Search

Background: Chronic hand eczema (CHE) is a highly prevalent, heterogeneous, skin disease that encompasses different aetiological and clinical subtypes. Severe CHE without atopic dermatitis has been associated with systemic inflammation; yet it remains unknown if specific CHE subtypes leave distinct, systemic, molecular signatures., Objectives: To characterize the inflammatory plasma signature of different aetiological and clinical CHE subtypes., Methods: We assessed expression levels of 266 inflammatory and cardiovascular disease risk plasma proteins as well as filaggrin gene mutation status in 51 well-characterized CHE patients without concomitant atopic dermatitis and 40 healthy controls. Plasma protein expression was compared between aetiological and clinical CHE subgroups and controls both overall and according to clinical CHE severity. Correlation analyses for biomarkers, clinical and self-reported variables were performed., Results: Very severe, chronic allergic contact dermatitis (ACD) on the hands was associated with a mixed Type 1/Type 2 systemic immune activation as compared with controls. Circulating levels of Type 1/Type 2 inflammatory biomarkers correlated positively with clinical disease severity among CHE patients with ACD. No biomarkers were found, that could discriminate between aetiological subtypes, for example, between ACD and irritant contact dermatitis. Hyperkeratotic CHE showed a distinct, non-atopic dermatitis-like, systemic footprint with upregulation of markers associated with Type 1 inflammation and tumour necrosis factor alpha, but not Type 2 inflammation. Increased levels of CCL19 and CXCL9/10 could discriminate hyperkeratotic CHE from both vesicular and chronic fissured CHE, whereas no difference was found between the latter two subtypes., Conclusion: Profiling of systemic biomarkers showed potential for identifying certain CHE subtypes. Peripheral blood levels of inflammatory biomarkers were associated and correlated with the clinical disease severity of chronic ACD on the hands, underlining that this is a systemic disease. We question whether hyperkeratotic CHE should be classified as eczema., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Purpose: The pathological process of atopic dermatitis (AD) progressing into other types of allergic diseases such as asthma and allergic rhinitis during the first several years of life is often referred to as the atopic march. Although the phenomenon of atopic march has been recognized for decades, how asthma stems from AD is still not fully understood, confounding a universal strategy to effectively protect people from the atopic march., Methods: We established experimental atopic march mice by first inducing allergic dermatitis with 0.5% fluorescein isothiocyante (FITC) applied to the skin, followed by an ovalbumin (OVA) airway challenge. In addition, by examining serum immunoglobulin (Ig) concentrations, airway cytokines, the levels of oxidative stress markers, histopathological changes in lung tissue and airway hyperresponsiveness (AHR), we were able to validate the successful establishment of the model. Furthermore, by detecting the attenuating effects of melatonin (MT) and the levels of oxidative stress in the atopic march mice, we explored the potential molecular mechanisms involved in the development of atopic march., Results: By successfully establishing an experimental atopic march mouse model, we were able to demonstrate that overproduction of oxidative stress in the lung significantly up-regulated the activation of nuclear factor-κB (NF-κB) signaling pathways causing thymic stromal lymphopoietin (TSLP) release, which further promotes the development of atopic march., Conclusions: To mitigate the development of the atopic march, antioxidants such as MT may be imperative to inhibit NF-κB activation in the lung, especially after the onset of AD., (© 2021 The Author(s).)

Occupational immune diseases are a serious public health burden and are often a result of exposure to low molecular weight (LMW) chemicals. The complete immunological mechanisms driving these responses are not fully understood which has made the classification of chemical allergens difficult. Antimicrobials are a large group of immunologically-diverse LMW agents. In these studies, mice were dermally exposed to representative antimicrobial chemicals (sensitizers: didecyldimethylammonium chloride (DDAC), ortho -phthalaldehyde (OPA), irritants: benzal-konium chloride (BAC), and adjuvant: triclosan (TCS)) and the mRNA expression of cytokines and cellular mediators was evaluated using real-time qPCR in various tissues over a 7-days period. All antimicrobials caused increases in the mRNA expression of the danger signals Tslp (skin), and S100a8 (skin, blood, lung). Expression of the T H 2 cytokine Il4 peaked at different timepoints for the chemicals based on exposure duration. Unique expression profiles were identified for OPA ( Il10 in lymph node, Il4 and Il13 in lung) and TCS ( Tlr4 in skin). Additionally, all chemicals except OPA induced decreased expression of the cellular adhesion molecule Ecad . Overall, the results from these studies suggest that unique gene expression profiles are implicated following dermal exposure to various antimicrobial agents, warranting the need for additional studies. In order to advance the development of preventative and therapeutic strategies to combat immunological disease, underlying mechanisms of antimicrobial-induced immunomodulation must be fully understood. This understanding will aid in the development of more effective methods to screen for chemical toxicity, and may potentially lead to more effective treatment strategies for those suffering from immune diseases.

Objective: Cutaneous adverse events (CAE) from FreeStyle Libre include allergic contact dermatitis (ACD) caused by the allergen isobornyl acrylate (IBOA). We aim to report CAE from this glucose sensor, ACD to IBOA in particular, and the outcome of using barrier films as a prevention., Research Design and Methods: A monocentric, retrospective review of medical files from adult and pediatric patients with diabetes using Freestyle Libre, in the period between December 2016 and April 2019, was performed with a focus on CAE., Results: Fifty-seven of 1,036 patients with diabetes (5.5%) were referred to our dermatology department because of CAE from FreeStyle Libre. Thirty-nine of 1,036 (3.8%) had ACD due to IBOA. Only two patients, of whom one sensitized to IBOA, had a benefit from using barrier films., Conclusions: CAE occurred in 5.5% of FreeStyle Libre users, and 3.8% suffered from ACD due to IBOA. Barrier films had limited value in the prevention., (© 2020 by the American Diabetes Association.)

Atopic dermatitis (AD) is a chronic inflammatory disease of the skin that substantially affects a patient's quality of life. While steroids are the most common therapy used to temporally alleviate the symptoms of AD, effective and nontoxic alternatives are urgently needed. In this study, we utilized a natural, plant-derived phenolic compound, phloretin, to treat allergic contact dermatitis (ACD) on the dorsal skin of mice. In addition, the effectiveness of phloretin was evaluated using a mouse model of ACD triggered by 2,4-dinitrochlorobenzene (DNCB). In our experimental setting, phloretin was orally administered to BALB/c mice for 21 consecutive days, and then, the lesions were examined histologically. Our data revealed that phloretin reduced the process of epidermal thickening and decreased the infiltration of mast cells into the lesion regions, subsequently reducing the levels of histamine and the pro-inflammatory cytokines interleukin (IL)-6, IL-4, thymic stromal lymphopoietin (TSLP), interferon-γ (IFN-γ) and IL-17A in the serum. These changes were associated with lower serum levels after phloretin treatment. In addition, we observed that the mitogen-activated protein kinase (MAPK) and NF-κB pathways in the dermal tissues of the phloretin-treated rodents were suppressed compared to those in the AD-like skin regions. Furthermore, phloretin appeared to limit the overproliferation of splenocytes in response to DNCB stimulation, reducing the number of IFN-γ-, IL-4-, and IL-17A-producing CD4 + T cells in the spleen back to their normal ranges. Taken together, we discovered a new therapeutic role of phloretin using a mouse model of DNCB-induced ACD, as shown by the alleviated AD-like symptoms and the reversed immunopathological effects. Therefore, we believe that phloretin has the potential to be utilized as an alternative therapeutic agent for treating AD.

