Occupational contact allergy in bricklayers, tile setters etc. - Current spectrum of sensitization and recent time trends.

BACKGROUND: Occupational exposure of bricklayers, construction workers, tile setters etc. has changed during the last years. For some years now, all manually handled cement in the European Union and in Switzerland is chromate-reduced. Epoxy resin systems are being used in more and more fields of application. Improved worker's protection, especially wearing protective gloves, is promoted. These changes influence the spectrum of occupational contact sensitization. OBJECTIVE: Description of the current allergen spectrum in patients working in the building trade who suffer from occupational contact dermatitis. MATERIAL AND METHODS: Retrospective analysis of data of the Information Network of Departments of Dermatology (IVDK), 2009 - 2011. RESULTS: During the study period, 245 bricklayers, construction workers, tile setters etc. with occupational dermatitis have been patch tested. Potassium dichromate was the most frequent allergen, yielding 15.1% positive reactions, followed by epoxy resin with 13.7% positive reactions. Beyond that, there were 8 additional components of epoxy resin systems (5 reactive diluents and 3 amine hardeners), as well as 9 rubber ingredients, mainly thiurams, among the 30 most frequent allergens. In the course of time, a decline of chromate sensitization could be noted, paralleled by a decline of cobalt sensitization. In contrast, sensitization to epoxy resin has increased. CONCLUSION: Thanks to the usage of chromate-reduced cement, chromate sensitization continues to decline in the building trade. The increase of epoxy resin sensitization must prompt intensified prevention efforts. When recommending protective gloves, thiuram-free products should be preferred. The most important allergens are covered by the following test series recommended by the German Contact Dermatitis Research Group (DKG): DKG baseline series, DKG test series "building trade", DKG rubber series.

Registries in Clinical Epidemiology: the European Surveillance System on Contact Allergies (ESSCA).

BACKGROUND: Disease registries rely on consistent electronic data capturing (EDC) pertinent to their objectives; either by using existing electronic data as far as available, or by implementing specific software solutions. OBJECTIVES: To describe the current practice of an international disease registry (European Surveillance System on Contact Allergies, ESSCA, www.essca-dc.org) against different state of the art approaches for EDC. METHODS: Since 2002, ESSCA is collecting data, currently from 53 departments in 12 countries. Departmental EDC software ranges from spreadsheets to comprehensive "patch test software" based on a relational database. In the Erlangen data centre, such diverse data is imported, converted to a common format, quality checked and pooled for scientific analyses. RESULTS: Feed-back to participating departments for quality control is provided by standardised reports. Varying author teams publish scientific analyses addressing the objective of contact allergy surveillance. CONCLUSIONS: Although ESSCA represents a historically grown, heterogeneous network and not one unified approach to EDC, some of its features have contributed to its viability in the last 12 years and may be useful to consider for similar investigator-initiated networks.

[Should metal alloy discs be used for patch testing in suspected metal implant intolerance reaction?]. / DKG-Stellungnahme zur Epikutantestung von Metalllegierungsplättchen bei Verdacht auf Metallimplantat-Unverträglichkeit.

Intolerance reactions to metal implants may be caused by metal allergy. However, prior to implantation, patch testing should not be done in a prophylactic-prophetic approach. Pre-implant patch testing should only be performed to verify or exclude metal allergy in patients with a reported respective history. In the case of implant-in particular arthroplasty-related complications like, for example, pain, effusion, skin changes, reduced range of motion, or loosening, orthopedic-surgical differential diagnostics should be performed first. Allergological workup of suspected metal implant allergy should be done with the DKG baseline series which contains nickel-, cobalt- and chromium-preparations. Various studies assessing the usefulness of metal alloy discs for patch testing proved that this approach does not give reliable information about metal allergy. Positive patch test reactions to the discs cannot be assigned to a specific metal within the disc alloy components. Furthermore, availability of such metal discs might be an invitation to uncritical testing. Accordingly, due to lack of benefit in comparison to patch testing with standardized metal salt preparations, we do not recommend patch testing with metal alloy discs.

