Search Results (1,265)

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by barrier dysfunction and susceptibility to Staphylococcus aureus colonization. Biofilm formation modifies antibiotic resistance and the host immune response. This longitudinal study analyzed antimicrobial susceptibility and biofilm formation in 136 S. aureus isolates obtained over 18 months from lesional, nonlesional, and nasal samples of 26 pediatric patients with moderate-to-severe AD. Antimicrobial susceptibility testing was determined by the disk diffusion method, and biofilm production was quantified using a crystal violet microtiter assay. Clinical parameters, including disease severity, treatment response, and the administration of dilute bleach baths, were evaluated in relation to bacterial characteristics. Overall, 60.2% of isolates exhibited moderate-to-strong biofilm production, significantly associated with severe AD at baseline (p = 0.01), lack of clinical improvement (p = 0.04), and persistent moderate-to-severe disease (p = 0.01). Resistance rates for penicillin, gentamicin, clindamycin, and erythromycin exceeded 15%. Isolates from patients using dilute bleach baths showed greater resistance to ciprofloxacin (p < 0.0001) and exhibited constitutive or inducible macrolide–lincosamide–streptogramin B (MLS_B) resistance, with ermA detected in 80% of inducible cases. In conclusion, S. aureus biofilm formation is linked to disease severity and treatment failure in pediatric AD, underscoring the importance of culture-guided, targeted therapeutic strategies. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease with early-age onset. While vitamin D (VitD) has been associated with AD alleviation, geographical factors should be considered as VitD synthesis depends on sunlight exposure and dietary intake. We conducted a mapping review to identify geography-related evidence gaps in interventional and observational studies on the VitD-AD inverse association. We analyzed latitude and the Human Development Index (HDI) as background geographical factors. The review identified 38 studies (17 interventional, 21 observational), of which 26 confirmed the inverse VitD-AD association. Of all reviewed studies, 73% were from latitudes above 35° N, and 70.3% were from developed countries. The median latitude and HDI were 37.5° N and 0.915, respectively. Conversely, only 5.4% of studies were from Africa and 8.1% from Latin America. Studies that did not confirm the inverse VitD-AD association tended to be concentrated in developed countries at higher latitudes (median latitude 42.4° N, median HDI 0.937). Only 8.1% of all studies were from low-latitude developed countries, and among interventional studies this share was even lower (6.3%). In addition, 52.6% of studies lacked data on baseline VitD variability and 13.2% had no baseline VitD data at all. More thorough data reporting and additional clinical studies from countries that do not follow the high latitude/high HDI overlap pattern would facilitate future meta-analyses aimed at clarifying the role of VitD in AD treatment. Full article

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease with critical unmet therapeutic needs. This study compared the efficacy of three probiotics—Bifidobacterium animalis subsp. lactis J12 (B. animalis J12), Lactiplantibacillus plantarum Zhang-LL (L. plantarum Zhang-LL), and Limosilactobacillus salivarius M18-6 (L. salivarius M18-6)—in a 2,4-dinitrofluorobenzene (DNFB)-induced mouse AD model. Interventions included topical fermented supernatants (J12S/Z-LL-S/M18-6-S), oral live cells (J12L/Z-LL-L/M18-6-L), and topical dexamethasone (Dex) as the positive control. Post-intervention, AD-related pathological and immunological indices were evaluated. Among the three probiotics, J12 exhibited superior efficacy, whereas L. plantarum Zhang-LL and L. salivarius M18-6 showed limited therapeutic effects. Both J12-derived formulations alleviated DNFB-induced AD symptoms: Topical J12S significantly reduced ear swelling, serum IL-4 and IL-17 levels, and increased the proportion of splenic Treg cells. Oral J12L exerted comparable immunomodulatory effects, while further improving skin pathology—epidermal thickness and mast cell infiltration were each reduced to approximately one-third of those in the model group. Additionally, J12L regulated gut microbiota by enhancing alpha diversity and altering functional predictions. Collectively, B. animalis J12 is a promising candidate for AD management: topical J12S serves as an effective, non-invasive alternative to oral J12L. Notably, the two formulations act through distinct yet complementary mechanisms—J12L exerts systemic effects via regulating immunity and the gut–skin axis, while J12S exerts local anti-inflammatory effects and protects the skin barrier—highlighting J12′s versatile therapeutic potential for AD. Full article

