Occupational contact dermatitis in blue-collar workers: results from a multicentre study from the Danish Contact Dermatitis Group (2003-2012).

BACKGROUND: Blue-collar workers have a high risk of occupational contact dermatitis, but epidemiological studies are scarce. OBJECTIVES: To investigate allergic contact dermatitis in blue-collar workers with dermatitis registered by the Danish Contact Dermatitis Group. METHODS: A retrospective analysis of patch test data from 1471 blue-collar workers and 1471 matched controls tested between 2003 and 2012 was performed. A logistic regression was used to test for associations. RESULTS: The blue-collar workers often had occupational hand dermatitis (p < 0.001). Atopic dermatitis was less commonly observed among blue-collar workers (19.6%) than among controls (23.9%) (p = 0.005). Allergens with a statistically significant association with the occupational group of blue-collar workers were epoxy resins, methyldibromo glutaronitrile, 2-bromo-2-nitro-1,3-propanediol, potassium dichromate, and methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI). The following occupations were additionally identified as risk factors for contact sensitization to MCI/MI and MI, epoxy resins, and potassium dichromate, respectively: painting, construction work, and tile setting/terrazzo work. CONCLUSION: Contact allergy is a major problem among blue-collar workers. The data indicate a healthy worker effect among blue-collar workers diagnosed with dermatitis, as blue-collar workers were diagnosed significantly less often with atopic dermatitis than were controls.

Occupational contact dermatitis in hairdressers: an analysis of patch test data from the Danish contact dermatitis group, 2002-2011.

BACKGROUND: Occupational contact dermatitis among hairdressers is frequent, owing to daily exposure to irritants and allergens. OBJECTIVES: To identify sensitization to the most common allergens associated with the occupation of hairdressing. METHODS: Patch test results of 399 hairdressers and 1995 matched controls with contact dermatitis, registered by the Danish Contact Dermatitis Group between January 2002 and December 2011, were analysed. All patients were patch tested with the European baseline series, and hairdressers were additionally tested with the hairdressing series. RESULTS: Occupational contact dermatitis (p < 0.001) and hand eczema (p < 0.001) were observed significantly more often among hairdressers than among controls. Atopic dermatitis was less commonly observed among hairdressers (21.3%) than among controls (29.4%) (p < 0.01). Allergens from the European baseline series with a statistically significant association with the occupation of hairdressing were p-phenylenediamine, thiuram mix, and benzocaine. Frequent sensitizers from the hairdressing series were ammonium persulfate, toluene-2,5-diamine, 3-aminophenol, and 4-aminophenol. Cysteamine hydrochloride and chloroacetamide emerged as new sensitizers. CONCLUSIONS: These results indicate a healthy worker effect among hairdressers diagnosed with eczema. Ammonium persulfate and p-phenylenediamine remain frequent sensitizers in hairdressers with contact dermatitis. Cysteamine hydrochloride and chloroacetamide should be included in future surveillance studies.

Occupational contact dermatitis in painters: an analysis of patch test data from the Danish Contact Dermatitis Group.

BACKGROUND: Painters are among the occupational groups that most commonly experience occupational contact dermatitis, but few investigations exist concerning this occupation. OBJECTIVES: To characterize painters with contact dermatitis and identify the most common allergens associated with the occupation. Materials and methods. All patch test results of 219 painters and 1095 matched controls registered by the Danish Contact Dermatitis Group between 2001 and 2010 were analysed. RESULTS: Hand eczema (p < 0.0001) and occupational contact dermatitis (p < 0.0001) were observed significantly more often in the painters than in the group of controls. Sensitizations to the following allergens from the European baseline series were associated with the occupation and were statistically significant: methylchloroisothiazolinone/methylisothiazolinone, epoxy resin, formaldehyde, and quaternium-15. Three different isothiazolinones emerged as the most frequent sensitizers of the allergens tested in addition to the baseline series. CONCLUSIONS: The results indicate that painters have an increased risk of developing occupational hand eczema. Isothiazolinones and epoxy resin proved to be the two most frequent sensitizers in painters.

Contact allergy to epoxy resin: risk occupations and consequences.

