Chronic Inflammatory Skin Disease Research Articles

Abrocitinib-associated adverse events: a real-world pharmacovigilance study using the FAERS database

ABSTRACT Background Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Janus kinase (JAK) modulates cytokines involved in AD pathophysiology, and JAK inhibitors have emerged as effective pharmacotherapeutic remedies for AD. Abrocitinib, an oral selective inhibitor of JAK1, is indicated for the management of moderate-to-severe AD. The current study evaluated the adverse events (AEs) associated with abrocitinib in a real-world setting. Methods To quantify the signals of abrocitinib-associated AEs, we used the US Food and Drug Administration Adverse Event Reporting System (FAERS) for this pharmacovigilance study with two established pharmacovigilance methods. Results A total of 1071 AEs of abrocitinib were investigated as the primary suspected from the FAERS to detect and characterize relevant safety signals. The analysis revealed 85 signals for abrocitinib. The most common AE for abrocitinib was drug ineffective. The signal strength of eczema herpeticum was 515.87 (277.80–957.98) and 510.59 (5148.65) and exhibited the highest strength for abrocitinib. Rare AEs such as aggravated condition, pruritus, and hypersensitivity were not listed on the label, and attention to these AEs is required. Conclusion The analysis of the AE signals may provide support for clinical monitoring and risk identification of abrocitinib.

Trifarotene: a new chapter in the treatment of acne. An overview of the data on efficacy and safety profile of a fourth-generation retinoid

Vulgar acne is a chronic inflammatory skin disease that has a significant impact on patients' quality of life. The search for new highly effective and treatments with favorable safety profile remains relevant due to the high incidence in the population. The launch of a 4th generation retinoid, trifarotene, which has a selective mechanism of action on RAR-γ (γ-retinoic acid receptors agonist), represents a new era in topical therapy of acne vulgaris and is of particular interest to practical healthcare. A systematic literature overview in PubMed, Google Scholar, and ClinicalTrials.Gov databases was conducted to evaluate the mechanism of action, efficacy, and safety profile of the selective 4th generation retinoid, trifarotene 50 µg/g (0,005%) in dosage form topical cream. In a systematic overview, 12 contemporary studies (2015–2023) were selected confirming the high efficacy of trifarotene in protocols for the treatment of acne vulgaris with localization on both facial and truncal skin. The drug demonstrates a unique ability to modulate cell adhesion, optimize transepidermal water loss and reduce the activity of membrane metalloendopeptidases, which determines its proven efficacy. Trifarotene, an innovative 4th generation topical retinoid approved by the FDA in 2019 for the treatment of acne in patients over 9 years of age, opens new possibilities in the treatment of acne vulgaris. Its selective activity to RAR-γ receptors, proven efficacy and favorable safety profile make it a promising agent in therapeutic practice.

Mesenchymal stem cell-derived exosomes decrease Hyperplasia in Psoriasis by inducing transforming growth factor β2 (TGF-β2).

Psoriasis, a chronic inflammatory skin disease, is increasingly effectively managed with the targeted immunotherapy; however, long-term immunotherapy carries health risks, and loss of response. Therefore, we need to develop the alternative treatment strategies. Mesenchymal stem/stromal cell (M.S.C.) exosomes stand out for their remarkable immunomodulatory properties, gaining widespread recognition. This study investigated whether M.S.C. exosomes can reduce psoriasis-induced hyperplasia by inducing Transforming Growth Factor beta 2 (TGF-beta2) signaling. Exosomes were isolated from M.S.C.s by ultracentrifugation. Then, scanning electron microscopy was used for the morphology of exosomes. To ascertain the exosome concentration, the Bradford test was used. To ascertain the cellular toxicity of exosomes in Human Umbilical Vein Endothelial Cells ( H.U.V.E.C), an MTT experiment was then conducted. Real-time PCR was used to quantify TGF beta2 expression levels, whereas an ELISA immunosorbent assay was used to determine the protein concentration of TGF beta2. In this study, the exosomes of 15-30nm in size that were uniform, and cup-shaped were isolated. Moreover, the IC50 value for this Treatment was calculated to be 181.750µg/ml. The concentration of TGF-β2 gene in the target cells significantly increased following Treatment with the exosomes. Furthermore, the expression level of the studied gene significantly increased due to the Treatment. Upregulating the expression of TGF-β2 in psoriatic cells via TGF-β2 signaling is one way exosomes can help reduce hyperplasia.