[Not Available]. / Kontaktallergien im Kindesalter.

Allergic contact eczema in children is frequent. If clinically suspected, a patch test should be performed. In the present study, data obtained from 116,742 patients who had undergone a patch test from 2005-2014 were analysed. The children group (range 0-12 years) included 925 patients. If at least 700 tested individuals were considered, the most frequent sensitizations in this group were nickel sulfate (8.5 %), fragrance mix I (5.5 %), and colophony (3.4 %), whereby sensitisation in adults was higher for nickel sulfate (15.5 %) and fragrance mix 1 (8.4 %), while being similar for colophony (3.7 %). In adolescents with and without a profession, nickel sulfate (11.1 and 13.6 %, respectively) and cobalt (II) chloride (3.9 and 3.4 %, respectively) were the most frequent positively tested contact allergens. Sensitisations toward fragrance mix I was low (3.9 and 3.4 %, respectively) in comparison to the adult group (8.4 %). In both children and adolescents, toluene diamine and paraphenylenediamine sensitizations were not infrequent, but it must be considered that these allergens were only tested if suspected. The data show that the sensitisation profile among children and adolescents display patterns similar to those in adults. Sensitisations in childhood and adolescence towards dyes like paraphenylendiamine may be associated with increased use of tattooing in these groups.

Contact allergy induced by bisphenol A diglycidyl ether leachables from aluminium tubes for pharmaceutical use.

BACKGROUND: Aluminium tubes for pharmaceutical use are internally lacquered with epoxy resins (ER) based on bisphenol A diglycidyl ether (BADGE). Recently, it was shown that remnants of ER polymerization like BADGE are extractable from epoxy-based coatings of commercially available tubes and may leach into semi-solid drug preparations. We aimed to evaluate the safety of BADGE-contaminated macrogol ointments in individuals sensitized to ER based on BADGE by use tests. METHODS: Repeated open application testing (ROAT) in 11 patients sensitized to ER based on BADGE with BADGE in macrogol ointments (3 mg/kg; 30 mg/kg, equivalent to BADGE concentration determined in macrogol ointment after storage in a commercially available tube; 300 mg/kg). RESULTS: The 30 mg/kg BADGE ointment elicited reactions in three patients, and another three patients reacted to 300 mg/kg BADGE ointment. No reactions to the vehicle control and 3 mg/kg BADGE were observed. CONCLUSIONS: Elevated BADGE concentrations in ER-coated aluminium tubes pose a risk of developing contact dermatitis to patients sensitized to ER based on BADGE. Quality standards are deemed necessary for the production of ER-coated aluminium tubes intended for pharmaceutical use and should consider the results of the present ROAT study.

Contact sensitization in patients with suspected cosmetic intolerance: results of the IVDK 2006-2011.

BACKGROUND: Ingredients of leave-on cosmetics and body care products may sensitize. However, not every case of cosmetic intolerance is due to contact sensitization. OBJECTIVE: To describe the frequency of contact sensitization due to cosmetics in a large clinic population, and a possible particular allergen pattern. METHODS: Retrospective analysis of data from the Information Network of Departments of Dermatology, 2006-2011. RESULTS: Of 69 487 patients tested, 'cosmetics, creams, sunscreens' was the only suspected allergen source category in 10 124 patients (14.6%). A final diagnosis 'allergic contact dermatitis' was stated in 2658 of these patients (26.3%).Compared to a control group, there were significantly more reactions to fragrance mixes I and II, balsam of Peru, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) and lanolin alcohols. No special pattern of fragrance sensitization could be identified. Among the preservatives, MI was by far the leading allergen, while sensitization to other widely used compounds like parabens or phenoxyethanol was rare. CONCLUSIONS: True allergic reactions to cosmetic ingredients are rarer than generally assumed. Limitation of exposure to MI in leave-on cosmetics and body care products is urgently needed.

