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Background: Our previous findings demonstrated that in vitro supplementation of polyphenols, extracted from seeds of red grape (Nero di Troia cultivar), to peripheral lymphomonocytes from patients affected by allergic contact dermatitis (ACD) to nickel (Ni) could reduce the release of proinflammatory cytokines and nitric oxide (NO), while increasing the levels of interleukin (IL)-10, an anti-inflammatory cytokine., Objective: To assess whether an intervention with oral administration of polyphenols leads to a reduction of peripheral biomarkers in ACD patients., Methods: At T0, 25 patients affected by ACD to Ni were orally administered with 300 mg polyphenols prodie extracted from seeds of red grape (Nero di Troia cultivar) (NATUR-OX®) for 3 months (T1). The other 25 patients affected by ACD to Ni received placebo only for the same period of time. Serum biomarkers were analyzed at T0 and T1. In both groups, seven dropouts were recorded., Results: At T1 in comparison to T0, in treated patients, values of interferon-γ, IL-4, IL-17, pentraxin 3 and NO decreased, while IL-10 levels increased when compared with T0 values. Conversely, in placebo- treated patients, no modifications of biomarkers were evaluated at T1., Conclusion: Present laboratory data rely on the anti-oxidant, anti-inflammatory and anti-allergic properties of polyphenols., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A 78-year-old man with no history of allergy, underwent endovascular aortic repair for abdominal aortic aneurysm rupture. Postoperatively, he had low-grade fever and persistently raised white blood cell counts, but tests showed no infection. A skin rash appeared on the trunk and upper arms; we suspected a drug allergy. Despite withdrawal and/or change of medications, the symptoms remained. Finally, a patch test for nickel showed a strongly positive result. Oral prednisone 5 mg·day -1 was started, and the clinical findings resolved thereafter. No recurrence of allergy, infection, or exacerbation of the treated abdominal aortic aneurysm was noted at the 2-year follow-up.

Allergic contact dermatitis to metals has become increasingly recognized in patients with endovascular implants. The ACD can lead to in-stent restenosis as well as a prominent eczematous reaction overlying the implant, often necessitating its removal. We present a case of refractory allergic contact dermatitis to nickel in a 44-year-old man with numerous endovascular stents and vascular clips. He developed numerous adverse effects of systemic therapy to manage his symptoms including recurrent infections leading to frequent hospitalizations. He was effectively transitioned to dupilumab, a monoclonal antibody against the IL-4α subunit currently approved by the Food and Drug Administration in the management of atopic dermatitis, with an improvement in symptoms and a reduction in infection rate.

Background: Nickel (Ni) is a metal largely present in the environment and prolonged exposure to it may lead to multiple pathological conditions in human subjects. Among these, the most frequent is allergic contact dermatitis., Methods: Peripheral blood mononuclear cells isolated from 25 patients with Ni-dependent contact dermatitis were evaluated in terms of cytokine release and nitric oxide (NO) production in the presence or absence of two doses (3 and 5 µg, respectively) of polyphenols., Results: Polyphenols were able to reduce the increased release of interferon-γ and interleukin (IL)-4, while maintaining the equilibrium between IL-10 and IL-17. At the same time, exaggerated release of NO was reduced by polyphenol supplementation., Conclusion: In view of their anti-inflammatory activities, polyphenols may represent a potential therapeutic tool to treat Ni-sensitized patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Topical corticosteroids (TC) consistently show effectiveness against itch, a paradigmatic symptom, in various eczemas. Rapid itch relief is a therapeutic goal. The early response of itch to TC has not been adequately studied., Objectives: To assess the effect on itch of a TC, methylprednisolone aceponate 0.1% ointment (MPA), in induced eczema in volunteers sensitized to nickel sulphate., Methods: Sixteen volunteers with a late positive patch-test reaction to nickel sulphate entered the study. Eczema was treated once daily with ¼ fingertip unit of MPA for 5 days. Pruritus intensity was assessed with a 10 cm visual analogue scale (VAS). Mean time to itch relief (TR ) defined as the time to reach a 30% decrease in the highest VAS value recorded was assessed, as well as TR-baseline, colorimetry and planimetric morphometry of the reaction., Results: Mean TR was 1.0 days [standard deviation (SD) = 1.1] and mean TR -baseline was 1.6 days (SD = 1.4). Five volunteers reached 100% decrease from itch baseline-VAS in 2.0 ± 1.2 days, whereas a 75% decrease was obtained in 1.7 ± 1.6 days by 16 volunteers. A clinical improvement of patch-test reaction was apparent at day 11, although erythema was still present., Conclusion: We present a valid model to assess the efficacy and speed of action of TC treatment to alleviate pruritus and the signs of eczema. The fast effect of MPA against pruritus supports the appropriateness of treating allergic contact eczema with TC., (© 2013 European Academy of Dermatology and Venereology.)

