Search Results (2,074)

Localized scleroderma (LSc), or morphea, is an autoimmune connective tissue disease causing inflammation and fibrosis of the skin and underlying tissues. While distinct from systemic sclerosis, its clinical presentation is highly diverse. This review summarizes recent advances in the understanding and management of LSc. Pathophysiological insights have evolved significantly; the somatic mosaicism hypothesis is now supported by the observation of all six of Happle’s classic lesion patterns in LSc. Furthermore, recent single-cell RNA sequencing has elucidated key cellular mechanisms, revealing an IFN-γ-driven pro-fibrotic crosstalk between T cells, dendritic cells, and specific inflammatory fibroblast subpopulations. The discovery of a rare monogenic form of LSc caused by a STAT4 gain-of-function mutation provides a powerful human model, solidifying the critical role of the JAK-STAT pathway. Clinically, LSc is classified into subtypes such as circumscribed, linear, and generalized morphea. Extracutaneous manifestations are common, particularly in juvenile LSc, and are associated with higher disease activity and reduced quality of life, necessitating a multidisciplinary approach. Management is becoming standardized, with methotrexate as the first-line systemic therapy for severe disease. For refractory cases, targeted treatments including abatacept, tocilizumab, and JAK inhibitors are emerging as promising options. In addition, reconstructive therapies like autologous fat grafting are crucial for managing atrophic sequelae. These recent advances are paving the way for more effective, targeted therapies to improve outcomes for patients with this complex disease. Full article

Priasis is a chronic inflammatory skin disease characterized by keratinocyte hyperproliferation, impaired differentiation, and dysregulated immune responses. Emerging evidence highlights the central role of keratinocytes as immune-competent cells that integrate signals from cytokines, metabolic cues, the gut–skin axis, and the tissue microenvironment. Key intracellular signaling pathways, including NF-κB, JAK/STAT, MAPK, and PI3K/AKT/mTOR, along with the IL-23/IL-17 axis, orchestrate keratinocyte-mediated inflammation and epidermal hyperplasia. Metabolic factors, nutrients, and redox balance further modulate these responses, while the intestinal microbiota and its metabolites, such as short-chain fatty acids, shape systemic and cutaneous inflammation. This review offers a critical, integrated perspective, that moves beyond descriptive summaries. We propose a conceptual framework in which the keratinocyte metabolic state, particularly the sirtuin/NAD+ axis, acts as a crucial convergence point for systemic nutritional, microbial, and inflammatory signals. Targeting sirtuins and associated pathways with natural or synthetic modulators represents a promising, host-centric strategy to restore keratinocyte function and reduce chronic inflammation. This synthesis underscores the potential of combining molecular, metabolic, microbial, and nutritional insights to develop personalized and effective approaches for psoriasis management.  Full article

Contact dermatitis is a highly prevalent inflammatory disease of the skin with substantial impact on patients’ quality of life and occupational function. Although randomized controlled trials (RCTs) provide the highest level of evidence for treatment evaluation, previous research has shown that the reporting quality of RCT abstracts is often suboptimal. This study aimed to assess the completeness of reporting of RCT abstracts on contact dermatitis according to the CONSORT extension for abstracts (CONSORT-A). A cross-sectional analysis of 304 abstracts indexed in PubMed between 1975 and 2024 was conducted. Each abstract was independently evaluated by two reviewers using the 17-item CONSORT-A checklist, with inter-rater agreement calculated by Cohen’s κ. The median adherence score was 5 out of 17 items (29.4%), with a range from 1 (5.9%) to 14 (82.4%). The reporting of study aims (82.9%), interventions (82.2%), and conclusions (91.1%) was frequent, whereas critical methodological elements such as participant criteria (4.6%), randomization (2.0%), trial registration (3.0%), and funding (0.7%) were rarely reported. Structured abstracts, hospital settings, significant study results, and more than seven authors were independent predictors of higher adherence in multivariate analysis. Abstracts published after 2008, when CONSORT-A was introduced, showed modest but significant improvement. These findings indicate that reporting quality of contact dermatitis RCT abstracts remains inadequate, underscoring the need for stricter journal requirements, structured abstract formats, and broader dissemination of CONSORT-A guidelines. Full article