BACKGROUND: Epoxy resin monomers are strong skin sensitizers that are widely used in industrial sectors. In Denmark, the law stipulates that workers must undergo a course on safe handling of epoxy resins prior to occupational exposure, but the effectiveness of this initiative is largely unknown. OBJECTIVES: To evaluate the prevalence of contact allergy to epoxy resin monomer (diglycidyl ether of bisphenol A; MW 340) among patients with suspected contact dermatitis and relate this to occupation and work-related consequences. PATIENTS/METHODS: The dataset comprised 20 808 consecutive dermatitis patients patch tested during 2005-2009. All patients with an epoxy resin-positive patch test were sent a questionnaire. RESULTS: A positive patch test reaction to epoxy resin was found in 275 patients (1.3%), with a higher proportion in men (1.9%) than in women (1.0%). The prevalence of sensitization to epoxy resin remained stable over the study period. Of the patients with an epoxy resin-positive patch test, 71% returned a questionnaire; 95 patients had worked with epoxy resin in the occupational setting, and, of these, one-third did not use protective gloves and only 50.5% (48) had participated in an educational programme. CONCLUSION: The 1% prevalence of epoxy resin contact allergy is equivalent to reports from other countries. The high occurrence of epoxy resin exposure at work, and the limited use of protective measures, indicate that reinforcement of the law is required.

Classification of hand eczema: clinical and aetiological types. Based on the guideline of the Danish Contact Dermatitis Group.

BACKGROUND: No generally accepted classification scheme for hand eczema exists. The Danish Contact Dermatitis Group recently developed a guideline defining common clinical types and providing criteria for aetiological types. OBJECTIVES: To test the concepts of this guideline in a group of hand eczema patients. METHODS: Seven hundred and ten hand eczema patients were included from seven dermatology clinics in Denmark. The hand eczema was classified into one of five clinical types, with standard photographs as reference. The severity was scored by the physician, who also made a final aetiological diagnosis. RESULTS: Irritant contact dermatitis was most frequent in chronic, dry fissured hand eczema (44.3%), pulpitis (41.7%), and nummular hand eczema (40.9%), whereas allergic contact dermatitis dominated in vesicular types of hand eczema, with recurrent (35%) and few (24.2%) eruptions. Hyperkeratotic palmar hand eczema was the only clinical type that constituted a distinct subgroup; it was found most frequently in older men and had the strongest relationship, although not significant, with non-specific dermatitis. CONCLUSIONS: The relationship between clinical type of hand eczema and aetiological diagnosis fitted with general experience, but no simple relationship was found. This emphasizes that patch testing and exposure analysis are mandatory. Hyperkeratotic palmar hand eczema was identified as a distinct clinical subtype.

Deodorants are the leading cause of allergic contact dermatitis to fragrance ingredients.

BACKGROUND: Fragrances frequently cause contact allergy, and cosmetic products are the main causes of fragrance contact allergy. As the various products have distinctive forms of application and composition of ingredients, some product groups are potentially more likely to play a part in allergic reactions than others. AIM: To determine which cosmetic product groups cause fragrance allergy among Danish eczema patients. METHOD: This was a retrospective study based on data collected by members of the Danish Contact Dermatitis Group. Participants (N = 17,716) were consecutively patch tested with fragrance markers from the European baseline series (2005-2009). RESULTS: Of the participants, 10.1% had fragrance allergy, of which 42.1% was caused by a cosmetic product: deodorants accounted for 25%, and scented lotions 24.4%. A sex difference was apparent, as deodorants were significantly more likely to be listed as the cause of fragrance allergy in men (odds ratio 2.2) than in women. Correlation was observed between deodorants listed as the cause of allergy and allergy detected with fragrance mix II (FM II) and hydroxyisohexyl 3-cyclohexene carboxaldehyde. CONCLUSION: Deodorants were the leading causes of fragrance allergy, especially among men. Seemingly, deodorants have an 'unhealthy' composition of the fragrance chemicals present in FM II.

Cobalt uptake and binding in human red blood cells.