Skin irritability to sodium lauryl sulfate is associated with increased positive patch test reactions.

BACKGROUND: As previous observations have indicated an inter-relationship between irritant and allergic skin reactions we analysed data of synchronous allergen and sodium lauryl sulfate (SLS) patch tests in terms of a relationship between SLS responsiveness and allergic patch test reactions. OBJECTIVES: To analyse differences in terms of allergen-specific and overall reaction profiles between patients with vs. those without an irritant reaction to SLS. METHODS: Clinical data of 26 879 patients patch tested from 2008 to 2011 by members of the Information Network of Departments of Dermatology were analysed. After descriptive analyses, including the MOAHLFA index, the positivity ratio and the reaction index, a negative binomial hurdle model was adopted to investigate the correlation between SLS reactivity and positive patch test reactions. RESULTS: Men, patients aged ≥ 40 years and patients with an occupational dermatitis background were over-represented in the SLS-reactive group. Patients with an irritant reaction to SLS showed a higher proportion of weak positive reactions, as well as more questionable and irritant reactions to contact allergens than patients not reactive to SLS. The risk of an additional positive patch test reaction increased by 22% for SLS-reactive patients compared with those who were SLS negative. CONCLUSIONS: The marked association between SLS reactivity and the number of positive reactions in patch test patients may be due to nonspecific increased skin reactivity at the moment of patch testing only. However, increased SLS reactivity could also be due to longer-lasting enhanced skin irritability, which may have promoted (poly-)sensitization. Further studies, for example with longitudinal data on patients repeatedly patch tested with SLS and contact allergens, are necessary.

Nickel allergy following European Union regulation in Denmark, Germany, Italy and the U.K.

BACKGROUND: Nickel allergy is common worldwide. It is associated with hand dermatitis, and sensitization is often induced by nickel-releasing jewellery. The European Union (EU) introduced legislation to control nickel content and release from jewellery and other consumer items through the EU Nickel Directive 1994, which came into force in 2001 and is now part of the REACH regulation. OBJECTIVES: To examine the effects of the EU nickel regulations on the prevalence of nickel allergy in four European countries. METHODS: Nickel patch-test data from 180,390 patients were collected from national databases in Denmark, Germany, Italy and the U.K. from between 1985 and 2002 to 2010. Patients with suspected allergic contact dermatitis who had been patch tested with nickel sulfate 5% in petrolatum were included in the analysis. The main outcomes studied were the percentage of positive results to nickel patch tests, and changes in trends with time in an age- and sex-stratified analysis. RESULTS: A statistically significant decrease in nickel allergy was observed in Danish, German and Italian women aged below 30 years. In female patients in the U.K. this was observed between 2004 and 2010. In young men, a statistically significant decrease in nickel allergy was observed in Germany and the U.K., whereas a nonsignificant increase was observed in Italy. CONCLUSIONS: There has been a reduction in the prevalence of nickel allergy in young women, contemporaneous with the introduction of the nickel regulation. A reduction is also suggested in men in Germany and the U.K. A causative effect of the regulatory intervention is the most likely explanation.

Risk factors of polysensitization to contact allergens.

BACKGROUND: 'Polysensitization' (PS) is usually defined as contact sensitization to three or more unrelated haptens of the baseline patch test series. Despite PS being an important clinical phenotype indicating increased susceptibility to contact allergy, statistical approaches to analyse PS have hitherto been preliminary. OBJECTIVES: To apply an appropriate regression model for count data, namely, negative binomial hurdle regression, to a large set of clinical patch test data with the aim of estimating PS risk in more detail than previously achieved. METHODS: The detailed information provided by the hurdle model includes a separate estimation of an 'increment factor' quantifying the likelihood of further positive reactions, i.e. PS. Clinical data of 126 878 patients patch tested by departments comprising the IVDK (Information Network of Departments of Dermatology) network (www.ivdk.org) between 1995 and 2010 were included. RESULTS: Regarding anatomical sites as exposure (surrogate), the axillae and the feet were found to be strong PS risk factors. Moreover, age was a strong PS risk factor, and less so, female sex. In comparison, atopic eczema and occupational dermatitis were less important risk factors. Single allergens contributed to PS to a varying extent. CONCLUSIONS: The data presented point to some, very likely exposure-related, risk factors which need to be considered in future PS research, e.g. addressing the genetic basis for PS.