Association between exposure to ambient air pollution, meteorological factors and atopic dermatitis consultations in Singapore—a stratified nationwide time-series analysis

Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting approximately 20% of children globally. While studies have been conducted elsewhere, air pollution and weather variability is not well studied in the tropics. This time-series study examines the association between air pollution and meteorological factors with the incidence of outpatient visits for AD obtained from the National Skin Centre (NSC) in Singapore. The total number of 1,440,844 consultation visits from the NSC from 2009 to 2019 was analysed. Using the distributed lag non-linear model and assuming a negative binomial distribution, the short-term temporal association between outpatient visits for AD and air quality and meteorological variability on a weekly time-scale were examined, while adjusting for long-term trends, seasonality and autocorrelation. The analysis was also stratified by gender and age to assess potential effect modification. The risk of AD consultation visits was 14% lower (RR10th percentile: 0.86, 95% CI 0.78–0.96) at the 10th percentile (11.9 µg/m3) of PM2.5 and 10% higher (RR90th percentile: 1.10, 95% CI 1.01–1.19) at the 90th percentile (24.4 µg/m3) compared to the median value (16.1 µg/m3). Similar results were observed for PM10 with lower risk at the 10th percentile and higher risk at the 90th percentile (RR10th percentile: 0.86, 95% CI 0.78–0.95, RR90th percentile: 1.10, 95% CI 1.01–1.19). For rainfall for values above the median, the risk of consultation visits was higher up to 7.4 mm in the PM2.5 model (RR74th percentile: 1.07, 95% CI 1.00–1.14) and up to 9 mm in the PM10 model (RR80th percentile: 1.12, 95% CI 1.00–1.25). This study found a close association between outpatient visits for AD with ambient particulate matter concentrations and rainfall. Seasonal variations in particulate matter and rainfall may be used to alert healthcare providers on the anticipated rise in AD cases and to time preventive measures to reduce the associated health burden.

Oral administration of Lactobacillus delbrueckii subsp. lactis LDL557 attenuates airway inflammation and changes the gut microbiota in a Der p-sensitized mouse model of allergic asthma.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder affecting up to 20% of children in developed countries. Although probiotics have shown promise as adjuvant treatments for AD, their mechanisms are not well understood. Building upon our previous studies, we investigated whether Lactobacillus gasseri and its moonlighting glyceraldehyde 3-phosphate dehydrogenase (GAPDH), namely LGp40, could be beneficial in AD management. In AD mouse models (SKH and C57BL/6J mice) with ovalbumin (OVA) and Dermatophagoides pteronyssinus (Der p) allergens, aligning with the "outside-in" and "inside-out" hypotheses, we administered L. gasseri orally and LGp40 intraperitoneally to investigate their protective effects. The evaluation involved measuring physiological, pathological, and immune function parameters. To delve deeper into the detailed mechanism of LGp40 protection in AD, additional assays were conducted using human skin keratinocytes (HaCaT) and monocytes (THP1) cell lines. L. gasseri and LGp40 enhanced skin barrier function and increased skin moisture retention. They also led to reduced infiltration of Langerhans cells in the dermis and mitigated skewed Th2 and Th17 immune responses. Moreover, LGp40 inhibited allergen-induced keratinocyte apoptosis through the blockade of the caspase-3 cascade and reduced the NLR family pyrin domain containing 3 (NLRP3) inflammasome in macrophages. These inhibitions were achieved through the activation of the peroxisome proliferator-activated receptor gamma (PPARγ) pathway. The results of this study provide a novel insight into the mechanism of action of probiotics in the prevention and treatment for allergic disorders through the moonlighting GAPDH protein.

Atopic dermatitis is associated with an increased risk of cardiovascular diseases: A large-scale, propensity-matched US-based retrospective study.