Allergic contact dermatitis (ACD) is an inflammatory skin disease caused by hapten-specific immune response. Silkworm droppings are known to exert beneficial effects during the treatment of inflammatory diseases. Here, we studied whether topical treatment and oral administration of silkworm dropping extract (SDE) ameliorate trimellitic anhydride (TMA)-induced ACD. In ACD mice model, SDE treatment significantly suppressed the increase in both ear thickness and serum IgE levels. Furthermore, IL-1β and TNF-α levels were reduced by SDE. In allergic responses, SDE treatment significantly attenuated the production of the Th2-associated cytokine IL-4 in both ear tissue and draining lymph nodes. However, it increased the production of the Th1-mediated cytokine IL-12. Thus, these results showed that SDE attenuated TMA-induced ACD symptoms through regulation of Th1/Th2 immune response. Taken together, we suggest that SDE treatment might be a potential agent in the prevention or therapy of Th2-mediated inflammatory skin diseases such as ACD and atopic dermatitis., Abbreviations: ACD: allergic contact dermatitis; AD: atopic dermatitis; APC: antigen presenting cells; CCL: chemokine (C-C motif) ligand; CCR: C-C chemokine receptor; Dex: dexamethasone; ELISA: enzyme-linked immunosorbent assay; IFN: interferon; Ig: immunoglobulin; IL: interleukin; OVA: ovalbumin; PS: prednisolone; SDE: silkworm dropping extract; Th: T helper; TMA: trimellitic anhydride; TNF: tumor necrosis factor.

In this study, we investigated the role of IL-26 in allergic contact dermatitis (ACD), highlighting its' contribute in the cytotoxic mechanism responsible for the tissue injury. IL-26 is a signature Th17 cytokine, and immune cells are its predominant sources. Recently, it has shown that Th17 cell-derived-IL-26 functions like an antimicrobial peptide. Here, we hypothesized that IL-26 could be involved in cytotoxicity mechanism that underlies ACD. Indeed, we have attributed a role to IL-26 in this context, through PBMC cytotoxicity assays vs HaCat. To demonstrate that IL-26 was effectively involved in this activity, we performed the assay using transfected ACD PBMCs by siRNA for IL-26. Indeed, we demonstrated that these cells were less able to kill keratinocytes compared with ACD PBMCs (P < .01). In conclusion, our findings support the idea that this emergent cytokine, IL-26, is implicated in the killing mechanisms of KC observed during ACD., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Accumulating evidence suggests that Toll-like receptor (TLR)-3 signaling is involved in non-infectious immune and inflammatory reactions as well as in viral infections. The skin of patients with atopic dermatitis (AD) is often infected with virus and bacteria, leading to the aggravation of atopic symptoms. These findings suggest TLR3 signaling may be involved in the pathogenesis of AD, but the exact role of TLR3 in AD remains to be defined., Objective: The purpose of this study was to investigate the role of TLR3 in chronic contact hypersensitivity reactions induced by repeated elicitation, resembling the features of AD., Methods: Wild-type (WT) and Toll-like receptor 3 knockout (Tlr3 KO) mice were sensitized, and chronic contact hypersensitivity reactions were elicited in their ear skin via repeated application of a hapten, 2,4,6-trinitro-1-chlorobenzene (TNCB) or oxazolone., Results: The Tlr3 KO mice exhibited less ear swelling, less leukocyte infiltration into the skin, and lower serum total IgE levels than WT mice after hapten challenge. The Tlr3 KO mice also displayed lower expression levels of inflammatory cytokines (interleukin (IL)-33, IL-4, IL-10, and interferon-ɤ in their TNCB-treated ear skin than WT mice., Conclusion: These results showed that TLR3 deficiency suppressed the development of chronic contact hypersensitivity reactions, suggesting that TLR3 signaling may participate in the pathogenesis of AD., (Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the possible role of IL17-and IL22-secreting cells combined with patch test for the prediction of formaldehyde-induced occupational allergic contact dermatitis(OACD). Methods: From October 2014 to October 2016, totally 131 formaldehyde-exposed workers(49 cases with inflammatory skin lesions,82 ones without inflammatory skin lesions)and 63 non-exposed health controls were recruited. Patch-test was performed in 49 cases of formaldehyde-exposed workers with inflammatory skin lesions. Circulating IL17+and IL22+Tcell subsets were assessed by flow cytometry(FCM). Results: Among 49 cases of formaldehyde-exposed workers with inflammatory skin lesions,32 cases were with positive patch-test while 17 cases with negative patch-test. The proportions of circulating CD3+CD8-IL17+ and CD3+CD8-IL22+ cells from patch-test(+) formaldehyde-exposed workers were significantly higher than that of patch-test(-)group, formaldehyde-exposed workers without skin lesions and non-exposed controls( P <0.05). The proportions of circulating CD3+CD8-IL17+ and CD3+CD8-IL22+cells from patch-test(-)group and formaldehyde-exposed workers without skin lesions were also higher than that of non-exposed controls( P <0.05). But there was no significant difference between patch-test(-)group and formaldehyde-exposed workers without skin lesions( P >0.05). Peripheral CD3+CD8+IL17+and CD3+CD8+IL22+cells were also detected in spite of small amounts. The percentages of CD3+CD8+IL17+and CD3+CD8+IL22+ cells inperipheral blood from patch-test(+)formaldehyde-exposed workers were enhanced significantly, compared to patch-test(-)group, formaldehyde-exposed workers without skin lesions and non-exposed controls( P <0.05). The proportions of circulating CD3+CD8+IL17+ and CD3+CD8+IL22+ cells from patch-test(-)group and formaldehyde-exposed workers without skin lesions were significantly higher than that of non-exposed controls( P <0.05). But there was no significant difference between patch-test(-) group and formaldehyde-exposed workers without skin lesions( P >0.05). Conclusion: The proportions of circulating IL17+ and IL22+T cells(both CD8-and CD8+)are enhanced in formaldehyde-exposed workers at proposed OEL, possibly involved in the development of formaldehyde-induced OACD.The detection of IL17-and IL22-secreting cells combined with formaldehyde patch test help to screen the workers with allergy property and prevent OACD.

