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Irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD) are common skin disorders that are characterized by inflammation, oozing, crusting, and pruritus. Atopic dermatitis (AD) is an inflammatory skin disease characterized by immune and barrier abnormalities and is additionally a risk factor for acquiring ICD and ACD. New work on allergic sensitization to common allergens (e.g., nickel and fragrance) in human skin has shown that different allergens have distinct molecular fingerprinting. For example, nickel promotes strong Th1/Th17 polarization, whereas fragrance allergy causes Th2/Th22 skewing, which is similar to the phenotype of AD. While ACD has previously been considered to be constant across all allergens, largely based on mouse models involving strong sensitizers, these new data suggest that ACD differs mechanistically according to allergen. Further, ACD in the setting of concurrent AD shows a different and attenuated phenotype as compared to healthy individuals with ACD, which influences the way AD patients respond to vaccination and other treatment modalities. As in contact sensitization, skin challenged by food patch testing shows that common food allergens (e.g., peanut and barley) also cause distinct immune polarizations in the skin. Additionally, house dust mite reactions in human skin have been profiled to show unique Th2, Th9, and Th17/22 activation as compared to controls, which are similar to the phenotype of psoriasis and contact responses to nickel. Given this information, ACD patients should be treated based on their unique allergen polarity. Refined understanding of the molecular behavior of contact dermatitis and related diseases translates to improved methods of inducing tolerance in sensitized allergic patients, such as with targeted drug therapy and epicutaneous immunotherapy.

Allergic contact dermatitis (ACD) is one of the most common skin diseases, consisting of sensitization and elicitation phases. With the advancement of technology and the discovery of new types of immune cells, our knowledge of the immunological mechanisms of contact hypersensitivity (CHS) as a murine model of ACD has expanded significantly in the past decade. For example, by introducing regulatory T cells, CD4+ T-helper 17 cells, and Langerin-positive dermal dendritic cells, the initiation and termination mechanism of CHS has been revealed. In addition, the role of mast cells in CHS, long a matter of debate, has become apparent by developing conditional mast cell–deficient mice. Moreover, the role of the innate immunity system, such as that of Toll-like receptor signaling, has made a breakthrough in this field. In this review, we will integrate the recent advancement of immunological mechanisms of both the sensitization and elicitation phases of CHS into the classic view, and we will discuss updated mechanisms on its development and future directions.

AbstractPurpose of ReviewOccupational hand dermatitis is a common work-related disorder of the skin. Prevention and management of this disease is critical to improving workers’ quality of life and for occupation-specific retention.Recent FindingsThis is a critical review of the current literature on occupational hand dermatitis. Occupational dermatitis continues to have a high prevalence among workers although the overall incidence may be slowly decreasing. Irritant contact dermatitis due to wet work exposure is the most common cause of occupational hand dermatitis. Healthcare workers, hairdressers, and metal workers are at particularly high risk for this disease. While some prevention programs have been ineffective in mitigating occupational hand dermatitis, other more resource-intensive initiatives may have benefit.SummaryContinued research is needed on ways to manage wet work exposures and on scalable, effective prevention programs for occupational hand dermatitis. The spectrum of culprit contact allergens continues to evolve, and vigilance for potential occupation-specific allergens remains important.

Contact allergy is common, affecting 27% of the general population in Europe. Original publications, including case reports, published since 2016 (inclusive) were identified with the aim of collating a full review of current problems in the field. To this end, a literature search employing methods of systematic reviewing was performed in the Medline® and Web of Science™ databases on 28 January 2018, using the search terms (“contact sensitization” or “contact allergy”). Of 446 non-duplicate publications identified by above search, 147 were excluded based on scrutiny of title, abstract and key words. Of the remaining 299 examined in full text, 291 were deemed appropriate for inclusion, and main findings were summarised in topic sections. In conclusion, diverse sources of exposures to chemicals of widely-differing types and structures, continue to induce sensitisation in man and may result in allergic contact dermatitis. Many of the chemicals are “evergreen” but others are “newcomers”. Vigilance and proper investigation (patch testing) are required to detect and inform of the presence of these haptens to which our populations remain exposed.