This report details the case of an 11-year-old boy with a history of atopic dermatitis who developed a widespread dermatitis 1 month after receiving a laptop for Christmas. Allergic contact dermatitis to nickel in the laptop was determined as the cause., (© 2014 Wiley Periodicals, Inc.)

Fiddler's neck refers to an irritant contact dermatitis on the submandibular neck of violin and viola players and an allergic contact dermatitis to nickel from the bracket attaching the violin to the chin rest on the violinist's supraclavicular neck. A 26-year-old woman developed submandibular and supraclavicular left neck lesions corresponding to the locations of the chin rest and bracket that was attached to her violin that held it against her neck when she played. Substitution of a composite chin rest, which did not contain nickel, and the short-term application of a low potency topical corticosteroid cream, resulted in complete resolution of the allergic contact dermatitis supraclavicular neck lesion. The irritant contact dermatitis submandibular neck lesion persisted. In conclusion, violin players are predisposed to developing irritant contact dermatitis or allergic contact dermatitis from the chin rest. We respectfully suggest that the submandibular neck lesions from contact with the chin rest be referred to as 'fiddler's neck - type 1,' whereas the supraclavicular neck lesions resulting from contact of the bracket holding the chin rest in place be called 'fiddler's neck - type 2.' A composite chin rest should be considered in patients with a preceding history of allergic contact dermatitis to nickel.

Background: Nickel contact allergy remains common in Western countries, and the dermatitis may require prolonged treatment. The development of new strategies aimed at improving the quality of life of affected individuals is needed., Objectives: To investigate the efficacy of oral hyposensitization in nickel-allergic individuals and how this affects in vitro T cell responsiveness to the metal., Methods: Twenty-eight nickel-allergic patients received a daily dose of 50 µg of elemental nickel (given as NiSO(4) ·6H(2) O) in cellulose capsules for 3 months. Severity of clinical manifestations, in vivo nickel responsiveness and in vitro T cell responses to the metal were assessed after 1 and 3 months., Results: Twenty-six patients finished the study. In these patients, oral hyposensitization ameliorated clinical manifestations despite continued nickel exposures, and increased the threshold of skin responsiveness to nickel. The 12 enrolled patients in the immunological study showed decreased in vitro T lymphocyte responsiveness to the metal, in terms of both cell proliferation and cytokine release. In the 1-year follow-up, 50% of the patients experienced relapses of the clinical manifestations at sites of topical exposure to nickel., Conclusions: Our study suggested therapeutic efficacy of oral hyposensitization in allergic individuals. Placebo-controlled studies are required to confirm the results and determine the optimal therapeutic regimen for prolonged beneficial effects., (© 2011 John Wiley & Sons A/S.)

Nickel is the most common allergen causing allergic contact dermatitis in patch-tested children, especially in female children. Allergy to this metal can manifest in a variety of ways. In this case series, we present four children to illustrate the different presentations of nickel allergy confirmed by patch testing. Localized, id, and systemic nickel reactions are reviewed, as well as the diagnosis and management of nickel allergic contact dermatitis. While localized dermatitis in areas of direct contact to the allergen is the most common and easiest form of nickel allergy to identify, recognition of varying presentations is critical as these can result in more chronic and severe symptoms, and can be misdiagnosed as atopic dermatitis., (© 2010 Wiley Periodicals, Inc.)

Background: Although topical glucocorticoids are effective for most inflammatory skin disorders, their use is limited by local and systemic side effects. Tacrolimus and pimecrolimus are immunomodulators that provide clinicians with steroid-sparing options in the long-term topical treatment of allergic contact dermatitis., Objective: To obtain pilot data regarding the relative efficacies of pimecrolimus 1% cream, tacrolimus 0.1% ointment, clobetasol propionate 0.05% ointment, and triamcinolone acetonide 0.1% ointment, as compared to control preparations (Vanicream and petrolatum), for treatment of experimentally induced nickel contact dermatitis., Methods: Twenty-one volunteers with positive patch test reactions to nickel sulfate 5% at six sites (three on each arm) applied each study medication to one nickel site, respectively, twice daily for 14 days. Study medications were prepared in identical syringes, and the site of application was randomly assigned by a computer-generated randomization schedule. Assessments were performed at 3, 7, 10, and 14 days after randomization., Results: Most reactions were coded as resolved or as almost resolved by day 14 regardless of treatment. Although most pairwise comparisons were not statistically significant, a clear trend was observed for sites treated with active drug to do better than control sites., Conclusion: Possible explanations for these results include contamination by neighboring medication sites, timing of assessments, and lack of repeated nickel applications.