Objectives: The aim of this study was to investigate the effects of formaldehyde exposure on Th17 and Th22 cells and its relevance to human occupational allergic contact dermatitis (OACD)., Methods: Circulating IL17-/IL22-secreting cells and serum IL17/IL22 levels in formaldehyde-exposed workers at Occupational Exposure Limit and nonexposed controls were assessed., Results: The IL17 and IL22 cell population were detected in both CD3CD8 and CD3CD8 cells. The percentages of circulating IL17 and IL22 T cells in the workers with and without ACD history were all elevated, which were more remarkable in the ones with ACD history. Serum levels of IL17 and IL22 between the workers and controls were not significantly different., Conclusions: Low-level formaldehyde exposure may increase circulating IL17-/IL22-producing T cells (CD8 and CD8), possibly involved in the development of human OACD. But it may not alter serum levels of IL17/IL22 before the appearance of OACD symptoms.

In this chapter we will first introduce the pathophysiological process of several skin diseases including allergic dermatitis, a common skin disease, including chronic allergic contact dermatitis (CACD), and atopic dermatitis (AD). In CACD and AD patients, repeated skin exposure to antigens contributes to the development of chronic eczematous lesions. Repeated application of haptens on mice allows emulation of the development of CACD in humans. Further, we will focus on H1, H2, and H4 histamine receptors and their effects on CACD and AD. Histamine-deficient mice, with a knockout histidine decarboxylase (HDC) gene, were used to investigate the role of histamine in CACD and AD. Histamine induces infiltration of inflammatory cells, including mast cells and eosinophils, and elevates Th2 cytokine levels in CACD. Histamine promotes the development of eczematous lesions, elevates IgE serum levels, and induces scratching behavior in CACD. The administration of H1 or H4 receptor antagonists was effective to ameliorate these symptoms in murine CACD models. The combination of H1 and H4 receptor antagonists is a potential therapeutic target for chronic inflammatory skin diseases such as CACD and AD, since combined therapy proved to be more effective than monotherapy.

Background: Allergic contact dermatitis (ACD) is associated with increased production of cytokines. The patch test is the "gold-standard" diagnostic method, but it poses a risk of false results., Objective: To evaluate a novel laboratory technique, the Luminex LiquiChip, which simultaneously measures blood levels of multiple cytokines, as a diagnostic tool in patients with chrome-induced ACD., Methods: The study group included 20 patients with ACD and relevant patch test results for potassium dichromate and 19 patients with ACD for nickel or fragrance as control. Peripheral blood mononuclear cells (PBMCs) were cultured in the presence and absence of potassium dichromate. The Luminex LiquiChip was used to measure levels of the following cytokines: granulocyte-macrophage colony-stimulating factor, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, interferon-γ, and tumor necrosis factor (TNF)-α., Results: Potassium dichromate-stimulated PBMCs secreted significantly higher amounts of all cytokines except TNF-α than nonstimulated PBMCs. PBMCs from patients with ACD to chromium secreted significantly higher amounts of all cytokines tested, except IL-4, compared to PBMCs from patients with ACD to nickel or fragrance., Conclusions: Potassium dichromate stimulates the production of both Th1- and Th2-type cytokines in patients with chrome allergy. The Luminex LiquiChip is a promising in vitro method and may serve as a diagnostic tool for ACD., (© 2017 S. Karger AG, Basel.)

Purpose: The aim of the study was to evaluate serum osteopontin (OPN) concentrations in patients with disseminated form of allergic contact dermatitis (ACD), and to assess the relationship between serum OPN level and disease severity., Patients and Methods: Twenty-four patients with numerous allergic contact dermatitis lesions and twenty-two age- and sex-matched healthy subjects as a control group were enrolled in the study. Serum osteopontin levels were measured in the ACD patients twice: in the acute stage and during disease remission by ELISA., Results: Serum OPN concentrations were significantly increased in patients with disseminated ACD examined in the acute stage as compared to healthy subjects and ACD patients during remission (p<0.01 and p<0.001, respectively). In the ACD patients with extensive skin lesions (EASI>10), OPN serum levels were significantly higher than in those with mild disease (EASI<10)., Conclusions: Acute disseminated ACD is characterized by elevated serum concentrations of osteopontin, with levels depending on ACD severity, which indicates its role in the elicitation phase of allergic contact dermatitis. The possibility of inhibition of OPN activity may create a new therapeutic perspective in severe forms of this troublesome skin disease., (Copyright © 2015 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Background: The skin is a key route of human exposure to nanomaterials, which typically occurs simultaneously with exposure to other chemical and environmental allergen. However, little is known about the hazards of nanomaterial exposure via the skin, particularly when accompanied by exposure to other substances., Results: Repeated topical treatment of both ears and the shaved upper back of NC/Nga mice, which are models for human atopic dermatitis (AD), with a mixture of mite extract and silica nanoparticles induced AD-like skin lesions. Measurements of ear thickness and histologic analyses revealed that cutaneous exposure to silica nanoparticles did not aggravate AD-like skin lesions. Instead, concurrent cutaneous exposure to mite allergens and silica nanoparticles resulted in the low-level production of allergen-specific IgGs, including both the Th2-related IgG1 and Th1-related IgG2a subtypes, with few changes in allergen-specific IgE concentrations and in Th1 and Th2 immune responses. In addition, these changes in immune responses increased the sensitivity to anaphylaxis. Low-level IgG production was induced when the mice were exposed to allergen-silica nanoparticle agglomerates but not when the mice exposed to nanoparticles applied separately from the allergen or to well-dispersed nanoparticles., Conclusions: Our data suggest that silica nanoparticles themselves do not directly affect the allergen-specific immune response after concurrent topical application of nanoparticles and allergen. However, when present in allergen-adsorbed agglomerates, silica nanoparticles led to a low IgG/IgE ratio, a key risk factor of human atopic allergies. We suggest that minimizing interactions between nanomaterials and allergens will increase the safety of nanomaterials applied to skin.

