Gramineae pollen as trigger factors of atopic eczema: evaluation of diagnostic measures using the atopy patch test

After contact with grass pollen, seasonal exacerbations of eczematous skin lesions have been described in a subgroup of patients with atopic eczema (AE). Epicutaneous patch testing with aeroallergens (atopy patch test, APT) has been used to investigate these patients. We performed comparative APT in 79 patients with AE and 20 control subjects (14 non-atopic volunteers and six patients with grass pollen allergic rhinoconjunctivitis). Subjects were tested with grass pollen allergen extract in petrolatum and with unprocessed native dry pollen of Dactylis glomerata . Results after 48 h were compared with the patient's history, corresponding skin prick test and specific IgE. Fifteen of the 79 AE patients showed clear-cut eczematous reactions to unprocessed D. glomerata pollen; 14 of these had an elevated serum IgE to D. glomerata and 13 had a positive skin prick test. Twenty patients had a positive APT reaction to grass pollen allergen extract, including 12 of the D. glomerata reactive subjects ( P  < 0.001). Positive patch test reactions to D. glomerata were seen in 66.7% of cases with and 10.5% of patients without a predictive history of exacerbations during the pollen season. For the standardized extract, these percentages were 75% vs. 16.4% ( P  < 0.001). No side-effects were observed. Control subjects showed no positive reactions. We conclude that grass pollen preparations may be used to investigate trigger factors for eczematous skin lesions in a subgroup of patients with AE.     

CD4+ T cells producing interleukin (IL)‐17, IL‐22 and interferon‐γ are major effector T cells in nickel allergy

Background It has been suggested that interleukin (IL)‐17 and IL‐22 play important roles in the elicitation of human allergic contact dermatitis; however, the frequencies of T cell subtypes producing IL‐17 and IL‐22 in human allergic contact dermatitis are unknown. Objectives To determine the frequencies of CD4⁺, CD8⁺ and γδ T cells producing IL‐17, IL‐22 and interferon (IFN)‐γ in the blood and skin from nickel‐allergic patients. Patients/materials/methods Blood samples were collected from 14 patients and 17 controls, and analysed by flow cytometry. Biopsies were taken from 5 patients and 6 controls, and analysed by immunohistochemistry and flow cytometry of skin lymphocytes. Results We found an increased frequency of γδ T cells in the blood, but no differences in the distribution of cytokine‐producing CLA⁺ T cell subtypes in nickel‐allergic patients as compared with controls. In nickel‐allergic patients, there was massive cellular infiltration dominated by CD4⁺ T cells producing IL‐17, IL‐22 and IFN‐γ in nickel‐challenged skin but not in vehicle‐challenged skin. Conclusion CD4⁺ T cells producing IL‐17, IL‐22 and IFN‐γ are important effector cells in the eczematous reactions of nickel‐induced allergic contact dermatitis in humans.     

Omalizumab therapy in atopic dermatitis: depletion of IgE does not improve the clinical course – a randomized,placebo‐controlled and double blind pilot study

Background: Our understanding of the pathogenic role of IgE in atopic dermatitis is incomplete. We asked whether blocking free IgE would alter the course of the disease. Patients and Methods: We administered either omalizumab, a humanized monoclonal mouse antibody against IgE, or placebo subcutaneously for 16 weeks to 20 atopic dermatitis patients and measured immunological and clinical disease parameters. Results: Omalizumab (I) reduced free serum IgE, (II) lowered surface IgE and Fc?RI expression on different peripheral blood mononuclear cells, (III) reduced the saturation of Fc?RI with IgE, (IV) increased the number of free Fc?RI and (V) lowered the number of IgE+, but not of Fc?RI+ cells in skin. The in vivo relevance of these results is evidenced by the increase in the threshold allergen concentration required to give a type I hypersensitivity reaction in the titrated skin test. While not significantly altering the clinical disease parameters, omalizumab treatment led to an improvement of the atopy patch test results in single patients, i.e. an eczematous reaction upon epicutaneous allergen challenge. Conclusions: The interference with immediate and delayed type skin tests may imply that a therapeutic benefit of omalizumab treatment, if present at all, would be seen in patients with acute rather than chronic forms of the disease.     