Tacrolimus ointment is a topical immunomodulator. Currently, there is available evidence regarding the potential use of topical tacrolimus in a range of dermatological disorders. The aim of this study was to evaluate the efficacy and safety of tacrolimus ointment 0.1% for the nickel sulfate-induced steroid-resistant allergic contact dermatitis (ACD). A randomized, double-blind, placebo-controlled, parallel-group study design was performed in a total of 28 patients affected by nickel sulfate-induced steroid-resistant ACD after a 14-day run-in period. Then, the enrolled patients were randomized into two subgroups. Group A was treated with tacrolimus for 14 days and finally observed for a 7-day follow-up period. Group B, instead, was treated with placebo (vehicle). Four major symptoms (erythema, oozing, scaling, and itching) were considered as outcomes during the different phases of the study. In group A, during the treatment period with tacrolimus, a significant improvement was observed in all four considered symptoms. On the other hand, no improvement in symptoms was observed in the placebo-treated group B. Local adverse events in the tacrolimus-treated group, such as burning/itching at the application site, were transient and well tolerated. No patients withdrew because of burning/itching. In our study, tacrolimus ointment 0.1% appeared to be both effective and safe in the treatment of nickel sulfate-induced steroid-resistant ACD.

Objective: Tolerability and safety of 0.1% tacrolimus ointment in treating nickel-induced allergic contact dermatitis (ACD) were evaluated., Methods: Patients allergic to nickel applied nickel patches to each upper inner aspect of the arm for 4 to 8 hours daily. Tacrolimus was applied to patch site on one arm and vehicle to patch site on the other, twice daily. Physician's Global Assessment, signs and symptoms of ACD, pruritus scores, and adverse events were evaluated., Results: After 8 weeks, dermatitis in 45% of patients was clear or almost clear (Physician's Global Assessment) with tacrolimus; and 1% with vehicle (P < .001). Significant results were achieved as early as day 8. Tacrolimus was superior in ACD signs and symptoms improvement and pruritus reduction (P < .001). Adverse events were similar between treatments., Limitations: This model, involving one agent, may not be generalizable for other agents., Conclusions: Tacrolimus ointment 0.1% is well tolerated and significantly more effective than vehicle in treating chronically exposed, nickel-induced ACD.

The aim of this study was to evaluate the ability of topical tacrolimus 0.1% under occlusion for 48 h to suppress nickel-elicited allergic contact dermatitis in a randomized, petrolatum- and mometasone furoate 0.1% ointment-controlled double-blind, intra-individual study which included 28 women volunteers. 3 closed patch tests (Finn Chambers on Scanpor, Epitest Ltd Oy, Tuusula, Finland) containing 0.1 ml of 5% nickel sulfate in petrolatum were applied on day 0. After removal on day 2, the study compounds were applied under occlusion for 48 h. The eczema reaction and the degree of erythema were evaluated clinically and by reflectance spectrophotometry at days 4 and 7, respectively. Mean visual scores corresponding to petrolatum-treated sites were significantly higher than those corresponding to both mometasone furoate and tacrolimus at days 4 (P < 0.001) and 7 (P < 0.001). In both tacrolimus- and mometasone furoate-treated sites, there was a significant decrease in visual scores with time (P < 0.001) from day 2 to day 7, and the corresponding mean decreases in scores were 0.73 and 1.04, respectively. The difference between both was 0.30 in favour of tacrolimus (95% confidence intervals, -0.04 and 0.65), although this did not reach statistical significance (P = 0.084). Mean erythema index values were similar at day 2. Significant differences among treatment sites were seen at days 4 (P < 0.001) and 7 (P < 0.001). The decrease was significantly more pronounced on day 7 in patches where tacrolimus had been supplied (P < 0.5). This method might provide useful means to compare different concentrations and/or presentations of tacrolimus or other calcineurin inhibitors and topical anti-inflammatory agents.