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by pruritic eczematous lesions that significantly alter quality of life of patients. Dupilumab, a new biologic agent, has demonstrated efficacy and safety in the general adult population with AD. However, evidence on its use in elderly patients is limited. Objectives: The objective of this work was to systematically assess the effectiveness and safety of dupilumab in patients aged ≥60 years with AD, based on published data. Methods: A systematic review and meta-analysis were conducted following the PICO(S) framework. Articles written in English and published before 31 December 2024 that investigated patients ≥ 60 years with AD treated with dupilumab were included. Meta-analysis of the observational studies was performed using a random-effects model with subgroup and meta-regression analyses. Results: Twenty-one articles met the inclusion criteria. After 16 weeks of treatment, dupilumab significantly reduced disease severity (EASI: 21.8; 95% CI: 18.3–25.2), intensity of pruritus (P-NRS: 5.8; 95% CI: 4.2–7.3), and quality of life impairment (DLQI: 11.3; 95% CI: 6.1–16.5); all p < 0.001. Meta-regression revealed previous treatment with cyclosporin A as a predictor of a poorer response to treatment. The generalized-prurigo phenotype was associated with worse control of pruritus. The most common adverse events were conjunctivitis, injection site reactions, and facial flushing. Conclusions: Dupilumab appears to be an effective and well-tolerated treatment for AD in elderly patients. More research is warranted to evaluate its long-term effectiveness and safety in this age group. Full article

Background and Objectives: Oral Janus kinase (JAK) inhibitors have become an important therapeutic class in dermatology, with approved indications including atopic dermatitis and alopecia areata. Owing to their broad immunomodulatory effects and rapid onset of action, these agents are increasingly used off label for a variety of inflammatory skin disorders that are often refractory to standard therapies. The objective of this review was to provide a comprehensive overview of the published literature on the off-label dermatologic use of oral JAK inhibitors, summarizing clinical outcomes, safety profiles and treatment durations reported in real-world settings. Materials and Methods: A literature search was conducted in PubMed to identify case reports and case series describing off-label dermatologic use of baricitinib, abrocitinib, upadacitinib, and ritlecitinib. Extracted data included authorship and year, article type, treatment regimen, treatment duration and follow-up, prior systemic therapies, clinical outcomes, and reported adverse events. Results: A total of 136 articles were included, comprising 45 articles on abrocitinib (63 patients), 55 on upadacitinib (94 patients), 35 on baricitinib (45 patients), and 2 on ritlecitinib (2 patients). Across a wide spectrum of dermatological conditions, oral JAK inhibitors showed consistent clinical efficacy. Responses were frequently rapid and disease control was often maintained over several months of treatment. In many cases, dose reduction or treatment discontinuation did not lead to immediate relapse. Overall tolerability was favorable, with adverse events reported in a minority of patients and predominantly described as mild and transient. Conclusions: Although our data is limited to case-based literature, this review highlights the broad off-label therapeutic potential of oral JAK inhibitors in dermatology. Their rapid onset of action, sustained clinical responses, frequent maintenance of remission after dose tapering or discontinuation and generally acceptable safety profile support their consideration as treatment options in selected patients. Full article

Micro-RNAs (miRNAs) are short, non-coding RNA molecules regulating genes’ expression. Studies published over last years demonstrated that they play an important role in allergic diseases by regulating humoral and cellular immunity, cytokine secretion and epithelium function. Some of them seem potential non-invasive biomarkers facilitating diagnosis of the most common allergic diseases, such as allergic rhinitis (miR-21, miR-126, miR-142-3p, miR-181a, miR-221), asthma (miR-16, miR-21, miR-126, miR-146a, miR-148a, miR-221, miR-223) and atopic dermatitis (miR-24, miR-124, miR-155, miR-191, miR-223, miR-483-5p), or objectively assessing severity of inflammation and endotype of the disease. In spite of the large body of literature available, its scientific value is limited due to the small numbers of study participants, heterogeneity of populations enrolled, and diverse methodology. Some studies have revealed significant changes in miRNAs’ profile in the course of allergen immunotherapy. Tolerance induction is associated with processes controlled by miRNAs: enhanced activity of Treg cells and increased production of tolerogenic IL-10 and TGF-β. Thus, miRNAs may be candidates as biomarkers of successful immunotherapy. Finally, they are also possible therapeutic agents or targets of therapies based on antagomirs blocking their activity. However, so far no studies are available that demonstrate efficacy in overcoming delivery barriers, tissue targeting or drugs’ safety. As a consequence, despite promising results of in vitro and animal model studies, translation into human therapeutic agents is uncertain. Full article

