Relationship between nickel and cobalt sensitization in hard metal workers

853 hard metal workers were examined and patch tested with 20 substances from their environment, including nickel and cobalt. Nickel sensitivity was found in 2 men and 38 women. 88% of the nickel-sensitive individuals had developed a jewelry dermatitis prior to employment in the hard metal industry or before the appearance of hand eczema. 29% of the hard metal workers gave a history of slight irritant dermatitis. In the nickel sensitized group, 40% had had severe hand eczema which generally appeared 6-12 months after starting employment. In 25% of the cases, nickel sensitive individuals developed cobalt allergy, compared with 5% in the total population investigated. Most facts indicate that nickel sensitivity and irritant hand eczema precede cobalt sensitization. Hard metal workers with simultaneous nickel and cobalt sensitivity had a more severe hand eczema than those with isolated cobalt or nickel sensitivity or only irritant dermatitis. 64% of the female population had pierced ear lobes. Among the nickel allergic women, 95% had pierced ear lobes. The use of earrings containing nickel after piercing is strongly suspected of being the major cause of nickel sensitivity. Piercing at an early age seems to increase the risk of incurring nickel sensitivity.     

Patch test results with serial dilutions of nickel sulfate (with and without detergent), palladium chloride, and nickel and palladium metal plates

Clinical experience suggests the existence of different degrees of sensitivity in nickel-allergic patients. For quantification of this phenomenon, 462 consecutive patients with previously diagnosed or strongly suspected nickel allergy were tested with serial dilution patch tests with 5 ppm to 5% nickel sulfate in pet. (Ni), and 5 ppm to 1% nickel sulfate in pet. with 1% detergent (Ni/D). Additionally, nickel and palladium metal plates were tested in 103, and cobalt salts, dichromate and palladium chloride (PdCl₂) in most patients. 332 patients reacted positively to Ni or Ni/D. The influence of a concomitantly administered detergent was not significant. A significant correlation was found between positive reactions to low concentrations of Ni (or Ni/D), i.e., 0.1% or less ( N =166), and concomitant reactions to nickel metal plates, cobalt salts and PdCl₂ and a history of ear piercing with metal intolerance. The clinical relevance of reactions to PdCl₂ is at present not clear. A subgroup of nickel-allergic patients with "high sensitivity" can be defined. In future studies further addressing the clinical relevance of high versus low sensitivity, patch testing with 0.01, 0.1, 1.0 and 5% nickel sulfate in pet is recommended instead of routine tests with 5% only.     

Open, closed and intradermal testing in nickel allergy

Open, closed and intradermal testing with NiCl₂ was performed in 15 subjects with patch-test-proven allergy to 5% NiSO₄ in pet. Intradermal testing proved to be a reliable method in confirming nickel sensitivity within 24 h. Open testing with non-toxic concentrations of NiCl₂ in alcohol resulted in 73% and 93% positive reactions at 24 h and 48 h readings, respectively. This test method can be used as a reliable screening method in nickel allergy. Open testing often resulted in positive reactions within a few hours. This makes it possible to investigate pathogenetic events of acquired allergic contact dermatitis at a much earlier stage than with the usual 48-h occlusion. 24-h occlusion with Finn Chambers is not sufficient if one is to avoid false negative reactions in nickel allergy. Occlusion with Finn Chambers seems to delay the reaction.     

Intradermal testing in doubtful cases of contact allergy to metals

Among 1670 consecutively patch tested patients an intradermal test with chromium, cobalt and nickel was added in 66 cases. There were three indications for intradermal testing: 1) the patch test reaction at 72 h was difficult to interpret; among 49 patients with one or more doubtful reactions a metal allergy was confirmed in 24 and rejected in 54. 2) ten patients with a negative patch test in spite of a positive history of metal allergy; among these, one was positive to cobalt, two to nickel and the other seven negative. 3) seven patients checked for a previously diagnosed allergy; a metal allergy was confirmed in four. Intradermal testing is recommended for confirmation of doubtful patch test reactions, particularly to disclose false positive reactions to metals.     

Chromated metal products may be hazardous to patients with chromate allergy

Background:  Hidden allergen exposure may contribute to persistence and relapse of chromate dermatitis. According to case reports, chromated metal products, such as screws, fittings, etc., may be relevant allergen sources for patients sensitized to chromate.
Objectives:  To examine concomitant patch test reactivity to potassium dichromate 0.5% petrolatum (pet.) and three different types of chromated metal rings.
Patients/Methods:  Patients with proven or suspected chromate allergy were patch tested with potassium dichromate 0.5% pet. and three different types of chromated metal rings (yellow, olive, and black). Hexavalent chromium Cr(VI) release from the patch tested rings was chemically analysed.
Results:  Ninety-five patients were tested: 49/95 (52%) reacted to potassium dichromate and 25/95 (26%) reacted to black chromated rings. Reactions to chromated rings exclusively occurred in patients reacting to potassium dichromate. Of 20 patients with a strong reaction to potassium dichromate, 14 reacted to black chromated rings. These were shown to have a high Cr(VI) release. Only two patients reacted to the other chromated rings, which had a very low Cr(VI) release.
Conclusions:  Handling chromated metal products must be regarded a hazard to chromate-sensitive patients, in particular those with a strong sensitization.     

