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.     

Cross-reactivity patterns of palladium and nickel studied by repeated open applications (ROATs) to the skin of guinea pigs

Cross-reactivity is usually studied with patch test techniques, but the relevance of a single 1-2 day exposure under occlusion can be questioned. To study relevance, animals were induced with PdCl2 or NiSO4 according to the guinea pig maximization test method and then treated for 10 days according to the repeated open application test (ROAT) method. Animals induced with PdCl2 reacted in the ROATs to PdCl2 (100%) but rarely to NiSO4. Animals induced with NiSO4 reacted in ROATs to the same degree with NiSO4 and PdCl2 (23-30%). The concordance between pre-ROAT patch test results and ROAT outcome was high for PdCl2 (100%) and low (10-40%) for NiSO4. Patch testing seems to overestimate the risk of skin reactions when guinea pigs sensitive to PdCl2 are treated topically with NiSO4. The finding from patch test studies that animals induced with NiSO4 react only to NiSO4 but not to PdCl2 was not confirmed. Repeated open applications more adequately mimic exposure conditions than does patch testing.     

Patch testing with nickel sulfate: comparison between 2 nickel sulfate preparations and 2 different test sites on the back

Among patients routinely undergoing patch testing for suspected allergic contact dermatitis (ACD), nickel is the most frequently sensitizing hapten, with a clear predominance in the female population. However, some patients who report the appearance of dermatitis upon exposure to metal objects show negative patch test results to a nickel sulfate 5% pet. application. In some cases, a positive response to nickel can be observed simply by repeating the patch test. The objective of our study was to assess if, during routine patch testing, positive responses to nickel sulfate are missed owing to contingent problems, referring to application site, patch test execution or variations in skin reactivity. To this end, we applied 2 different patch test materials containing nickel sulfate 5% pet. to 3040 consecutive patients, undergoing patch testing for suspected allergic contact dermatitis, during the same session. The rôle of the test site was also investigated by applying the preparation on 2 different sites of the back in 30 patients. Of the whole, 612 patients (20%) showed positive patch test responses. The 2 nickel materials were almost equivalent: 78% of nickel-sensitive patients had positive reactions to both, whereas 11% showed a positive response to 1 preparation alone. No variations in patch test responses in relation to application site were observed. Our data show that false-negative patch test responses to nickel are frequent. The use of 2 different preparations during the same patch test session increases the response rate by 10%.     

Patch testing with the irritant sodium lauryl sulfate (SLS) is useful in interpreting weak reactions to contact allergens as allergic or irritant

Several contact allergens are tested at concentrations which might cause irritant reactions. In this study we investigated whether the reactivity to a standard irritant is useful in identifying subjects with hyperreactive skin yielding a higher rate of doubtful or irritant reactions. Sodium lauryl sulfate (SLS) 0.5% (aqua) was tested in addition to the standard series routinely for 5 years in the Department of Dermatology, Dortmund. For data analysis, we compared reactions at D3 to the standard series, the vehicle/emulsifier and preservative series and benzoyl peroxide to the reactions obtained with SLS. Proportions were standardized for age and sex. The association between reactivity to a certain allergen and SLS reactivity as a dichotomous outcome, controlled for age and sex as potential confounders, was assessed with logistic regression analysis. Results showed that of the 1600 tested patients, 668 (41.8%) had an irritant reaction to SLS which exceeded 2 + in only 41 patients. Seasonal variation was statistically significant, showing reduced SLS reactivity in summer vs. winter. Patients with irritant reactions to SLS showed significantly more erythematous reactions to the following 10 allergens of the standard series: fragrance mix, cobalt chloride, balsam of Peru (Myroxylon pereirae), lanolin alcohol, 4-phenylenediamine base (PPD), propolis, formaldehyde, N-isopropyl-N'-phenyl-p-phenylenediamine (IPPD), benzocaine, and 4-tert-butylphenol-formaldehyde resin. No significant differences regarding strong positive allergic reactions were observed. Concerning other allergens, significantly more erythematous reactions were observed in SLS-reactive patients to benzoyl peroxide, octyl gallate, cocamidopropyl betaine, Amerchol L-101, tert-butylhydroquinone, and triethanolamine. In the SLS-reactive group of patients, the reaction index was negative for 10 allergens of the standard series compared to only 5 in the SLS non-responder group. For the first time, this study, based on a large data pool, revealed a significant association between reactivity to the irritant SLS and erythematous reactions to certain allergens. With SLS as a marker for hyperreactive skin at hand, some of these reactions can now be classified as irritant more confidently, particularly if there is no history of exposure to the allergen.     

