Occupational contact sensitization in female geriatric nurses: Data of the Information Network of Departments of Dermatology (IVDK) 2005-2014.

BACKGROUND: Geriatric nurses (GN) have a high risk of occupational contact dermatitis (OCD), with chronic irritant contact dermatitis predominating. However, allergic contact dermatitis is an important issue as well. Little is known whether the relevant occupational allergen spectrum reported in the 1990s, including fragrances, preservatives, rubber chemicals and ingredients of surface disinfectants to be the most common sensitizers in GN, is still valid. OBJECTIVES: To monitor the current allergen spectrum in GN with OCD and verify the validity of the patch test recommendations (baseline-, preservative-, ointment base-, rubber-, disinfectant, series and fragrances) in GN with suspected OCD given by the German Contact Dermatitis Research Group (DKG). METHODS: Retrospective analysis of IVDK data (2005-2014) of 743 female GN with OCD, in comparison to 695 GN without OCD. RESULTS: GN with OCD reacted significantly more frequently to both fragrance mixes, hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC), thiuram mix, zinc diethyldithiocarbamate and mercaptobenzothiazole than GN without OCD. Reactions to MDBGN, methylchloroisothiazolinone/methylisothiazolinone and oil of turpentine occurred substantially, but not significantly more frequently among GN with OCD. The latter may be due to former use of a special alcoholic liniment in geriatric care. Among material from the patients' workplaces, tetrazepam was a frequent allergen, due to dust exposure from pill crushing. Furthermore, occupationally used protective gloves, body care products as well as surface disinfectants were often tested positively. CONCLUSIONS: The general allergen spectrum in GN with OCD is unchanged, so the DKG patch test recommendations are still valid. Prevention of occupational sensitization should focus on fragrance-free hygiene and body care products, usage of accelerator-free protective gloves and avoidance of drug dust exposure.

Limonene and its ozone-initiated reaction products attenuate allergic lung inflammation in mice.

Inhalation of indoor air pollutants may cause airway irritation and inflammation and is suspected to worsen allergic reactions. Inflammation may be due to mucosal damage, upper (sensory) and lower (pulmonary) airway irritation due to activation of the trigeminal and vagal nerves, respectively, and to neurogenic inflammation. The terpene, d-limonene, is used as a fragrance in numerous consumer products. When limonene reacts with the pulmonary irritant ozone, a complex mixture of gas and particle phase products is formed, which causes sensory irritation. This study investigated whether limonene, ozone or the reaction mixture can exacerbate allergic lung inflammation and whether airway irritation is enhanced in allergic BALB/cJ mice. Naïve and allergic (ovalbumin sensitized) mice were exposed via inhalation for three consecutive days to clean air, ozone, limonene or an ozone-limonene reaction mixture. Sensory and pulmonary irritation was investigated in addition to ovalbumin-specific antibodies, inflammatory cells, total protein and surfactant protein D in bronchoalveolar lavage fluid and hemeoxygenase-1 and cytokines in lung tissue. Overall, airway allergy was not exacerbated by any of the exposures. In contrast, it was found that limonene and the ozone-limonene reaction mixture reduced allergic inflammation possibly due to antioxidant properties. Ozone induced sensory irritation in both naïve and allergic mice. However, allergic but not naïve mice were protected from pulmonary irritation induced by ozone. This study showed that irritation responses might be modulated by airway allergy. However, aggravation of allergic symptoms was observed by neither exposure to ozone nor exposure to ozone-initiated limonene reaction products. In contrast, anti-inflammatory properties of the tested limonene-containing pollutants might attenuate airway allergy.

Limonene hydroperoxide analogues show specific patch test reactions.

BACKGROUND: The fragrance terpene R-limonene is a very weak sensitizer, but forms allergenic oxidation products upon contact with air. The primary oxidation products of oxidized limonene, the hydroperoxides, have an important impact on the sensitizing potency of the oxidation mixture. One analogue, limonene-1-hydroperoxide, was experimentally shown to be a significantly more potent sensitizer than limonene-2-hydroperoxide in the local lymph node assay with non-pooled lymph nodes. OBJECTIVES: To investigate the pattern of reactivity among consecutive dermatitis patients to two structurally closely related limonene hydroperoxides, limonene-1-hydroperoxide and limonene-2-hydroperoxide. METHODS: Limonene-1-hydroperoxide, limonene-2-hydroperoxide, at 0.5% in petrolatum, and oxidized limonene 3.0% pet. were tested in 763 consecutive dermatitis patients. RESULTS: Of the tested materials, limonene-1-hydroperoxide gave most reactions, with 2.4% of the patients showing positive patch test reactions. Limonene-2-hydroperoxide and oxidized R-limonene gave 1.7% and 1.2% positive patch test reactions, respectively. Concomitant positive patch test reactions to other fragrance markers in the baseline series were frequently noted. CONCLUSIONS: The results are in accordance with the experimental studies, as limonene-1-hydroperoxide gave more positive patch test reactions in the tested patients than limonene-2-hydroperoxide. Furthermore, the results support the specificity of the allergenic activity of the limonene hydroperoxide analogues and the importance of oxidized limonene as a cause of contact allergy.

