy controls, comparing male and female cohorts. Our findings reveal 2760 overlapping differentially expressed genes (DEGs) between sexes, highlighting shared pathways like IL-17 signaling and Th17 differentiation. However, sex-specific pathways emerged, including male-enriched PI3K-Akt signaling and chemokine receptor activity, and female-enriched glycolysis and AHR-NRF2 pathways. Upstream regulator analysis identified sex-specific drivers, including VEGFA activation and CFTR inhibition in males, and AHR activation and FGF21 inhibition in females. Notably, Regulatory T cells (Tregs) and neutrophil abundance differed by sex, aligning with disease severity trends. These results highlight sex-associated molecular and cellular disparities that may be relevant to understanding differences in disease manifestation and treatment response. As an exploratory, hypothesis-generating transcriptomic analysis, this study lays the groundwork for future experimental and clinical validation of sex-specific mechanisms in psoriasis. Full article

Background/Objectives: Chronic inflammatory skin diseases are frequently associated with pruritus, in which the neurokinin-1 receptor (NK₁R) and its ligand substance P (SP) play a central role. The development of compounds combining anti-inflammatory and antipruritic effects represents a promising therapeutic strategy. This study aims to identify fiscalin B derivatives as anti-inflammatory agents with high affinity to NK₁R using an integrated in silico and in vitro approach. Methods: A library of fiscalin B derivatives was screened through molecular docking against NK₁R to identify high-affinity ligands. Selected compounds were further evaluated using in silico ADMET and toxicity predictions. In vitro assays were conducted in HaCaT keratinocytes, RAW264.7 macrophages, and NIH/3T3 fibroblasts to assess cytotoxicity, nitric oxide production, inflammatory proteins expression, and cell migration. Results: Docking studies identified several derivatives with predicted binding affinities comparable to or exceeding those of aprepitant, a well-established NK₁R antagonist. Several compounds, particularly 2, 3, 4, 6, and 7, reduced lipopolysaccharide-induced nitric oxide production to 41–51% without relevant cytotoxicity. This effect was associated with reduced iNOS protein levels, suggesting modulation of inflammatory pathways rather than direct nitric oxide scavenging. Most compounds showed positive safety profiles, although in silico analysis indicated limited biodegradability and potential aquatic toxicity. Conclusions: The fiscalin B derivatives, 2, 3, and 4, demonstrate potential as anti-inflammatory agents, in vitro, and as NK₁R high affinity ligands, in silico. These findings support their potential as lead compounds for topical therapies for inflammatory skin disorders associated with pruritus, although further optimization and validation are required. Full article

Background/Objective: Psoriasis is a systemic inflammatory disease often associated with metabolic comorbidities, including hyperuricemia. While biological therapies effectively target inflammatory pathways, their specific impact on serum uric acid (SUA) levels remains debated. This study aimed to evaluate whether biological therapy, while reducing systemic inflammation, influences SUA levels in patients with moderate-to-severe plaque psoriasis. Methods: A prospective longitudinal cohort study was conducted involving 30 patients with moderate-to-severe plaque psoriasis. Patients received biological treatment (adalimumab, secukinumab or ustekinumab) and tsDMARDS (apremilast). Clinical severity was assessed using the Psoriasis Area and Severity Index (PASI). C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), SUA levels and other laboratory markers were measured at baseline and after 48 weeks of therapy. Results: Biological therapy led to a significant reduction in PASI scores (from 21.6 ± 10.7 at baseline to 0.4 ± 0.86 after 48 weeks of therapy, p < 0.001), and CRP decreased from a median of 5.75 mg/L at baseline to 3.55 mg/L, p < 0.001. ESR also declined from 26.2 ± 11.4 mm/h to 19.0 ± 8.06 mm/h, p < 0.001. However, no statistically significant change was observed in mean SUA levels 5.49 ± 1.55 vs. 5.55 ± 1.60 mg/dL; p = 0.758. Subgroup analysis revealed that SUA levels remained stable regardless of the specific biological agent used or the degree of clinical improvement. Conclusions: Our findings suggest that while biological therapy is highly effective in controlling skin and systemic inflammation in psoriasis, it does not modify SUA levels. These results imply that hyperuricemia in psoriasis may be driven by metabolic factors independent of the primary inflammatory pathways targeted by current biologics. Full article