Dermatomyositis (DM) is a prototypic idiopathic inflammatory myopathy in which characteristic skin disease frequently precedes or parallels muscle involvement and signals risks such as interstitial lung disease (ILD) and malignancy. This literature review integrates recent advances across dermatology, neuromuscular medicine, and immunology to refine diagnosis and management. We surveyed the literature from 2000 to 2025, prioritizing randomized trials, large cohorts, and translational studies that spanned classic and juvenile DM, amyopathic/hypomyopathic variants, and overlap phenotypes. Key insights include the diagnostic weight of pathognomonic cutaneous lesions with nailfold microangiopathy; the utility of myositis-specific autoantibodies for endotyping and risk (e.g., anti-TIF1-γ/anti-NXP2 and cancer, anti-MDA5 and rapidly progressive ILD); and the value of myxovirus-resistance protein A (MxA) immunohistochemistry and muscle MRI patterning (including distinctions from immune-mediated necrotizing myopathy) when enzymes are normal, or biopsies are treatment-modified. Management is anchored in early steroid-sparing immunosuppression tailored to phenotype, with evidence for IVIG in active DM and growing support for JAK inhibition, particularly in interferon-high or anti-MDA5 ILD, alongside selective use of calcineurin inhibitors and rituximab, with plasma exchange considered for refractory, rapidly progressive ILD. We highlight risk-stratified malignancy screening (IMACS 2023) and complications, including calcinosis, lipodystrophy, and chronic cutaneous damage. Skin-led recognition coupled with antibody-guided, phenotype-directed therapy and interdisciplinary care offers a pragmatic precision framework to improve outcomes and reduce long-term disability. Full article

Inflammation is a hallmark of atherosclerosis (AS), a complex chronic vascular disease. This study investigates the anti-atherosclerotic effects of the frog skin antimicrobial peptide(AMP) C-1b(3-13) in vitro and in vivo, focusing on the anti-inflammatory mechanism mediated by the miR-590-5p/KLF12/p300 axis in ox-LDL-induced PMA-THP-1 foam cells. MicroRNA(miRNA) sequencing was used to investigate the effects of AMP C-1b(3-13) on miRNA expression in ox-LDL-induced foam cells. Pro-inflammatory cytokine secretion regulated by miR-590-5p was detected by ELISA. Potential targets of miR-590-5p were bioinformatically predicted and validated through dual-luciferase reporter and RNA Immunoprecipitation(RIP)-qPCR assays. Western blot was used to assess the effects of C-1b(3-13) on Krüppel-like factor 12(KLF12), nuclear p300, and nuclear factor kappa B(NF-κB) pathway proteins; ApoE^−/− mice were utilized to establish the AS mouse model. Oil Red O (ORO) and hematoxylin and eosin (H&E) staining detected plaque formation and morphological changes in the aortic root. Immunohistochemistry analyzed CD68⁺(M1) and CD206⁺(M2) macrophage distribution within arterial plaques. miR-590-5p significantly suppressed pro-inflammatory cytokine secretion in ox-LDL-induced foam cells. Mechanistically, miR-590-5p directly targeted the 3′-untranslated region of KLF12 mRNA, inhibiting KLF12 expression, reducing nuclear p300 accumulation, and subsequently attenuating NF-κB signaling pathway activation. Furthermore, AMP C-1b(3-13) treatment effectively attenuated inflammatory responses by upregulating miR-590-5p, which downregulated KLF12 expression, diminished nuclear p300 levels, and inhibited NF-κB signaling. In ApoE^−/− AS mice, C-1b(3-13) treatment markedly reduced aortic plaque formation, improved lipid metabolism, and suppressed inflammatory responses through the same signaling axis. These findings reveal a novel miR-590-5p-mediated regulatory mechanism in AS and identify AMP C-1b(3-13) as a promising therapeutic agent targeting miR-590-5p/KLF12/p300/NF-κB pathway. Full article

Atopic dermatitis is the most prevalent chronic inflammatory skin disease, posing a significant individual and healthcare burden. Traditionally managed with topical agents and broad immunosuppressants, the treatment landscape has shifted significantly in recent years. This review explores the transition from immunopathogenic understanding to personalized treatment strategies through advanced systemic therapies. We provide a thorough description of the current therapeutic arsenal, including approved monoclonal antibodies and Janus kinase (JAK) inhibitors, as well as experimental agents under clinical investigation. Key cytokines and receptors implicated in type 2 inflammation are explored alongside relevant intracellular signaling pathways. Special attention has been given to literature published from 2015 onwards. By synthesizing the latest scientific and clinical knowledge, this review aims to provide clinicians with practical guidance for navigating the evolving landscape of atopic dermatitis management and improving patient outcomes. Full article