Atopic dermatitis is a chronic relapsing inflammatory skin disease characterized by intense itch impacting heavily on patients' and caregivers' quality of life. Its clinical presentation is accompanied by a variety of type 2 comorbidities, e.g. asthma, hay fever, food allergies. However, current data on cardiovascular comorbidities are inconsistent. To identify risk of cardiovascular diseases in patients with atopic dermatitis. Data from Electronic Health Records (EHRs) of 1,070,965 atopic dermatitis patients and equally propensity score matched controls were retrieved from the US Collaborative Network part of the federated TriNetX network. Hazard ratios for risk of onset of cardiovascular diseases with a prevalence of ≥1% in both cohorts within 20 years after diagnosis were determined. A total of 55 cardiovascular diseases belonging to 8 major cardiovascular groups were identified. Of those, 53 diagnoses displayed a significantly increased risk in atopic dermatitis patients. Different diagnoses of heart failure and heart disease were found most often, followed by valve insufficiencies, arrhythmia, tachycardia, atrial fibrillation, flutter, but also MACE and venous thromboembolism. The individual diagnoses venous insufficiency, atherosclerosis of native arteries of the extremities, and unspecified diastolic (congestive) heart failure displayed highest hazard ratios. Atopic dermatitis is associated with an increased risk for multiple cardiovascular diseases.

Thymic Stromal Lymphopoietin Activates Mouse Dendritic Cells Through the JAK/SYK Pathway in Promoting Th17 Response in Psoriasis.

Psoriasis is a chronic inflammatory skin disease that has no cure. While the specific cause of psoriasis is unknown, interactions between immune cells and inflammatory cytokines are believed to be important in its pathogenesis. Thymic stromal lymphopoietin (TSLP) is a cytokine produced by epithelial cells that profoundly affects dendritic cells (DCs) and is involved in allergy and inflammatory diseases. In some studies, its expression is higher in the skin of psoriasis patients, whereas it is increased in treated psoriasis patients when compared with untreated patients in others. To investigate the role of TSLP in the pathogenesis of psoriasis. In vitro and in vivo study. To investigate the effect of TSLP on psoriasis in vivo, a mouse psoriasis model and shRNA targeting TSLP to reduce its expression were used. Mouse primary bone marrow dendritic cells (BMDCs) were cultured in vitro and used to investigate the signaling pathways activated by TSLP. Results: We found that reducing TSLP expression in psoriasis skin alleviated disease severity. TSLP activated the Janus kinase (JAK)/SYK pathway in psoriatic skin. In vitro studies with BMDCs demonstrated that TSLP increased DC maturation through the JAK/SYK pathway and activated DCs-secreted cytokines that stimulated CD4+ T cells to develop into T helper 17 (Th17) cells by activating STAT3 signaling. The JAK/SYK pathway inhibitor reduced the effect of TSLP on activating BMDCs and promoting Th17 differentiation by CD4+ T cells. These findings indicated that TSLP exerted its immune-modulating effect in psoriasis through the JAK/SYK pathway.

Foxp3+ Treg control allergic skin inflammation by restricting IFN-γ-driven neutrophilic infiltration and NETosis

BackgroundAtopic dermatitis (AD), a chronic inflammatory skin disease with T cell activation as a key feature, in which Th2 cell–mediated responses play a pivotal role. Regulatory T cells (Treg) are central immune cells that restrict autoimmunity and inflammation in the body. Patients with immune dysregulation, polyendocrinopathy, or enteropathy X-linked syndrome, an immune disease characterized by a deficiency in Treg, develop skin inflammation and allergic disorders, indicating that Treg play a crucial role in the development of allergic skin inflammation. Objectivewe investigated the underlying mechanisms by which Treg control cutaneous allergic inflammation. MethodsAn allergic skin inflammation mouse model was constructed using MC903, and Treg-depleted mouse model was constructed using diphtheria toxin. Neutralization of IFN-γ was constructed using anti-mouse-IFN-γ mouse antibody. Neutrophil infiltration was analyzed by flow cytometry and immunohistochemistry. Neutrophil extracellular traps(NETs), a process called NETosis, were detected using immunofluorescence. In vitro neutrophil stimulation and immunocytochemistry was conducted to demonstrate the effect of IFN-γ on NETosis. ResultsThe depletion of Foxp3+ Treg led to significantly exacerbated AD-like skin inflammation, including increased recruitment of neutrophils and expression of Th1 cytokine IFN-γ. Neutrophil infiltrating in skin of Treg-depleted mice released more NETs than wild type. Neutralization of IFN-γ abolished neutrophil infiltration and NETosis in Treg-depleted mice. Neutrophils stimulated with IFN-γ were more prone to release NETs in vitro. Finally, Foxp3+ Treg control cutaneous allergic inflammation by regulating IFN-γ-driven neutrophilic infiltration and NETosis. ConclusionOur results highlight the previously underestimated Treg-IFN-γ-neutrophil inflammatory axis.