Allergic contact dermatitis (ACD) is a hapten-specific CD4(+) T-cells mediated inflammatory response of the skin. Its pathomechanism involves 2 phases, an induction phase and an elicitation phase. Langerhans cells (LCs) and dendritic cells (DCs) in the skin play key roles in presenting low molecular weight chemicals (haptens) to the lymph nodes. Therefore, inhibition of the migration of LCs or DCs and T-cell proliferation is each expected to control ACD disease. To explore the effectiveness of paeoniflorin (PF) on the migration of LCs and T-cell proliferation in vivo, we establish a murine model of ACD, promoted by repeated exposure to an allergen (specifically 1-Chloro-2,4-dinitrobenzene (DNCB)). Administration of PF inhibits DC migration in this DNCB-induced model in the induction phase. As a result, epidermal LC density in the elicitation phase increased in PF-treated mice when compared to PF-untreated mice. At the same time, PF reduced IFN-γ(+)CD4(+) and IL-17(+)CD4(+) T cells proliferation (but not IL-4(+)CD4(+) T cells proliferation), leading to an attenuated cutaneous inflammatory response. Consistent with this T-cell proliferation profile, secretions of IFN-γ and IL-17 were reduced and IL-10 secretion increased in PF-treated mice, but production of IL-4 and IL-5 remained unchanged in the skin and blood samples. These results suggest that oral administration of PF can treat and prevent ACD effectively through inhibition of DC migration, and thus decrease the capacity of DCs to stimulate Th1 and Th17 cell differentiation and cytokine production., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Allergic contact dermatitis (ACD) is an inflammatory skin disease caused by repeated skin exposure to contact allergens. The goal of this pilot study was to identify inflammatory proteins which can serve as biomarkers for ACD., Methods: We measured levels of 102 cytokines, chemokines, and growth factors in the sera of 16 ACD patients during acute and remission phases, and 16 healthy volunteers., Results: Serum levels of adiponectin, chemokine (C-C motif) ligand 5 (CCL5), C-reactive protein (CRP), chitinase 3-like 1 (CHI3L1), complement factor D (CFD), endoglin, lipocalin-2, osteopontin, retinol-binding protein 4 (RBP4), and platelet factor 4 (PF4) were significantly higher, whereas levels of trefoil factor 3 (TFF3) were significantly lower, in ACD patients than in healthy controls. In ACD patients, serum levels of CCL5 were elevated, whereas levels of TFF3, soluble intercellular adhesion molecule-1 (sICAM-1), and platelet-derived growth factor (PDGF)-AB/BB were found to be lower during the remission phase of the disease., Conclusions: Serum levels of adiponectin, CCL5, CRP, CHI3L1, CFD, endoglin, lipocalin-2, osteopontin, RBP4, PF4, and TFF3 might be exploited as biomarkers for ACD, whereas levels of CCL5, TFF3, sICAM-1, and PDGF-AB/BB might be exploited for evaluation of disease progression and efficacy of ACD treatment., (© 2016 S. Karger AG, Basel.)

Background: Allergy to volatile anaesthetics is extremely rare, but capable of damaging the professional career., Methods: This article presents the case of a 60-year-old surgeon who developed a skin rash on the reverse of hands, which progressively worsened and extended to distant fold areas. Blood tests were normal but for eosinophilia and risen total IgE, with normal specific globulins and skin prick tests for common allergens. After 8 years, a malfunction in the anaesthetic gas scavenging system was found, and symptoms remitted within a week following its replacement. Repeated open application test with sevoflurane led to the appearance of the same lesions in the tested areas and in distant body folds., Results: We hypothesize that the most probable mechanism for the reaction in our patient is systemic allergic contact dermatitis, which is caused by repeated systemic exposure to a hapten that reaches the skin through haematogenous transport in a sensitized patient., Conclusions: The report aims to warn about the potential aetiological relationship between exposure to inhaled anaesthetics and allergic manifestations with cutaneous symptoms., (© 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Occupational allergic contact dermatitis (OACD), to which atopy contributes to a as yet unspecified degree, accounts for a considerable number of work-related diseases., Objectives: We studied the prevalence of atopy in OACD patients. We also compared the ability of prick tests and specific IgE assays to detect it., Methods: In 329 patients diagnosed with OACD at the Occupational Medicine Unit of Cagliari University Hospital between 2000 and 2009, we aimed at detecting atopic conditions with prick tests and IgE assays specific for allergens most frequently responsible for atopic reaction. A kappa test was used to assess concordance between the two assays. The 2 test for trend was used in the analysis of prevalence of atopy by age at diagnosis., Results: A positive response was more frequently detected with prick tests (35.9%) than the specific IgE assays (31%). IgE assays for all the allergens we tested were more frequently positive among males (p range = 0.001-0.037). With either test, the highest observed prevalence of a positive response was to Dermatophagoides pteronyssinus. A significantly inverse trend with increasing age in the prevalence ofpositive reaction to Dermatophagoides pteronyssinus, Phleum pratense and Olea europaea (olive) allergens was also observed. The concordance between the two tests ranged between good (Dermatophagoides pteronyssinus, Phleum pratense and Olea europaea and moderate Artemisia vulgaris (mugwort) and Parietaria judaica., Conclusions: Our results showed a prevalence of atopic conditions in 31-35.9% of OACD patients., Results: with the two assays were largely consistent, indicating that both prick tests an specific IgE assays are valid diagnostic tools for atopy.

Background: Mast cells are involved in a number of diseases, including inflammatory diseases such as asthma. Tryptase is a known marker of mast cell burden and activity. However, little is known about the genetic influence on serum tryptase variation. Also, only few and conflicting data exist on serum tryptase in asthma., Objective: To estimate the overall contribution of genetic and environmental factors to the variation in serum tryptase and to examine the correlation between serum tryptase and asthma, rhinitis, markers of allergy, airway inflammation, and airway hyperresponsiveness (AHR) in a sample of Danish twins., Methods: A total of 575 twins underwent a skin prick test and had lung function, AHR to methacholine, exhaled nitric oxide and serum tryptase measured. Multiple regression and variance components models (using the statistical package SOLAR) were computed., Results: Serum tryptase values were available in 569 subjects. Intraclass correlations of serum tryptase in monozygotic and dizygotic twin pairs were 0.84 and 0.42 (P < .001). Variance decomposition showed that genetic factors accounted for 82% (95% confidence interval 74-90, P < .001) of the variation in serum tryptase. Body mass index and sex, but not asthma, rhinitis, or AHR, were correlated to serum tryptase., Conclusion: As much as 82% of the variation in serum tryptase is due to genetic factors. Body mass index and sex, but not asthma or AHR to methacholine, correlate to serum tryptase. A genetic overlap may exist between serum tryptase and body mass index., (Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The efficacy of AQX-1125, a small-molecule SH2-containing inositol-5'-phosphatase 1 (SHIP1) activator and clinical development candidate, is investigated in rodent models of inflammation., Experimental Approach: AQX-1125 was administered orally in a mouse model of passive cutaneous anaphylaxis (PCA) and a number of rodent models of respiratory inflammation including: cigarette smoke, LPS and ovalbumin (OVA)-mediated airway inflammation. SHIP1 dependency of the AQX-1125 mechanism of action was investigated by comparing the efficacy in wild-type and SHIP1-deficient mice subjected to an intrapulmonary LPS challenge., Results: AQX-1125 exerted anti-inflammatory effects in all of the models studied. AQX-1125 decreased the PCA response at all doses tested. Using bronchoalveolar lavage (BAL) cell counts as an end point, oral or aerosolized AQX-1125 dose dependently decreased the LPS-mediated pulmonary neutrophilic infiltration at 3-30 mg kg⁻¹ and 0.15-15 μg kg⁻¹ respectively. AQX-1125 suppressed the OVA-mediated airway inflammation at 0.1-10 mg kg⁻¹. In the smoke-induced airway inflammation model, AQX-1125 was tested at 30 mg kg⁻¹ and significantly reduced the neutrophil infiltration of the BAL fluid. AQX-1125 (10 mg kg⁻¹) decreased LPS-induced pulmonary neutrophilia in wild-type mice but not in SHIP1-deficient mice., Conclusions: The SHIP1 activator, AQX-1125, suppresses leukocyte accumulation and inflammatory mediator release in rodent models of pulmonary inflammation and allergy. As shown in the mouse model of LPS-induced lung inflammation, the efficacy of the compound is dependent on the presence of SHIP1. Pharmacological SHIP1 activation may have clinical potential for the treatment of pulmonary inflammatory diseases., (© 2012 Aquinox Pharmaceuticals Inc. British Journal of Pharmacology © 2012 The British Pharmacological Society.)