Background/Objectives: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease traditionally viewed through a purely dermatologic lens. However, this perspective fails to explain stress-induced flares, menstrual cycle-linked exacerbations, and severe pain and itch disproportionate to visible cutaneous inflammation. This narrative review synthesizes evidence supporting a neuroendocrine–immune model of HS pathogenesis, with emphasis on mechanisms underlying pain and itch. Methods: A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science databases (January 1990–September 2025) with terms including hidradenitis suppurativa, neuroendocrine mechanisms, HPA axis, sex hormones, neuropeptides, pain (including nociceptive and neuropathic pain, burning, and dysesthesia), and pruritus (itch). Eligible studies included peer-reviewed research examining hormonal, stress-related, or neuropeptide mechanisms in HS. Data were synthesized into thematic categories: endocrine influences, HPA axis function, neuropeptide signaling, immune crosstalk, and clinical implications. Results: Sex hormones promote follicular occlusion and modulate immune responses, explaining perimenstrual flares. Prolactin amplifies inflammation during stress through immune cell activation. Insulin resistance and adipokine imbalance create pro-inflammatory conditions. Chronic stress induces HPA axis dysfunction with cortisol resistance, exacerbating inflammation. Neuropeptides released from cutaneous nerves amplify immune activation and directly mediate pain and itch. These pathways establish self-perpetuating feedback loops wherein inflammation drives stress, and neuroendocrine dysfunction amplifies immune responses. Conclusions: HS represents a systemic disorder with a strong neuroendocrine–immune component, rather than a purely dermatologic condition. This framework supports multidisciplinary management integrating hormonal therapies, targeted immunomodulation, and stress reduction. Future research should characterize neuroendocrine biomarkers and test combination therapies targeting multiple system nodes. Full article

Chronic inflammatory skin diseases, including psoriasis, hidradenitis suppurativa (HS), and atopic dermatitis (AD), are increasingly recognized as systemic disorders associated with chronic immune dysregulation. Growing evidence supports their links with metabolic disorders, reflected in heightened interest in therapeutic strategies targeting the immunometabolic axis. This review summarizes current knowledge on the role of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in the regulation of immune and metabolic processes in chronic inflammatory skin diseases, with particular emphasis on molecular mechanisms and available experimental and clinical data. GLP-1RAs, widely used in the treatment of type 2 diabetes and obesity, may also exhibit anti-inflammatory and immunomodulatory properties beyond their classical metabolic effects. GLP-1 signalling can influence keratinocyte function, immune cell activity, and wound healing. Furthermore, it modulates multiple intracellular signalling pathways, including cAMP/PKA, AMPK, PI3K/Akt, and NF-κB, as well as immune axes such as IL-23/Th17/IL-17 and inflammasome-related signalling. Available evidence suggests that GLP-1RAs may reduce inflammation and disease activity in selected inflammatory dermatoses. However, current evidence remains limited and is based primarily on experimental studies, case reports, and small-scale observational studies. Further well-designed clinical trials are needed to better define the therapeutic potential of GLP-1RAs and their role in dermatological practice. Full article