Belastung durch gestörten Schlaf und dessen Verbesserung durch topische Behandlung bei Psoriasis und atopischer Dermatitis

Patients with chronic inflammatory skin diseases often suffer from sleep disturbances. However, objective data on sleep architecture, especially to evaluate potential overall influences under therapy, are lacking. Pilot study on sleep quality changes including psoriasis and atopic dermatitis patients before and 2weeks after intensive topical treatment. In addition to disease activity rating, patient-rated outcomes for itch severity and sleep quality and polygraphy was performed before and after topical therapy. 14 psoriasis, eleven atopic dermatitis patients (10 female, 15 male) with a mean age of 49 years were included. Disease activity scores (EASI and PASI) were significantly reduced with topical therapy after 2weeks (p<0.001). Pruritus intensity (NRS) showed a significant influence on deep sleep, which resolved after therapy. Insomnia severity significantly decreased (r>0.50, p<0.05) and daytime sleepiness showed a significant reduction in 40% of patients. N3 (deep sleep) and REM sleep significantly improved, showing a strong effect (r>0.50). The apnea-hypopnea index decreased in one of four patients independent of the individual BMI. Through polygraphy, we demonstrated impaired sleep patterns in psoriasis and atopic dermatitis patients with itch as a relevant factor and beyond that, rapid sleep improvement under 2weeks of topical treatment.

Evaluation of the efficacy and safety of cold laser (Diode 808 nm) therapy in the treatment of localized plaque psoriasis: clinical, dermoscopic and ultrastructural study

Background Psoriasis is a chronic, recurring, and immune-mediated inflammatory skin disease. Throughout the period of the last few decades, phototherapy has become widely used in treating stable psoriatic lesions. For the treatment of psoriasis, several light/laser therapies with distinct modes of action have been developed. Cold laser therapy might be an effective therapeutic choice for localized plaque psoriasis. Objective To assess the safety and efficacy of cold laser therapy clinically and microscopically in localized plaque psoriasis treatment. Patients and methods 40 patients with localized mild plaque psoriasis were selected from the Dermatology and Venereology outpatient clinic–Tanta University Hospitals and enrolled in the clinical trial. They were treated by cold laser 808 nm wavelength (Endolaser 422, Enraf–nonious B.V. Rotterdam, Netherlands) one session for 10 min on each plaque twice weekly separated by 2 days until clinical cure or for a maximum of 8 weeks. Evaluation was done immediately after the last session by taking the average of three blinded dermatologists of the photos, the modified Psoriasis Area and Severity Index [mPASI], dermoscopic examination, patients’ satisfaction scale and histopathological and electron microscopic examination of punch biopsy specimens taken before and after the end of treatment from psoriatic lesions in four patients only. Results There was a statistically significant clinical improvement after the end of treatment compared with before treatment as 16 patients (40%) showed excellent improvement, 8 patients (20%) showed good improvement, 9 patients (22.5%) showed mild improvement, and 7 patients (17.5%) showed poor improvement. As regard mPASI, a statistically significant decrease in mPASI was found after the end of treatment (P&lt;0.001). Regarding dermoscopic examination, a statistically significant reduction in the percentage of patients showing dermoscopic red dots and white scales after the end of treatment (P&lt;0.01). As regard the patients’ satisfaction scale, 82.5% of patients were satisfied from the results. Histopathological and ultrastructural evaluation revealed normalization of the psoriatic microscopic changes with cold laser. Conclusion The use of cold laser therapy for the management of localized mild plaque psoriasis is safe, tolerable, effective, and can be used as an alternative therapy for psoriasis.

