Search Results (44)

This study focused on the poly(DL-lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(DL-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer, which was recently reported as a novel material for polymeric nanoparticles to replace poly(DL-lactide-co-glycolide) (PLGA) as a drug carrier for prednisolone (PSL), and aimed to evaluate the efficacy of PSL-loaded PLGA-PEG-PLGA nanoparticles (NPs) against allergic contact dermatitis (ACD). PSL-loaded PLGA-PEG-PLGA NPs were prepared using the nanoprecipitation method, and their particle size distribution and mean particle size were measured using dynamic light scattering. 1-Fluoro-2,4-dinitrobenzene (DNFB) was used to create a mouse model of contact hypersensitivity (CHS). PSL-loaded PLGA-PEG-PLGA NPs were administered before sensitization with DNFB, and the therapeutic effect was evaluated by quantifying intracutaneous TNF-α and IL-4 levels suing ELISA. When PSL-loaded PLGA-PEG-PLGA NPs were administered before sensitization, TNF-α expression and IL-4 statements were significantly lower in the PSL-loaded PLGA-PEG-PLGA NP group than in the non-treated group. No significant difference was observed between the PSL-loaded PLGA-PEG-PLGA NP and PSL-loaded ointment groups, even though the steroid dose was 40 times lower than in the PSL-containing ointment. These results suggest that PSL-loaded PLGA-PEG-PLGA NPs may have a better effect in the treatment of ACD than PSL-loaded PLGA NPs. Full article

Allergic contact dermatitis (ACD) is an immunologic reaction to a dermal chemical exposure that, once triggered in an individual, will result in an allergic response following subsequent encounters with the allergen. Air Force epidemiological consultations have indicated that aircraft structural maintenance workers may experience ACD at elevated rates compared to other occupations. We aimed to better understand the utility of non-animal testing methods in characterizing the sensitization potential of chemicals used during Air Force operations by evaluating the skin sensitization hazard of Air Force-relevant chemicals using new approach methodologies (NAMs) in a case study. We also evaluated the use of NAM data to develop preliminary candidate surface guidelines (PCSGs, maximum concentrations of chemicals on workplace surfaces to prevent induction of dermal sensitization) for chemicals identified as sensitizers. NAMs for assessing skin sensitization, including in silico models and experimental assays, were leveraged into an integrated approach to predict sensitization hazard for 19 chemicals. Local lymph node assay effective concentration values were predicted from NAM assay data via previously published quantitative models. The derived values were used to calculate PCSGs, which can be used to compare the presence of these chemicals on work surfaces to better understand the risk of Airmen developing ACD from occupational exposures. Full article

Recent studies have emphasized the impact of gut microbiota on skin health, but the reverse, how skin diseases affect gut homeostasis, has received less attention. Allergic contact dermatitis (ACD), a common skin disorder affecting one in four people worldwide, can be accompanied by intestinal disturbances. To explore this, we used an experimental model of ACD to investigate the intestinal changes induced by the disease. Parameters assessed included intestinal microbiota, short-chain fatty acids (SCFAs), gene expression related to intestinal permeability, inflammatory cytokines, and mucus production. To evaluate potential therapeutic interventions, the probiotic Bifidobacterium longum strain BB536 was administered via gavage, starting 10 days before dermatitis induction and continuing until the last day of disease induction. ACD caused alterations in the composition of intestinal microbiota compared to naïve mice but did not affect SCFA production. The probiotic altered microbiota composition and increased acetate production in dermatitis-induced mice. ACD decreased the gene expression of TjP1, ATHO1, and MUC2, while probiotic treatment restored TjP1 and ATHO1 to normal levels. The cytokine IL-6 increased in the ACD group compared to naïve mice, whereas IL-10 decreased; probiotic treatment also restored these levels. Intestinal mucus production, affected by ACD, was partially restored by probiotic treatment. The findings suggest that probiotics could be a therapeutic strategy to prevent intestinal issues caused by skin diseases. Full article