Background and Objectives: Atopic dermatitis and psoriasis are life-long inflammatory diseases affecting more than just the skin. Although their link with mental comorbidities has been established, the role of using self-assessment questionnaires is still debated. The aim of our study was to evaluate differences in the quality of life (DLQI) as well as depression (PHQ-9) and anxiety (GAD-7) questionnaire data and determine their link with individual patient and skin disease factors. Materials and Methods: Demographic, clinical and questionnaire data were collected from Riga 1st hospitals archive. For statistical evaluation, the Mann–Whitney U test and Spearman’s rank correlation coefficient were used. Results: The median DLQI for atopic dermatitis and psoriasis was 10.5 and 10, respectively. The prevalence among women with atopic dermatitis who had a PHQ-9 ≥ 10 was 42.9%, compared to 50.0% in men, and GAD-7 ≥ 10 prevalence was 14.3% and 20.0%, respectively. Psoriatic women had a PHQ-9 ≥ 10 prevalence of 25.0% compared with 28.9% in men. The prevalence of GAD-7 ≥ 10 was 20.0% in females and 15.8% in males. GAD-7 score was elevated in patients with psoriatic genital involvement. Multiple positive correlations were noted between PHQ-9, GAD-7 and DLQI scores. Conclusions: Patient quality of life and prevalence of anxiety and depression symptoms are impacted by psoriasis and atopic dermatitis, with similar patterns observed across genders and comorbidities. Genital involvement could be associated with more severe anxiety symptoms. The correlations between PHQ-9, GAD-7 and DLQI scores indicate that further evaluation might be necessary if quality of life is impaired. Full article

Sarcoidosis is an immune-mediated granulomatous disease whose etiology has remained unresolved despite more than a century of investigation. Accumulating microbiological and immunopathological evidence now implicates Cutibacterium acnes—a ubiquitous indigenous commensal—as the most consistent antigenic trigger. Its frequent detection within sarcoid granulomas by quantitative PCR, in situ hybridization, and species-specific immunohistochemistry suggests latent intracellular persistence and the potential for endogenous reactivation. To explain how a noncontagious commensal can drive granulomatous inflammation, this review proposes the concept of Endogenous Hypersensitivity Infection (EHI). EHI describes a host-centered process in which reactivation of latent intracellular microbes leads to the breakdown of immune tolerance and provokes Th1-dominant hypersensitivity responses in genetically and immunologically susceptible individuals. This framework bridges the traditional divide between infection and autoimmunity, reframing sarcoidosis as a disorder of disrupted host–commensal homeostasis rather than a classical infectious or autoimmune disease. By integrating microbiological, immunological, and pathological evidence, this review synthesizes the mechanistic basis of EHI and outlines how tolerance failure to C. acnes can account for the paradoxical clinical behavior of sarcoidosis. The EHI paradigm further provides a unifying conceptual lens through which related chronic inflammatory disorders—including Crohn’s disease, chronic rhinosinusitis, and atopic dermatitis—may be reinterpreted. Full article

Background/Objectives: GATA-binding protein 3 (GATA-3) is a crucial transcription factor that drives type 2 immune responses, and it is actively involved in allergic conditions such as asthma, allergic rhinitis (AR), and atopic dermatitis (AD). However, the molecular mechanisms GATA-3 uses to modulate immune responses and its potential therapeutic targeting are not fully understood. This systematic review aimed to summarize studies on the role of GATA-3 in immune responses, particularly in allergic diseases, and evaluate GATA-3’s potential as a therapeutic target. Methods: We searched PubMed, Scopus, Web of Science, Cochrane, and Science Direct for studies published before April 2025. Articles were sifted through using predefined criteria, and risk of bias was measured with RoB 2 for clinical trials and SYRCLE for animal models and in vitro studies; evidence was graded using the GRADE system. Results: Twenty-nine eligible studies reported that GATA-3 is a key regulator of Th2 and ILC2 differentiation, promoting the production of IL-4, IL-5, and IL-13. Animal models and in vitro studies demonstrated its role in exacerbating allergic inflammation and highlighted the promise of targeting strategies such as DNAzymes and nanocapsules. Clinical trials showed that targeting GATA-3, particularly with DNAzymes, can reduce allergic responses in asthma. Conclusions: GATA-3’s role in driving allergic inflammation through Th2 and ILC2 pathways suggests it as a promising therapeutic target. Understanding its broader regulatory mechanisms is imperative for designing effective GATA-3 targeting-based therapies. Full article