Background: Tacrolimus is a macrolactam that prevents the transcription of messenger RNA for various inflammatory cytokines in both helper T cells (types 1 and 2) (T(H)1 and T(H)2). It is currently approved for the treatment of moderate to severe atopic dermatitis, a Th2-mediated disease, in children and adults., Objective: We sought to evaluate the safety and efficacy of tacrolimus ointment 0.1% in the treatment of nickel-induced allergic contact dermatitis, a T(H)1-mediated disease., Methods: This was a double-blind, randomized, vehicle-controlled, bilateral paired comparison study to assess the safety and efficacy of topical tacrolimus (Protopic, Fujisawa Healthcare Inc, Deerfield, Ill) ointment 0.1% in the treatment of allergic contact dermatitis induced by nickel sulfate. Volunteers were individuals with known hypersensitivity to nickel. Reactivity to nickel was graded both as the investigator's global assessment and total signs and symptoms, which consisted of the cumulative grade from 0 to 4 for each of the following parameters: erythema, induration, vesiculation, and pruritus (range of scores: 0-16). Reactivity was assessed in the per-protocol group at 1 and 2 weeks after beginning treatment with study drug and control. Adverse events were assessed in the intent-to-treat population., Results: Of the 19 volunteers who completed the study (per protocol), 18 had an improvement in total signs and symptoms with tacrolimus versus 10 patients with the vehicle. Of patients, 80% had an improvement in the investigator's global assessment score on the tacrolimus-treated site versus 30% of patients on the placebo-treated site. Overall, tacrolimus was more effective than placebo in ameliorating the nickel reaction. Although the tacrolimus treated site was clear or almost clear in a greater number of individuals at week 1, this difference did not become significant until the second week of the study. Other than application site burning in 25% of volunteers, no significant adverse events were noted in the intent-to-treat population., Conclusion: Topical tacrolimus (Protopic, Fujisawa Healthcare Inc) ointment 0.1% may be an option for the treatment of allergic contact dermatitis induced by nickel.

In this study we used the nickel contact allergy patch (CAP) test to investigate the effect of topical corticosteroids on allergic contact dermatitis (ACD). On day 1, three CAP tests were applied for 48 h on the forearms of 20 female volunteers with a known nickel ACD. CAP of the right forearm contained 5% nickel, and of the left forearm physiological saline. Clinical scoring, transepidermal water loss and skin hydration were measured on day 1 before CAP application, on day 4 (0, 2 and 6 h) after ACD and from days 5 to 8 (0 h). A topical corticosteroid and its vehicle were applied twice daily starting from day 4 on two ACD sites. Transepidermal water loss values were significantly decreased on the topical-corticosteroid-treated sites in the early phase of ACD (day 4, 6 h after the first application) while clinical efficacy showed significant improvement on days 7 and 8. The vehicle was found to improve skin hydration only on day 8. In conclusion the topical corticosteroid improved the skin barrier function in the early inflammatory phase of ACD (day 4, 6 h). The lack of improvement in transepidermal water loss in the later phase of ACD might be accounted for by the secondary effects of the corticosteroid on proliferation and differentiation of keratinocytes.

We adapted our mouse model of allergic contact hypersensitivity to nickel for the study of tolerance. Sensitization in this model is achieved by the administration of nickel ions with H(2)O(2); nickel ions alone are unable to prime naive T cells, but can restimulate primed ones. A 4-wk course of oral or i.p. administration of 10 mM NiCl(2) to naive mice induced tolerance, preventing the induction of hypersensitivity for at least 20 wk; long term desensitization of nickel-sensitized mice, however, required continuous NiCl(2) administration. When splenic T cells of orally tolerized donors, even after a treatment-free interval of 20 wk, were transferred to naive recipients, as with lymph node cells (LNC), they specifically prevented sensitization of the recipients. The LNC of such donors were anergic, because upon in vivo sensitization with NiCl(2) in H(2)O(2) and in vitro restimulation with NiCl(2), they failed to show the enhanced proliferation and IL-2 production as seen with LNC of mice not tolerized before sensitization. As few as 10(2) bulk T cells, consisting of both CD4(+) and CD8(+) cells, were able to specifically transfer tolerance to nickel. A hypothesis is provided to account for this extraordinarily high frequency of nickel-reactive, suppressive T cells; it takes into account that nickel ions fail to act as classical haptens, but form versatile, unstable metal-protein and metal-peptide complexes. Furthermore, a powerful amplification mechanism, such as infectious tolerance, must operate which allows but a few donor T cells to tolerize the recipient.

