Search Results (1,582)

Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa L., has emerged as a promising multifunctional agent in dermatology and cosmetic science. The review provides an updated synthesis of CBD’s topical therapeutic potential, challenges, and evolving regulatory frameworks. CBD exhibits diverse biological effects, including anti-inflammatory, antioxidant, antibacterial, analgesic, lipostatic, antiproliferative, moisturising, and anti-ageing properties through interactions with the skin’s endocannabinoid system (ECS), modulating CB1, CB2, TRPV channels, and PPARs. Preclinical and clinical evidence support its efficacy in managing acne, psoriasis (including scalp psoriasis), atopic and seborrheic dermatitis, and allergic contact dermatitis. CBD also relieves pruritus through neuroimmune modulation and promotes wound healing in conditions such as pyoderma gangrenosum and epidermolysis bullosa. In hair disorders such as androgenetic alopecia, it aids follicular regeneration. CBD shows promise in managing skin cancers (melanoma, squamous cell carcinoma, Kaposi sarcoma) and pigmentation disorders such as melasma and vitiligo. It enhances skin rejuvenation by reducing oxidative stress and boosting collagen and hydration. However, there are challenges regarding CBD’s physicochemical stability, skin penetration, and regulatory standardisation. As consumer demand for natural, multifunctional skincare grows, further research is essential to validate its long-term safety, efficacy, and optimal formulation strategies. Full article

Atopic dermatitis (AD) is a chronic inflammatory disorder with immune imbalance, including elevated IgE levels and mast cell activation mediated by Th2 cytokines, leading to allergic inflammation and impaired skin barrier function. Current treatment limitations highlight the need for safer and more effective AD alternatives. We aimed to evaluate the therapeutic effects of multi-strain probiotics, BCL-2 (comprising Lactiplantibacillus plantarum LRCC5264 and Bifidobacterium longum RAPO), in alleviating AD clinical signs and elucidate its underlying immunomodulatory mechanisms. In vitro, BCL-2 treatment significantly reduced IL-4 secretion in RBL-2H3 cells, with higher inhibitory effects than single-strain treatment. In vivo, BCL-2 (10⁶–10⁸ CFU/day) was orally administered for 28 days to AD-induced Nc/Nga mice. BCL-2 treatment improved the clinical signs and histopathological features of AD, including epidermal hypertrophy, hyperkeratosis, and mast cell infiltration (p < 0.05). It also reduced neutrophil and eosinophil counts and modulated cytokine and chemokine profiles, notably decreasing IL-17, IL-5, IL-6, TNF-α, IL-1β, TARC, and eotaxin, while increasing IL-10, IFN-γ, and IL-12 (p < 0.05). Among the tested concentrations, 10⁷ CFU exhibited the most effective immune modulation with no adverse effects on body weight. These findings demonstrate the therapeutic potential of BCL-2 in AD; however, further studies are required to validate its clinical relevance. Full article

The rising prevalence of pediatric food allergies represents a growing public health concern, with hospitalizations for food-induced anaphylaxis on the rise. Early cutaneous manifestations, particularly in the setting of atopic dermatitis (AD), may indicate sensitization via the skin—a critical route for allergen exposure in early life. Pediatric food allergies can be IgE-mediated, non-IgE-mediated, or mixed, with each type presenting distinct pathophysiological and clinical features. IgE-mediated reactions often involve acute urticaria and angioedema, while non-IgE forms, such as food protein-induced enterocolitis syndrome (FPIES), manifest with delayed gastrointestinal symptoms and limited skin involvement. AD is closely linked with food allergies, both in pathogenesis and symptom exacerbation, with a high prevalence of co-occurrence. Diagnosis primarily relies on clinical evaluation, supported by testing such as skin prick testing, serum IgE, and oral food challenges, though limitations exist in sensitivity and specificity. Management emphasizes allergen avoidance, symptom control, and multidisciplinary care. While many pediatric food allergies resolve with age, others persist or present chronically, necessitating long-term strategies. Coordinated management between allergy and dermatology is key to minimizing complications and supporting better long-term outcomes for affected children. Full article