Atopie-Patch-Test mit Aeroallergenen und Nahrungsmitteln

The atopy patch test (APT), a patch test employing allergens known to elicit IgE-mediated reactions which is assessed by evaluating eczematous skin lesions after 24 h to 72 h, was developed as a diagnostic tool for characterizing patients with aeroallergen-triggered atopic eczema (AE, atopic dermatitis). Positive APT reactions are associated with allergen-specific T-cell responses. The specificity of APT is higher than the specificity of skin prick tests or RAST. More studies for the standardization of APT methods are necessary, especially with regard to food APT.     

The disturbance of epidermal barrier function in atopy patch test reactions in atopic eczema

Summary Atopic eczema (AE) is a common skin disorder. Eczematous lesions showing macroscopic, microscopic and immunopathological resemblance to lesional AE can be induced by aeroallergens by epicutaneous testing (atopy patch test, APT). Altered epidermal barrier function, as determined by transepidermal water loss (TEWL), is a typical feature of patients with AE. The present investigation was performed to define the differences in the epidermal barrier function between positive APT reactions to aeroallergens and positive patch test reactions to contact allergens in AE patients. Allergen extracts from grass pollen, birch pollen, cat dander and house dust mite (Dermatophagoides pteronyssinus) were applied in large Finn chambers on Scanpor for 48h on the clinically unaffected and untreated skin of the back, in 11 patients with AE. The same procedure was done with 27 contact allergens of a standard test battery. Test reactions were read and TEWL was measured after 48 and 72h. Eight of the 11 patients developed positive APT reactions toD. pteronyssinus, two to cat dander and one to birch pollen. Seven of the 11 patients showed positive patch test reactions to nickel sulphate, two to potassium dichromate, one to thiuram-mix and one to paraphenylenediamine. Vehicle controls were negative. The TEWL of the positive APT reactions was significantly higher, both after 48 h (mean ± standard deviation 10·0±6·5 g/m²h) and after 72 h (9·7±5·4g/m²h) as compared with the control site (48/72h: 4·4±1.5/4·1±1·4 g/m²h) (P<0·01). In contrast, TEWL of the positive patch test reactions to contact allergens (48/72h; 5·4±2·2/5·4±1·9g/m²h) was similar to that of the control site (48/72 h: 5·2±2·1/5·0± 1·8g/m²h) (not significant). The relative TEWL at 48 h and 72 h, expressed as the ratio between the positive patch test and the control site, was significantly higher in the positive APT reactions (48/72 h: 218·8±80·4%/232·0±85·9%) compared with positive patch test reactions to contact allergens (48/72 h: 102·1±12·0%/107·1±9·5%) (P<0·01). It is concluded that the epidermal barrier function in AE patients is altered only in positive APT reactions, in contrast to positive patch test reactions to contact allergens. As a consequence of this aeroallergen-induced altered epidermal barrier function, further allergens can more easily penetrate the skin, inducing a vicious circle and perpetuating the eczematous lesions.     

The atopy patch test: an increased rate of reactivity in patients who have an air-exposed pattern of atopic eczema

Summary In a subgroup of patients with atopic eczema (AE), eczematous skin lesions can he induced by epicutaneous testing with aeroallergens (the atopy patch test: APT). An increased frequency of positive APT has been found in AK patients showing a predictive lesional pattern affecting air-exposed skin areas. This study investigates the dose-response ofthe APT in two dilTerent patient groups with AE. Petrolatum preparations of house dust mite, cat dander and grass pollen allergens in four concentrations (500–10,000) protein nitrogen imits) were tested epicutaneously in 57 patients with AE. who were prospectively divided in two groups according to whether their AE pattern was with (group I) or without (group II) a predictive distribution. Sixty-nine per cent of patients in group I. and 39% in group II. had positive APT reactions (P = 0.02). The reactions in group I were elicitable with lower allergen concentrations (P = 0.03). A clinically recognizable subgroup of patients with AE showed increased cutaneous sensitivity to aeroallergens.     