Dissolution of cobalt from hard metal alloys by cutting fluids

On grinding hard metal alloys containing cobalt, the dissolution of cobalt during 5 days was studied for nine commercial cutting fluids. After 1 day, a major part of the cobalt liberated from the material ground is found in solution. This percentage decreases when grinding is continued using the same coolant fluid. Only a small fraction of the cobalt is found in particles in the circulating fluid. The bulk must be in the sediment in the storage tank, where it does no harm to the workers' skin. The final concentration of cobalt found in some fluids may be hazardous.     

Dose per unit area - a study of elicitation of nickel allergy

BACKGROUND: Experimental sensitization depends upon the amount of allergen per unit skin area and is largely independent of the area size. OBJECTIVES: This study aimed at testing if this also applies for elicitation of nickel allergy. PATIENTS/METHODS: 20 nickel allergic individuals were tested with a patch test and a repeated open application test (ROAT). Nickel was applied on small and large areas. The varying parameters were area, total dose and dose per unit area. RESULTS: In the patch test, at a low concentration [15 microg nickel (microg Ni)/cm(2)], there were significantly higher scores on the large area with the same dose per area as the small area. At higher concentrations of nickel, no significant differences were found. In the ROAT at low concentration (6.64 microg Ni/cm(2)), it was found that the latency period until a reaction appeared was significantly shorter on the large area compared to the small area. It was also found that the ROAT threshold (per application) was lower than the patch test threshold. CONCLUSION: For elicitation of nickel allergy, the size of the exposed area and therefore the total amount of applied nickel, influence the elicitation reaction at some concentrations, even though the same dose per unit area is applied.     

The frequency of fragrance allergy in patch-tested patients increases with their age

Background The most likely age of sensitization to fragrance chemicals is unknown. Objectives To investigate the frequency of allergy to the 8% fragrance mix (FM) in each decade of life in patients undergoing patch testing for the investigation of skin symptoms. Methods Patients (n = 23 846; 14 104 female and 9742 male) underwent patch testing to a standard series between 1 January 1984 and 31 December 1998. All data were recorded on a computerized database. Results We found that 8·4% of females and 6·4% of males were allergic to the FM. The frequency of fragrance allergy was low in the first two decades of life (2·5–3·4%). It gradually increased in females after the age of 20 years to peak in the 60s at 14·4% of those tested, with a decline to 11·6% in the 80s. The prevalence in males rose more slowly and peaked at 13·7% in the 70s, declining to 10·8% in the 80s. The youngest patients sensitized were aged 2 years. Conclusions These findings support the hypothesis that allergy to fragrance results from a combination of repeated environmental exposure and age‐related susceptibility factors.     

Nickel allergy: relationship between patch test and repeated open application test thresholds

BACKGROUND: The frequency of nickel allergy varies between different population groups. Exposure regulation has proven effective in decreasing the frequency. Experimental studies with other allergens have shown a significant relation between patch test reactivity and repeated open application test (ROAT) reactivity. OBJECTIVES: This study was aimed at determining the elicitation threshold in nickel-allergic individuals in a patch test and a ROAT, and comparing the threshold from these two test methods. METHODS: Twenty nickel-allergic persons were tested with a dilution series of 19 concentrations in a patch test and a dilution series of three concentrations in a ROAT, with duration of up to 21 days. Eighteen persons with no nickel allergy were included as control group for the ROAT. RESULTS: The predicted dose which will elicit a reaction in 10% of allergic individuals was calculated to be 0.78 microg nickel cm(-2) in the patch test. The threshold for the ROAT (in microg nickel cm(-2) per application) was significantly lower than the threshold for the patch test, while the dose-response for the accumulated ROAT dose at 1 week, 2 weeks and 3 weeks was very similar to the patch test dose-response; indeed, there was no statistically significant difference. CONCLUSIONS: For elicitation of nickel allergy the elicitation threshold for the patch test is higher than the elicitation threshold (per application) for the ROAT, but is approximately the same as the accumulated elicitation threshold for the ROAT. This may be important for risk assessment based on dose-response results from allergic patients.     

Metal patch testing in patients with oral symptoms

The number of patients with metal allergies has increased recently, and patch testing is useful for investigating such patients. However, the efficacy of restoration removal in patients with oral metal allergies is disputed. This study aimed to investigate the relationships between oral symptoms and metal allergies. We conducted a retrospective analysis of 60 patients with oral symptoms. The most common oral symptom was an abnormal oral sensation. Thirty‐eight percent of the patients exhibited positive allergic reactions to one or more metal. Nickel was the metal allergen that produced positive reactions most frequently. Of the seven patients whose restorations were removed, complete and partial remission were achieved in one and two patients, respectively. Interestingly, metal alloy removal was effective in 33% (n = 1) of the positive patch test group and 50% (n = 2) of the non‐positive patch test group. Our results demonstrated the difficulty of predicting the efficacy of restoration removal at ameliorating oral metal allergies based on patch testing alone.     