Epigenetic and biological age acceleration in a pediatric cohort of atopic dermatitis

BackgroundAtopic dermatitis is a chronic inflammatory skin disease resulting from the complex interplay of genetic and environmental factors, meriting exploration using temporally-dynamic biomarkers. DNA methylation-based algorithms have been trained to accurately estimate biological age, and deviation of predicted age from true age (epigenetic age acceleration) has been implicated in several inflammatory diseases, including asthma. ObjectiveTo determine the role of epigenetic and biological aging, telomere length, and epigenetically-inferred abundance of seven inflammatory biomarkers in atopic dermatitis. MethodsWe performed DNA methylation-based analyses in a pediatric atopic dermatitis cohort (n=24, mean age 2.56±0.28y) and age-matched healthy subjects (n=24, mean age 2.09±0.15y) derived from blood, using five validated algorithms that assess epigenetic (Horvath, Skin&Blood) and biological age (PhenoAge, GrimAge), telomere length (TelomereLength), and inflammatory biomarker levels. ResultsEpigenetic and biological age, but not telomere length, were accelerated in atopic dermatitis patients for four algorithms: Horvath (+0.88 years; 95%CI 0.33-1.4; p=2.3x10-3), Skin&Blood (+0.95 years; 95%CI 0.67-1.2; p=1.8x10-8), PhenoAge (+8.2 years; 95%CI 3.4-13.0; p=1.3x10-3), and GrimAge (+1.8 years 95%CI 0.22-3.3; p=0.026). Moreover, patients had increased levels of beta-2-microglobulin (+47,584.4 ng/ml; p=0.029), plasminogen activation inhibitor 1 (+3,432.9 ng/ml; p=1.1x10-5) and cystatin C (+31,691 ng/ml; p=4.0x10-5), while levels of tissue inhibitor metalloproteinase 1 (-370.7 ng/ml; p=7.5x10-4) were decreased versus healthy subjects. ConclusionDNA methylation changes associated with epigenetic and biological aging, and inflammatory proteins appear early in life in pediatric atopic dermatitis and may be relevant clinical biomarkers of pathophysiology.

How to Prevent Atopic Dermatitis (Eczema) in 2024: Theory and Evidence

Atopic dermatitis (AD) or eczema is a chronic inflammatory skin disease characterized by dry, itchy, and inflamed skin. We review emerging concepts and clinical evidence addressing the pathogenesis and prevention of atopic dermatitis. We review several interventions ranging from skin barrier enhancement strategies; probiotics, prebiotics, and synbiotics, and conversely, antimicrobial exposure; vitamin D and omega fatty acid supplementation; breastfeeding and hydrolyzed formula; house dust mite avoidance and immunotherapy. We appraise the available evidence base within the context of the GRADE approach. We also contextualize our findings in relation to concepts relating atopic dermatitis and individual-patient allergic life trajectories versus a linear concept of the atopic march and provide insights into future knowledge gaps and clinical trial design considerations that must be addressed in future research. Finally, we provide implementation considerations to detect population-level differences in AD risk. Major international efforts are required to provide definitive evidence regarding what works, and what does not, for preventing AD.

Cardiovascular Considerations and Implications for Treatment in Psoriasis: An Updated Review.

Psoriasis, a prevalent chronic inflammatory skin disorder affecting 2-3% of the global population, has transcended its dermatological confines, revealing a profound association with cardiovascular diseases (CVD). This comprehensive review explores the intricate interplay between psoriasis and cardiovascular system, delving into genetic links, immune pathways, and adipose tissue dysfunction beyond conventional CVD risk factors. The pathophysiological connections unveil unique signatures, distinct from other inflammatory skin conditions, in particular psoriasis-specific genetic polymorphisms in IL-23 and TNF-α have consistently been linked to CVD. The review navigates the complex landscape of psoriasis treatments, addressing challenges and future directions in particular relevance to CVDs in psoriasis. Therapeutic interventions, including TNF inhibitors (TNFi), present promise in reducing cardiovascular risks, and methotrexate could constitute a favourable choice. Conversely, the relationship between IL-12/23 inhibitors and cardiovascular risk remains uncertain, while recent evidence indicates that Janus kinase inhibitors may not carry CVD risks. Emerging evidence supports the safety and efficacy of IL-17 and IL-23 inhibitors in patients with CVDs, hinting at evolving therapeutic paradigms. Lifestyle modifications, statins, and emerging therapies offer preventive strategies. Dedicated screening guidelines for CVD risk assessment in psoriasis are however lacking. Further, the impact of different disease phenotypes and treatment hierarchies in cardiovascular outcomes remains elusive, demanding ongoing research at the intersection of dermatology, rheumatology, and cardiology. In conclusion, unraveling the intricate connections between psoriasis and CVD provides a foundation for a holistic approach to patient care. Collaboration between specialties, advancements in screening methodologies, and a nuanced understanding of treatment impacts are essential for comprehensive cardiovascular risk management in individuals with psoriasis.