The association between hand eczema and nickel allergy has weakened among young women in the general population following the Danish nickel regulation: results from two cross‐sectional studies

Background: An association between nickel contact allergy and hand eczema has previously been demonstrated. In 1990, Denmark regulated the extent of nickel release in the ear‐piercing process as well as nickel release from consumer products. Objectives: This study aimed to evaluate the effect of the Danish nickel regulation by comparing the prevalence of concomitant nickel allergy and hand eczema observed in two repeated cross‐sectional studies performed in the same general population in Copenhagen. Materials: In 1990 and 2006, 3881 18–69 year olds completed a postal questionnaire and were patch tested with nickel. Data were analysed by logistic regression analyses and associations were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Results: The prevalence of concomitant nickel contact allergy and a history of hand eczema decreased among 18–35‐year‐old women from 9.0% in 1990 to 2.1% in 2006 (P < 0.01). The association between nickel contact allergy and a history of hand eczema decreased in this age group between 1990 (OR = 3.63; CI = 1.33–9.96) and 2006 (OR = 0.65; CI = 0.29–1.46). Among older women, no significant changes were observed in the association between nickel contact allergy and hand eczema. Conclusions: Regulatory control of nickel exposure may have reduced the effect of nickel on hand eczema in the young female population.     

Mast cell lines HMC‐1 and LAD2 in comparison with mature human skin mast cells – drastically reduced levels of tryptase and chymase in mast cell lines

Please cite this paper as: Mast cell lines HMC‐1 and LAD2 in comparison with mature human skin mast cells – drastically reduced levels of tryptase and chymase in mast cell lines. Experimental Dermatology 2010; 19 : 845–847. Abstract: To circumvent the costly isolation procedure associated with tissue mast cells (MC), two human MC lines, i.e. HMC‐1 and LAD2, are frequently employed, but their relation to mature MC is unknown. Here, we quantitatively assessed their expression of MC markers in direct comparison to skin MC (sMC). sMC expressed all lineage markers at highest and HMC‐1 cells at lowest levels. LAD2 cells expressed comparable high‐affinity IgE receptor α (FcεRIα) and FcεRIγ but less FcεRIβ than sMC and displayed slightly reduced, but robust FcεRI‐mediated histamine release. Only minor differences were found for total histamine content and c‐Kit expression. Huge, and to this level unexpected, differences were found for MC tryptase and chymase, with sMC >>> LAD2 > HMC‐1. Taken together, HMC‐1 cells represent very immature malignantly transformed MC, whereas LAD2 cells can be considered intermediately differentiated. Because of the minute levels of MC proteases, MC lines can serve as surrogates of tissue MC to a limited degree only.     

In‐situ‐topoproteome analysis of cutaneous lymphomas: Perspectives of assistance for dermatohistologic diagnostics by Multi Epitope Ligand Cartography (MELC)

Background: Immunophenotyping is essential for diagnostics of cutaneous lymphomas. In this regard we present a skin tissue‐adapted application platform of MELC technology. Patients and Methods: This topoproteome analysis allows the subcellular colo‐calization of at least n = 100 epitopes in situ. For this purpose the specimen is processed by a Toponome Imaging Cycler^® for a n‐fold repetition of the following cycle: 1) staining with a fluorophore‐labeld antibody, 2) fluorescence‐imaging, and 3) photobleaching. Overlay and binarization of fluorescence images lead to combinatorial molecular phenotypes (CMP), which relate to a pixel or microtopographic unit (450 × 450 nm², 20× objective). Skin biopsies were derived from patients with mycosis fungoides (patch/plaque lesions), psoriasis, atopic eczema and from healthy skin donors. Results: In orientation to the WHO‐EORTC‐classification of cutaneous lym‐phomas a MELC‐library of 23 markers was established. According to an inaugurative detailed procedure the CMP frequency was determined in a normalization to 100 μm horizontal skin width. By a TopoMiner strategy mycosis fungoides could be separated from the other states with a maximum of significance (p ≤ 0.03) by at least 10‐fold overexpression of the following tumor cell‐representative CMP‐motif: CD3+/CD4+/CD1a‐/CD7‐/CD8‐/CD45R0+/CD45RA‐/CD11a+. Conclusions: The skin tissue‐adapted MELC‐application‐platform extends substantially conventional lymphoma diagnostics by an unprecedented dimension of in‐situ‐analysis of marker combinatorics including its exact quantification and visualization.     

