[Current contact allergens]. / Aktuelle Kontaktallergene.

Ever-changing exposure to contact allergens, partly due to statutory directives (e.g. nickel, chromate, methyldibromo glutaronitrile) or recommendations from industrial associations (e.g. hydroxyisohexyl 3-cyclohexene carboxaldehyde), requires on-going epidemiologic surveillance of contact allergy. In this paper, the current state with special focus in fragrances and preservatives is described on the basis of data of the Information Network of Departments of Dermatology (IVDK) of the year 2010. In 2010, 12,574 patients were patch tested in the dermatology departments belonging to the IVDK. Nickel is still the most frequent contact allergen. However the continuously improved EU nickel directive already has some beneficial effect; sensitization frequency in young women is dropping. In Germany, chromate-reduced cement has been in use now for several years, leading to a decline in chromate sensitization in brick-layers. Two fragrance mixes are part of the German baseline series; they are still relevant. The most important fragrances in these mixes still are oak moss absolute and hydroxyisohexyl 3-cyclohexene carboxaldehyde. However, in relation to these leading allergens, sensitization frequency to other fragrances contained in the mixes seems to be increasing. Among the preservatives, MCI/MI has not lost its importance as contact allergen, in contrast to MDBGN. Sources of MCI/MI sensitization obviously are increasingly found in occupational context. Methylisothiazolinone is a significant allergen in occupational settings, and less frequently in body care products.

Nickel, cobalt and chromate sensitization and occupation.

BACKGROUND: Exposure to nickel, cobalt and chromate are important causes of occupational contact dermatitis. OBJECTIVES: To estimate the prevalence of nickel, cobalt and chromate allergy in a population of consecutive patients and to investigate the possible association with individual and occupational risk factors. PATIENTS/METHODS: A total of 14 464 patients (67.6% women and 32.4% men) with suspected allergic dermatitis underwent patch tests. The associations between patch test results and occupations were studied by multivariate logistic regression analysis. RESULTS: About 24.6% of the patients reacted positively to nickel sulphate, 10.2% to cobalt chloride and 8.7% to potassium dichromate. Nickel sensitization was higher in women aged 26-35 years in comparison with the youngest group (15-25 years) and the older group (> 45 years). In women, the prevalence of positive reactions to nickel was positively associated with metal and mechanical work (OR 1.54; 95%, CI 1.16-2.05). Chromate sensitization was more prevalent in building trade workers for both women (OR 1.58; 95% CI 1.00-2.49) and men (OR 2.24; 95% CI 1.55-3.22). Cobalt sensitization was associated with textile and leather work in women (OR 1.52; 95% CI 1.09-2.12) and with cleaning work in men (OR 1.86; 95% CI 1.18-2.93). CONCLUSIONS: Our study showed interesting associations between some occupations and nickel, chromate and cobalt allergy.

Sirolimus-eluting stents suppress neointimal formation irrespective of metallic allergy.

BACKGROUND: Metallic allergy is associated with restenosis following bare metal stent implantation, but the impact of metallic allergy on the outcome after implantation of drug-eluting stents (DES) has not been investigated. METHODS AND RESULTS: The present study group consisted of 88 consecutive patients (109 lesions) who underwent percutaneous coronary intervention with sirolimus-eluting stents (SES). Follow-up angiography was obtained at 8 months in all patients. At that time, the patients underwent epicutaneous patch tests for nickel, chromate, molybdenum, manganese, and titanium, which were evaluated after 48 h of contact. The patch test was positive in 14 patients (16%) (5 for manganese, 3 for nickel, 1 for chromate, 1 for Nickel and manganese, and 4 for manganese and chromate). The binary restenosis rate in the patients with a positive patch test was similar to those with negative patch test (6.3% vs 6.5%, p=0.98). Serial quantitative coronary angiography analyses identified no significant differences in late lumen loss of in-stent segments between patients with positive patch test and those with negative patch test (0.19+/-0.49 mm vs 0.12+/-0.48 mm, p=0.55). CONCLUSION: SES prevent restenosis irrespective of metallic allergy. The classic relationship between metallic allergy and in-stent restenosis, seen with bare metal stents, does not appear to arise with DES, possibly because of the immunosuppressive effect of sirolimus.

Immunotoxicologic effects of inhaled chromium: role of particle solubility and co-exposure to ozone.