Background: Nickel (Ni) allergic contact dermatitis (ACD) alters the skin barrier., Objective: Our aim was to compare the efficacy of combination therapies on ACD, using a topical corticosteroid and a corneotherapy agent (barrier cream), with that of a single therapy with corticosteroids., Methods: On day 1, 3 Ni test patches were applied on each forearm of 14 Ni-patch-test-positive females. Four contained 5% Ni and 2 physiological saline. Either topical corticosteroid or barrier cream were matched with the combination of both products on 3 of the 4 Ni ACD. The fourth was not treated. Clinical scoring, transepidermal water loss (TEWL) and stratum corneum (SC) capacitance were measured before (day 1) and after (days 4-8) ACD., Results: The combination therapy showed a significant decrease in TEWL values and an increase in SC capacitance., Conclusion: Combining a topical corticosteroid with corneotherapy agents prevents the delay in the healing process of skin barrier disruption due to ACD., (Copyright 2001 S. Karger AG, Basel)

We review controlled trials of corticosteroid effect in experimentally elicited acute nickel contact dermatitis in man, in the hope of clarifying optimal efficacy for clinical use. To maximize discrimination and objectivity, we focus on data with 1 well-characterized allergen, nickel, in studies utilizing bioengineering documentation. Higher potency corticosteroids are effective (unlike in experimental irritant contact dermatitis), but optimum schedules still require definition.

Techniques to determine efficacy of topical agents on allergic contact dermatitis (ACD) may benefit from refinement. The aim of this study was to develop an in vivo human model system for the bioengineering and visual quantification of the effect of topical agents on nickel ACD, and to correlate ACD parameters. 14 nickel patch-test-positive subjects were included in a placebo-controlled, double-blind study after a pre-screening procedure with a standard diagnostic patch test with nickel sulfate in 54 healthy human volunteers. 5% nickel sulfate in petrolatum in a Finn Chamber was applied on forearm skin for 48 h to create a standardized dermatitis. Thereafter, the dermatitis was treated with a model topical agent and a placebo control while recording endpoint parameters daily for 10 days. Resolution was quantified with 4 parameters: visual scoring (VS), transepidermal water loss (TEWL) (Tewameter), skin blood flow volume (BFV) (laser Doppler flowmeter), and skin color (a* value) (Colorimeter). The model agent reduced cutaneous allergic reactions, especially on day 8 to 10, in comparison with the placebo control. A highly significant linear relationship exists among all parameters, except between a* and BFV. This model may provide robust biometrics for determining the efficacy of topical therapeutics on experimentally induced ACD.

In a group of nickel sensitized women, we investigated the effects of topical application of testosterone propionate on the epidermic density of CD1 + dendritic cells and on the response to patch tests performed with scaled nickel concentrations. In a significant number of examined subjects, treatment with testosterone propionate induced an increase of the minimum eliciting dose of nickel and an evident reduction of CD1 + dendritic cell epidermic density. In those subjects in which the minimum eliciting dose resulted unmodified, the epidermic density of CD1 + dendritic cells also did not undergo significant variations following treatment with testosterone propionate. This parallelism between the behaviour of the responses to patch tests and the epidermic density of CD1 + dendritic cells induces us to think it possible that testosterone propionate is able to increase the tolerance to contact with allergen by interfering with the activity of Langerhans cells. The possible mechanisms of testosterone action on Langerhans cells remain to be elucidated.

We report a confirmed case of intraoral contact mucositis secondary to nickel dental alloy hypersensitivity. The lesion resolved after removal of the offending prosthesis. The patient responded negatively to dermatologic patch tests, but a positive intraoral rechallenge confirmed the mucositis diagnosis. A nonreactive, gold alloy prosthesis was inserted for a successful result.

Background: Nickel sensitivity is a common problem, often causing significant morbidity from chronic eczematous dermatitis. The main treatment, topical steroids, usually is unable to suppress the dermatitis completely., Objective: Our purpose was to study the effects of "barrier" ointments containing either chelating agents (clioquinol or ethylenediaminetetraacetic acid [EDTA]) or antioxidants (ascorbic acid or alpha-tocopherol) and 1% hydrocortisone on nickel-induced hypersensitivity reactions., Methods: Nickel-sensitive subjects were challenged with nickel-containing coins coated with the desired barrier ointment and their inhibitory effects observed. Patients with bilateral hand or earring dermatitis explored the efficacy of these agents in clinical use., Results: Clioquinol (3%) completely abolished the allergic reaction in all 29 subjects tested. EDTA (15%), ascorbic acid (20%), and alpha-tocopherol (10%) were less effective, and 1% hydrocortisone had no significant effect. In clinical use sites treated with a commercially available preparation containing 3% clioquinol and 1% hydrocortisone showed marked clinical improvement in all 10 subjects., Conclusion: Clioquinol is a potent inhibitor of nickel-induced hypersensitivity reactions and is feasible to use as a barrier ointment to block the allergenic effects of nickel in sensitive patients.