Background. Skin contact with items containing p-tert-butylphenol-formaldehyde resin (PTBP-FR) may induce sensitization and allergic contact dermatitis (ACD). Methods. This multi-centric cross-sectional study investigated the prevalence of sensitization to PTBP-FR in 30,629 consecutive outpatients patch-tested during 1997–2021 in four research centers from Northern Italy: Padua; Pordenone; Trieste; and Trento/Bolzano/Rovigo. Patch tests were applied on the upper back of patients with suspected ACD. All patches were removed after 48 h and read at 72 or 96 h. Results. The overall prevalence of PTBP-FR sensitization was 1.11% (=341/30,629) of cases, with lower prevalence occurring in the Province of Trento/Bolzano/Rovigo (0.36%). The body area most frequently affected were the hands (36.32%), followed by face (19.52%) and legs (8.09%). During 1997–2004, the prevalence of PTBP-FR positivity was significantly lower in Trento/Bolzano/Rovigo (aOR = 0.19; 95%CI: 0.11; 0.35), whereas it was higher among restaurant workers (aOR = 2.44; 95%CI: 1.44; 4.13). During the entire study period (1997–2021), excluding Trento/Bolzano/Rovigo, PTBP-FR positivity significantly decreased in the period 2011–2021 (aOR = 052; 95%CI: 0.39; 0.69) compared to 1997–2010 in males (OR = 0.69; 95%CI: 0.52; 0.91). Conclusions. Females were likely to react to PTBP-FR at patch tests. Prevalence of PTBP-FR sensitization significantly decreased over time, possibly reflecting reduced occupational and non-occupational exposure due to replacement of the resin with other adhesive products (acrylates or epoxy agents). Full article

Background/Objectives: Patch testing is a valuable clinical tool for identifying the causes of allergic contact dermatitis (ACD). This study aimed to identify common allergens in southern Taiwan. Methods: A retrospective review of patch test data from April 2019 to May 2023 was conducted at a tertiary medical center. The European Baseline Series of allergens was utilized to evaluate and identify the causes of dermatitis. The prevalence rates of contact sensitization to each allergen were calculated. Results: A total of 57 patients (mean age 41.8 years) with contact dermatitis who underwent patch testing were included. The most common allergens were cobalt chloride (24.6%), followed by fragrance mix I (19.3%), Peru balsam (17.5%), nickel (II) sulfate hexahydrate (15.8%), benzisothiazolinone (15.8%), 4-Phenylenediamine (PPD) base (10.5%), and methyldibromo glutaronitrile (10.5%). Patients with positive patch test results frequently had a history of allergic rhinitis (26.3%), atopic dermatitis (24.6%), urticaria (21.1%), and elevated immunoglobulin E (IgE) levels (28.1%). The hairdressing profession was associated with a higher risk of hand eczematous dermatitis. Conclusions: Positive patch test results were observed in 86% of patients diagnosed with contact dermatitis. This study found that cobalt, rather than nickel, was the most prevalent allergen in patients with contact dermatitis. Elevated IgE levels were observed in ACD patients, with the hands being the most frequently affected area. Occupations as accountants, secretaries, and in the hairdressing and cosmetics industries were strongly associated with hand eczematous dermatitis. The early identification of allergens and appropriate treatment strategies significantly reduced recurrence rates and improved outcomes. For individuals with specific allergies, ongoing avoidance of identified allergens is crucial to managing and preventing allergic reactions. Further research is needed to elucidate the mechanisms and responses to novel therapies, including biologic agent- and nanotechnology-based treatments. Full article

Allergic contact dermatitis (ACD) is a skin condition characterized by inflammation resulting from hypersensitivity upon contact with certain allergens. Although ACD is characterized by an immune-mediated pathomechanism, the involvement of the nervous system in this condition has increasingly been considered, particularly in the amplification and persistence of inflammation. This paper aims to present a comprehensive overview of the mechanisms involved in neurogenic inflammation in ACD, focusing on the role of sensory neurons, the release of neuropeptides, their interaction with immune cells, and the potential therapeutic implications related to neurogenic pathways, diversified by age and gender. Innovative therapies for ACD, including topical formulations, may target the mass-bound X2 G-protein-coupled receptor (MRGPRX2) and endocannabinoid systems. Full article