Emerging evidence suggests a critical role of the gut microbiome in modulating systemic immune responses, with increasing relevance in dermatological diseases. Chronic spontaneous urticaria (CSU), traditionally viewed as an isolated cutaneous disorder, is now recognized as a systemic immune condition involving complex interactions between innate and adaptive immunity, mast cell dysregulation, and non-IgE-mediated pathways. This review explores the gut–skin axis as a unifying concept linking intestinal dysbiosis to inflammatory skin diseases, including atopic dermatitis, psoriasis, rosacea, and acne. Special emphasis is placed on CSU, where altered gut microbial composition, characterized by reduced diversity, depletion of short-chain fatty acid-producing bacteria, and expansion of Proteobacteria, may contribute to increased intestinal permeability, systemic immune activation via toll-like receptors, and heightened mast cell sensitivity. We discuss findings from animal models demonstrating that gut microbiota modulation can attenuate mast cell hyperreactivity and reduce urticarial symptoms. In parallel, we examine clinical evidence supporting the potential role of probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation as adjunctive strategies in CSU management. Despite promising findings, challenges remain in translating microbiome research into effective therapies due to interindividual variability, the complexity of host–microbiome interactions, and a lack of standardized protocols. Future research should focus on identifying predictive microbial patterns and developing personalized microbiome-targeted interventions. Understanding the bidirectional gut–skin relationship may open new therapeutic avenues beyond symptomatic treatment, positioning the microbiome as a novel target in CSU and related inflammatory dermatoses. Full article

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder characterized by immune dysregulation and epidermal barrier dysfunction. Advances in understanding the interplay of genetic predisposition, cytokine signaling, and environmental triggers have led to the emergence of targeted therapies. Although biologic agents such as dupilumab, tralokinumab, and lebrikizumab have revolutionized AD management, their high costs, injectable administration, and limited global accessibility highlight the need for alternative options. Small molecule therapies are gaining momentum as they target intracellular pathways central to AD pathogenesis and offer oral or topical administration routes. This review provides a comprehensive analysis of key agents including Janus kinase (JAK) inhibitors (upadacitinib, abrocitinib, baricitinib, ruxolitinib, delgocitinib), phosphodiesterase 4 (PDE4) inhibitors (crisaborole, difamilast, roflumilast, apremilast), as well as STAT6 degraders (KT621, NX3911), aryl hydrocarbon receptor modulators, histamine H4 receptor antagonists (adriforant, izuforant), and sphingosine-1-phosphate receptor modulators (etrasimod, BMS-986166). We summarize their mechanisms of action, pharmacological profiles, and pivotal clinical trial data, emphasizing their potential to address unmet therapeutic needs. Finally, we discuss safety concerns, long-term tolerability, and future directions for integrating small molecule therapies into precision treatment strategies for moderate-to-severe AD. Full article

Objectives: Atopic dermatitis (AD) is a long-term, recurring inflammatory skin condition characterized by impaired epidermal barrier function and abnormal immune system regulation. Pine pollen has traditionally been used for dermatological treatments, though its active components remain unclear. The primary objective of this study was to pinpoint the active constituents of pine pollen and elucidate its therapeutic effects against AD. Methods: The safety concentration ranges and protective efficacy of nine pine pollen constituents against 2,4-dinitrochlorobenzene (DNCB)-induced HaCaT cell damage were evaluated using the CCK-8 assay. Furthermore, models of DNCB-induced damage were established both in vitro (HaCaT cells) and in vivo (BALB/c mice) to explore the protective effects of the key functional component. Results: Our findings identified pine pollen polysaccharides (PPPS) as the principal bioactive constituent, characterized by a unique infrared absorption spectral profile and a sponge-like architecture with three-dimensional interconnected porous networks. In vitro, PPPS inhibited DNCB-induced decreases in cell viability, morphological abnormalities, oxidative stress, and apoptosis. In vivo, PPPS alleviated DNCB-induced skin lesions by attenuating epidermal hyperplasia, suppressing mast cell infiltration, inhibiting cell apoptosis, and downregulating the expression of IL-4 and IL-17A. Conclusions: This study provides evidence that PPPS from pine pollen can alleviate epidermal damage in AD, offering a novel therapeutic strategy for AD treatment. Full article

Lactate dehydrogenase (LDH) is a serum biomarker well known to correlate with disease severity in atopic dermatitis (AD). The aim of this study was to explore the cutaneous immune responses and the clinical profile of AD patients in relation to serum LDH levels. To this end, 47 untreated, adult patients with moderate-to-severe AD were stratified by median levels of serum LDH. Circulating memory T-cell responses to house dust mite (HDM) extract, in the presence of autologous lesional epidermal cells, were compared between AD subgroups. The LDH^high group exhibited significantly higher IL-13, IL-5 and IL-9 in vitro responses confined to the cutaneous lymphocyte-associated antigen (CLA)⁺ subset compared to LDH^low patients. Clinically, LDH^high patients were younger and exhibited more severe disease, elevated eosinophil counts in their blood, increased total and specific IgE levels in their plasma, and a higher prevalence of allergic rhinitis. Our data suggests that high LDH levels identify a subgroup of AD patients with a specific immune and clinical profile, and highlight the potential of LDH as a clinical parameter that may enable patient stratification for treatment selection. Full article