Background and Objectives: Postoperative enterocutaneous fistulas, defined as abnormal communications between the intestinal lumen and the skin, represent one of the most challenging complications following abdominal surgery. Regenerative medicine, particularly through the use of adipose-derived mesenchymal stem cells (ADSCs), has recently emerged as a promising therapeutic option for chronic inflammatory and non-healing conditions. However, most studies have focused on complex perianal fistulas in Crohn’s disease. This prospective, single-center observational study aimed to evaluate the feasibility, safety, and preliminary efficacy of autologous ADSC injection in patients with complex postoperative enterocutaneous fistulas. Materials and Methods: Six patients (four males and two females) with persistent postoperative enterocutaneous fistulas were enrolled. Autologous adipose tissue was harvested via lipoaspiration from the abdominal wall or flank and processed in a GMP-certified laboratory to obtain a suspension containing 5–10 million viable ADSCs in 3–5 mL of isotonic solution. ADSCs were injected directly into the fistulous tract under ultrasound guidance, following CT image review. Clinical and radiologic follow-up was performed to assess closure and output reduction. Results: Four of the six patients (66.7%) achieved complete fistula closure, with no residual output and radiologic confirmation of healing within 4–12 weeks. One patient (16.7%) demonstrated a significant reduction in fistula output (>80%), while another (16.7%) showed minimal improvement and subsequently required surgical repair at 6 weeks. No complications related to ADSC administration were observed. Conclusions: Autologous ADSC therapy appears to be a feasible, safe, and minimally invasive option for managing complex postoperative enterocutaneous fistulas. These encouraging preliminary results—showing complete closure in two-thirds of treated patients—support further investigation through larger, controlled trials to validate these findings and optimize treatment protocols. Full article

Background: Psoriasis is a chronic inflammatory skin disease driven by keratinocyte hyperproliferation and immune dysregulation. Despite the availability of biologics and immunosuppressants, recurrence and adverse effects remain major limitations. Myricetin (Myr), a natural flavonoid with well-documented anti-inflammatory and immunomodulatory properties, has shown promise in inflammatory disorders; however, its efficacy and mechanisms in psoriasis have not been fully elucidated. Methods: The therapeutic effects of topical Myr (0.5–2%) were evaluated in an imiquimod (IMQ)-induced psoriatic mouse model. Network pharmacology and molecular docking were employed to predict potential targets, followed by validation using histological analysis, cytokine profiling, qPCR, and Western blotting. Results: Network analysis identified 52 overlapping targets between Myr and psoriasis, including TNF, PTGS2, MMP9, and EGFR, with enrichment in TNF, IL-17, and PI3K/AKT signaling pathways. Myr treatment significantly alleviated IMQ-induced erythema, scaling, and epidermal thickening, improved skin-barrier function, and reduced the expression of IL-6, IL-17A, and TNF-α. Molecular docking showed strong binding affinities of Myr with TNF, PTGS2, MMP9, and EGFR. Western blotting confirmed that Myr suppressed EGFR and AKT phosphorylation and downregulated Mmp9, Ptgs2, and Tnf expression. Conclusions: Myr exerts multi-target anti-psoriatic effects by inhibiting the EGFR/AKT axis and inflammatory mediators, highlighting its potential as a safe and effective natural therapeutic agent for psoriasis. Full article

Pines are edifying woody species for forest habitats, having crucial importance for ecosystems in both cold (boreal or mountainous) and warm (Mediterranean and tropical) areas. Pine trees include about 120 species, many of which have had an important ornamental role. Despite their ecological importance, many pine forests are threatened by increasing deforestation and habitat degradation, leading to progressive declines in species distribution and genetic diversity worldwide. Humans have used pine wood since the Stone Age, gradually discovering their outstanding medical properties. This review synthesizes global knowledge on the medicinal potential of pines. Using a comprehensive literature survey of major international scientific databases, we evaluated documented traditional and modern medical applications across all regions where pines naturally occur. The vast majority (86) of pine species were described as having medicinal properties, and the uses of the main pine species in representative regions of all continents supporting forest vegetation were examined. Various organs or secretions (needles, branches, bark, buds, cones, seeds, pollen, roots, wood, sap, resin, pitch, etc.) have been used to prevent or treat numerous diseases or to strengthen the organism. Their reported therapeutic activities include antioxidant, antimutagenic, antitumor, antimicrobial, skin-protective, antinociceptive, anti-inflammatory, neuroprotective, antiallergenic, laxative, circulatory-enhancing, antihypertensive, anti-atherosclerotic, anti-aging, and antithrombotic effects. Given the remarkable phytochemical diversity and broad pharmacological value of these species, the conservation of pine genetic resources and natural habitats is urgent. Protecting these species is essential not only for maintaining ecosystem resilience but also for preserving their substantial pharmaceutical and industrial potential. Full article