Cinnamaldehyde (CIN), which is a cosmetic fragrance allergen regulated by the European Union, can induce allergic contact dermatitis in consumers, reducing their quality of life. Autophagy may be associated with the dendritic cell (DC) response to chemical sensitizers. We hypothesized that CIN would activate DCs through autophagy during skin sensitization. In this study, Tohoku Hospital Pediatrics-1 cells (THP-1 cells) were used as an in vitro DC model, and we evaluated the expression of cell activation markers, intracellular oxidative stress, and autophagy pathway-related genes in response to CIN in THP-1 cells. CIN exposure activated THP-1 cells, which presented increases in CD54 and CD86 expression and ROS generation. Transcriptomic analysis revealed that the genes that were differentially expressed after CIN stimulation were mostly associated with autophagy. The autophagy markers LC3B, p62, and ATG5 had upregulated mRNA and protein levels after CIN exposure. Furthermore, the effects of the autophagy inhibitor Baf-A1 and the autophagy activator rapamycin were investigated on CIN-treated cells. Pretreatment with Baf-A1 in THP-1 cells impaired autophagic flux and dramatically promoted cell activation and oxidative stress triggered by CIN. Conversely, rapamycin inhibited cell activation and the ROS content in CIN-challenged cells while increasing autophagy levels via a reduction in mTOR expression. These results suggest that the autophagy pathway has a pivotal influence on the regulation of CIN-induced activation in THP-1 cells, which provides new insight into the pathogenesis and precise therapeutic strategies for ACD. Full article

Introduction: Allergic contact dermatitis (ACD) is a form of late hypersensitivity reaction of skin contact with allergens. As an inflammatory skin disease, ACD has a negative impact on the quality of life and there is a need to elucidate the etiopathogenetic factors of the disease, whereby using the psychoneuroimmunological (PNI) approach can be helpful. Psychological stress (PS), as a component of PNI, leads to aggravation of the contact hypersensitivity reaction. In response to the perception of PS, cortisol secretion is enhanced by activation of the hypothalamic–pituitary–adrenal (HPA) axis. Furthermore, the pro-inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) play a role in activating the HPA axis as well as initiating and maintaining inflammatory responses. Recent studies show that IL-6, IL-1, and TNF-α values are increased in the serum of patients with contact dermatitis, as well as in keratinocyte cell culture. Methods: The study examined the association of PNI factors (serum IL-6 and TNF-α, stress intensity with a Perceived Stress Scale (PSS) questionnaire, quality of life of dermatology patients with a Dermatology Life Quality Index (DLQI)) with the disease severity evaluated using the Hand Eczema Extent Score (HEES) and the duration of disease in hand ACD patients. Results: Patients with hand ACD had higher PSS (p = 0.001) than healthy people, with no difference in IL-6 and TNF-α. Higher DLQI was associated with higher HEES and PSS (p = 0.002 and p < 0.001) and these were the only predictors of DLQI. The duration of the disease was not related to the investigated factors. Conclusion: This study is the first so far, to our knowledge, in which a detailed analysis of PNI factors in patients with hand ACD was conducted. The results show that patients with ACD have higher PS intensity, which can chronically indicate changes in the balance of the HPA axis and indirectly affect the quality of life and disease severity of this disease. The results of the research provide more knowledge about hand ACD and contribute to and emphasize the importance of a multidisciplinary approach to treatment, thus improving the quality of life of these patients. Full article

Background/Objectives: Chromium, a common environmental and occupational sensitizer, frequently induces allergic contact dermatitis (ACD). This study investigates the role of CD4⁺ (T helper), CD8⁺ (T cytotoxic), regulatory (Tregs: CD4⁺CD25⁺ and CD8⁺CD25⁺), and gamma delta (Tγδ) T cells in chromium tolerance versus hypersensitivity. Methods: Six chromium-allergic patients and six healthy controls were recruited, confirmed via patch testing. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured, with chromium exposure and proliferation assays conducted. Specific T cell subtypes were isolated and analyzed for chromium-specific proliferative responses, cytokine production, and metabolic activity. Results: Chromium-allergic individuals exhibited broad proliferation across PBMC and T cell subsets, contrasting with restricted responses in controls. Treg cells in healthy subjects effectively suppressed T cell proliferation in response to chromium, while allergic individuals showed unmodulated T cell activity, indicative of impaired regulatory function. Cytokine analysis revealed elevated IL-2 and TNF-α but absent IL-10 in allergic patients. Metabolic assessments showed higher glycolytic activity in Tregs of healthy controls, suggesting enhanced regulatory potential. Conclusions: These findings highlight the importance of balanced effector and regulatory T cell interactions for chromium tolerance. Dysregulated Treg and Tγδ cell functions in allergic individuals may contribute to hypersensitivity, with implications for targeted therapeutic strategies to restore immune balance and reduce allergic responses in chromium-sensitive patients. Full article