Surveillance of contact allergies: methods and results of the Information Network of Departments of Dermatology (IVDK).

Contact allergy (CA) surveillance networks provide information to a multitude of stakeholders, which is indispensable for evidence-based decision-making in the field of prevention. Methods and results of the German surveillance system on CA are reviewed and discussed with reference to other systems. The German network structure comprises 56 departments of dermatology and includes all patients who are patch-tested for suspected CA. Data analysis considers the results of patch testing and further pertinent information for each patient. Following aspects are addressed: (i) the description of the clinical population, (ii) evaluation of patch test reactions, (iii) relationship between patch test results and population characteristics. Trend analyses on chromate (decreasing), epoxy resin (increasing) and nickel (heterogeneous) served as examples for surveillance system analyses, with the identification of sentinel events, as well as proof of success or failure of prevention. In addition, external data sources can be used such as sales data of patch test preparations to estimate frequencies of sensitization on a population level. National prescription data of drugs and statistics of labelling of preservatives on cosmetics can be included, the latter two approaches allowing for risk estimates conferred by specific allergens.

[Clinical epidemiology and prevention of contact allergies. The Information Network of Departments of Dermatology (IVDK) as a register and surveillance system]. / Klinische Epidemiologie und Prävention der Kontaktallergien. Der Beitrag des Informationsverbundes Dermatologischer Kliniken (IVDK).

A total of 56 departments of dermatology from Germany, Austria, and Switzerland collaborate to study the clinical epidemiology of contact allergies (CA). Data generated in the course of the diagnostic work-up of CA (e.g., patch test data) have been stored since 1989 in the data center in Göttingen, Germany, including data for more than 200,000 patients (March 2011). These data can be used as a register and as a surveillance system. Analysis of the register may identify and quantify risk factors of sensitization to an allergen, which is exemplified with the case of the allergen para-phenylenediamine. It turned out that-in addition to the risk factor hair dyeing-other important risk factors must be considered. In contrast, data collected every 6 months (from approximately 6,000 patients) allow for time-trend analyses of allergens, thus, identifying allergens of concern, which is of utmost importance for early preventive intervention. Here, the epidemiology of allergies to epoxy resins serves as an example. Continuous monitoring of contact allergens will also be mandatory in the future, as the CA premarketing screening systems will have imperfect predictive values with regard to human CA risk. Unfortunately, the (current) national regulatory framework severely hampers clinical surveillance/epidemiology of contact sensitization and, thus, prevention of contact allergy.

Allergic contact dermatitis: epidemiology, molecular mechanisms, in vitro methods and regulatory aspects. Current knowledge assembled at an international workshop at BfR, Germany.

Contact allergies are complex diseases, and one of the important challenges for public health and immunology. The German 'Federal Institute for Risk Assessment' hosted an 'International Workshop on Contact Dermatitis'. The scope of the workshop was to discuss new discoveries and developments in the field of contact dermatitis. This included the epidemiology and molecular biology of contact allergy, as well as the development of new in vitro methods. Furthermore, it considered regulatory aspects aiming to reduce exposure to contact sensitisers. An estimated 15-20% of the general population suffers from contact allergy. Workplace exposure, age, sex, use of consumer products and genetic predispositions were identified as the most important risk factors. Research highlights included: advances in understanding of immune responses to contact sensitisers, the importance of autoxidation or enzyme-mediated oxidation for the activation of chemicals, the mechanisms through which hapten-protein conjugates are formed and the development of novel in vitro strategies for the identification of skin-sensitising chemicals. Dendritic cell cultures and structure-activity relationships are being developed to identify potential contact allergens. However, the local lymph node assay (LLNA) presently remains the validated method of choice for hazard identification and characterisation. At the workshop the use of the LLNA for regulatory purposes and for quantitative risk assessment was also discussed.