Purpose: Despite the importance of skin exposure, studies of skin symptoms in relation to exposure and respiratory symptoms are rare. The goals of this study were to describe exposure-response relationships for skin symptoms, and to investigate associations between skin and respiratory symptoms in bakery and auto body shop workers., Methods: Data from previous studies of bakery and auto body shop workers were analyzed. Average exposure estimates for wheat allergen and isocyanates were used. Generalized linear models were constructed to describe the relationships between exposure and skin symptoms, as well as between skin and respiratory symptoms., Results: Data from 723 bakery and 473 auto body shop workers were analyzed. In total, 5.3% of bakery and 6.1% of auto body shop workers were female; subjects' mean age was 39 and 38 years, respectively. Exposure-response relationships were observed in auto body shop workers for itchy or dry skin (PR 1.55, 95% CI 1.2-2.0) and work-related itchy skin (PR 1.97, 95% CI 1.2-3.3). A possible exposure-response relationship for work-related itchy skin in bakery workers did not reach statistical significance. In both groups, reporting skin symptoms was strongly and significantly associated with reporting respiratory symptoms, both work-related and non-work-related., Conclusions: Exposure-response relationships were observed for skin symptoms in auto body shop workers. The lack of significant exposure-response associations in bakery workers should be interpreted cautiously. Workers who reported skin symptoms were up to four times more likely to report respiratory symptoms. Improved awareness of both skin and respiratory outcomes in exposed workers is needed.

Ethnopharmacological Relevance: Indirubin, isolated from Indigo naturalis (Apiaceae) is a purple 3,2- bisindole and a stable isomer of indigo. Although it is known to have anti-inflammatory activities, its mechanism of action has not been elucidated., Materials and Methods: Seven-week-old female BALB/c mice were sensitized with 1-chloro-2,4-dinitrobenzene (DNCB) to induce skin inflammation. Hematoxylin and eosin staining was performed to assess epidermal and dermal hyperplasia, which were determined by measuring the thicknesses of the epidermis and dermis, respectively. We also evaluated serum immunoglobulin E (IgE) levels and cytokines production, such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, 6 and Interferon (IFN)-gamma. In addition, we investigated nuclear factor (NF)-κB, IκB-α and mitogen-activated protein (MAP) kinase activities for verifying the molecular mechanism of inflammation., Results: Indirubin treatment suppressed skin inflammation in DNCB-exposed mice. The skin lesions were significantly thinner in the Indirubin-treated group than in untreated controls, and the hyperkeratosis disappeared. Indirubin reduced the total serum IgE level and cytokines production. In addition, it normalized NF-κB, IκB-α and MAP kinase expression., Conclusions: Indirubin might be a useful treatment for allergic contact dermatitis via regulating the co-expression of T helper (Th) 1 and 2 cell-mediated immune responses., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: To obtain the prevalence of allergic rhinitis (AR) in different regions of northern China, to analyze the correlation and interaction between AR and bronchial asthma (BA) or atopic dermatitis (AD), and to provide reference for the prevention and treatment of allergic diseases such as AR., Methods: To obtain the indexes including age, occupation, atopic physical fitness, smoking, alcohol, lifestyle and so on. To explore the correlation between AR and BA or AD. From April 2007 to May 2010, the serum specific IgE (sIgE) was investigated in different regions (rural areas of Qingxian, Hebei; coastal fishing village of Bohai Bay, Huanghua; area of Wuling Mountain, Chengde; urban areas of Tianjin) by randomly multi-stage and cluster sampling, with total population of 1524., Results: The prevalence of AR, BA and AD were 9.1%, 5.4% and 6.0%. The prevalence of BA and AD were 30.9% and 29.5% in AR patients, but were 2.9% and 3.7% in non-AR, and the differences were of statistical significance (χ(2) values were 192.97 and 148.40, respectively, all P < 0.01). The risk of people with BA suffering from AR was as 8.619 times as those free from BA, the risk of people with AD suffering from AR was as 1.817 times as those free from AD and, the risk of workers suffering from AR was as 2.320 times as farmers in terms of working factor by analysis of Logistic regression for AR and BA, AD, age, occupation, atopic physical fitness and other factors., Conclusions: The prevalence of AR are correlated with BA and AD. It is greater between BA and AR than AD and AR in the strength of correlation.

This work was designed to assess the pharmacological effectiveness as a novel anti-atopic dermatitis remedy of a phopholipid mixture purified from pig lung tissues, named KT&G101, using the BALB/c mouse model of allergic contact dermatitis. Allergic contact dermatitis was induced by applying 2,4-dinitrofluorobenzene (DNFB) epicutaneously onto the dorsal skins of mice, and KT&G101 was topically applied onto the skin areas with the lesions. The topical application of KT&G101 (0.05 ml of 10 mg/ml and 20 mg/ml KT&G101, twice a day for 15 days) decreased the total IgE level elevated in the sera of mice undergoing allergic contact dermatitis. KT&G101 was also able to decrease the 2,4-dinitrophenyl (DNP)-specific IgE level elevated in the sera of the model mice. It reduced the incidences of scratching behaviors in the mice undergoing DNFB-induced allergic contact dermatitis. It attenuated some histopathological changes, such as pustule, epidermal hyperplasia, dermatitis and fibroplasia, while it could enhance the recovery of epidermis, in the damaged skin tissues within a relatively short period after the topical application of KT&G101. KT&G101 lessened the expression of cytokines mRNAs, such as Th1-specific IL-2, TNF-β and IFN-γ, and Th2-specific IL-4, in the mouse skin tissues showing the lesions. In brief, it is concluded that KT&G101 alleviates the symptoms involved in induced allergic contact dermatitis in BALB/c mice.