Atopy in subjects with a history of nickel allergy but negative patch tests

Various markers of atopy were studied in 20 subjects with a history of nickel allergy but negative patch test reactions, and compared with 2 control groups: 13 subjects with no history of nickel allergy and negative patch tests; 11 subjects with a history of nickel allergy and positive patch tests. No significant difference in the incidence of atopy was detected in the 3 groups.     

No association between metal allergy and cardiac in-stent restenosis in patients with dermatitis-results from a linkage study

Background. Percutaneous coronary intervention (PCI) with implantation of a metal stent is a common procedure performed in patients with symptomatic ischaemic heart disease. Intracoronary stents typically have a backbone of stainless steel, which contains nickel, chromium, and molybdenum, and it remains unclear whether individuals who are allergic to these metals have an increased risk of restenosis after PCI with stent implantation. Objectives. To further evaluate whether dermatitis patients with nickel and/or chromium allergy had an increased risk of developing cardiac in‐stent restenosis with stainless steel stents. Methods. An individual‐level linkage study was performed to identify dermatitis patients who had been patch tested with the European baseline series between 1979 and 2007 at Gentofte University Hospital (N = 18794) and who had also undergone PCI at some point in a Danish hospital. Results. One hundred and forty‐nine (0.8%) dermatitis patients who had undergone PCI with a metal stent were included. One hundred and forty‐seven were patch‐tested before undergoing PCI. Of the patients, 14.1% (21/149) had cardiac in‐stent restenosis. Among patients with metal allergy, 2 (11.8%) had restenosis. Conclusions. Nickel and/or chromium allergy in dermatitis patients does not appear to increase the overall risk of in‐stent restenosis after PCI.     

Nickel allergy: analysis of metal clothing objects and patch testing to metal samples

In 22 nickel-sensitive subjects, 57 metal clothing objects were said to be not tolerated (37) or tolerated (20). They were analysed by X-ray energy dispersion in electron microscopy, and by the dimethylglyoxime spot test. The correlation between the analytical results and the statements of patients is discussed. Patch tests to nickel-plated metal samples with various thicknesses of chromium (0.25 mu to 1 mu) or gold/copper/cadmium (0.5 mu) were performed in human subjects or in guinea pigs sensitive to nickel. Surface-plating and anticorrosive techniques, as well as the results in nickel-sensitive subjects, are described and discussed. Good tolerance will not be obtained under experimental conditions if nickel in any form is a component of the object. It is to be hoped that appropriate regulations will prohibit the use of nickel in the manufacture of clothing objects.     

In vitro and in vivo evaluation of the effect of barrier gels in nickel contact allergy

The protective effect of various ethylenediaminetetraacetate (EDTA) barrier gels on nickel skin penetration was investigated in an in vitro model using human skin. Application of the gels seemed to cause an increased release of nickel from nickel alloys. This nickel did not penetrate the skin barrier but was found to be immobilized on the skin surface. This emphasized the importance of washing the skin surface to remove any surplus of barrier formulation after use, since considerable amounts of nickel will be bound in this formulation. It was found that application of the barrier gels beneath the nickel alloy in contact with the skin significantly reduced the amount of nickel found in the epidermal skin layer. In vivo patch testing with a disc of nickel alloy, with and without use of barrier gel, was performed in 21 nickel-sensitive patients. Patch testing with the nickel alloy without use of barrier gel resulted in positive patch test reactions in 11/21 (52.4%) of the patients tested. Application of a Carbopol gel with 10% CaNa₂-EDTA beneath the nickel disc completely abrogated the allergic contact response in all 21/21 (100%) patients. A Carbopol gel without CaNa₂-EDTA was less effective, inhibiting the response in 15/21 (71.4%). A high concordance was found between epidermal nickel levels found in vitro and the in vivo patch test.     

Patch testing with nickel chloride in a hydrogel

Various concentrations of NiCl2 in a hydrogel were evaluated as a possible alternative to the standard patch test material of 5% NiSO4 pet. Patch test responses were recorded on a total of 430 patients with known or suspected contact allergy. A NiCl2 concentration of 1% or less in the hydrogel failed to elicit a response in some patients who reacted to 5% NiSO4 pet. The 2% NiCl2 hydrogel produced a small increase in response frequency and may reduce false-negative reactions. Along with the ability of the material to improve the topical bioavailability of nickel ions, more irritant reactions were observed. However, in cases with a positive history and a negative patch test with petrolatum, the hydrogel prepared from Methocel-E-4M seems to be a useful alternative vehicle for water-soluble allergens.