Soluble and insoluble hexavalent chromium (Cr6+) agents are concomitantly released with ozone (O3) during welding. Although pulmonary/immunologic implications from exposure to each agent individually have been investigated, the effects from simultaneous exposure, as occurs under actual working conditions, are unclear. To investigate immunomodulatory effects of inhaled Cr6+, F-344 rats were exposed for 5 h/day, 5 days/week for 2 or 4 weeks to atmospheres containing soluble potassium chromate (K2CrO4) or insoluble barium chromate (BaCrO4), each alone at 360 micrograms Cr/m3 or in combination with 0.3 ppm O3. One day after the final exposure, rats were euthanized, their lungs were lavaged, and pulmonary macrophages (PAM) were recovered for assessment of basal and inducible functions. Rats inhaling K2CrO4-containing atmospheres had greater levels of total recoverable cells, neutrophils, and monocytes in bronchopulmonary lavage compared to rats exposed to insoluble Cr6+ atmospheres, O3 alone, or air; these rats also had a reduced percentage of PAM, although total PAM levels remained unaffected. Although Cr exposure-related changes in PAM functionality were evident, any dependence upon Cr solubility was variable. K2CrO4-containing atmospheres modulated PAM-inducible interleukins-1 and -6, and tumor necrosis factor-alpha production to a greater degree than those containing BaCrO4. Conversely, BaCrO4-containing atmospheres affected PAM basal nitric oxide production and interferon-gamma-primed/zymosan-stimulated reactive oxygen intermediate production to a greater extent than did those containing K2CrO4. In none of the PAM assays did co-inhalation of O3 result in a modulation of the effects obtained with either Cr6+ compound itself. The results indicate that, while immunomodulatory effects of inhaled Cr6+ upon PAM are related to particle solubility, the co-inhalation of O3 apparently does not cause further modifications of the metal-induced effects.

Immunologic findings in workers formerly exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin and its congeners.

One hundred ninety-two workers in a German pesticide factory who were exposed to polychlorinated dibenzodioxins and -furans (PCDD/PCDF) were investigated for former and present diseases and laboratory changes of the immune system. Moreover, in a subgroup of 29 highly exposed and 28 control persons, proliferation studies were performed. In addition to assays such as blood count, immunoglobulins, serum electrophoresis, monoclonal bands, surface markers, autoantibodies, and lymphocyte proliferation, two new methods, the rise of tetanus antibody concentration after vaccination and the in vitro resistance of lymphocytes to chromate, were used to diagnose the morphologic and functional state of the immune system. There was no stringent correlation of actual PCDD/PCDF concentrations with the occurrence of infections or with one of the immune parameters. In addition, outcomes of the tetanus vaccination and the chromate resistance test were not correlated with PCDD/PCDF. However, the chromate resistance of lymphocytes stimulated by phytohemagglutinin of highly exposed persons was significantly lower than that for the control group. These findings indicate that the function of lymphocytes can be stressed and possibly impaired by high exposure to PCDD/PCDF.

Brief reversible bronchospasm resulting from bichromate exposure.

A 50-y-old male worker developed an asthmatic reaction after exposure to bichromate in a metal-plating plant. Evaluation included skin tests, bronchial provocation tests, and specific radioallergosorbent tests with metal salts. A 49-y-old worker who suffered from hard metal asthma was the control. These workers were not atopic, and they exhibited similar bronchial hyperresponsiveness in methacholine-PC20 (74 mg/ml versus 81 mg/ml, respectively) and IgE titers (129 IU/ml versus 130 IU/ml). Positive intradermal and patch tests to bichromate were found in the subject. A bronchial provocation test with inhalation of .01 % bichromate produced an immediate decrease in forced vital capacity in 1 s, followed by a rapid recovery within 5 min absent any treatment. There was no reaction to cobalt (1% cobalt chloride) or to nickel (2% nickel sulfate) salts. In the control, a positive bronchial provocation occurred (absent chromium) with cobalt and nickel. Administration of a subcutaneous preparation of 1 mg atropine sulfate or of 1 puff of disodium cromoglycate or beta-stimulant reduced bronchial responsiveness to methacholine-PC20, and no asthmatic reaction occurred following inhalation of 1% bichromate. No blocking of asthmatic reaction occurred after pretreatment with beclomethasone dipropionate inhalation. Administration of propranolol, however, potentiated the acute bronchoconstriction induced by bichromate. The 50-y-old worker had evidence of IgE antibody to chromium-conjugated human serum albumin and to chromium-conjugated exchange resin. His serum selectively bound 51Cr, but antibodies specific to cobalt and nickel were absent. These results, if viewed collectively, suggest that bichromate exposure causes brief reversible bronchospasm via alteration of autonomic balance and increased vagal activation.

Decreases of CD4- and CD8-positive T lymphocytes in retired chromate workers.

To investigate the effects of chromates on the human immune system, we measured total T lymphocytes and their two major subpopulations (CD4+ and CD8+ T lymphocytes) in the peripheral blood of 19 retired male workers who had been exposed to chromate at a chemical plant. The results indicated that both CD4+ and CD8+ T lymphocytes were significantly decreased, resulting in decreases in total T lymphocytes and total lymphocytes.

Chromate sensitization and elicitation from cement with iron sulfate.

For some years, iron sulfate has been added to cement manufactured in the Scandinavian countries to prevent sensitization to and elicitation from chromate in cement. Allergic contact dermatitis from chromate is reported here in 3 workers with hand dermatitis and exposure to cement containing iron sulfate. Although iron sulfate had been added to the cement, high chromate concentrations were found in many samples of cement to which these workers were exposed.