Objective assessment of nickel sulfate patch test reactions with laser Doppler perfusion imaging

The laser Doppler perfusion scanning technique was used to assess the superficial blood flow of nickel sulfate hexahydrate patch test reactions. There was good agreement between laser Doppler and visual assessments when the highest assessment values of reactions were studied. Earlier detection of reactions was possible with the laser technique. There was great inter-individual variance in perfusion between identically tested patients. 4 patients were visually negative when a TRUE Test^TM patch test dose of 0.20 mg/cm² was applied for 48 h and the test area read 4× up to 168 h. These 4 showed a dose-related increase in perfusion and visually positive reactions using longer application times. The instrument allowed a dose reduction not possible for visual assessments. Reading transparent patches in contact with the skin through transparent semi-occlusive plastic foil or through windows in the tape strip over the patches, allowed us to detect perfusion at 48 h, where a longer application would have been needed using tape and visual assessments.     

Patch test results with patients' own perfumes, deodorants and shaving lotions: results of the IVDK 1998-2002.

OBJECTIVE: Assessment of the value of patch testing patients' own perfumes, eau de toilette, deodorants and shaving lotions with regard to diagnosing contact allergy to fragrances, and an analysis of the spectrum of concurrent patch test reactions to single fragrance allergens. STUDY DESIGN: Data of the Information Network of Departments of Dermatology (IVDK; http://www.ivdk.org) regarding patch test results with above products brought in by the patient, considered as possible cause of contact dermatitis, were retrospectively analysed. Between 1998 and 2002, 1468 patients were patch tested with 2557 single products (deodorants, n = 1094; eau de toilette, n = 598; perfume, n = 530; and pre- or after-shave, n = 325; remainder not classifiable), mostly 'as is'. RESULTS: Positive reactions were observed in 129 patients (to 191 products). In 58 of these patients, no further patch test reactions to the fragrance mix (FM-I), Myroxylon pereirae resin (balsam of Peru) or 4-(4-hydroxy-4-methyl-pentyl)-3-cyclohexencarboxaldehyde (e.g. Lyral(R)) were found. A strong association between contact sensitivity to the above commercial allergens and positive reactions to products was observed. Some single compounds such as ylang-ylang oil, propolis and especially oak moss absolute are important allergens in the 'perfume-positive' subgroup, but less in a subgroup positive to own deodorants. DISCUSSION: Patch testing this scope of products, brought in by the patient, can be regarded as a simple, safe and effective method to diagnose clinically relevant contact sensitization - the more so, as the composition of such products is ever-changing, and the sensitivity of established 'screening allergens' is thus insufficient.     

Contact allergies to nickel sulfate, gold sodium thiosulfate and palladium chloride in patients claiming side-effects from dental alloy components

397 patients claiming various subjective symptoms related to dental restoration materials have been tested for the presence of metal allergy. The resultant data have been com pared with the corresponding allergies of eczematous patients. The frequency difference of metal allergy in the dental group is statistically significant or close to significance for nickel sulfate, potassium dichromate, cobalt chloride, palladium chloride and gold sodium thiosulfate. The findings suggest that the dental patient group represents a subgroup with a high frequency of metal allergy.     

Evaluation and relevance of isolated test reactions to cobalt

During a 5-year period, 286 of 4,034 (7.1%) standard tested eczema patients reacted to cobalt. Fifty (1.2%) showed "isolated" cobalt reactions (i.e. without simultaneous reaction to chromium and/or nickel). A follow-up study of 36 of these patients included a serial dilution test (SDT). Eleven of 15 patients with negative reactions in the SDT had demonstrated weak reactions in the previous standard test, whereas stronger initial reactions had been noted in 19 of 21 patients who reacted positively. Sixteen SDT-positive and six SDT-negative patients were definitely or probably exposed to cobalt in their working or home environments. The majority of patients with "isolated" cobalt sensitivity also had other contact sensitivities (especially to rubber chemicals) or atopic dermatitis. Therefore in some cases of "isolated" cobalt reactions another contact sensitivity or skin disease may be a prerequisite for the development of cobalt allergy. It is however possible that the simultaneous presence of reactivities to different test substances is only a reflection of general skin vulnerability. An uncertainty in testing methodology must also be considered when evaluating test reactions to cobalt. Finally, present results show that cobalt allergy unassociated with contact sensitivity to other substances or other skin diseases is rare.     

The association between ambient air conditions (temperature and absolute humidity), irritant sodium lauryl sulfate patch test reactions and patch test reactivity to standard allergens

To support the decision as to whether erythematous patch test reactions to allergens are irritant or allergic, sodium lauryl sulfate (SLS, 0.5% in water) has been added to the standard patch tests since July 1996 in the Dortmund Department of Dermatology. Data on 1600 patients patch tested up until June 2001, as well as standardized data on ambient temperature and humidity obtained by the German Meteorological Service, were included in a logistic regression analysis taking age, sex and atopy as potential confounders into account. The pattern of association was heterogeneous: while doubtful reactions to nickel sulfate were significantly associated with dry/cold weather conditions, but not with SLS reactivity, the opposite was observed for lanolin alcohol, benzocaine and Myroxylon pereirae resin (balsam of Peru). Doubtful reactions to other allergens, namely formaldehyde, fragrance mix or p-phenylenediamine, were associated with both factors. For several other allergens of the standard series, no distinct, significant pattern could be discerned. In conclusion, meteorological conditions and SLS reactivity independently contribute information on individual irritability at the time of patch testing, and both should be considered.     