The emerging field of dermatogenomics, which examines visible dermatologic phenotypes alongside their polygenic factors, offers insights for early disease recognition and initiation of preventative measures. This review explores key dermatologic manifestations serving as clinical markers of systemic diseases, emphasizing cardiovascular, autoimmune, neuropsychiatric, metabolic/endocrine, and cancer-related conditions. Importantly, the pathogenesis of certain skin conditions including psoriasis, atopic dermatitis, vitiligo, and hidradenitis suppurativa is linked to systemic disease through shared genetic and epigenetic mechanisms. The diagnostic markers for these integumentary diseases are discussed alongside their shared mechanisms to systemic diseases, highlighting the clinical manifestation typically seen in primary care settings. This narrative review integrates dermatology with genomics, primary care, preventative care, public health, and internal medicine perspectives, underscoring the importance of an interdisciplinary and collaborative approach to patient care. Lastly, this review advocates for standardized dermatogenomic screening thresholds, inclusivity and expansion of genomic datasets, and the leverage of artificial intelligence and multi-omic technologies in preventative healthcare. Full article

Background and Objectives: Nationwide registries that provide comprehensive insights into the atopic dermatitis (AD) population and management in routine practice are lacking in Baltic countries. Real-world studies to explore the clinical and economic burden of AD are highly needed. We present findings from the Baltic cohort of the larger observational study ESSENTIAL AD, conducted in Europe, the Middle East, and Africa. Materials and Methods: This cross-sectional, retrospective chart review study enrolled adult AD patients routinely managed with systemic and/or non-systemic therapy in Estonia, Latvia, and Lithuania. Data was collected during one office visit. AD severity was assessed using the Eczema Area and Severity Index (EASI) and SCORing Atopic Dermatitis (SCORAD) and impact on quality of life was assessed using the Dermatology Life Quality Index (DLQI) (primary endpoints). Results: Fifty patients were enrolled, with a mean (standard deviation [SD]) age of 33.6 (11.67) years, and 60% were women. Mean (SD) time since AD diagnosis was 21.8 (14.8) years. An equal proportion of patients received systemic therapy (including combination therapy) or non-systemic therapy (50% each). Mean (SD) EASI, SCORAD, and DLQI total scores were 9.8 (9.76), 38.0 (16.5), and 10.5 (7.1), respectively. No significant difference was observed between patients receiving systemic and non-systemic therapy in terms of EASI (mean [SD] 11.5 [12.2] versus 8.2 [6.3]; p = 0.7636), SCORAD (35.4 [20.8] versus 40.6 [11.5]; p = 0.2563), and DLQI (9.5 [7.6] versus 11.5 [6.5]; p = 0.1962). Hospitalization rate (95% confidence interval) was significantly higher in patients on systemic versus non-systemic therapy (0.4 [0.2–0.8] versus 0.1 [0.0–0.4]; p = 0.0424). Monthly out-of-pocket expenses (USD) were higher in Latvia (mean [SD]: 103.7 [2.64]) versus Estonia (55.6 [1.82]) and Lithuania (53.8 [1.90]). Conclusions: Adult AD patients from the Baltic region still face a considerable disease and economic burden, regardless of treatment received. Improved disease management and better access to guideline-recommended advanced systemic therapies are necessary. Full article