SERPINB3/B4 is Increased in Psoriasis and Rosacea Lesions and has Pro-inflammatory Effects in Mouse Models of these Diseases

Psoriasis and rosacea are both chronic inflammatory skin disorders resulted from aberrant keratinocyte-immune cell crosstalk, but the common molecular foundations for these two conditions are poorly understood. Here, we reveal that both psoriasis and rosacea patients, as well as their mice models, have significantly elevated expressions of SERPINB3/B4 (members of serine protease inhibitor) in the lesional skin. Skin inflammation in mice that resembles both psoriasis and rosacea is prevented by SERPINB3/B4 deficiency. Mechanistically, we demonstrate that SERPINB3/B4 positively induces NF-κB signaling activation, thereby stimulating disease-characteristic inflammatory chemokines and cytokines production in keratinocytes, and promoting the chemotaxis of CD4+ T cells. Our results suggest that, in keratinocytes, SERPINB3/B4 may be involved in the pathogenesis of both psoriasis and rosacea by stimulating NF-κB signaling, and they indicate a possible treatment overlap between these two diseases.

Formulation characterization of lecithin organogel as topical drug delivery system for psoriasis: In-vitro permeation and preclinical evaluation.

Psoriasis is a chronic inflammatory and proliferative skin disease that causes pathological skin changes and has a substantial impact on the quality of patient life. Apremilast was approved by the US Food and Drug Administration as an oral medication for psoriasis and is beneficial in mild to moderate conditions for chronic usage. However, 5%-7% of withdrawals were reported due to severe side effects. To address the issue, a localized drug delivery strategy via the topical route may be a viable approach. However, poor physicochemical properties make it vulnerable to passing through the skin, requiring a specialized drug delivery system to demonstrate its full potential via a topical route like lecithin organogel. The formulation was optimized by screening the suitable lecithin type and non-polar solvents based on the gel formation ability of lecithin and the solubility of apremilast in the solvent. The pseudo-ternary diagram was used to optimize the water content required to form the gel. The optimized gel was found to be shear thinning characterized for rheological parameters, in-vitro diffusion studies, and in-vitro skin distribution studies. Preclinical studies in Imiquimod-induced mice showed a better reduction in severity index, cytokine levels, and epidermal hyperplasia from the lecithin organogel group compared to the apremilast oral administration and marketed standard topical gel group. Based on these results, lecithin organogel can be considered a promising approach to deliver molecules like apremilast by topical route in psoriatic-like conditions.

Atopic March; The Skin is the Clue

Atopic Dermatitis (AD) is a chronic relapsing inflammatory skin disease characterized by recurrent eczematous skin lesions and intense itching. Globally, it affects 10-30% of children and 2-10% of adults, with a two- to three-fold increase in prevalence noted over the last decades

A Novel Recombinant Human Filaggrin Segment (rhFLA-10) Alleviated a Skin Lesion of Atopic Dermatitis

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

Research progress on the role of macrophages in acne and regulation by natural plant products.

Acne vulgaris is one of the most common skin diseases. The current understanding of acne primarily revolves around inflammatory responses, sebum metabolism disorders, aberrant hormone and receptor expression, colonization by Cutibacterium acnes, and abnormal keratinization of follicular sebaceous glands. Although the precise mechanism of action remains incompletely understood, it is plausible that macrophages exert an influence on these pathological features. Macrophages, as a constituent of the human innate immune system, typically manifest distinct phenotypes across various diseases. It has been observed that the polarization of macrophages toward the M1 phenotype plays a pivotal role in the pathogenesis of acne. In recent years, extensive research on acne has revealed an increasing number of natural remedies exhibiting therapeutic efficacy through the modulation of macrophage polarization. This review investigates the role of cutaneous macrophages, elucidates their potential significance in the pathogenesis of acne, a prevalent chronic inflammatory skin disorder, and explores the therapeutic mechanisms of natural plant products targeting macrophages. Despite these insights, the precise role of macrophages in the pathogenesis of acne remains poorly elucidated. Subsequent investigations in this domain will further illuminate the pathogenesis of acne and potentially offer guidance for identifying novel therapeutic targets for this condition.