The basal uptake and cytoplasmic binding of cobalt was studied in human red cells using (57)Co as tracer. The basal uptake is linear with time, at a rate of about 10 µmol (l cells)(-1) h(-1) at 100 µM [Co(2+)](o), and is almost irreversible, as there is hardly any efflux into excess EDTA. Ionophore A23187 mediates a rapid equilibration of Co(2+) across the cell membrane leading to a marked accumulation, reflecting effective cytoplasmic buffering. The fraction (α(Co)) of total cell cobalt being present as free, ionized Co(2+) is estimated at α(Co)=0.01 from the equilibrium distribution of cobalt, and also from the initial slope of the cobalt buffering curve. The cobalt accumulation is similar in fed and ATP-depleted cells. The buffering curve for [Co(T)](c) can be fitted by a Michaelis type function with B(max)=24 mmol (l cells)(-1) and half-saturation at 240 µM [Co(2+)](c). The tracer influx curves are adequately fitted by single exponentials, whereas the net influx curves all require at least double exponential fits, probably due to non-stationary A23187 kinetics. The rate of tracer influx decreases with increasing cobalt concentration, and increases with delayed addition of (57)Co tracer during net uptake. This might be explained by an 'auto-inhibition' by cobalt. The kinetics for A23187-mediated net and tracer influx of (54)Mn is very similar to that of (57)Co, whereas the net influx of (65)Zn can be fitted by single exponentials. In cobalt-loaded cells the cobalt is partly reversibly bound, being releasable by excess extracellular EGTA in the presence of A23187, and partly tightly bound, remaining in the cells even at high ionophore concentrations. The tightly bound fraction builds up over time, and is larger and develops earlier in fed cells compared to ATP-depleted cells. However, all cell cobalt appears to exchange with (57)Co during tracer influx. It is speculated that oxidation of Co(2+) to Co(3+) could lead to the high affinity binding. Tight binding is not observed in the case of (54)Mn. Tightly bound and the major part of reversibly bound (57)Co co-migrate with hemoglobin in Sephadex column chromatography of a lysate of (57)Co-loaded cells. (57)Co also co-migrates with hemoglobin when added to a lysate of unlabeled cells or to a solution of purified hemoglobin, in both cases with a time-dependent development of tight binding. Cobalt is known to bind to the globin moiety of hemoglobin. The results imply that during long-term cobalt exposure in vivo cobalt will be taken up practically irreversibly in the red cells during their 120 days life span. Thus, for biomonitoring of cobalt exposure, it could be appropriate to measure the cobalt content in red cells to give, compared with timed or in-competition whole-blood and serum analysis, an average value for the exposure over the last couple of months.

Fragrance mix II in the baseline series contributes significantly to detection of fragrance allergy.

BACKGROUND: Fragrance mix II (FM II) is a relatively new screening marker for fragrance contact allergy. It was introduced in the patch test baseline series in Denmark in 2005 and contains six different fragrance chemicals commonly present in cosmetic products and which are known allergens. AIM: To investigate the diagnostic contribution of including FM II in the baseline series by comparing it with other screening markers of fragrance allergy: fragrance mix I (FM I), Myroxylon pereirae and hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC). METHOD: Retrospective study of 12 302 patients consecutively patch tested with FM II by members of the Danish Contact Dermatitis Group 2005-2008. RESULTS: FM II gave a positive patch test in 553 patients (4.5%), and in 72.2% of these patients the reaction was judged to be clinically relevant. FM II ranked second in detecting fragrance allergy, after FM I. If FM II had not been included as a screening marker in the baseline series, 15.6% (n = 202) of individuals with fragrance allergy would not have been identified by the other fragrance screening markers (FM I, M. pereirae or HICC). CONCLUSION: FM II contributes substantially to detecting fragrance allergy. It ranked second among the fragrance screening markers tested in the baseline series and detects individuals with an allergy who otherwise would not have been identified.

Characteristics of nickel-allergic dermatitis patients seen in private dermatology clinics in Denmark: a questionnaire study.

The use of nickel in certain consumer goods has been regulated in Denmark since 1990. The aim of this study was to reveal the clinical characteristics of nickel-allergic patients seen in seven private dermatology clinics and to identify current sources of nickel that may elicit nickel dermatitis. During 2006 to 2007, 634 patients with dermatitis aged 17-91 years were patch-tested and completed a questionnaire including a question about the occurrence of dermatitis following skin contact with ear-rings or ear-pins, watches, buttons or metal clasps (i.e. metal dermatitis). chi2 tests were applied to test for statistical significant differences. Analysis revealed a lower prevalence of nickel allergy among women in the youngest age group (17-22 years) in comparison with older age groups (23-34 years and 35-46 years) (p < 0.03). Most patients experienced metal dermatitis on the first occurrence be-tween 1975 and 1985. No new cases of metal dermatitis were identified after 1985. We conclude that nickel allergy has decreased among young females with dermatitis due to the nickel regulation.

Decreasing trends in methyldibromo glutaronitrile contact allergy--following regulatory intervention.