Contact hypersensitivity (CHS) is thought to be associated mainly with the activation of T helper (Th) type 1 cells. However, evidence also suggests that Th type 2 cells (Th2) and cytokines play roles in the development of CHS in humans. The present study examines the Th2 response during the development of CHS in response to 2,4,6-trinitrochlorobenzene (TNCB) in GATA-3-transgenic (GATA-3 Tg) mice. GATA-3 Tg mice were immunized with 7% TNCB applied to abdominal shaved skin. Seven days later, the mice were challenged with 1% TNCB applied to the left ear. Ear swelling, cytokine production in the skin of the ear, and the levels of IgE, IgG1 and IgG2a were measured. Furthermore, we examined the effects of medical treatment on TNCB-induced contact dermatitis using this model. The ear-swelling responses of TNCB-sensitized/challenged GATA-3 Tg mice were significantly greater than those of similarly treated wild-type (WT) mice. The expression of both IL-5 and IL-13 in TNCB sensitized/challenged skin tissues and the IgE response after challenge were obviously increased in the GATA-3 Tg mice, whereas the expression of IFN-γ was identical in the challenged skin tissues of GATA-3-Tg and WT mice. When TNCB-sensitized GATA-3 Tg mice were treated with a high dose of tacrolimus, ear swelling was not significantly decreased, compared with the results in WT mice. These results suggest that GATA-3-induced Th2-dominant responses play a critical role in the pathogenesis of allergic types of dermatitis, such as atopic dermatitis, and may lead to useful new drug development in the future., (Crown Copyright © 2011. Published by Elsevier GmbH. All rights reserved.)

Background: The mechanisms underlying the association between filaggrin (FLG) deficiency and asthma are not known. It has been hypothesized that FLG deficiency leads to enhanced percutaneous exposure to environmental substances that might trigger immune responses. We hypothesized that interactions between FLG deficiency and environmental exposures play a role in asthma development., Objective: We sought to investigate possible interactions between FLG null mutations and tobacco smoking in relation to asthma., Methods: A total of 3471 adults from a general population sample participated in a health examination. Lung function and serum specific IgE levels to inhalant allergens were measured, and information on asthma and smoking was obtained by means of questionnaire. Participants were genotyped for the 2 most common FLG null mutations in white subjects: R501X and 2282del4. Another Danish population was used for replication., Results: The FLG null mutation genotype was significantly associated with a higher prevalence of asthma and decreased FEV(1)/forced vital capacity ratio. In logistic regression analyses with asthma as the outcome, a significant interaction was found between FLG null mutations and smoking status (P = .02). This interaction was confirmed, although it was not statistically significant, in another Danish population study. Interactions between FLG genotype and cumulated smoking exposure were found in relation to asthma (P = .03) and decreased FEV(1)/forced vital capacity ratio (P = .03). A 3-way interaction was found among FLG genotype, smoking, and asthma, suggesting that the FLG-smoking interaction mainly played a role in nonatopic subjects., Conclusion: FLG null mutations modified the effects of smoking on the risk of asthma. This finding might have implications for risk stratification of the population., (Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: Psoriasis vulgaris (PV) is associated with low-grade systemic inflammation., Objective: Cytokines' and growth factors' serum patterns in patients with PV, allergic contact dermatitis (ACD) and healthy subjects were investigated to describe and compare systemic inflammatory responses in these diseases., Methods: A total of 12 inflammation-sensitive biomarkers were analyzed simultaneously by means of the Evidence Investigator™ biochip technology., Results: In PV, proinflammatory tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukins (IL)-1β, -2, -6, -8, and monocyte chemoattractant protein (MCP)-1 were elevated. In ACD, 2 markers, TNF-α and MCP-1, were increased, and regulatory cytokine IL-10 was decreased. Proinflammatory IL-2 had the strongest correlations with other pro- as well as anti-inflammatory cytokines in PV and ACD, whilst IL-6 correlated positively with the Psoriasis Area and Severity Index. Growth factors' levels correlated with MCP-1, but only in PV., Conclusion: Although psoriasis induces a more variegated proinflammatory systemic response, ACD is likewise associated with a systemic increase in inflammatory mediators., (Copyright © 2012 S. Karger AG, Basel.)

In this study, specific oral tolerance induction using interferon-gamma (IFN-γ) could successfully treat food allergies. Allergen-specific IL-10-producing regulatory B cell (Br1) responses are characteristic in immune tolerance of food allergies. The in-vivo effects of IFN-γ on allergen-induced changes in Br1 proportion and numbers in food allergies were investigated. Oral food challenges were conducted and 20 allergic patients to cow's milk were selected. Of these 20 patients, five were treated with IFN-γ and milk (SOTI group), five were treated with only milk, five were treated with only IFN-γ, and five did not receive any treatment. In addition, 10 milk-tolerant subjects were involved in this study. Peripheral blood mononuclear cells (PBMCs) were stimulated using casein and stained for CD5, CD19, annexin V, and IL-10 before and after treatment. Allergy tolerance was induced only in the SOTI group along with induction of allergen-induced Br1 changes. Thus, IFN-γ can show tolerogenic effects in vivo when introduced with an allergen, which may be at least partly due to its effect on allergen-induced Br1 responses., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Leptin belongs to the helical cytokine family and has structural similarity to interleukin (IL)-6, IL-12, IL-15, prolactin, and growth hormone. It is mainly secreted by adipocytes but (at lower levels) also by stomach, skeletal muscle, and placenta. Initially, leptin was considered an antiobesity hormone, but experimental evidence has also shown pleiotropic effects on hematopoiesis, angiogenesis, lymphoid organ homeostasis, and T-lymphocyte functions. Recent evidence indicates that leptin modifies T-cell immunity by promoting T helper 1 proinflammatory immune response and production of cytokines., Objective: The aim of the present study was to evaluate leptin serum levels in patients with allergic contact dermatitis (ACD) and atopic dermatitis and to evaluate the correlation of these levels with different patterns of lymphocyte subpopulations., Methods: Serum leptin was assayed by enzyme-linked immunosorbent assay. Immunophenotypic analysis of peripheral blood was performed by flow cytometry., Results: We found that serum leptin levels were higher in ACD patients than in healthy controls (p = .02). In these patients, an inverse correlation between serum leptin and the percentage of CD4CD25 T lymphocytes was observed (p = .002)., Conclusion: These data seem to suggest that leptin might play a role in the pathogenesis of ACD and thus have implications for the therapy for ACD.