Background: Statins have anti-inflammatory properties beyond their lipid-lowering effects, but their impact on skin and soft tissue infections (SSTIs) remains unclear. This study evaluated whether statins improve clinical outcomes in patients hospitalised with SSTIs. Methods: Adults aged ≥18 years hospitalised with SSTIs at a tertiary hospital in Australia between 1 June 2021 and 31 December 2021 were identified using the International Classification of Diseases 10th Revision Australian Modification (ICD-10-AM) codes. Patients were categorised into two groups based on statin use at admission. Multivariable regression models assessed differences in clinical outcomes including length of hospital stay (LOS), septic shock, Medical Emergency Response Team (MET) calls, intensive care unit (ICU) admission, mortality and 30-day readmissions, adjusting for age, sex, Charlson Comorbidity Index and C-reactive protein levels. Results: Of 387 admissions, complete data were available for 381 patients. The mean (standard deviation [SD]) age was 58.5 years (21.9 years), and 55.9% were male. Statins were used by 110 patients (28.9%) at admission. Statin users were older, had more comorbidities, and were more likely to have positive culture results than statin non-users (p < 0.05). Median (interquartile range [IQR]) LOS was significantly longer for statin users compared to non-users (4 [2, 7] versus 3 [2, 5] days, p < 0.05). However, after adjusted analysis, LOS was not significantly different between the two groups (adjusted incidence risk ratio [aIRR] 1.08; 95% confidence interval [CI] 0.97–1.20, p = 0.134). Other clinical outcomes were also similar between the two groups. Conclusions: This study found that statin use at admission was not associated with statistically significant differences in clinical outcomes among patients hospitalised with SSTIs. Full article

Background/Objectives: The efficacy of topical therapies in dermatology is often limited by the barrier function of the stratum corneum, which restricts drug penetration. Iontophoresis is a non-invasive transdermal delivery technique that uses a low-intensity electrical current to enhance the transport of charged and polar molecules across the skin. It has emerged as a strategy to improve local drug bioavailability while minimizing systemic exposure. We systematically reviewed the clinical evidence on the efficacy, safety, and pharmacologic performance of iontophoresis-assisted topical drug delivery in dermatologic diseases. Methods: This systematic review followed PRISMA guidelines and was prospectively registered in PROSPERO (CRD420251234877). PubMed, Embase, Web of Science, CENTRAL, and ClinicalTrials.gov were searched through 19 November 2025 without language restrictions. Records were screened against predefined eligibility criteria, and data were extracted on study design, participants, dermatologic indications, intervention/comparator, iontophoresis parameters, efficacy outcomes, and adverse events. The risk of bias was assessed using RoB 2 for randomized trials and the JBI checklist for non-randomized studies. Because of substantial clinical and methodological heterogeneity, the findings were synthesized narratively and no meta-analysis was performed. Results: Twenty-one studies published between 1990 and 2025 met the inclusion criteria, including 15 randomized and 6 non-randomized studies. Investigated conditions included psoriasis, eczema, melasma, post-inflammatory hyperpigmentation, herpes labialis, onychomycosis, chronic ulcers, systemic sclerosis-related digital ulcers, acne scarring, and actinic keratosis. Across studies, findings were mixed. The most consistent signals of benefit were observed in pigmentary disorders and infectious diseases, whereas results were more heterogeneous in inflammatory dermatoses and some studies did not show superiority over active comparators. Tolerability was generally favorable, with adverse events limited to mild, reversible local reactions such as erythema, tingling, burning, or transient irritation. No serious treatment-related adverse events were reported. Conclusions: Iontophoresis may represent a useful non-invasive delivery-enhancement strategy in selected dermatologic settings, particularly when topical efficacy is limited by anatomical or physicochemical barriers. However, heterogeneity in protocols, formulations, outcomes, and clinical indications limits direct comparison and does not support broad conclusions of efficacy across all dermatologic conditions. Larger, standardized trials are needed to clarify its therapeutic role, long-term efficacy, and indication-specific benefit. Full article

Hidradenitis suppurativa (HS) is a chronic, relapsing inflammatory skin disease associated with significant physical and psychosocial burden. Increasing evidence identifies the interleukin (IL)-17 pathway as a central driver of HS pathogenesis. Elevated levels of IL-17 family cytokines, particularly IL-17A and IL-17F, have been consistently demonstrated in lesional skin, where they contribute to keratinocyte activation, neutrophil recruitment, and amplification of proinflammatory cascades. This review provides a comprehensive overview of the pathogenic role of IL-17 in HS and summarizes current evidence on IL-17-targeted therapies from clinical trials and real-world studies. Secukinumab, a selective IL-17A inhibitor, has shown significant efficacy in phase III trials, with clinically meaningful improvements in Hidradenitis Suppurativa Clinical Response (HiSCR), pain, and quality of life, sustained over long-term follow-up. Bimekizumab, a dual inhibitor of IL-17A and IL-17F, has demonstrated robust and consistent efficacy across multiple endpoints, including higher response rates and greater improvements in patient-reported outcomes, supporting the relevance of dual cytokine inhibition. Despite these advances, treatment responses remain heterogeneous, reflecting the multifactorial nature of HS. Further research is needed to identify predictive biomarkers and optimize therapeutic strategies. Full article