Rosacea is a chronic inflammatory skin disorder of multifactorial pathogenesis, in which dysregulated innate immunity, neurovascular dysfunction, oxidative stress, and microbiome imbalance are central contributors. Recent molecular studies have revealed altered cytokine expression (e.g., IL-1β, IL-6, IL-36 family), aberrant activation of signaling pathways (STAT3, NF-κB, MAPKs), and enhanced expression of innate immune receptors such as TLR2,b TLR4, and TLR7, all of which promote chronic inflammation, angiogenesis, and barrier dysfunction. This systematic review was performed according to PRISMA guidelines. A total of 1425 records were retrieved from PubMed, Scopus, and Web of Science, and 14 studies met the inclusion criteria. The included studies comprised both clinical cohorts and translational experimental investigations using human samples. Reported findings consistently confirmed systemic and tissue-specific inflammatory activity, with elevated circulating monocytes, indoleamine 2,3-dioxygenase, and inflammatory indices, as well as tissue expression of STAT3, NF-κB, MAPKs, and cathelicidin fragments. Oxidative stress markers (TOS, OSI, AOPP, MMP-9) and hypoxia-related molecules (HIF-1α) were significantly increased in patients, correlating with disease severity and vascular manifestations. Taken together, these results highlight that rosacea involves both cutaneous and systemic molecular alterations. The evidence identifies multiple biomarkers with diagnostic potential and provides mechanistic insights into immune, vascular, and metabolic dysregulation. Future research should aim to validate these findings in larger cohorts, establish standardized biomarker panels, and explore novel therapeutic strategies targeting key molecular pathways. Full article

Background/Objectives: Cutaneous lupus erythematosus (CLE) is a complex autoimmune skin disease driven by genetic predisposition, environmental triggers, and immune dysregulation. Environmental factors such as ultraviolet radiation, smoking, and certain drugs can initiate disease onset by inducing keratinocyte apoptosis. The subsequent release of nucleic acids and danger-associated molecular patterns activates pattern recognition receptors (PRRs) on keratinocytes and immune cells, leading to the production of type I and type III interferons (IFNs) and pro-inflammatory cytokines. The objective of this review is to summarize recent advances in understanding the immunopathogenesis of CLE, with particular attention to emerging cellular players and their therapeutic implications. Methods: A narrative review of the recent literature was performed, including experimental, translational, and clinical studies investigating the cellular and molecular mechanisms underlying CLE and novel targeted treatments derived from these findings. Results: Although plasmacytoid dendritic cells (pDCs) have traditionally been considered the major producers of IFN-I, recent data indicate that pDCs in CLE are functionally impaired and are not the primary source. Other cells, such as keratinocytes have emerged as key producers of IFN-I, contributing to a prelesional, IFN-rich microenvironment. This promotes the recruitment and activation of dendritic cells and other inflammatory myeloid subsets, which are now recognized as central players in amplifying local inflammation. Concurrently, T cells infiltrate the skin, where cytotoxic CD8⁺ T cells attack keratinocytes and CD4⁺ T cells further propagate inflammation via cytokine production. B cells and plasma cells produce autoantibodies, forming immune complexes that perpetuate inflammation. Neutrophils release neutrophil extracellular traps (NETs), exposing autoantigens and further stimulating IFN pathways. Macrophages contribute by presenting autoantigens, producing pro-inflammatory mediators, and failing to effectively clear apoptotic cells and immune complexes. Conclusions: The dynamic interplay between the innate and adaptive immune systems sustains the chronic inflammatory state characteristic of CLE. Based on the pathogenetic novelties, new therapeutic agents targeting specific molecules have been developed, which may improve the treatment of this complex disease in the future. Full article