[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.

[Genetics of contact allergy]. / Genetik der Kontaktallergie.

The genetics of contact allergy (CA) is still only partly understood, despite decades of research. This might be due to inadequately defined phenotypes used in the past. Therefore we suggested studying an extreme phenotype, namely, polysensitization (sensitization to 3 or more unrelated allergens). Another approach to unravel the genetics of CA has been the study of candidate genes. In this review, we summarize studies on the associations between genetic variation (e.g. SNPs) in certain candidate genes and CA. The following polymorphisms and mutations were studied: (1) filaggrin, (2) N-acetyltransferase (NAT1 and 2), (3) glutathione-S-transferase (GST M and T), (4) manganese superoxide dismutase, (5) angiotensin-converting enzyme (ACE), (6) tumor necrosis factor (TNF), and (7) interleukin-16 (IL16). The polymorphisms of NAT1/2, GST M/T, ACE, TNF, and IL16 were shown to be associated with an increased risk of CA. In one of our studies, the increased risk conferred by the TNF and IL16 polymorphisms was confined to polysensitized individuals. Other relevant candidate genes may be identified by studying diseases related to CA in terms of clinical symptoms, a more general pathology (inflammation) and possibly an overlapping genetic background, such as irritant contact dermatitis.

Classification of skin sensitizing substances: a comparison between approaches used by the DFG-MAK Commission and the European Union legislation.

A systematic classification of substances (or mixtures of substances) with regard to various toxicological endpoints is a prerequisite for the implementation of occupational safety strategies. As its principal task the "Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area" of the "Deutsche Forschungsgemeinschaft" (DFG-MAK Commission) derives and recommends maximum workplace concentrations and biological tolerance values (MAK and BAT values) based exclusively on scientific arguments. Several endpoints are evaluated separately in detail, e.g. carcinogenicity, risks during pregnancy, germ cell mutagenicity or contribution to systemic toxicity after cutaneous absorption. Skin- and airway sensitization is also considered; the present paper focuses on these two endpoints.

Contact allergy to preservatives. Analysis of IVDK data 1996-2009.

BACKGROUND: Preservatives are well-known and important contact allergens. OBJECTIVES: To examine the frequency of sensitization to preservatives, including time trends. METHODS: Retrospective analysis of data on patch testing of preservatives contained in the standard series and special series collected by the IVDK during 1996-2009. RESULTS: Some 120,000 and 80,000 patients were tested with the baseline and the preservative series, respectively. Sensitization frequencies of the standard series allergens all ranged above 1%: methyldibromoglutaronitrile (MDBGN) 2·36-4·5%, methy(chloro)isothiazolinone (MCI/MI) 2·22%, formaldehyde 1·54%, paraben mix 1·33% and Bronopol® 1·25%. Regarding the special preservative series, 1·54% reacted positive to methylisothiazolinone (MI), and < 1% to the other preservatives. Concomitant reactions to formaldehyde in formaldehyde releasers ranged from 15% to almost 50%, and 67% of MI positives reacted to MCI/MI. As indicated by the MOAHLFA index, sensitization to MI, iodopropynylbutyl carbamate (IPBC) and quaternium 15 was associated more often with occupational dermatitis, whereas sensitization to imidazolidinyl urea and diazolidinyl urea was associated with face dermatitis, indicating cosmetic exposure. Epidemiologically relevant decreases (> 10%) were seen in chloroacetamide, benzyl alcohol and MDBGN. Epidemiologically relevant increases were noted in IPBC, sodium benzoate and MI. CONCLUSIONS: Preservatives are still important contact allergens. The introduction of new preservatives should consider the specific characteristics of occupational and of nonoccupational (cosmetic, household) exposure, and preventive measures should aim equally at both areas.