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

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.

Contact allergy to colophony. Clinical and experimental studies with emphasis on clinical relevance.

Colophony--also called rosin--is a material obtained from coniferous trees. It is used widely in many products, particularly because of its good tackifying properties. Colophony is also used in paper sizing to increase water resistance. Colophony may cause contact allergy, and around 5% of Swedish dermatitis patients show allergic reactions to colophony at patch testing. There are many case reports of colophony in different products causing contact dermatitis. Often, however, the clinical relevance of a positive patch-test reaction to colophony is difficult to evaluate. The principal aims of the present thesis were to study the prevalence of contact allergy to colophony and of skin disease in individuals with an occupational exposure to colophony; to study the prognosis of dermatitis in colophony-sensitive subjects, and to investigate the outcome of repeated open applications of colophony, thereby trying to elucidate the clinical relevance of contact allergy to colophony. Employees of a tall-oil rosin (colophony) factory (n = 180), and of an opera company where colophony was used in dancers' rosin, mascara and wig glues (n = 132), were interviewed, examined and patch tested. 3.9% and 2% of these two groups respectively had a positive patch test to colophony. More than every fourth participant showed some kind of skin disease, but only few cases were related to work. Eighty-three patients with previously diagnosed contact allergy to colophony were followed-up 72% showed a positive patch-test reaction to colophony at re-testing. Around one third had hand eczema. There was no significant correlation between colophony exposure and current hand eczema. Adhesive bandages containing colophony and zinc oxide (ZnO), colophony and mixes of colophony and ZnO, were tested in 7 colophony-sensitive subjects to see whether addition of zinc oxide inhibited elicitation of allergic dermatitis to colophony, which has been proposed. No difference in reactivity between colophony and colophony/ZnO was seen at patch testing, and there were positive patch-test reactions to all colophony-containing bandages. Thus no inhibitory effect of ZnO was shown. Repeated open application tests were performed with cobalt chloride and colophony in sensitized guinea pigs. The animals were also patch-tested. A dose-response correlation was found with both cobalt chloride and colophony. There was a concordance between patch-test reactions and reactions at repeated open application tests, the higher the concentration of the allergen at the open test the stronger the concordance. In 13 colophony-sensitive subjects serial dilution patch tests with colophony were performed followed by repeated open application tests using colophony of different concentrations once daily for two weeks. Reactions were assessed visually, by laser Doppler flowmetry and by measurements of transepidermal water loss. Ten subjects reacted at open applications with colophony 20%. The strength of the reaction varied greatly. A correlation between the threshold concentration at patch testing and the outcome of the repeated open application tests was found and also a dose-response relationship. Nine healthy controls did not react to repeated open applications with colophony. The measurements of transepidermal water loss and bloodflow was of no additional use to visual assessment when evaluating repeated open application test reactions with colophony.

Repeated open application tests (ROAT) in patients allergic to colophony--evaluated visually and with bioengineering techniques.

It is desirable to further evaluate the clinical relevance of a positive patch test. The repeated open application test (ROAT) has been suggested as such a supplementary method. To compare the results of patch testing with the outcome of ROATs, 13 colophony-sensitive subjects and 9 controls were patch-tested with colophony in a serial dilution test. Five microliters, of three concentrations of a colophony solution and the vehicle were then applied to small test areas on the lower arm, once daily for 2 weeks. Prior to each application, all test sites were examined visually and with bioengineering techniques. In the ROATs, 10/13 colophony-sensitive subjects--but no controls--reacted to a 20% colophony solution, 4 also 1%. A correlation was found between the threshold concentration at patch testing and the outcome of ROATs. There was great variation in the reactivity in the ROATs. Objective measures for evaluating the ROAT reactions gave no further information than visual assessment.

Quantification and specificity of the repeated open application test (ROAT). A methodological study using cobalt and colophony in guinea pigs.

