Managing Allergic Nickel Dermatitis in Occupational Settings: A Case Report.

Contact dermatitis is a common cutaneous inflammatory condition, triggered by exposure to irritant substances or allergens. Nickel is the most prevalent allergen, a metal widely used in accessories, furniture, office materials, food and in industry, with multiple exposure pathways, making it difficult to assess which exposure is causing allergic dermatitis. Here, we report a case of an administrative worker with chronic hand eczema, limited to the radial metacarpophalangeal region of the left hand, caused by occupational exposure to nickel, confirmed by nickel deposition test on the hand and a positive test with a metallic stapler used at her workplace.

The omega-3 postbiotic trans-10-cis-15-octadecadienoic acid attenuates contact hypersensitivity in mice through downregulation of vascular endothelial growth factor A.

Intestinal bacteria metabolize dietary substances to produce bioactive postbiotics, among which some are recognized for their role in promoting host health. We here explored the postbiotic potential of two omega-3 α-linolenic acid-derived metabolites: trans-10-cis-15-octadecadienoic acid (t10,c15-18:2) and cis-9-cis-15-octadecadienoic acid (c9,c15-18:2). Dietary intake of lipids rich in omega-3 α-linolenic acid elevated levels of t10,c15-18:2 and c9,c15-18:2 in the serum and feces of mice, an effect dependent on the presence of intestinal bacteria. Notably, t10,c15-18:2 mitigated skin inflammation in mice that became hypersensitive after exposure to 2,4-dinitrofluorobenzene, an experimental model for allergic contact dermatitis. In particular, t10,c15-18:2-but not c9,c15-18:2-attenuated ear swelling and edema, characteristic symptoms of contact hypersensitivity. The anti-inflammatory effects of t10,c15-18:2 were due to its ability to suppress the release of vascular endothelial growth factor A from keratinocytes, thereby mitigating the enhanced vascular permeability induced by hapten stimulation. Our study identified retinoid X receptor as a functional receptor that mediates the downregulation of skin inflammation upon treatment with t10,c15-18:2. Our results suggest that t10,c15-18:2 holds promise as an omega-3 fatty acid-derived postbiotic with potential therapeutic implications for alleviating the skin edema seen in allergic contact dermatitis-induced inflammation.

Subclinical immune responses to nickel in sensitized individuals-a dose-response study.

BACKGROUND: Nickel is the leading cause of contact allergy in Europe, with 14.5% of the adult population being sensitized. Despite regulations limiting nickel release from consumer items, the incidence and prevalence of nickel allergy remain high. OBJECTIVE: To investigate the clinical and subclinical immune response to low-dose nickel exposure on nickel pre-exposed skin to assess the adequacy of current regulatory limits. METHOD: Nickel-allergic and healthy controls were patch tested with nickel twice with a 3-4 weeks interval. The first exposure used the diagnostic concentration of 2000 µg/cm2 nickel sulphate, and the same skin areas were then re-exposed to 0.2, 0.5, 12.8 and 370 µg/cm2 nickel sulphate. After 48 h, the patch reactions were examined for clinical signs of eczema, and skin biopsies were collected. The transcriptomic immune profile was analysed with Nanostring nCounter and quantitative polymerase chain reaction. RESULTS: Two nickel-allergic participants (15%) had clinical reactions to the regulatory limiting doses for nickel (0.2/0.5 µg/cm2) following re-exposure. There was immune activation in all skin areas following re-exposure to nickel, predominantly mediated by up-regulation of cytokines and chemokines. In all nickel re-exposed skin areas, 81 genes were up-regulated independent from the clinical response. In skin areas exposed to 0.2 µg/cm2, 101 immune-related genes were differentially expressed, even when no clinical response was observed. Healthy controls showed up-regulation of three genes in response to nickel re-exposures without any clinical reactions. CONCLUSION: Immune activation can be induced in skin with local memory to nickel upon challenge with nickel doses within the regulatory limits. Our findings suggest that the regulatory limits in the European nickel regulation may not provide sufficient protection for consumers against low-dose exposures.