Contact dermatitis tremendously impacts the quality of life of suffering patients. Currently, diagnostic regimes rely on allergy testing, exposure specification, and follow-up visits; however, distinguishing the clinical phenotype of irritant and allergic contact dermatitis remains challenging. Employing integrative transcriptomic analysis and machine-learning approaches, we aimed to decipher disease-related signature genes to find suitable sets of biomarkers. A total of 89 positive patch-test reaction biopsies against four contact allergens and two irritants were analyzed via microarray. Coexpression network analysis and Random Forest classification were used to discover potential biomarkers and selected biomarker models were validated in an independent patient group. Differential gene-expression analysis identified major gene-expression changes depending on the stimulus. Random Forest classification identified CD47, BATF, FASLG, RGS16, SYNPO, SELE, PTPN7, WARS, PRC1, EXO1, RRM2, PBK, RAD54L, KIFC1, SPC25, PKMYT, HISTH1A, TPX2, DLGAP5, TPX2, CH25H, and IL37 as potential biomarkers to distinguish allergic and irritant contact dermatitis in human skin. Validation experiments and prediction performances on external testing datasets demonstrated potential applicability of the identified biomarker models in the clinic. Capitalizing on this knowledge, novel diagnostic tools can be developed to guide clinical diagnosis of contact allergies.

Allergic contact dermatitis (ACD) is a cutaneous inflammatory disorder mediated by allergen-specific memory T cells. Methylisothiazolinone (MI), a preservative widely used in industrial and cosmetic products and a component of Kathon CG, has led to a substantial rise in ACD cases. Despite increasing sensitization rates, the innate immune mechanisms and transcriptional responses induced by MI in the skin remain poorly understood. Individuals with positive patch tests exclusively to MI were recruited at the Contact Dermatitis Clinic of Hospital das Clínicas (São Paulo). Participants were re-exposed to MI or saline, and skin biopsies were collected 48 hours later. Healthy MI-negative controls were also exposed to MI and saline. Histopathology and RNA-sequencing were performed. Differentially expressed genes (DEGs) were analyzed, and key findings were validated by qPCR and protein expression of IL-9 and IL-24. Two distinct MI-responsive groups emerged among ACD patients:ACD-A (high responders): pronounced histopathology (spongiosis, microvesicles). ACD-B (low responders): milder reactions with absence of spongiosis. In ACD-A, MI exposure resulted in 1,588 upregulated and 2,090 downregulated genes compared to ACD-B. DEGs were enriched for innate immune and inflammatory pathways, including IL-24, IL-9, IL-13, and NTRK1 (upregulated), while IL-37 and IL-18 were downregulated. Compared to MI-negative ACD controls, ACD-A showed 1,169 upregulated and 321 downregulated genes. qPCR confirmed increased NTRK1 and IL-9 expression and reduced IL-18 levels. IL-9 and IL-24 protein levels were higher in the dermal layer of ACD-A. MI-sensitized individuals exhibit heterogeneous innate immune responses despite uniformly positive patch tests. IL-9, IL-24, and NTRK1 appear to play important roles in the heightened inflammatory response observed in high-responder individuals, while downregulation of IL-18 and IL-37 may contribute to impaired regulatory pathways. These findings highlight previously undescribed heterogeneity in MI-induced ACD and identify potential targets for better understanding disease pathogenesis.

Patients with atopic dermatitis (AD) have increased penetration of allergens, immune dysregulation (including shared cytokine pathways), and frequent use of emollients and topical medications, all of which may predispose toward developing allergic contact dermatitis (ACD). Recent systematic reviews have suggested that ACD is a significant clinical problem in both children and adults with AD. While this remains controversial, ACD remains an important comorbidity and potential exacerbant of AD in clinical practice. Common relevant allergens, include lanolin, neomycin, formaldehyde, sesquiterpene lactone mix, compositae mix, and fragrances that are commonly found in AD patients’ personal care products. We herein review the clinical scenarios where patch testing is indicated in AD. In addition, we review the contraindications, preferred patch-testing series, pitfalls, and challenges determining the relevance of positive patch-test reactions in AD patients.