The repeated open application test is used to assess the clinical relevance of positive patch test reactions to ingredients of formulated products. The great variation in outcome is usually claimed to be related to the concentration of the allergen responsible. We have here studied the quantitative aspects, specificity and effect of patch testing on the outcome of the repeated open application test in an animal model, using guinea pigs sensitized with cobalt chloride or colophony. Thresholds of sensitivity were determined before and after the topical treatments. Clear dose-response relationships were established. The reactivity in sham-treated controls and to the vehicles was minimal. The concordance between patch test results and outcome of the use tests was concentration-dependent and at low concentrations < 50%. The repeated open application test is a useful method, but some of the basic issues need further evaluation. This animal model will hopefully serve this purpose.

Contact allergy to colophony and hand eczema. A follow-up study of patients with previously diagnosed contact allergy to colophony.

Colophony is commonly used in many products that we are exposed to both at work and during leisure. At our Department, about 5% of patch tested dermatitis patients show positive reactions to colophony. 83 patients in whom contact allergy to colophony had been diagnosed were followed up after 9-13 years. They were interviewed, examined and retested. At least 30% had current hand eczema on follow-up examination. Among those in whom the dermatitis had started on the hands, there were proportionally more individuals with current hand eczema than among those in whom the onset had been on other parts of the body. 72% of the participants were still patch-test-positive to colophony, and more than 1/2 had additional positive reactions to other allergens. Some of these additional reactions were new compared to the previous test occasion. The degree of exposure to colophony throughout the years was difficult to estimate. Contact allergy to colophony was considered occupational in individuals with, e.g., soldering jobs.

Rosin (colophony) and zinc oxide in adhesive bandages. An appropriate combination for rosin-sensitive patients?

Adhesives and bandages containing zinc oxide (ZnO) and rosin are often used for treatment of ulcers. The aim of this work was to study a possible inhibitory effect of ZnO on the elicitation of allergic contact reactions to rosin and to determine whether such an effect might be due to the formation of zinc resinates. Patch testing in rosin-sensitive patients was performed with mixes of ZnO and rosin. The eliciting capacities of one mix in which zinc resinates might be formed and another mix in which the formation of zinc resinates was prevented, were compared to the eliciting capacity of rosin alone. If a reduction of the allergic response was observed for the mix in which zinc resinates might form and if no reduction was observed for the mix in which formation of zinc resinates was prevented, this would support the hypothesis that the reduction in eliciting capacity was due to formation of zinc resinates. However, we could not see any difference in eliciting capacity when comparing the 2 mixes with a test preparation of rosin. Commercial adhesives (bandages) containing ZnO and rosin were patch tested in 7 rosin-sensitive patients. The concentration of abietic acid in the adhesives was determined with HPLC. Abietic acid was detected in all but one of those declared to contain rosin. The patients reacted to the adhesives in which abietic acid was detected. For rosin-sensitive persons, the addition of ZnO to rosin-containing adhesives cannot be regarded as an appropriate measure to inhibit the elicitation of allergic reactions.

Are opera-house artistes afflicted with contact allergy to colophony and cosmetics?

The frequencies of cosmetics intolerance and contact allergy to colophony were investigated among 116 singers and dancers and 16 make-up artists. Participants were interviewed, examined and patch tested with a standard series and materials from the opera house. Common skin lesions were found in 1/3 of participants and more than 50% had a history of intolerance to cosmetics. Colophony gave positive patch test reactions in only 3 subjects. The prevalence of positive patch test reactions to fragrance mix and balsam of Peru was about the same as among dermatitis patients generally. Contact allergy to colophony did not seem to be a problem regarding cosmetics.

A clinical and patch test study in a tall-oil rosin factory.

Rosin of different sources is commonly used in many technical products and is known to cause contact allergy. The aim of the present investigation was to study the frequency of occupational dermatoses and of contact allergy to rosin in a factory producing tall-oil rosin. 163/180 present employees and 17/35 former employees participated in the study, which consisted of interview, clinical examination and patch testing with a standard series and additional rosins. 1/4 of those examined had some kind of current skin lesion. There were 10 cases of hand eczema. 7 subjects were patch-test-positive to gum rosin in the standard series. This frequency is about the same as among dermatitis patients at our clinic. Only 1 reaction to tall-oil rosin and none to the modified rosins tested were found. No relation between a positive patch test reaction to rosin and current skin disease could be established. No case of ongoing occupational skin disease was proved.