Background/Objectives: Eyelid dermatitis is an inflammatory disease affecting the palpebral skin characterized by itching, edema, and scaling of the periorbital area. This entity can be a manifestation of various underlying dermatological diseases, but allergic contact dermatitis (ACD) is the predominant etiology of eyelid dermatitis among patients, being diagnosed in 43.4% of cases. The thin and highly permeable nature of eyelid skin increases its susceptibility to allergens, making it a distinct clinical entity. This study aimed to identify the primary haptens associated with eyelid ACD and compare these findings with the allergens implicated in non-eyelid ACD over a 25-year period in a large cohort of patients. Methods: We conducted a monocentric, retrospective study on a dataset of 7955 patients patch-tested for ACD at the Outpatient Allergy Dermatology Clinic of the Azienda Ospedaliera Universitaria Senese (AOUS) from 1997 to 2021. Eyelid ACD cases were identified based on clinical features and positive patch test results. Data on demographics, occupation, and personal history of atopy were collected. The statistical analyses assessed the associations between allergens and eyelid ACD. The trends in the sensitization rates for the most prevalent allergens were also evaluated. Results: Eyelid ACD was identified in 4.6% of the study population, predominantly affecting women (88.6%). Patients with eyelid ACD were more likely to exhibit single-hapten positivity (54.6%) and an atopic phenotype (52.3%) compared to non-eyelid ACD cases. Nickel sulfate (54%), cobalt chloride (13.4%), and thimerosal (12.6%) were the most common allergens associated with eyelid ACD. While thimerosal sensitization decreased significantly following its removal from topical products, nickel sensitization increased, likely due to exposure from electronic devices and hand–eye contact. Conclusions: The haptens identified in eyelid ACD largely overlap with those found in other body regions, including metals, fragrances, and preservatives. However, the unique characteristics of eyelid skin and hand–eye contact patterns play a significant role in sensitization. This study highlights the need for further investigation into the pathophysiology of eyelid allergic contact dermatitis, with particular emphasis on elucidating the mechanisms of hapten sensitization. Such insights could contribute to the development of effective strategies aimed at reducing allergen exposure. Full article

Background/Objectives: Allergic contact dermatitis (ACD), an inflammatory skin condition, is commonly treated with topical corticosteroids; however, long-term use of these drugs is associated with various risks, such as skin atrophy and steroid resistance. Triacetin (TA), a triglyceride metabolized to acetate, exerts anti-inflammatory affects by activating AMP-activated protein kinase (AMPK) and suppressing mast cell degranulation. Here, we aimed to assess the immediate and long-term effects of TA on ACD suppression, focusing on AMPK activation, using a 2,4-dinitrofluorobenzene-induced rodent model. Methods: Various concentrations of TA were topically applied to rats with 2,4-dinitrofluorobenzene-induced dermatitis. Ear thickness was measured, and histological analysis was performed to assess the inflammation, mast cell infiltration, and degranulation in the established models. AMPK activation was analyzed via Western blotting, and TA degradation was assessed via gas chromatography-mass spectrometry. Dorsomorphin (an AMPK inhibitor) was used to evaluate the effects of AMPK on ACD. Results: TA significantly inhibited inflammation and mast cell degranulation in a dose-dependent manner, with 0.25 mmol/L showing the most potent effects. It also activated AMPK activation. Notably, AMPK inhibition reversed the effects of TA. Conclusions: Overall, TA exerted immediate and long-term anti-inflammatory effects via AMPK activation and inhibition of mast cell degranulation, showing potential as a non-steroidal therapeutic for ACD. Full article

The skin epidermis provides a barrier that is imperative for preventing transepidermal water loss (TEWL) and protecting against environmental stimuli. The underlying molecular mechanisms for regulating barrier functions and sustaining its integrity remain unclear. RORα is a nuclear receptor highly expressed in the epidermis of normal skin. Clinical studies showed that the epidermal RORα expression is significantly reduced in the lesions of multiple inflammatory skin diseases. In this study, we investigate the central roles of RORα in stabilizing skin barrier function using mice with an epidermis-specific Rora gene deletion (Rora^EKO). While lacking spontaneous skin lesions or dermatitis, Rora^EKO mice exhibited an elevated TEWL rate and skin characteristics of barrier dysfunction. Immunostaining and Western blot analysis revealed low levels of cornified envelope proteins in the Rora^EKO epidermis, suggesting disturbed late epidermal differentiation. In addition, an RNA-seq analysis showed the altered expression of genes related to “keratinization” and “lipid metabolism” in RORα deficient epidermis. A lipidomic analysis further uncovered an aberrant ceramide composition in the Rora^EKO epidermis. Importantly, epidermal Rora ablation greatly exaggerated percutaneous allergic inflammatory responses to oxazolone in an allergic contact dermatitis (ACD) mouse model. Our results substantiate the essence of epidermal RORα in maintaining late keratinocyte differentiation and normal barrier function while suppressing cutaneous inflammation. Full article