Contact hypersensitivity (CHS), or allergic contact dermatitis (ACD), is an inflammatory skin disorder characterized by an exaggerated allergic reaction to specific haptens. During this delayed-type allergic reaction, the first contact with the allergen initiates the sensitization phase, forming memory T cells. Upon repeated contact with the hapten, the elicitation phase develops, activating mostly macrophages, cytotoxic T cells, and neutrophilic granulocytes. Our group previously demonstrated that the leukocyte-specific GTPase-activating protein ARHGAP25 regulates phagocyte effector functions and is crucial in the pathomechanism of autoantibody-induced arthritis. Here, we investigate its role in the pathogenesis of the more complex inflammatory process of contact hypersensitivity. For sensitization, the abdomens of wild-type and ARHGAP25 deficient (KO) mice on a C57BL/6 background, as well as bone marrow chimeric mice, were coated with 3% TNCB (2-chloro-1,3,5-trinitrobenzene) or acetone in the control group. After five days, ears were treated with 1% TNCB for elicitation. Swelling of the ears caused by edema formation was evaluated by measuring the ear thickness. Afterward, ears were harvested, and histological analysis, investigation of leukocyte infiltration, cytokine production, and changes in relevant signaling pathways were carried out. ARHGAP25 expression at the mRNA and protein levels was measured using murine ear and human skin samples. ARHGAP25 expression increased in human patients suffering from contact dermatitis and in contact hypersensitivity induced in mice. Our data suggest that ARHGAP25 expression is infinitesimal in keratinocytes. In the CHS mouse model, the absence of ARHGAP25 mitigated the severity of inflammation in a leukocyte-dependent manner by reducing the infiltration of phagocytes and cytotoxic T cells. ARHGAP25 altered cytokine composition in the sensitization and elicitation phase of the disease. However, this protein did not affect T cell homing and activation in the sensitization phase. Our findings suggest that ARHGAP25 is essential in developing contact hypersensitivity by modulating the cytokine environment and leukocyte infiltration. Based on these findings, we propose ARHGAP25 as a promising candidate for future therapeutic approaches and a potential ACD biomarker.

Allergic contact dermatitis (ACD) is a delayed-type hypersensitivity reaction mediated by hapten-specific T cells. Dinitrochlorobenzene (DNCB)-induced mouse models are widely used to investigate the pathogenesis of contact dermatitis. Inhibitor K562 (IK) cytokine suppresses IFN-γ-induced MHC class II expression on B cells by increasing cAMP levels. Previously, we reported that truncated IK (tIK) expression in transgenic (Tg) mice ameliorated rheumatoid arthritis by suppressing CD4 T helper cells (Th)-1 and Th17 cell differentiation, as well as macrophage activation. However, its role in hypersensitivity diseases such as ACD remains underexplored. This study aimed to evaluate whether tIK Tg mice exhibit reduced susceptibility to DNCB-induced ACD and passive systemic anaphylaxis (PSA). ACD was induced in BALB/c and tIK Tg mice through repeated DNCB application. Ear thickness and scratching behavior were assessed. Serum IgE levels and mast cell-associated gene expression were analyzed. Th cell differentiation was evaluated using flow cytometry. PSA, an experimental model used to study systemic allergic reactions, was induced by IgE sensitization followed by antigen challenge, and hypothermia, serum IgE, and mast cell activation were measured. DNCB-treated BALB/c mice developed severe dermatitis, including increased ear thickness and scratching behavior, whereas tIK Tg mice exhibited milder symptoms. tIK over-expression also led to lower serum IgE levels and reduced mast cell-associated gene expression. T cell analysis revealed suppressed Th2 and Th17 differentiation, while Tregs and Th1 cells remained unaffected. Beyond ACD, tIK Tg mice exhibited attenuated PSA responses, with less severe hypothermia, lower serum IgE levels, and reduced mast cell activation compared to wild-type controls. tIK suppresses both localized and systemic hypersensitivity by modulating Th cell differentiation and mast cell activity. tIK may serve as a potential therapeutic target for allergic and inflammatory diseases.