Background: Tralokinumab is an anti-IL-13 monoclonal antibody approved for moderate-to-severe atopic dermatitis (AD). While pivotal trials have demonstrated its efficacy, real-world data remain limited. Methods: We conducted a retrospective, multi-center study in the Basque Country including 109 adults with moderate-to-severe AD treated with tralokinumab. Clinical outcomes (EASI, IGA, BSA, DLQI, and NRS-pruritus/sleep) were assessed at baseline, weeks 16, 24, and 52. Results: EASI-75/90/100 responses were 66%/44%/16% at week 16 and increased to 83%/70%/34% at week 52. Pruritus NRS decreased from 7.1 to 3.1 and DLQI from 17.8 to 9.0. Adverse events were uncommon, with only three cases of conjunctivitis (two discontinued). Conclusions: Our findings support tralokinumab as a safe and effective long-term therapy for AD in routine practice. Results were consistent with, or superior to, pivotal and other RWE studies. Full article

Interleukin (IL)-15 is primarily known as a pro-inflammatory and anti-apoptotic cytokine, which stimulates the proliferation and survival of key immunocytes, including macrophages (MACs). Yet, it remains unclear how IL-15 specifically impacts MACs in intact human skin, particularly immunoinhibitory, IL-10-producing/secreting M2 MACs (CD206⁺IL-10⁺). In the current pilot study, we explored this in organ-cultured healthy human eyelid skin in the presence of IFNγ (100 IU/mL) to mimic a pro-inflammatory signaling milieu found in several chronic immunodermatoses. Quantitative immunohistomorphometry showed that IFNγ significantly reduced the number of CD68⁺MACs, M2 CD206⁺MACs, and immunoinhibitory CD206⁺IL-10⁺MACs. Moreover, co-administering recombinant human (rh) IL-15 after inducing inflammation by IFNγ largely reversed the IFNγ-induced decline in MAC populations. To investigate if this was mediated via the private IL-15 receptor alpha (IL-15Rα), we successfully silenced IL-15Rα in human skin ex vivo. Indeed, co-administration of IL-15Rα siRNA abrogated the rhIL-15 protection of M2 CD206⁺MACs against IFNγ, but not of the CD206⁺IL-10⁺MAC subpopulation. These pilot data suggest that IL-15 maintains immunoinhibitory M2 CD206⁺IL-10⁺MACs in human skin under IFNγ-dominated inflammatory conditions. Therefore, it deserves to be explored whether IL-15 or IL-15Rα agonists can exert therapeutic benefit in chronic inflammatory dermatoses by preserving the intracutaneous pool of anti-inflammatory dermal M2 MACs. Full article

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder affecting 10–20% of the population. In this study, we investigate the anti-inflammatory effect on the skin of eight compounds isolated from Digitalis purpurea L., using tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ)-stimulated human keratinocytes (HaCaT cells) and a three-dimensional (3D) reconstructed human skin model. Among the tested compounds, desrhamnosyl acteoside exhibited the most potent activity, significantly reducing the secretion of pro-inflammatory cytokines (IL-6, IL-8) and chemokines (CCL17, CCL22), suppressing the expression of inflammatory proteins, and modulating key signaling pathways, including NF-κB, JAK2/STAT1, and MAPK. Notably, this is the first report demonstrating that desrhamnosyl acteoside simultaneously targets all three pathways, indicating a multi-modal mechanism distinct from conventional single-target approaches. In the 3D skin model, desrhamnosyl acteoside further exhibited barrier-protective effects by downregulating inflammatory mediators and upregulating epidermal differentiation markers such as involucrin and loricrin. These findings reveal a previously uncharacterized phytochemical with dual anti-inflammatory and barrier-restorative activities, supporting its potential as a novel therapeutic candidate for AD and other inflammatory skin diseases. Full article

Chronic itch is a debilitating condition characterized by persistent pruritus lasting more than six weeks, significantly impairing quality of life. While the role of the immune system and neural circuits in itch is increasingly understood, the contribution of the skin microbiome, especially in non-atopic itch disorders, remains underexplored. This review synthesizes emerging evidence on how microbial dysbiosis contributes to chronic pruritus through multiple molecular pathways: disruption of skin barrier integrity, modulation of neuroimmune signaling axes, and direct activation of pruriceptors. We highlight recent studies identifying microbiome shifts in prurigo nodularis (PN) and lichen simplex chronicus (LSC), independent of atopic dermatitis (AD). We also evaluate advances in biologics and small-molecule therapeutics, exploring how targeted immune modulation may restore microbial balance and alleviate neuroinflammation. A systems biology approach integrating microbial genomics, neurobiology, and host immunity is critical to unraveling the complex interplay between host and microbes in chronic itch, particularly in understudied non-atopic conditions that disproportionately affect vulnerable populations. Full article