Patch test reactions to metal salts in patients with oral mucosal lesions associated with amalgam restorations

Patch testing with various metal salts was performed in patients with oral mucosal lesions associated with amalgam restorations, by using polypropylene-coated aluminium discs. Positive reactions to mercuric chloride were obtained in 5/12 (42%) of these patients, but only in 1/11 patients (9%) with oral mucosal lesions unassociated with amalgam restorations and in 3/36 patients (8%) in a control group without mucosal lesions. The difference between the former group and the control patients is statistically significant (p less than 0.05). In addition, a positive test reaction to copper sulfate was obtained in 2 patients (16%) with amalgam-associated mucosal lesions and negative reactions to mercuric chloride. 2 of the 5 positive test reactions to mercuric chloride, in the patients with lichenoid mucosal lesions associated with amalgam, became lichenoid and persisted for at least 3 weeks. The patients with these reactions were also positive at a concentration of 0.05% mercuric chloride, but were negative to metallic mercury, in contrast to 2 other patients in the same group. This indicates the necessity of including mercuric chloride when patch testing such patients.     

Patch testing with budesonide in serial dilutions: the significance of dose,occlusion time and reading time*

Budesonide is advocated as a marker molecule for corticosteroid contact allergy. When patch testing corticosteroids, one must consider their sensitizing potential but also their anti-inflammatory properties, as well as the possibility of different time courses for such properties. The dose-response relationship for budesonide was therefore investigated with regard to dose, occlusion time, and reading time. 10 patients were patch tested with budesonide in ethanol in serial dilutions from 2.0% down to 0.0002% with occlusion times of 48, 24, and 5 h. Readings were on D2, D4, and D7. The 48-h occlusion picked up most positive reactors, 8/10. The D4 reading (48-h occlusion) detected most positive reactors, 8/10, and here 0.002% picked up most contact allergies. Late readings favoured high concentrations. The “edge effect” was noted for several concentrations at early readings. Due to the individual corticosteroid reactivity, the dose-response relationship and the time courses of the elicitation and the anti-inflammatory capacity, several features may be explained, i.e., that lower concentrations may detect budesonide allergy better at early readings, that patients with an “edge reaction” can have positive reactions to lower concentrations.     

Concentration threshold of non-occluded nickel exposure in nickel-sensitive individuals and controls with and without surfactant

Most cases of primary nickel sensitization are caused by occluded exposure to nickel released from earrings, buttons, etc. Nickel-sensitive females are both domestically and occupationally exposed lo trace amounts of nickel. The present study was designed to define the minimum eliciting threshold concentration of nickel exposure in previously nickel-sensitized individuals, after open application on normal forearm skin with and without surfactant. A dilution series of NiCl₂, ranging from 0.1 to 4000 ppm nickel with and without 4% sodium Lauryl sulfate, was applied to healthy volar forearm skin. None reacted with definite allergic reactions to 100 ppm and below. Follicular reactions were seen in the concentration range from 0.1–100 ppm in a few patients and 1 healthy control. The results are discussed in relation to consumer products containing 1–10 ppm nickel.     

Pretreatment of the test area with 1-day occlusion improves the response rate to NiSO4 5% pet. Patch tests in subjects with a positive history of nickel allergy

A group of 58 women, aged 18 to 51 years, with a clinical history of nickel allergy, who exhibited equivocal or negative reactions to nickel sulfate 5% pet, patch tests performed on the skin of the back, were recruited consecutively from the patch test clinic from September 1993 to June 19944. In order to improve the response rate to NiSO₄ 5% pet, patch tests, a testing procedure utilizing pretreatment of the test area by 1-day (24-h) occlusion was introduced. Patients underwent 2 patch tests on adjacent sites of the volar surface of both forearms. 3 of the patch tests were performed with 40 mg nickel sulfate 5% pet., whereas a control test was carried out by occluding with an empty chamber. 2 of the nickel sulfate test sites were pretreated with 1-day occlusion performed with an empty chamber. A visual grading system and echographic measurement were used to quantify the responses 30–40 min after patch test removal. Echographic evaluations were carried out using a 20 MHz B-scanner. Measurement of skin thickness and determination of the hypoechogenic dermal area, both considered to be parameters of inflammation, were used to evaluate the intensity of the allergic reaction. At the 3-day (72-h) evaluation. 19 subjects out of 58 clearly showed positive reactions to nickel sulfate 5% pet, at pre-occluded skin sites. Moreover, values of skin thickness and of 0–30 areas at positive pre-occluded nickel test areas were higher in respect to control test areas, confirming clinical evidence of increased response to NiSO₄, after occlusion.