Skin inflammation and immune regulation have been suggested to be associated with allergic contact dermatitis (ACD) progression, but whether the system’s immune regulation is a cause or a potential mechanism is still unknown. This study aims to assess the upstream and downstream of systemic immune factors on ACD within a bidirectional Mendelian-randomization design. A bidirectional two-sample MR analysis was employed to implement the results from genome-wide association studies for 52 system immune factors and ACD. Genetic associations with systemic immune factors and ACD were obtained from the IEU Open GWAS project database. The inverse-variance weighted (IVW) method was adopted as the primary MR analysis, MR-Egger, weighted median, MR-pleiotropy residual sum, and outlier (MR-PRESSO) was also used as the sensitivity analyses. Only Tumor necrosis factor ligand superfamily member 11 (TNFS11) from among 52 systemic immune factors was associated with a protective effect of ACD. However, ACD was associated with a decrease in Interleukin-9 (IL9) and an increase in C-X-C motif chemokine 1 (GROα), Tumor necrosis factor ligand superfamily member 10 (TRAIL), C4, and complement factor B of the assessed systemic immune factors. This study identified TNFS11 as the upstream regulator and IL9, GROα, TRAIL, C4, and complement factor B as the downstream regulator of ACD, providing opportunities for new therapeutic exploitation of ACD. Nonetheless, these associations of systemic immune factors need to be verified in vivo. Full article

Allergic contact dermatitis (ACD) is the most common chronic inflammatory skin disease (or immune-mediated disease), causing disruption to our psychological condition and life quality. In this study, the therapeutic properties of probiotic Bifidobacterium longum (B. longum) was investigated by using an ACD-induced animal model. For ACD induction, BALB/c mice ear and dorsal skin were sensitized with 240 µL of 1% (w/v) 2,4-dinitrochlorobenzene (DNCB) twice (3-day intervals). After a week of the first induction, the mice were re-sensitized by painting on their dorsal skin and ear with 0.4% (w/v) DNCB for a further three times (once per week). Before the ACD induction of 2 weeks and throughout the trial period, the BALB/c mice were supplemented daily with 1 mL of 1.0 × 10⁹ CFU or 5.0 × 10⁹ CFU B. longum using an intragastric gavage method. The ACD-induced mice without B. longum supplementation were used as a control. Results show that B. longum supplementation significantly alleviated ACD symptoms (e.g., ear swelling, epidermal damage) and immune response (e.g., reduced immune cell recruitment, serum IgE level, and cytokine production). The therapeutic efficiency of B. longum increased as the supplementation dose increased. Thus, daily supplementation with 5.0 × 10⁹ CFU probiotic B. longum could be an effective method for the prevention and treatment of ACD. Full article

PAPLAL, a mixture of platinum (nPt) and palladium (nPd) nanoparticles, is widely used as a topical agent because of its strong antioxidant activity. Allergic contact dermatitis (ACD) is one of the most common occupational skin diseases worldwide. However, the role of oxidative stress in ACD remains unclear. In the present study, we investigated the protective effects of topical PAPLAL treatment on 2,4-dinitrofluorobenzene (DNFB)-induced ACD. DNFB treatment increased 8-isoprostane content; upregulated Xdh, Nox2, and Nox4, pro-oxidant genes; and downregulated Sod1, an antioxidant gene, indicating oxidative damage in the ear skin. PAPLAL therapy significantly reduced ear thickness associated with the downregulation of inflammatory cytokine-related genes. PAPLAL also significantly increased the expression of the stress-response-related genes Ahr and Nrf2, as well as their target genes, but failed to alter the expression of redox-related genes. Furthermore, Sod1 loss worsened ACD pathologies in the ear. These results strongly suggest that PAPLAL protects against ACD through its antioxidant activity and activation of the AHR and NRF2 axes. The antioxidant PAPLAL can be used as a novel topical therapy for ACD that targets oxidative stress. Full article