Benchmarking of BMDC assay and related QSAR study for identifying sensitizing chemicals.

The Bone-Marrow derived Dendritic Cell (BMDC) test is a promising assay for identifying sensitizing chemicals based on the 3Rs (Replace, Reduce, Refine) principle. This study expanded the BMDC benchmarking to various in vitro, in chemico, and in silico assays targeting different key events (KE) in the skin sensitization pathway, using common substances datasets. Additionally, a Quantitative Structure-Activity Relationship (QSAR) model was developed to predict the BMDC test outcomes for sensitizing or non-sensitizing chemicals. The modeling workflow involved ISIDA (In Silico Design and Data Analysis) molecular fragment descriptors and the SVM (Support Vector Machine) machine-learning method. The BMDC model's performance was at least comparable to that of all ECVAM-validated models regardless of the KE considered. Compared with other tests targeting KE3, related to dendritic cell activation, BMDC assay was shown to have higher balanced accuracy and sensitivity concerning both the Local Lymph Node Assay (LLNA) and human labels, providing additional evidence for its reliability. The consensus QSAR model exhibits promising results, correlating well with observed sensitization potential. Integrated into a publicly available web service, the BMDC-based QSAR model may serve as a cost-effective and rapid alternative to lab experiments, providing preliminary screening for sensitization potential, compound prioritization, optimization and risk assessment.

Effect of smoking on the clinical and allergological profile of contact dermatitis.

INTRODUCTION: Several clinical and epidemiological data point to a possible link between smoking exposure and contact dermatitis (CD). AIMS: To identify the clinical and epidemiological differences of CD in smoking and non-smoking subjects, and to determine the influence of smoking on the allergological profile of CD. METHODS: Retrospective descriptive study who consulted the Department of Occupational Medicine and Occupational Pathology of the Farhat Hached University Hospital of Sousse (Tunisia) during a period of 8 years for exploration of CD and who were tested with the European Standard Battery (ESB). RESULTS: A total of 767 patients were enrolled during the study period, 40% of whom were smokers. The group of smokers was characterized by a male predominance (p=10-3) and a greater professional seniority compared to non-smokers (p=0.01). Personal history of atopy was predominant in non-smokers (p=0.02). Among the ESB allergens, there was a significant association between smoking and CD due to metals (chromium, cobalt) and conservatives. After binary logistic regression, the variables associated with smoking exposure were male gender (OR=12.12 ; 95% CI=[6.07 - 24.21]; p=10-3), Kathon CG allergy (OR=3.69 ; 95% CI=[1.24 - 10.81]; p=0.018), and right hand involvement (OR= 2.83; 95% CI=[1.29 - 6.17]; p=0.005). CONCLUSION: Our study revealed an effect of smoking on the clinical and allergological characteristics of CD.

Nail cosmetology.

Nail cosmetics is enjoying growing success due to recent technological advances. Manicures can be responsible for mechanical, infectious or allergic adverse effects. Nail cosmetics (e.g., nail varnishes, acrylic false nails, light-curing gels, and adhesive false nails) incorporate substances that harden after solvent evaporation or after polymerization. Allergic reactions can occur, remotely with conventional varnishes and locally with polymerizing substances. Artificial nails incur a risk of carrying infectious agents which can cause serious infection, and should not be used by caregivers. Recently, there has been a worrisome increase in the frequency of acrylate allergy, due to the appearance of home kits and lack of information in the general public. The infectious, allergic and toxic risks incurred by consumers and professionals regarding manicure or pedicure treatments and the application of nail cosmetics are the subject of recommendations and monitoring measures.

Allergic contact dermatitis due to 1,6-hexanediol diacrylate in ostomy patients.