Objective: To investigate the effects of palladium (Pd) nanoparticles on cytokine release from peripheral blood mononuclear cells (PBMCs) of control or Pd-sensitized nonatopic women., Methods: TNF-α, IL-5, IL-10 and IFN-γ release and/or expression from PBMCs incubated in presence of 5 to 10 nm Pd nanoparticles or Pd salt (potassium hexachloropalladate) were determined by enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction analysis. Transmission electronmicroscopy was performed., Results: In lipopolysaccharide-stimulated PBMCs from controls, Pd salt inhibited IFN-γ and IL-10 release, whereas Pd nanoparticles enhanced IFN-γ release and inhibited TNF-α secretion. In lipopolysaccharide-stimulated PBMCs from Pd-sensitized women showing high IFN-γ release, Pd nanoparticles inhibited TNF-α release and Pd salt IL-10 release. TNF-α and IFN-γ release and messenger RNA expression were correlated. Transmission electronmicroscopy demonstrated uptake of nanoparticles in the endocytic compartment and activation of autophagy., Conclusions: Palladium ions and nanoparticles exert different effects in vitro on the expression and release of cytokines., ((C)2011The American College of Occupational and Environmental Medicine)

Osteopontin (OPN) is a phosphoglycoprotein that is expressed by various immune cells in a secreted and intracellular form. It has cytokine, chemotactic and cell signaling functions enhancing Th1 and Th17 immunity and protects against apoptosis. Recent studies found OPN to be modulatory in cell-mediated and immediate-type allergic diseases. In allergic asthma, OPN enhances sensitization but downmodulates Th2-driven IL-4-dominated inflammation. The finding that OPN expression is augmented during specific immunotherapy supports a Th2 suppressive effect of OPN. In Th1-driven delayed-type allergy, such as allergic contact dermatitis, OPN supports dendritic cell migration and IL-12 expression and is secreted by T effector cells and keratinocytes, augmenting Th1-mediated allergy and supporting disease chronification. There are numerous missing links as to how OPN variants modulate allergic inflammation through different OPN receptors. OPN research in allergy is an interesting, rapidly expanding field that has high potential for translational research.

The aim of this study was to evaluate regulatory T lymphocytes (Tregs) in the course of allergic contact dermatitis (ACD) and to elucidate the role of IL-10 and TGF-β in Tregs activity. Peripheral blood CD4(+)CD25(+) and CD4(+)CD25(high) cells were determined by flow cytometry in patients with acute disseminated ACD ('ad', n = 36), acute localized ACD ('al', n = 26), and disseminated ACD during remission ('rd', n = 27) as well as in controls (n = 22). Serum levels of cytokines were measured using ELISA. The mean percentage of CD4(+)CD25(+) and CD4(+)CD25(high) cells in patients with ad ACD was significantly higher than in controls (p < 0.01) and the remaining patients (p < 0.05). Both cell populations were significantly elevated in persons with widespread skin lesions (p < 0.05). In ad patients the CD4(+)CD25(+) increased during three weeks of disease, although the significant increase of CD4(+)CD25(high) was noted only in the third week. Patients with ad ACD showed a significantly decreased serum level of TGF-β1 as compared with controls and the remaining ACD patients. IL-10 level did not differ between all groups. The elevated population of CD4(+)CD25(high) cells in ad ACD patients, and its dependence on the extension of skin lesions, suggest a role of Tregs in regulating the course of ACD. The growing Tregs percentages may indicate their peripheral generation during ACD. The development of lesions despite an increased population of Tregs suggests their functional defect. The role of TGF-β1 in the suppressive activity of Tregs cannot be excluded.

Background: Wheat protein and its derivatives can cause protein contact dermatitis (PCD), which mainly occurs in bakers. Few studies have attempted to identify the allergens responsible for wheat PCD., Objectives: The aim of this study was to identify allergenic wheat proteins in patients with wheat PCD., Methods: Water-soluble and water-insoluble wheat flour proteins were separated by 1- or 2-dimensional gel electrophoresis. IgE-binding proteins were detected by immunoblotting with sera from 3 wheat PCD patients and identified by N-terminal amino acid sequence analysis. The IgE-binding proteins were recombinantly expressed in Escherichia coli and tested against patients' sera., Results: IgE antibodies from the patients' sera reacted with water-soluble proteins rather than water-insoluble proteins, and the 2-dimensional electrophoresis and immunoblotting produced individual IgE-binding patterns. Analysis of the N-terminal amino acid sequence of the IgE-binding proteins from the 2-dimensional gel led to the identification of three glycoproteins, wheat 27-kDa allergen, peroxidase, and purple acid phosphatase. No specific IgE antibodies to their non-glycosylated recombinant proteins were observed., Conclusions: We identified wheat 27-kDa allergen, peroxidase and purple acid phosphatase as candidate allergens for wheat PCD. Our results suggest that glycan moieties in these proteins are involved in IgE binding.

The high frequency of contact allergy to gold in patients with dermatitis was established after exhaustive skin testing, determining the right test agent, the best concentration, and repeated test readings. Metallic gold in contact with skin is slowly ionized, permitting absorption and haptenisation. Contact allergy to gold is statistically correlated to the presence of dental gold. But in many case reports it has also been attributed to wearing gold jewellery, albeit not statistically demonstrated. Epicutaneous testing with gold salts increases the blood gold level, and by intramuscular injection systemic contact dermatitis is provoked in an allergic individual. In coronary heart disease, gold-coated intravascular stents have been shown to be correlated to contact allergy and even to an increased risk of restenosis. Gold is far from inert.

Allergic contact dermatitis to cement is a delayed-type hypersensitivity reaction in which cytokines interferon-gamma (IEN-y) and vascular endothelial growth factor(VEGF) may be involved in persisting erythema and oedema. VEGF and IFN-gamma levels in serum and skin lesions were measured in 32 Egyptian building workers with chronic allergic contact dermatitis due to occupational exposure to cement and 20 healthy controls. Dermatitis patients had significantly higher levels of serum and lesional skin VEGF and IFN-gamma than controls. A significant positive correlation was found between tissue VEGF and the eczema area and severity index (EASI) score in dermatitis patients (r = 0.86). VEGF and IFN-gamma may play a role in the pathogenesis of cement allergic contact dermatitis.