Vitamin D deficiency is associated with the risk of atopic diseases and respiratory infections. The activated vitamin D receptor (VDR) forms a dimer with the retinoid X receptor alpha (RXRA) and binds to VDR/RXRA composite elements (CEs) in enhancers of target genes. However, VDR/RXRA CEs are identified in only 11.5% of cases in ChIP-Seq peaks. Our hypothesis was that VDR could form a VDR-Partner complex with transcription factor for which CEs have not yet been identified. We utilized Web-MCOT to search for novel VDR/Partner CEs in regulatory DNA. The potential formation of the VDR-Partner protein complex was assessed using the AlphaFold machine learning model. Through real-time RT-PCR, we measured the expression of immune system genes in a culture of U937 macrophage-like cells incubated with the active metabolite of vitamin D, calcitriol. We have predicted novel VDR/NR2C2 and VDR/PPARG CEs in the regulatory regions of immune system genes. We found potential synergism of VDR/NR2C2 and VDR/RXRA CEs in relation to the IRF5 gene, as well as potential synergism of VDR/PPARG and VDR/RXRA CEs for MAPK13. Predicting new regulatory relationships through the identification of new potential VDR/Partner CEs may provide insight into the deep mechanisms of vitamin D involvement in the pathogenesis of atopic dermatitis, bronchial asthma, allergic rhinitis, and pulmonary infections. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease in which barrier impairment, immune dysregulation, and gut–skin dysbiosis intersect, prompting growing interest in probiotics as microbiota-modulating adjuncts. We conducted a narrative review of peer-reviewed articles indexed in PubMed, Scopus, and Google Scholar, restricted to publications from 1 January 2018 to 31 October 2025 (searches last run in December 2025). Eligible evidence included randomized controlled trials (RCTs), observational studies, and mechanistic or conceptual reviews addressing microbiome alterations and microbiota-modulating interventions in AD. Most pediatric RCTs using multistrain, Lactobacillus-dominant formulations (often combined with Bifidobacterium) reported modest improvements in AD severity and pruritus and in selected barrier- and inflammation-related biomarkers. However, direct cutaneous microbiome “restoration” outcomes were reported in a minority of studies, and most clinical evidence relies on clinical endpoints and gut–skin axis plausibility rather than longitudinal skin microbiome readouts. Single-strain regimens showed inconsistent effects, and evidence in adolescents and adults remained heterogeneous. Mechanistically, probiotics may enhance short-chain fatty acid (SCFA) signaling, dampen toll-like receptor 2/4 (TLR2/4)-nuclear factor kappa B (NF-κB) activation, and promote interleukin-10 (IL-10)- and transforming growth factor-β (TGF-β)-driven tolerance. Probiotics are a biologically plausible adjunct targeting the gut–skin axis in AD and are generally well tolerated; however, heterogeneity across trials, limited follow-up, inconsistent adverse-event reporting, and scarce skin microbiome endpoints preclude firm clinical recommendations. Full article

Background and Objectives: Atopic dermatitis (AD) is a prevalent, chronic, relapsing itchy skin disorder, affecting up to 20% of the pediatric population. Topical corticosteroids are the cornerstone of AD treatment, but their use is often limited due to topical corticosteroid phobia among parents. Research on chronic illnesses highlights the significant role of personality traits in treatment adherence, with emotional stability and conscientiousness—within the framework of the Five-Factor Model—emerging as key predictors. The aim of our study was to examine the relationship between parental personality traits and their adherence to the treatment of their children with AD. Materials and Methods: A cross-sectional study was conducted at the Department of Dermatovenereology, University Hospital of Split, involving 90 parents of children diagnosed with AD. Personality traits were evaluated using the abbreviated version of the International Personality Item Pool Big-Five Personality Questionnaire (IPIP 50s). Treatment adherence was assessed through a valid and reliable questionnaire, the Morisky Medication Adherence Scale (MMAS-8). Statistical analyses were performed using JASP v.0.18.1.0. Results: According to MMAS-8, only a small proportion of the sample reported having high adherence (14.4%). The only significant associations between personality traits and adherence were found between conscientiousness and adherence and emotional stability and adherence, where more conscientious participants and more emotionally stable participants reported higher scores. Conclusions: The results suggest that parents of children with AD with higher scores on conscientiousness and emotional stability are more likely to demonstrate better treatment adherence. These insights may encourage a holistic and multidisciplinary approach to the treatment of children with AD, with an emphasis on providing psychological support to both the children and their parents in order to improve treatment adherence and the further clinical course of the disease. Full article

Psoriasis is a chronic inflammatory skin disease driven by the IL-23/IL-17 axis and characterized by keratinocyte hyperproliferation, epidermal thickening, and immune infiltration. While immune cell-intrinsic roles of hypoxia-inducible factor-1α (HIF-1α) have been reported, the contribution of keratinocyte HIF-1α remains less clear. In this study, we investigated epithelial HIF function in murine models of skin inflammation using keratinocyte-specific HIF-1α knockout (K14-Cre Hif1a^fl/fl) mice. HIF-1α deficiency attenuated epidermal hyperplasia and type 3 inflammation in the imiquimod (IMQ)-induced psoriasiform model but had little effect in DNFB-induce contact hypersensitivity and MC903-induced atopic dermatitis model. Flow cytometry of draining lymph nodes revealed reduced frequencies of inflammatory cells including IL-17-producing γδ T cells in HIF-1α-deficient mice. In IMQ-treated skin, HIF-1α deficiency led to reduced Il17, Il23 and neutrophil-attracting chemokine transcript levels and diminished Ly6G⁺ neutrophil infiltration. These findings identify keratinocyte HIF-1α as a central regulator of psoriasiform inflammation and suggest that epithelial HIF signaling could be a potential therapeutic target for psoriasis. Full article