Expression, but lack of calcium mobilization by high-affinity IgE Fcε receptor I on human epidermal and dermal Langerhans cells

Abstract In atopic dermatitis (AD) patients, IgE molecules are demonstrated on the surface of Langerhans cells (LC). FcεRI molecules, which are present on the surface of LC in AD patients as well as normal individuals, are responsible for this binding. In this study, we have investigated phenotypic and functional characteristics of FcεRI on epidermal and dermal cell populations. Epidermal and dermal cell suspensions were prepared enzymatically with dispase followed by either trypsin or collagenase treatment, respectively. Peripheral blood basophils were negatively selected by excluding other leukocytes with surface marker staining. Consistent with previous reports, both peripheral blood basophils and epidermal LC were positively stained with anti FcεRI monoclonal antibody. In addition, an FcεRI positive population was demon-strated among dermal HLA-DR positive cells. These cells express significant amounts of HLA-DR molecules (DR^Hi) and co-express CD la molecules, which identifies them as LC-like dendritie APC of the dermis. No other FcεRI positive population was found in the other dermal DR^Mid or DR populations, except for a minor DR^lo population, presumably mast cells. To analyze whether these FcεRI molecules are signal transducing for LC, intracellular calcium mobilization after crosslinking of FcεRI was measured with How cytometry. Following crosslinking, peripheral blood basophils clearly increased intracellular calcium. On the other hand, neither normal epidermal LC nor dermal DR^HiCD Ia⁺ cells changed their intracellular calcium level after FcεRI crosslinking. These data indicate that normal epidermal and dermal LC, but not basophils, are resistant to calcium flux following FcεRI engagement.     

Nickel allergy as risk factor for hand eczema: a population-based study

Summary Background In population‐based studies using self‐reported nickel allergy, a hand eczema prevalence of 30–43% has been reported in individuals with nickel allergy. In a previous Swedish study, 958 schoolgirls were patch tested for nickel. In a questionnaire follow up 20 years later no association was found between nickel allergy and hand eczema. Objectives To investigate further the relation between nickel allergy and hand eczema. Methods Three hundred and sixty‐nine women, still living in the same geographical area, now aged 30–40 years, were patch tested and clinically investigated regarding hand eczema. Results Patch testing showed 30·1% nickel‐positive individuals. The adjusted prevalence proportion ratio (PPR) for hand eczema after age 15 years in relation to nickel patch test results was 1·03 (95% confidence interval, CI 0·71–1·50). A history of childhood eczema was reported by 35·9%, and the PPR for hand eczema in relation to childhood eczema was 3·68 (95% CI 2·45–5·54). When analysing the relation separately in women with and without a history of childhood eczema a statistical interaction was found. The hand eczema risk was doubled in nickel‐positive women without a history of childhood eczema, with a PPR of 2·23 (95% CI 1·10–4·49) for hand eczema after age 15 years. Conclusions A doubled risk for hand eczema was found in nickel‐positive women without a history of childhood eczema. When analysing all participants, there was no statistically significant difference between nickel‐positive and nickel‐negative women regarding occurrence of hand eczema. The most important risk factor for hand eczema was childhood eczema. The risk for hand eczema in nickel‐positive women may previously have been overestimated.     

Allergy to 3-nitro-p-hydroxyethylaminophenol and 4-amino-3-nitrophenol in a hair dye

Contact allergy to 3‐nitro‐p‐hydroxyethylaminophenol in a hair dye is described for the first time. p‐Phenylenediamine is the most common screening allergen when allergic contact dermatitis is suspected, but sometimes the allergen is not sufficient for diagnosing allergic contact dermatitis to hair dyes. A 50‐year‐old woman developed a severe scalp dermatitis and developed vesicular hand eczema for the first time in her life. Patch testing was performed with the European Standard Series. The patch testing was supplemented with a local series of cosmetic allergens and the hairdresser's series. At the initial patch testing, there was a + reaction to nickel and a +? to PPD at days 3 and 7. Further, she reacted with a +? to her own hair collected at day 3 after the hair dying which elicited the dermatitis reaction. Open exposure to the product, which had initiated the dermatitis, was negative both before and after the allergic reaction to the product. None of the screening chemicals in the hairdresser's series gave a definite positive reaction. Only by patch testing with the individual hair dye product ingredients, the patient's reactions were explained. The patient gave a positive patch test to 4‐amino‐3‐nitrophenol and 3‐nitro‐p‐hydroxyethylaminophenol at days 3–4 reading.     