Nail varnish allergy with far-reaching consequences.

Contact allergy to nail varnish is well-known, and toluene-sulphonamide formaldehyde resin (TSAfr) was identified as the main allergen in 1943. During the period October 1989-December 1991 we identified 18 cases of contact allergy to nail varnish. The aim of the study was to describe the clinical picture, patch-test results, course and socio-medical consequences. Seventeen of the 18 patients were patch-test positive to TSAfr and 17/18 were positive to their own nail varnishes. Fourteen of the 18 were also positive to one or more substances in the standard patch-test series. The lesions were scattered, involving the face, eyelids, neck and hands. Periungual lesions were recorded in 11/18. The dermatitis resolved within a few weeks when the use of nail varnish was stopped. The socio-medical consequences of contact allergy to nail varnish had been severe: sick leave (nine cases), hospitalization (four cases), cessation of visual-display-unit (VDU) work (two cases), and job-loss (two cases). Our conclusions are that contact allergy to nail varnish and TSAfr is common; the socio-medical consequences may be severe; periungual lesions occur more frequently than previously stated, and the presence of other contact allergies makes the diagnosis easy to miss. TSAfr should be included in the standard patch-test series and patients should also be tested with their own nail varnishes. The study illustrates the need for mandatory declaration of the ingredients of cosmetics, as is required in the U.S.A.

Isothiazolinones (MCI/MI): 200 ppm versus 100 ppm in the standard series.

In an attempt to define the optimal test concentration for isothiazolinones, 200 and 100 ppm of 5-chloro-2-methyl-4-isothiazolin-3-one/2-methyl-4- isothiazolin-3-one (MCI/MI) in aq. solution were tested simultaneously in 918 consecutive eczema patients. 3.4% were positive to 200 ppm and 1.7% to 100 ppm, indicating that up to 50% of the cases might have been missed. Among the 33 cases with positive reactions, 21 showed stronger reactions to 200 than to 100 ppm, while 9 had reactions of the same strength. Use tests were carried out in 7 cases, of which 2 were positive. MCI/MI remains a peculiar allergen and some of the problematic factors are: the morphology of the test reactions, the difficulties in tracking down the exposure (past or current relevance), the multisensitivity (MCI/MI plus other allergens), the outcome of the use tests and the optimal test concentration. Our present strategy is to use 200 ppm as an indicator and then to carry out serial dilution and use tests in each "positive" case.

Differential effects of sodium lauryl sulphate and non-anoic acid on the expression of CD1a and ICAM-1 in human epidermis.

Normal human skin was exposed to two different detergents, sodium lauryl sulphate in distilled water and non-anoic acid in isopropanol at different concentrations. The detergents were applied under occlusion in epicutaneous tests for 24 h and biopsies were taken at 24 or 48 h. Frozen sections were labelled with monoclonal antibodies against CD1a, CD3 and ICAM-1. The evaluation of the labelled sections showed that there were differential effects on the expression of ICAM-1 and CD1a+ cells in epidermis. After non-anoic acid application ICAM-reactivity could not be detected and there was a decrease of staining for CD1a after exposure to 80% non-anoic acid. Sodium lauryl sulphate treatment, however, induced ICAM-1 expression on keratinocytes and had minor effects on the number of CD1a+ cells. ICAM-1 expression was also detected in normal epidermis in 3 of 9 unexposed control biopsies and after occlusion with the vehicles distilled water and isopropanol. An increased amount of CD3+ cells was found in the skin exposed to both detergents. The results show that there are dose and time dependent variations in the epidermal response to irritants which might influence the immunological events taken place in the epidermis.