Allergic contact dermatitis is a T cell-mediated immune response, which in its relapsing chronic form is of high socioeconomic impact. The phosphoglycoprotein osteopontin (OPN) has chemotactic and Th1 cytokine functions and in various models is essential for robust T cell-mediated immunity. Here we demonstrate that OPN is abundantly expressed by both effector T cells and keratinocytes in allergic contact dermatitis lesions. T cells from nickel-allergic donors secrete high levels of OPN following antigen-specific stimulation. OPN may substitute for missing IFN-gamma secretion in T effector cells because low IFN-gamma-producing T cell clones secrete high levels of OPN, and OPN down-modulates their interleukin-4 expression. Furthermore, interferon-gamma from T effector cells augments OPN in allergic contact dermatitis by inducing OPN in keratinocytes, which in turn polarizes dendritic cells and attracts inflammatory cells. In the murine contact hypersensitivity (CHS) model for allergic contact dermatitis, OPN is strongly induced in antigen-specific proliferating T cells, and OPN null mice display a reduced chronic CHS inflammatory response due to a decreased influx of effector T cells. Importantly, because of its function for chronic allergic contact dermatitis, OPN may well be a therapeutic target, because anti-OPN antibody treatment in part suppresses established chronic CHS.

We examined the immunomodulatory effect of Eriobotrya japonica seed extract (ESE) on rat allergic dermatitis elicited by repeated dinitrofluorobenzene (DNFB) application on the ear. Oral administration of ESE significantly inhibited development of allergic dermatitis based on lower ear thickness and serum immunoglobulin E (IgE) levels. Th1 cytokine interferon-gamma (IFN-gamma) and interleukin-2 (IL-2), Th2 cytokine interleukin-4 (IL-4) and interleukin-10 (IL-10) in the lesional skin were determined. Oral administration of ESE significantly decreased IL-4 while significantly increasing IL-10 in lesional skin, and the lower levels of IFN-gamma and IL-2 were reversed by oral administration of ESE. The infiltration of eosinophils in the lesional skin was decreased by oral administration of ESE. These results suggested that ESE exerts anti-allergic actions by improving the balance of Th1/Th2 in allergic dermatitis.

Nickel sensitization can not only induce allergic contact dermatitis (ACD), but also can induce an overlapping disease referred to as "systemic nickel allergy syndrome" (SNAS), characterized by urticaria/angioedema and gastrointestinal symptoms correlated to the ingestion of nickel-containing foods. This study was designed to determine if oxidative stress occurs in patients with nickel allergy. Thirty-one female patients (mean age 31.26 + 13.04 years, range 16-64 years) with confirmed nickel CD underwent oral nickel challenge because of clinically suspected SNAS; serum concentrations of protein carbonyl groups (PCGs) and nitrosylated proteins (NPs; biomarkers of oxidative stress) were measured before and after oral nickel challenge as well as in healthy female controls. Twenty-three of these 31 patients were diagnosed with SNAS because they had a positive reaction to the oral nickel challenge, and 8 patients had no reaction and therefore were classified as patients with contact nickel allergy only. Although both nickel-allergic patients and controls presented similar serum levels of PCGs, NP values in nickel-allergic patients appeared higher than in controls and tended to decrease after the challenge; furthermore, serum levels of NPs in patients affected by SNAS were higher (although not significantly) than in patients with nickel ACD only. The involvement of specific biomarkers of oxidative stress such as NPs and the lack of involvement of other biomarkers such as PCGs may help to better understand the alteration of the redox homeostasis occurring in nickel ACD and particularly in SNAS.

Background: We have recently found a correlation between contact allergy to gold sodium thiosulphate (GSTS) and gold concentration in the blood (B-Au) in a stented population: the higher the B-Au, the stronger the patch-test reaction., Objectives: To further investigate the correlation between B-Au and patch-test reactivity to gold., Methods: In this provocation control cross-over trial of 24 patients with dermatitis with a known contact allergy to gold, the patients were randomized into two groups where one was topically provoked to gold (15 mg GSTS) and one to the control. All patients were simultaneously patch tested with GSTS in 10 aqueous dilutions (1.1 mg GSTS). Patch-test readings were performed and blood was drawn. After 6 weeks, the experiment was repeated and the group that had previously been provoked with gold was now provoked with the control and vice versa., Results: B-Au was higher after gold provocation whereas no treatment effect was discerned for minimal eliciting concentration (MEC) or summarized test score (STS). Instead, significant differences in period effect were observed implying higher B-Au and STS and lower MEC on test occasion II. The most likely explanation is the increased B-Au and /or booster effect from test occasion I. There was a correlation between B-Au and MEC: the higher the B-Au, the lower the MEC., Conclusions: The correlation between B-Au and MEC indicates that the B-Au is of importance for the skin reactivity to gold.

Background: Patients with dental gold restorations are known to have a higher level of gold concentration in blood (B-Au)., Objectives: To further investigate, in a study on patients with intracoronary stents and contact allergy to metals, the gold and nickel release from stainless steel stent with (Au stent) and without (Ni stent) gold plating., Method: A total of 460 patients treated with stenting underwent patch testing with metals, and information on gold and nickel exposure and blood samples were collected. About 200 blood samples were randomly selected and the analysis of B-Au and nickel concentration in blood (B-Ni) was made using inductively coupled plasma mass spectrometry., Results: There was a correlation between the intensity of Au patch test reaction and B-Au (P < 0.001). This correlation could not be seen between Ni patch test reaction and B-Ni. A Au stent gave a fivefold higher B-Au than a Ni stent., Conclusions: Gold is released from the Au stent and patients with a Au stent have a fivefold higher B-Au than patients with an Ni stent. The patch test reactions for gold were correlated with B-Au.

Background: Construction workers exposed to cement are known to suffer from occupational contact dermatitis because of chromate sensitization. It is not clear whether certain genotypes are associated with increased susceptibility of chromate sensitization in those workers regularly exposed to cement., Objective: The objective of this study was to determine the genotypes predisposing workers to cement-induced contact dermatitis., Methods: A total of 153 current cement workers who had regular contact with cement were telephone interviewed for skin problems in the past 12 months, work exposure, and personal protection. A dermatologist examined their skin and conducted patch test with common skin allergens. Blood samples were donated for genotypic determination by polymerase chain reaction-based assays for GST-T1, GST-M1 (null/non-null), tumour necrosis factor (TNF) alpha promoter-308G/A, and interleukin (IL) 4-590C/T., Result: High percentage of dermatitis was noted in the 153 workers examined, which was correlated with reported skin problems. By patch testing, construction workers had a high-prevalence rate (12%) of sensitivity to chromate. Sensitivity to chromate was significantly associated with TNF alpha promoter-308 heterozygous (GA) as compared with GG genotype (odds ratio 3.9, 95% confidence interval 1.1-13.2), as well as with GST-T1 null genotype (odds ratio 5.5, 95% confidence interval 1.4-36.2), but neither the GST-M1 nor the IL-4 genotypes., Conclusion: It is concluded that among workers frequently exposed to cement in Southern Taiwan, those with TNF alpha promoter-308 heterozygous (GA) genotype or GST-T1 null genotype had increased risk of chromate sensitization.