BACKGROUND: Many people live with ostomies after life-saving surgery. Ostomy patients often suffer from peristomal dermatitis. Allergic contact dermatitis (ACD) has been reported, mostly due to contact allergy (CA) to topical agents. OBJECTIVES: We present three patients with therapy resistant peristomal dermatitis, suggesting ACD caused by different stoma products. METHODS: Patch testing was performed with baseline series, additional series, and selected allergens. They were also tested with their own ostomy products as is and separate extracts of the products. Extracts were analysed using Gas Chromatography-Mass Spectrometry (GC-MS). RESULTS: In all three patients we diagnosed CA to 1,6-hexanediol diacrylate (HDDA), +++ in case (C) 1 and 3, ++ in C 2. HDDA was detected in C 2's ostomy pouch adhesive and in C 1's and 3's flange extenders used to improve the adhesion of the ostomy pouches. CONCLUSION: Therapy resistant peristomal dermatitis should always be suspected of ACD and patch testing, especially with the patient's own products, should be performed.

Development of a hierarchical support vector regression-based in silico model for the prediction of the cysteine depletion in DPRA.

Topical and transdermal treatments have been dramatically growing recently and it is crucial to consider skin sensitization during the drug discovery and development process for these administration routes. Various tests, including animal and non-animal approaches, have been devised to assess the potential for skin sensitization. Furthermore, numerous in silico models have been created, providing swift and cost-effective alternatives to traditional methods such as in vivo, in vitro, and in chemico methods for categorizing compounds. In this study, a quantitative structure-activity relationship (QSAR) model was developed using the innovative hierarchical support vector regression (HSVR) scheme. The aim was to quantitatively predict the potential for skin sensitization by analyzing the percent of cysteine depletion in Direct Peptide Reactivity Assay (DPRA). The results demonstrated accurate, consistent, and robust predictions in the training set, test set, and outlier set. Consequently, this model can be employed to estimate skin sensitization potential of novel or virtual compounds.

The Involvement of Cysteine-X-Cysteine Motif Chemokine Receptors in Skin Homeostasis and the Pathogenesis of Allergic Contact Dermatitis and Psoriasis.

Members of the C-X-C motif chemokine receptor (CXCR) superfamily play central roles in initiating the innate immune response in mammalian cells by orchestrating selective cell migration and immune cell activation. With its multilayered structure, the skin, which is the largest organ in the body, performs a crucial defense function, protecting the human body from harmful environmental threats and pathogens. CXCRs contribute to primary immunological defense; these receptors are differentially expressed by different types of skin cells and act as key players in initiating downstream innate immune responses. While the initiation of inflammatory responses by CXCRs is essential for pathogen elimination and tissue healing, overactivation of these receptors can enhance T-cell-mediated autoimmune responses, resulting in excessive inflammation and the development of several skin disorders, including psoriasis, atopic dermatitis, allergic contact dermatitis, vitiligo, autoimmune diseases, and skin cancers. In summary, CXCRs serve as critical links that connect innate immunity and adaptive immunity. In this article, we present the current knowledge about the functions of CXCRs in the homeostasis function of the skin and their contributions to the pathogenesis of allergic contact dermatitis and psoriasis. Furthermore, we will examine the research progress and efficacy of therapeutic approaches that target CXCRs.

Rodent models of dermatological disorders.

To assess the possible beneficial effects of drugs and drug candidates, different dermatological disease models are available in rodents. These models are able to mimic one or more characteristic features of the disorders, but not completely recapitulate the pathogenesis of the human skin diseases. Therefore, to improve the technology many new models have been developed both by genetic engineering and by chemical or physical induction. Currently the in vivo rodent models provide the physiologically most relevant approach to produce the pathology related to the majority of dermatological diseases. In this short review some widely used animal techniques (psoriasis, allergic contact dermatitis, atopic dermatitis, wound healing, melanoma and non-melanoma type skin cancers and UV erythema) are shown which are currently applied in pharmacological, pharmacokinetic, pharmaceutical and dermatological research. First the main points of the human pathomechanism are shown and afterwards the rodent models are briefly discussed. Finally critical evaluation is provided by the authors. However, according to the 3R rule the number of experimental animals is strongly suggested to be reduced, therefore the advanced in vitro and ex vivo techniques become more and more important contrary to in vivo preclinical methods also in dermatological research. As it is described in the outlook section, although the 2D/3D in vitro and skin on-a-chip techniques are promising and have many advantages they are not able to completely substitute the animal models in their vascular, immunological, secretory and neural complexity.