BACKGROUND: The preservative methyldibromo glutaronitrile (MDBGN) has been banned, first from stay-on, and later from rinse-off cosmetics, in the EU countries because of increasing rates of contact allergy. OBJECTIVES: To evaluate the frequency of contact allergy to MDBGN among patients patch tested by the Danish Contact Dermatitis Group just before and following regulatory decisions. PATIENTS/METHODS: The data set comprised 19 279 consecutive eczema patients patch tested from 2003-2007 with MDBGN 0.3% in petrolatum (pet.) or, in a minority of patients, with Euxyl K 400 1.5% in pet. RESULTS: A significantly decreasing trend in the frequency of positive patch tests to MDBGN was found from 4.6% in 2003 to 2.6% in 2007 (P < 0.001). The decreasing trend was seen for both men and women. A significantly decreasing proportion of cases with a current relevance of contact allergy to MDBGN was also seen from 51.3% in 2003 to 29% in 2007 (P < 0.001). CONCLUSIONS: Regulatory interventions have already had a major effect on allergic disease due to MDBGN in Denmark. The same trends are likely to be seen in other EU countries.

Pharmacology of the human red cell voltage-dependent cation channel. Part II: inactivation and blocking.

Pharmacological modulation of the nonselective voltage-dependent cation (NSVDC) channel from human erythrocytes was studied. Using the inorganic cations ruthenium red and La3+, as well as the organic thiol group reagents iodoacetamide (IAA) and N-ethylmaleimide (NEM), it was possible to demonstrate a concentration-dependent decrease in the voltage-activated conductance, reflecting an inhibition or inactivation of the channel. Initial voltage activation was achieved by injecting human red cells into sucrose-substituted Ringers with a low chloride concentration, which causes a strongly positive membrane potential to develop, initially determined by the equilibrium potential for Cl- ( approximately +100 mV). Due to the voltage- and time-dependent activation of the cation channel, net effluxes, minimized by addition of a chloride conductance blocker, occurred and Vm gradually decreased and stabilized at a value less positive than E(Cl), reflecting the increased cation conductance, g+, reaching 1.5-2.0 microS/cm2. In the presence of inhibitors of the NSVDC channel, both the membrane potential repolarization and the cation efflux were diminished.

Pharmacology of the human red cell voltage-dependent cation channel; Part I. Activation by clotrimazole and analogues.

The activation and pharmacological modulation of the nonselective voltage-dependent cation (NSVDC) channel from human erythrocytes were studied. Basic channel activation was achieved by suspending red cells in a low Cl(-) Ringer (2 mM), where a positive membrane potential (V(m) = E(Cl)) immediately developed. Voltage- and time-dependent activation of the NSVDC channel occurred, reaching a cation conductance (g+) of 1.5-2.0 microS cm(-2). In the presence of the classical Gárdos channel blocker clotrimazole (0-50 microM), activation occurred faster, and g+ saturated dose-dependently (EC50 = 14 microM) at a value of about 4 microS cm(-2). The clotrimazole analogues TRAM-34, econazole, and miconazole also stimulated the channel, whereas the chemically more distant Gárdos channel inhibitors nitrendipine and cetiedil had no effects. Although the potency for modulation of the NSVDC channel is much lower than the IC50 value for Gárdos channel inhibition, clotrimazole (and its analogues) constitutes the first chemical class of positive modulators of the NSVDC channel. This may be an important pharmacological "fingerprint" in the identification of the cloned equivalent of the erythrocyte channel.

Voltage activation and hysteresis of the non-selective voltage-dependent channel in the intact human red cell.

Suspension of intact human red cells in media with low chloride and sodium concentrations (isotonic sucrose substitution) results in strongly inside positive membrane potentials, which activate the voltage-dependent non-selective cation (NSVDC) channel. By systematic variation of the initial Nernst potentials for chloride (degree of ion substitution) as well as the chloride conductance (block by NS1652), and by exploiting the interplay between the Ca(2+)-permeable NSVDC channel, the Ca(2+)-activated K+ channel (the Gárdos channel) and the Ca(2+)-pump, a graded activation of the NSVDC channel was achieved. Under these conditions, it was shown that the NSVDC channels exist in two states of activation depending on the initial conditions for the activation. The hysteretic behaviour, which in patch clamp experiments has been found for the individual channel unit, is thus retained at the cellular level and can be demonstrated with red cells in suspension.