An international multicentre study on the allergenic activity of air-oxidized R-limonene.

BACKGROUND: Limonene is a common fragrance terpene that, in its pure form, is not allergenic or is a very weak allergen. However, limonene autoxidizes on air exposure, and the oxidation products can cause contact allergy. Oxidized R-limonene has previously been patch tested in multicentre studies, giving 2-3% positive patch test reactions in consecutive patients. OBJECTIVES: To investigate whether oxidized R-limonene 3.0% in petrolatum, with a stable concentration of the main haptens, limonene hydroperoxides (Lim-OOHs), could be a useful tool for the detection of contact allergy in an international setting. METHODS: Oxidized R-limonene 3.0% (Lim-OOHs 0.33%) pet. was tested in 2900 consecutive dermatitis patients in Denmark, the United Kingdom, Singapore, Spain, Sweden, and Australia. RESULTS: Overall, 5.2% (range 2.3-12.1%) of the patients showed a positive patch test reaction to oxidized R-limonene. Doubtful reactions were found in 7.0% of the patients (range 0-24%). Few irritant reactions were seen. CONCLUSIONS: Oxidized R-limonene at 3.0% pet. with a specified content of Lim-OOHs 0.33% is a standardized and useful tool for the detection of contact allergy in dermatitis patients. Many patients showing positive patch test reactions to oxidized R-limonene would not be informed of their fragrance allergy if this specific test had not been performed.

[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.

Enhanced sensitization and elicitation responses caused by mixtures of common fragrance allergens.

BACKGROUND: Perfumes are complex mixtures composed of many fragrance ingredients, many of which are known to be only weak allergens when tested individually. It is therefore surprising that fragrance contact allergy is one of the most common forms of contact allergy. OBJECTIVES: To investigate whether mixing different fragrance allergens leads to increased sensitization potency, and to examine the difference in the challenge response to one chemical in mice sensitized either with the mixture of allergens or with only the relevant allergen. METHODS: CBA mice were sensitized with three different concentrations of three fragrance allergens alone or as a mixture. The sensitization and elicitation responses were measured by ear thickness plus infiltration of B and T cells and T cell proliferation in the draining lymph nodes. RESULTS: We found a dose-dependent sensitization response for each of the allergens. An increased response was seen when the allergens were mixed. A stronger challenge response to cinnamal was seen in mice sensitized with the allergen mixture than in mice sensitized with cinnamal alone. CONCLUSIONS: Our findings suggest that mixtures of allergens increase the primary response that potentiates the generation of memory T cells in response to the specific allergen. Thus, allergen mixtures enhance both induction and elicitation of contact allergy.

Structural influence on radical formation and sensitizing capacity of alkylic limonene hydroperoxide analogues in allergic contact dermatitis.

Hydroperoxides are known to be strong contact allergens and a common cause of contact allergy. They are easily formed by the autoxidation of, for example, fragrance terpenes, compounds that are common in perfumes, cosmetics, and household products. A requirement of the immunological mechanisms of contact allergy is the formation of an immunogenic hapten-protein complex. For hydroperoxides, a radical mechanism is postulated for this formation. In our previous investigations of allylic limonene hydroperoxides, we found that the formation of carbon- and oxygen-centered radicals, as well as the sensitizing capacity, is influenced by the structure of the hydroperoxides. The aim of the present work was to further investigate the connection between structure, radical formation, and sensitizing capacity by studying alkylic analogues of the previously investigated allylic limonene hydroperoxides. The radical formation was studied in radical-trapping experiments employing 5,10,15,20-tetraphenyl-21H,23H-porphine iron(III) chloride as an initiator and 1,1,3,3-tetramethylisoindolin-2-yloxyl as a radical trapper. We found that the investigated hydroperoxides initially form carbon- and oxygen-centered radicals that subsequently form alcohols and ketones. Trapped carbon-centered radicals and nonradical products were isolated and identified. Small changes in structure, like the omission of the endocyclic double bond or the addition of a methyl group, resulted in large differences in radical formation. The results indicate that alkoxyl radicals seem to be more important than carbon-centered radicals in the immunogenic complex formation. The sensitizing capacities were studied in the murine local lymph node assay (LLNA), and all hydroperoxides tested were found to be potent sensitizers. For two of the hydroperoxides investigated, the recently suggested thiol-ene reaction is a possible mechanism for the formation of immunogenic complexes. For the third investigated, fully saturated, hydroperoxide, the thiol-ene mechanism is not possible for immunogenic complex formation. This strongly indicates that several radical reaction pathways for immunogenic complex formation of limonene hydroperoxides are active in parallel.