Background: Superficial fungal infections caused by dermatophyte and non-dermatophyte species are increasing globally. While several comorbid diseases and risk factors have been associated with fungal infections at the individual level, their epidemiological relationships at the population level remains poorly characterized. Objective: We aimed to examine population-level associations between the burden of superficial fungal infections and selected comorbid conditions and risk factors, stratified by age, sex and country. Methods: We obtained years lived with disability (YLDs) for superficial fungal infections, diabetes, psoriasis, and atopic dermatitis and summary exposure values (SEVs) for high body mass index (BMI) and high alcohol intake from Global Burden of Disease Study 2023. Data were obtained for Australia, Brazil, the United Kingdom and the United States for males and females younger than 20 years, 20 to 54 years and 55+ years old. Pearson correlation coefficients were calculated between fungal infection YLDs and each comorbid condition (YLDs) and risk factor (SEVs). Results: Significant positive correlations were observed between superficial fungal infection burden and diabetes (R = 0.6–0.98), high BMI (R = 0.75–0.95), psoriasis (R = 0.59–0.96), and atopic dermatitis (R = 0.51–0.93) in older adults (55 years+). Correlations with high alcohol consumption were more variable across regions and sex. In young–middle-aged adults (20–54 years), moderate-to-strong correlations (R ~ 0.8–0.9) were observed, although patterns were less consistent across countries. In individuals < 20 years, associations were generally weaker, with some positive correlations observed for atopic dermatitis (R = 0.4–0.7) in select countries. Conclusions: The findings demonstrate population-level associations between superficial fungal infections and metabolic, inflammatory, and behavioural risk factors, with stronger correlations observed in older age groups. These patterns may reflect shared demographic, epidemiologic, and clinical patterns across conditions. Full article

Background: ASD is a class of neurodevelopmental disorders with onset in early childhood, whereas AD is a common chronic inflammatory skin disease. An increasing number of studies suggest that immune dysregulation and inflammatory responses play important roles in the onset and progression of both conditions; however, their shared molecular mechanisms remain unclear. Methods: First, ASD-related and AD-related datasets were obtained from the GEO database. After removal of batch effects, the common DEGs between the two diseases were identified. Subsequently, 107 machine learning-based model configurations were employed to screen for key genes. Functional enrichment analyses and PPI network construction were performed to systematically explore their potential functions. Finally, the CIBERSORT was applied to analyze immune cell infiltration and to assess the correlation between hub gene expression and immune cell infiltration. Results: 164 common genes between ASD and AD were identified. GO and KEGG enrichment analyses revealed that these shared differentially expressed genes were mainly enriched in pathways related to immune regulation and inflammatory responses, suggesting that immuno-inflammatory processes may constitute an important biological basis linking ASD and AD. Further screening and validation using machine learning identified BEX4, BIN2, BNIP3L, CCNO, JAK2, SLC39A7, and WASF3 as hub genes serving as common potential biomarkers for both diseases. Among them, BIN2, SLC39A7, and JAK2 may represent key shared genes and demonstrated good diagnostic value in ROC curve and nomogram analyses. In addition, immune infiltration analysis indicated that these key genes were significantly correlated with the infiltration levels of multiple immune cell types, further supporting their potential roles in immune regulation. Conclusions: This study reveals potential shared immuno-inflammatory molecular mechanisms between ASD and AD. Genes screened based on 107 machine learning models were verified as potential diagnostic biomarkers for both diseases after integrated analysis, providing a theoretical basis for further investigation of their immune-related pathogenesis and early clinical diagnosis. Full article