Prevalence,incidence rates and persistence of contact allergy and allergic contact dermatitis in The Odense Adolescence Cohort Study: a 15‐year follow‐up

Background A cohort of 1501 unselected 8th grade schoolchildren was established 15 years ago with the aim to follow the course of contact allergy and allergic contact dermatitis (ACD) from school age into adult life. To date no studies have evaluated incidence rates and persistence of contact allergy and ACD in an unselected population from adolescence to adulthood. Objectives To estimate the incidence rates and persistence of contact allergy and ACD from adolescence to adulthood, and the point prevalence in adulthood. Methods In total, 1206 young adults from the cohort were contacted and asked to complete a questionnaire and participate in a clinical examination including patch testing with TRUE Test^®. The questionnaire was answered by 899 (74.6%), however, only 442 (36·7%) of those invited participated in patch testing. Results Over the 15‐year period the incidence rates of contact allergy and ACD were 13·4% and 7·8%, respectively. The point prevalence of contact allergy was 20·1%, and present or past ACD was found in 12·9% of those followed. Nickel was the most common contact allergen (11·8%), followed by cobalt (2·3%), colophony (2·0%), thiomersal (1·4%) and p‐phenylenediamine (1·1%). Most nickel reactions were persistent, and a significant number of new nickel sensitizations were found. Fragrance mix I reactions from adolescence could not be reproduced. Conclusions From adolescence to adulthood the incidence rates of contact allergy and ACD were high. Nickel was still the most common contact allergen, and new sensitizations occurred despite the European Union nickel regulation. Fragrance mix I was a poor marker for history of eczematous skin reaction to perfumed products.     

Patch testing and contact allergens in Ethiopia – results of 514 contact dermatitis patients using the European baseline series

Background: Patch testing is essential to diagnose allergic contact dermatitis. Dermatologists in many countries use a baseline (standard) series covering the major allergens responsible for allergic contact dermatitis in their population, with the addition of relevant allergens for the individual patient. However, a baseline series has not yet been developed for Ethiopia. Our objective in this study is to identify common contact allergens to form the basis of a future baseline series in Ethiopia. Methodology: We patch tested 514 subjects with dermatitis according to the recommended procedure using the European baseline series for 1 year. Results: 52.7% of the tested subjects showed positive reaction for at least one allergen tested. The top five contact allergens identified were nickel sulfate, fragrance mix I, cobalt chloride, p‐tert‐butylphenolformaldehyde (PTBP) resin and potassium dichromate. Positive reactions to nickel and PTBP were commoner in females. PTBP positivity was strongly associated with foot eczema. Positive test reactions were commoner in cement workers, notably to potassium dichromate, which was also a commoner allergen in patients presenting with hand dermatitis. There were no reactions to several allergens, including neomycin, benzocaine, budesonide, primin and quaternium‐15. Conclusion: Comparable patch test results with other countries have been shown and the European baseline series can be used as a baseline series in Ethiopia with some modification.     

Patch testing is a useful investigation in children with eczema

Background. Allergic contact dermatitis in children is less recognized than in adults. However, recently, allergic contact dermatitis has started to attract more interest as a cause of or contributor to eczema in children, and patch testing has been gaining in recognition as a useful diagnostic tool in this group. Objectives. The aim of this analysis was to investigate the results of patch testing of selected children with eczema of various types (mostly atopic dermatitis) attending the Sheffield Children's Hospital, and to assess potential allergens that might elicit allergic contact dermatitis. Patients and methods. We analysed retrospectively the patch test results in 110 children aged between 2 and 18 years, referred to a contact dermatitis clinic between April 2002 and December 2008. We looked at the percentages of relevant positive reactions in boys and girls, by age groups, and recorded the outcome of treatment following patch testing. Results. One or more positive allergic reactions of current or past relevance was found in 48/110 children (44%; 29 females and 19 males). There were 94 allergy‐positive patch test reactions in 110 patients: 81 had a reaction of current or past relevance, 12 had a reaction of unknown relevance, and 1 had reaction that was a cross‐reaction. The commonest allergens with present or past relevance were medicaments, plant allergens, house dust mite, nickel, Amerchol® L101 (a lanolin derivative), and 2‐bromo‐2‐nitropropane‐1,3‐diol. However, finding a positive allergen was not associated with a better clinical outcome. Conclusions. We have shown that patch testing can identify relevant allergens in 44% of children with eczema. The commonest relevant allergens were medicament allergens, plant allergens, house dust mite, nickel, Amerchol® L101, and 2‐bromo‐2‐nitropropane‐1,3‐diol. Patch testing can be performed in children as young as 2 years with the proper preparation.     