The complex interrelationship between the gut microbiota and the skin, commonly known as the “gut–skin axis” has become a crucial field of study for comprehending skin health and illness. Systemic immunity, inflammation, and metabolism are all modulated by this two-way communication mechanism, which ultimately affects skin homeostasis. Numerous dermatological disorders, such as rosacea, psoriasis, atopic dermatitis, and acne vulgaris, have been linked to dysbiosis in the gut microbiota. On the other hand, the composition of the gut microbiome may be impacted by skin disorders. Highlighting the important microbial metabolites and immunological processes involved in this interaction, this abstract examines the current understanding of the gut–skin axis. It also talks about the possible therapeutic benefits of using probiotics, synbiotics, and prebiotics to target the gut microbiota to treat and prevent skin conditions. Gaining insight into this intricate interaction opens up exciting possibilities for creating innovative, all-encompassing dermatological treatment strategies. Full article

Atopic dermatitis (AD), a common chronic inflammatory disease in children and adults, is often studied to find the best way to prevent or reduce its severity. One of the substances tested so far is vitamin D. The main aim of this paper was to determine whether vitamin D truly brings benefits to people with AD or whether its action is too insignificant to have clinical significance. The review covered articles—observational studies, several animal studies and randomized controlled trials (RCTs)—available in the PubMed database and published after 2019. Full-text manuscripts in English were used. Observational studies presented both therapeutic effects of vitamin D and its lack of influence on AD. They also determined that vitamin D receptor (VDR) polymorphism may indeed affect the occurrence and severity of this disease. Similarly, the results of vitamin D’s effect on AD are inconclusive in RCTs. Meanwhile, animal studies showed only the attenuation of disease symptoms in mice. The still-growing number of studies on vitamin D and its association with AD, due to many internal and external distorting factors, has not been able to provide us with definitive results. It is necessary to conduct further appropriately designed large-scale studies, including long-term observation. Full article

Mount Etna, located on the eastern coast of Sicily, is Europe’s most active volcano. Over the past five years, it has experienced numerous significant eruptive episodes, with the most recent occurring in August 2024. During this event, substantial amounts of volcanic ash were dispersed over densely populated areas, particularly in the province of Catania. Environmental factors, such as volcanic eruptions, are known to influence inflammatory skin conditions, including atopic dermatitis. We analyzed a cohort of patients with atopic dermatitis who were exposed to volcanic ash during the Mount Etna eruption in August 2024, aiming to evaluate the impact of the eruption on respiratory and cutaneous symptoms, treatment response, use of protective equipment, and changes in EASI scores over an eight-week period. A total of 67 Caucasian atopic dermatitis patients (mean age 41.2) were assessed after a volcanic eruption. Symptom worsening occurred in 58.9% (respiratory) and 26.9% (skin) of patients. EASI scores significantly increased (p < 0.05). No clinical difference was found between treatment types or mask use, which did not prevent symptom exacerbation. Volcanic ash exposure significantly worsened respiratory and skin symptoms in atopic dermatitis patients, underscoring the need for improved protective measures and further research on environmental triggers of chronic inflammatory conditions. Full article

Atopic dermatitis (AD) remains a therapeutic challenge due to the limitations of current treatments, creating demand for safer multi-target alternatives to corticosteroids. Our integrated study establishes Hibiscus syriacus L. (H. syriacus) as a mechanistically validated solution through computational and biological validation. The fraction’s two main compounds, linoleic acid and palmitic acid, exhibit favorable drug-like properties including high lipophilicity (LogP 5.2) and 87% oral absorption. Molecular docking collectively predicts comprehensive NF-κB pathway blockade. Experimental validation showed that the fraction (100 μg/mL) inhibited LPS-induced nitric oxide (NO) by 78% and TNF-α/IFN-γ-induced reactive oxygen species (ROS) by 40%, while significantly downregulating the chemokines TARC (73%) and MDC (71%). In DNCB-induced AD mice, the treatment (200 mg/kg/day) produced a 62% improvement in clinical severity scores, reduced serum IgE by 27%, decreased transepidermal water loss by 36%, and doubled skin hydration while normalizing pH levels from the alkaline to physiological range. While both treatments reduced DNCB-induced epidermal hyperplasia, H. syriacus (62.9% reduction) restored the normal thickness without pathological thinning, a critical advantage over corticosteroids that cause atrophy. This dual-action therapeutic achieves corticosteroid-level anti-inflammatory effects while restoring skin barrier integrity to normal levels and avoiding corticosteroid-associated atrophy, positioning it as a next-generation AD treatment. Full article