Inflammatory skin diseases are characterized by complex interactions between immune pathways, epidermal barrier function, and environmental triggers, leading to distinct clinical and histopathological features. This narrative review aims to integrate current knowledge on the cutaneous immune microenvironment across major inflammatory skin diseases, including atopic dermatitis, psoriasis, hidradenitis suppurativa, and vitiligo. A comprehensive literature search was conducted using PubMed, Web of Science, and Scopus, focusing on studies published between 2021 and early 2026. The findings highlight disease-specific immune signatures, such as Th2-driven inflammation in atopic dermatitis, IL-23/Th17 axis activation in psoriasis, neutrophil-dominated responses in hidradenitis suppurativa, and cytotoxic T-cell-mediated melanocyte destruction in vitiligo. These molecular pathways are closely reflected in histopathological patterns, emphasizing the link between morphology and immunopathogenesis. Advances in targeted therapies, including biologics and Janus kinase inhibitors, demonstrate the clinical relevance of these pathways and support a transition toward mechanism-based treatment strategies. Dermatopathology is increasingly contributing to precision medicine approaches by supporting correlations between tissue features, immune pathways, and potential therapeutic targets. This review provides a framework for improved disease stratification and for the development of personalized treatment strategies in inflammatory skin diseases. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease increasingly prevalent in adults. Vitamin D plays an important role in regulating immune responses, cellular differentiation, and inflammation. Several single-nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene have been suggested as biomarkers of AD susceptibility and severity. The aim of this study was to investigate six SNPs in the VDR gene (rs3847987, rs731236, rs7975232, rs1544410, rs2228570, and rs11168293) and their association with AD and blood biomarkers. Genotyping was performed in 91 adult patients with AD and 102 controls using real-time polymerase chain reaction. The genotype and allele distributions did not differ significantly between AD patients and controls. However, the G and T alleles of VDR rs731236 and rs1544410 were more frequently detected in individuals with serum 25-hydroxyvitamin D (25(OH)D) levels above 30 ng/mL. In contrast, the VDR rs7975232 C allele appears to be associated with lower odds of having a serum 25(OH)D level above 30 ng/mL. In genotype-stratified analysis, the T allele of VDR rs11168293 was more prevalent among individuals with eosinophil counts of 300 cells/μL. These findings suggest that VDR polymorphisms may contribute to variability in vitamin D status and inflammatory responses in adults with AD. Full article

Background/Objectives: Psoriasis and Hashimoto’s thyroiditis are chronic immune-mediated disorders affecting distinct target organs but sharing overlapping pathogenic mechanisms, including gut dysbiosis, impaired intestinal barrier function, and systemic immune dysregulation. Growing evidence highlights the gut–skin and gut–thyroid axes as important interfaces linking microbial alterations to immune-mediated inflammation. This review aims to synthesize current knowledge on gut microbiota alterations in psoriasis and Hashimoto’s thyroiditis, with particular emphasis on intestinal permeability, immune pathways, and microbiome-derived metabolites. Methods: A narrative review of experimental and human observational studies was conducted to evaluate evidence on gut microbiota composition, intestinal barrier integrity, immune regulation, bile acid metabolism, and dietary influences in psoriasis and Hashimoto’s thyroiditis. The relevant literature examining mechanistic pathways and clinical associations was included. Results: Both conditions are associated with altered gut microbial composition, including reduced abundance of short-chain fatty acid–producing taxa, which may impair epithelial barrier integrity and promote systemic immune activation. Increased intestinal permeability and enhanced Th17-driven inflammatory responses are reported in both diseases. Recent studies suggest that dysregulated bile acid metabolism may influence intestinal permeability and immune balance along the gut–skin–thyroid axis, although direct clinical data remain limited. Dietary patterns, particularly anti-inflammatory and Mediterranean diets, are consistently associated with increased microbial diversity, improved metabolic profiles, and reduced systemic inflammation. However, most human evidence is observational. Conclusions: The gut microbiome represents a potential mechanistic link connecting diet, intestinal barrier function, immune regulation, and organ-specific autoimmunity in psoriasis and Hashimoto’s thyroiditis. While microbiome-targeted interventions show biological plausibility, well-designed, mechanistically informed randomized controlled trials are required to establish causality and clinical relevance. Full article