The reaction index and positivity ratio revisited

Background and Objectives: Assessing the quality of patch test preparations continues to be a challenge. 2 parameters, the reaction index (RI) and positivity ratio (PR), have been proposed as quality indicators by the Information Network of Departments of Dermatology (IVDK). The value of these statistics has not been examined by others. Methods: We calculated the RI and PR for the 24 TRUE^® test allergens in 7635 patients with consecutive eczema tested at the Department of Dermatology, Odense University Hospital over a 15‐year period, and data for 7 selected standard allergens were compared with corresponding data from the original IVDK papers. Results and Conclusions: At our patch test laboratory, RI’s are lower, even negative, and the PR’s are considerably lower than the IVDK results. The most likely explanation is a difference in reading/scoring tradition between the different departments of the IVDK and our department. Calculation of RI’s and PR’s for patch test allergens is of limited value as a measure of quality of the patch test materials, because it predominantly reflects differences in scoring and reading of patch test reactions. Further, questionable reactions (+?) may be clinically relevant and very important for the individual patient. Focus on standardization of patch test materials, patch test technique, and reading of patch test reactions is mandatory.     

Hämatogene Kontaktekzeme durch Nahrungsmittel

Oral ingestion or parenteral administration of certain contact allergens may elicit eczematous skin reactions "from inside" in sensitized individuals; this phenomenon has been termed "systemically-induced eczema" or "hematogenous contact eczema". There is a wide range of clinical features from polyetiological dyshidrotic hand and foot eczema to baboon syndrome. The most important contact allergens known to elicit systemically-induced contact eczema are metal salts, drugs, phytoallergens and balsam of Peru. Diagnosis is based on proof of delayed type hypersensitivity by patch testing and oral challenge. Until more and better data is acquired, special diets (for instance low nickel) should be instituted only in carefully selected patients.     

Die Bedeutung der Nahrungsmittelallergie bei Patienten mit atopischer Dermatitis

Besides other trigger factors food allergens have been shown to play a major role in the exacerbation and maintenance of eczematous lesions in patients with atopic dermatitis (AD), particularly in children. Food allergy may not only present as a flare up up of eczema in these patients, but also immediate type reactions and mixed reactions can be observed under food challenge tests.Whereas cow's milk hen's egg, wheat and soy have been identified as important triggers in infants, pollen related foods like nuts, fruit und vegetable have a greater impact in adolescents and adult Food specific T cells have been identified as effector cells in food responsible eczema and food specific T cell clones could be generated from lesional skin of patients who reacted with a worsening of their AD upon oral challenge tests. Due to the poor reliability of in-vitro (RAST) and skin tests (skin prick test (SPT), atopy patch test (APT)) the double blind placebo controlled food challenge (DBPCFC) is regarded as the gold standard in the diagnostic work-up of food allergy. Once a food allergy has been diagnosed, a specific elimination diet represents the first line therapy, which has to consider the supplementation of essential nutrients.     

No skin reactions to mineral powders in nickel-sensitive subjects

Background. Cosmetic products are known to be able to induce contact dermatitis. Contact dermatitis may also be induced by nickel, and it is estimated that up to 17% of women are allergic to nickel. Objectives. The aim of the present study was to investigate whether nickel sensitized individuals react to make‐up products containing pigments with nickel as an impurity. Patients/Materials/Methods. Twenty‐three individuals with a clinical history of nickel allergy and/or with positive patch test reactions to nickel were exposed to mineral make‐up products and individual pigments dispersed in alkylbenzoate (50%) in small Finn Chambers^® for 48 hr. The skin reactions were evaluated visually and with a non‐invasive instrument that quantifies skin erythema. Results. The results showed that 74% of the included individuals showed a visible reaction to the positive control nickel sulfate, and a significant correlation was found between the visual and instrumental readings. However, none of the nickel sensitive individuals reacted to the test products. A subgroup analysis of the 50% most sensitive individuals also confirmed the absence of skin reactions to the powders. Conclusions. The bioavailability of the trace amounts of nickel in the particles was below the level needed to elicit an eczematous reaction in any of the nickel‐sensitized individuals.