Follow-up of workers from the prefabricated concrete industry after the addition of ferrous sulphate to Danish cement.

Ferrous sulfate has been added to cement manufactured in Denmark, reducing the water soluble chromate content to not more than 2 ppm, since September 1981. A comparison is made between the medical and employment status of a cohort of workers engaged, or who had been engaged, in the manufacture of prefabricated concrete building components in 1981 and in 1987. Workers who had allergic cement eczema in 1981 appeared to show no improvement 6 years after the reduction of chromate in the cement. Improvement was seen, however, in the eczema of those workers with irritant cement eczema. The 1987 study showed that a larger number of chromate-sensitized workers required medical services and topical steroid treatment than did those who were not sensitized to chromate. This difference was statistically significant. The worse medical prognosis of the chromate-sensitized workers could in part be due to the fact that some of these had secondary contact sensitivity to cobalt and rubber chemicals. The chromate-sensitized workers also took earlier retirement. Younger workers with allergic and irritant cement eczema continued to work and their employment status was not influenced by chromate sensitization.

Epidemiology of contact allergy in Singapore.

The prevalence of contact allergy in 2471 patients patch tested in Singapore was 49.2% (571/1160) in women and 49.8% (653/1311) in men (sex difference not significant). The rate appeared to increase with age (43.7% in those less than 20 years, 50.6% between 20 and 49 years, and 63.1% in those greater than 49 years). There was no significant difference in the prevalence of contact allergy among the major races (Chinese, Malay, and Indian) of Singapore. Contact allergies in 16.8% (96/571) of women and 38.9% (254/653) of men (p less than 0.001) were occupational. Nickel, fragrance mix, proflavine, and chromate were common sensitizers. The male:female prevalence of nickel allergy was 1:2 (sex difference p less than 0.001) and for chromate was 7:1 (sex difference p less than 0.001). Chromate sensitivity was occupational in 87.7% (121/138) of men and 47.1% (8/17) of women (sex difference p less than 0.001). Proflavine, neomycin, and clioquinol were the more common medicament sensitizers.

Patch testing with hexavalent chromium salts in different vehicles and with nickel and cobalt in petrolatum.

In approaching the question as to which test preparations are most suitable for patch testing of metals, 25 chromium sensitive patients were tested with 0.5% potassium dichromate either in water or petrolatum. The aqueous solution proved better than the petrolatum preparation at a 48 h reading with Neodermtest Roc. No difference in sensitivity was recorded between 4 hexavalent chromium salts. 3 patients who were only sensitive to chromium solution in water also reacted positively to a 1% cobalt chloride solution and a 5% nickel sulfate solution in petrolatum.

A postal survey of patients with nickel and chromate dermatitis.

A postal survey was made of 75 patients with nickel and chromate dermatitis who had been discharged from the clinic; 69% of patients replied to the questionnaire and in 81% of these the dermatitis was still active. In many patients (48%) this was causing significant disability long after initial presentation to the clinic (average of 56.5 months). All patients had patch tests performed and the relevance of this is discussed with reference to nickel dermatitis.

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.

Epidemiological survey of occupational contact dermatitis of the hands in Belgium.

A total of 400 patients suffering from hand eczema were patch tested to 25 chemicals (20 from the standard series of the ICDRG plus five from the Tri-Contact of Belgium); 197 (49.2%) had a positive patch test to one or more substances, and there was no significant difference in the prevalence between males and females. Potassium dichromate and PPD mix were statistically more frequently involved as skin allergens in males than in females, whereas nickel sulphate, thiuram mix and neomycin sulphate gave a significantly higher number of positive responses in women than in men. Results of this epidemiological survey are discussed in the light of similar studies from the literature.

Persistence of contact allergy to chromium.

Forty-eight patients with a positive patch test to potassium dichromate 0.5% were retested after 4-7 years; 38 patients (79%) still had a positive patch test. Chromate allergy seems to be persistent. In 72% of the cases a history of occupational exposure to chromates could be proved.

HLA-antigens and contact hypersensitivity.

The HLA-A, -B -C typing of 100 bricklayers was performed. 50 bricklayers had developed contact allergy to chromium while 50 were healthy bricklayers. The distribution of HLA antigens were equal in the 2 groups.

[Comparative estimate of methods used in the examination of the sensitizing properties of chemical compounds]. / Porównawcza ocena metod stosowanych do badania wlasciwosci uczulajacych zwiazków chemicznych.

The studies carried out aim at comparing and determining the usefulness of two methods most frequently used to evaluate the sensitizing properties of chemical compounds. In the studies, compounds of known sensitizing properties have been used: potassium dichromate and 2,4-dinitrochlorobenzene. Comparison of the percentage of sensitized guinea--pigs, intensity of sensitizing reaction and the time at which the reaction is being kept up, indicates a greater usefulness of Magnusson and Kligman's method for routine evaluation of sensitizing properties of chemical compounds.