Background: Contact dermatitis (CD) is a prevalent inflammatory skin condition, with diagnostic challenges in distinguishing allergic (ACD) from irritant contact dermatitis (ICD). This study aimed to explore cholesterol-derived biomarkers as potential diagnostic tools. As cholesterol derivatives play key roles in skin barrier integrity and inflammation, they are promising candidates for assessing skin barrier disruption in CD. Methods: Stratum corneum samples were collected by tape stripping from experimentally induced and chronic lesions, as well as healthy non-lesional skin. Biomarkers Cholesterol Sulfate (Chol-Sulf), Cholesterol Glucosyl (Chol-Glc) and their ratio were quantified. Data were analyzed using ANOVA, Pearson’s correlation, logistic regression and ROC curves. Results: Chol-Glc and the Chol-Glc/Chol-Sulf ratio differed significantly across the diagnostic groups, while Chol-Sulf did not. Logistic regression and ROC analyses revealed a limited standalone diagnostic accuracy for the individual biomarkers (all AUC < 0.6). Conclusions: Chol-Glc and the ratio exhibit disease-specific patterns relevant for subtype discrimination. Although insufficient as independent diagnostic tools, these markers may contribute to future multivariate diagnostic models for CD diagnosis. Full article

The skin is exposed to many environmental stressors, such as UV rays, pollution, and smoke, and psychological stress, which can compromise its structure and function. These factors can cause premature aging, weaken the skin barrier, worsen or induce pathological conditions such as acne and eczema, hyperpigmentation, and melanoma, and slow healing. Ellagic acid (EA) is a polyphenol with various pharmacological effects important for the treatment of skin conditions. It has antioxidant, anti-inflammatory, and depigmenting properties, and it inhibits the enzyme tyrosinase, involved in melanin production, helping reduce dark spots and exhibiting antiproliferative effects against melanoma cells. With its antioxidant effect, it protects the skin against photoaging, combats oxidative stress and signs of aging, such as wrinkles and loss of elasticity, and strengthens collagen and elastin. However, the main limits of EA are its low aqueous solubility, instability, and poor skin permeability that limit its clinical efficacy. This review focuses on EA formulations developed to overcome these limitations and improve its therapeutic effects for skin diseases. Nano-delivery systems such as vesicles, lipidic and polymeric nanoparticles, nanospheres, cyclodextrins, and nanogels have been reported alongside other innovative preparations such as biscuits, sponges, and nanosheets and conventional ones such as ointments, creams, and films. Full article

Mycobacterium abscessus (Mab) is a rapidly growing, non-tuberculous mycobacterium and opportunistic pathogen that causes lung and skin infections in immunocompromised individuals. In recent years, Mab has gained attention due to its resistance to multiple antibiotics and its ability to evade the immune response by transitioning into different morphotypes. Macrophages and neutrophils play key roles during the acute phase of infection and granuloma formation, utilising clearance mechanisms that affect the smooth and rough morphotypes differently. Despite considerable research, the inflammatory response elicited by Mab and its impact on disease outcomes remain not well understood. This perspective examines the interactions between Mab and immune cells, proposing potential receptors that may mediate Mab-driven immune communication. By drawing insights from immune evasion and signalling strategies employed by other mycobacterial species, it aims to deepen our understanding of Mab pathogenicity and to outline innovative approaches for infection control. Full article

Rare diseases are conditions that affect up to 65 people per 100,000 individuals. They are also known as “orphan diseases”, because they attract limited interest from researchers and pharmaceutical industries. Epidermolysis bullosa (EB), ichthyosis, Hailey–Hailey disease (HHD), Darier disease (DD), erythrokeratoderma, porokeratosis, inflammatory linear verrucous epidermal nevus (ILVEN) and piebaldism are examples of rare genetic skin diseases with few approved treatments. Topical treatments are the principal approach for rare dermatological diseases, and it can be useful to manage the symptoms or the patophysiology of these diseases. This study aimed to conduct a comprehensive review of the topical treatments of EB, ichthyosis, HHD, DD, erythrokeratodermias, porokeratosis, ILVEN, and piebaldism. The search was performed across the SciELO, MEDLINE^®/PubMed^®, Embase and Cochrane databases. This review identified porokeratosis, EB, and congenital ichthyosis as the rare genodermatoses with the highest number of reported studies and topical treatment options. In contrast, conditions such as piebaldism, erythrokeratodermia, and HHD have fewer reported topical interventions. For most rare genetic dermatological diseases, treatment aims to improve quality of life and control clinical signals and symptoms. Creams, gels, and ointments are frequently used as the main pharmaceutical approaches, and several pharmacological classes are employed, including keratolytics, retinoids, vitamin D analogs, topical corticosteroids, calcineurin inhibitors, and cytotoxic or antiproliferative agents. This review highlights the potential of off-label use of topical therapies as cost-effective alternatives in the treatment of rare genetic skin disorders. It also reinforces the critical role of compounded medicines in allowing for dose optimization, drug repurposing, and formulation adjustments, personalizing treatment to achieve improved therapeutic outcomes. Full article