Comparative analysis of whole plant, flower and root extracts of Chamomilla recutita L. and characteristic pure compounds reveals differential anti-inflammatory effects on human T cells.

Chronic inflammation is a hallmark of chronic wounds and inflammatory skin diseases. Due to a hyperactive and prolonged inflammation triggered by proinflammatory immune cells, transitioning to the repair and healing phase is halted. T cells may exacerbate the proinflammatory milieu by secreting proinflammatory cytokines. Chamomilla recutita L. (chamomile) has been suggested for use in several inflammatory diseases, implying a capability to modulate T cells. Here, we have characterized and compared the effects of differently prepared chamomile extracts and characteristic pure compounds on the T cell redox milieu as well as on the migration, activation, proliferation, and cytokine production of primary human T cells. Phytochemical analysis of the extracts was carried out by LC-MS/MS. Primary human T cells from peripheral blood (PBTs) were pretreated with aqueous or hydroethanolic chamomile extracts or pure compounds. Subsequently, the effects on intracellular ROS levels, SDF-1α induced T cell migration, T cell activation, proliferation, and cytokine production after TCR/CD3 and CD28 costimulation were determined. Gene expression profiling was performed using nCounter analysis, followed by ingenuity pathway analysis, and validation at protein levels. The tested chamomile extracts and pure compounds differentially affected intracellular ROS levels, migration, and activation of T cells. Three out of five differently prepared extracts and two out of three pure compounds diminished T cell proliferation. In line with these findings, LC-MS/MS analysis revealed high heterogeneity of phytochemicals among the different extracts. nCounter based gene expression profiling identified several genes related to T cell functions associated with activation and differentiation to be downregulated. Most prominently, apigenin significantly reduced granzyme B induction and cytotoxic T cell activity. Our results demonstrate an anti-inflammatory effect of chamomile- derived products on primary human T cells. These findings provide molecular explanations for the observed anti-inflammatory action of chamomile and imply a broader use of chamomile extracts in T cell driven chronic inflammatory diseases such as chronic wounds and inflammatory skin diseases. Importantly, the mode of extract preparation needs to be considered as the resulting different phytochemicals can result in differential effects on T cells.

Cost-effectiveness analysis of abrocitinib compared with standard of care in adult moderate-to-severe atopic dermatitis in Japan.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a significant clinical, economic, and human burden. The JAK1 Atopic Dermatitis Efficacy and Safety (JADE) program's Phase 3 trials demonstrated that as a treatment for moderate-to-severe AD in adults with previous exposure to immunotherapy, abrocitinib showed superior efficacy and safety compared with standard of care (SoC), consisting of topical corticosteroids. This study assessed the cost-effectiveness of abrocitinib with SoC versus SoC alone for this patient population in Japan from a societal perspective. A hybrid decision tree and Markov model were used to capture the initial treatment and long-term maintenance phases. Clinical inputs at 16 weeks were obtained through a Bayesian network meta-analysis of four pivotal trials from the JADE program. Clinical inputs at 52 weeks were derived from the JADE EXTEND trial. Response-specific utility inputs were obtained from published literature. Resource use, costs, and productivity inputs were gathered from Japanese claims analysis, literature, public documents, and expert opinion. Costs and quality-adjusted life years (QALYs) were discounted at 2.0% per year and incremental cost-effectiveness ratios (ICERs) were calculated. Sensitivity and scenario analyses were performed to validate the base case results and explore a payer perspective. Over a lifetime horizon and with the base-case societal perspective, abrocitinib produced a mean gain of 0.75 QALYs, incremental costs of JPY (¥) 2 270 386 (USD [$] 17 265.6), and a resulting ICER of ¥3 034 514 ($23 076.5) per QALY compared with SoC. From a payer perspective, the incremental costs increased to ¥4 476 777 ($34 044.4), with an ICER of ¥5 983 495 ($45 502.6) per QALY. The results were most sensitive to treatment-specific, response-based utility weights, drug costs, and productivity-related inputs. From a Japanese societal perspective, abrocitinib demonstrated superior QALYs and with a willingness-to-pay threshold of ¥5 000 000 ($38 023.4) per QALY, can be considered cost-effective compared with SoC as a treatment for moderate-to-severe AD in adult patients with previous immunosuppressant exposure.