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.

[Occupational allergies against pepsin, chymosin and microbial rennet]. / Berufliche Allergien gegen Pepsin, Chymosin und mikrobielle Labersatzstoffe.

Rennet is a mixture of the proteolytic enzymes pepsin and chymosin (rennin), which is usually obtained from the fourth stomach of young ruminants. While pepsin is also used in the pharmaceutical industry, both enzymes (pepsin and chymosin) are used for the coagulation of milk protein in the manufacture of cheese. Additionally, microbial rennet, which is naturally produced by certain microorganisms, has been used as a substitute for natural rennet in the cheese production for decades. Exposure to enzyme dusts has long been known to cause occupational immediate hypersensitivities. The present paper reviews the results of an evaluation of the literature data concerning occupational airway sensitisation due to natural and microbial rennet. Cases of specific airway sensitisation caused by rennet could be shown clearly by several studies. Positive skin prick and challenge tests as well as specific IgE antibodies have been described, thus suggesting an immunological mechanism.

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.

[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.

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.

[Allergological diagnostics and current allergens in occupational dermatology]. / Allergologische Diagnostik und aktuelle Allergene in der Berufsdermatologie.

A broad spectrum of various substances may cause occupational allergic contact dermatitis. Often, it is difficult to identify potentially or truly relevant allergens at the workplace. Therefore, the consulting physician must have a comprehensive knowledge of possible allergens in different occupations to perform specific diagnostics and to initiate efficient secondary prevention by allergen avoidance. In this review, we give some practically relevant general comments on patch testing in occupational dermatitis, followed by a discussion of important occupational allergens in those occupational groups most frequently affected by occupational dermatitis. Finally, recommendations on which allergens should be tested in the respective occupational groups are given or reported from the literature.

para-Phenylenediamine: the profile of an important allergen. Results of the IVDK.

BACKGROUND: para-Phenylenediamine (PPD) is an important contact allergen and primarily used in hair dyeing. OBJECTIVES: To quantify cases of contact allergy (CA) to PPD attributed to sources of exposure. METHODS: Patients with PPD CA, diagnosed by the Information Network of Departments of Dermatology (IVDK; n = 3307 of 83 030 patients tested), were divided into five subgroups of exposure. Demographic variables and pattern of concomitant reactions were used to characterize the subgroups further. The impact of individual factors on the risk of PPD CA was examined with a logistic regression analysis. Clinical epidemiology and drug utilization research (CE-DUR) methods were employed to estimate the 10-year prevalence of PPD CA in the general population. RESULTS: The 4% prevalence of PPD CA in patients was extrapolated to a prevalence of 0.96% in the general population. The defined profiles were found to 'explain' the following percentages of PPD CA: (i) hair dyeing in clients 22% (0.2% of the general population); (ii) different occupational exposures, namely hair dyeing by hairdressers, paint- and rubber-associated exposures 23% (0.22% of the general population); (iii) clothing/shoes 12% (0.12% of the general population). A probable causal exposure to PPD could not be identified in about 44% of patients with PPD CA. CONCLUSIONS: In more than 50% of cases of PPD CA, a (very) probable causal exposure was identified. In the large remainder (44%) this was not possible. 'Historical' CA without current relevance and active sensitization through patch testing (a further important exposure to PPD) must be considered in these patients.

Contact allergy to neomycin sulfate: results of a multifactorial analysis.

PURPOSE: To perform a comprehensive, multifactorial analysis of potential risk factors (demographic and clinical) for contact allergy to neomycin sulfate, a common adverse reaction resulting from the topical use of this drug; especially in some subgroups of the population. METHODS: Retrospective analysis of allergy test data of the Information Network of Departments of Dermatology (IVDK, www.ivdk.org) between 1998 and 2003, including all patients patch tested with a standard screening series because of suspected allergic contact dermatitis (ACD). As one outcome, a positive (allergic) test reaction to neomycin sulfate was considered. An alternative outcome included only those patients with a positive test to neomycin sulfate and a final diagnosis of ACD. The association between outcome and potential risk factors was analyzed with Poisson regression analysis, deriving prevalence ratios (PR) as risk estimates. RESULTS: Of the 47,559 patients tested, 2.5% had positive reactions to neomycin sulfate, while in 1.1% ACD was additionally diagnosed. The results of the multifactorial analysis indicated that the risk of both outcomes decreased slightly during the period covered; was higher among patients with leg dermatitis; varied significantly with age and increased progressively with the number of additional positive reactions to other standard series allergens. Cross-reactivity to other, selectively tested, aminoglycoside antibiotics was substantial (kappa = 0.67; 95%CI: 0.63-0.71) for framycetin sulfate, to low (kappa = 0.33; 95%CI: 0.27-0.37) for gentamicin sulfate. CONCLUSIONS: The prevalence of contact sensitization to neomycin sulfate was noteworthy among patients patch tested in the IVDK centers. Supplementing clinical epidemiology, neomycin contact allergy has been estimated to be relatively common even on the level of the unselected population (prevalence approx. 1%). Hence, the topical use of neomycin sulfate by patients should be carefully monitored, considering its potential to induce ACD, with emphasis on subgroups at risk.

Chemical substances and contact allergy--244 substances ranked according to allergenic potency.

From 1985 to 2001 a group consisting of thirty experts including dermatologists from universities, representatives from the chemical industry and from regulatory authorities elaborated and consequently decided on the potency ranking of chemicals with contact allergenic properties. These chemicals were defined either as synthetic chemicals or as chemicals identified as ingredients in natural products. On 244 substances clinical and experimental data on humans and results of animal tests as documented in the scientific literature were carefully collected and evaluated. This careful evaluation and assessment of these chemicals clearly demonstrate that ranking of substances according to their allergenic potency is possible and justified. It was decided to rank the most potent contact allergens in Category A of substances having significant allergenic properties. Substances with a solid-based indication of a contact allergenic potential and substances with the capacity of cross-reactions were listed in Category B and substances with insignificant or questionable allergenic effects were listed in Category C. An assessment of these compiled data is published here. Three Appendices give a comprehensive overview of the 98 substances listed in Category A, the 77 substances listed in Category B and the 69 substances listed in Category C.

[Epidemiologic surveillance of contact allergens. The "monitoring series" of IVDK (Information Network ofDermatologic Clinics for Detection and Scientific Evaluation of Contact Allergy]. / Epidemiologische Uberwachung von Kontaktallergenen. Der "Monitorblock" des IVDK.

The selection of the most important contact allergens is subject to a continuous change. Several factors may influence the sensitization rates and thus the decision, which substances to include in the standard series of the most frequent allergens. The Information Network of Departments of Dermatology adds substances of interest for a certain time period to the standard series in order to evaluate parameters such as sensitization rate, grade of reaction, and clinical relevance of positive reactions. In 6 testing periods starting in 1996, 13 test substances were evaluated. Due to the results, propolis, compositae mix, and bufexamac were included in the standard series in 1999, while lyral was added in 2002. Sorbitansesquioleat, dispers blue mix, and iodopropynyl butylcarbamate are under further discussion. Substances such as glutaraldehyde and p-aminoazobenzole should be tested in certain risk groups only, whereas the steroids budesonide and tixocortol should be tested when clinically suspected.

[Occupational allergies to cellulases]. / Berufliche Allergien gegen Cellulasen.

In the 1960s an increasing number of occupational allergies in the detergent industry against the proteolytic enzyme Subtilisin were observed. In this context the high sensitization potential of enzyme dusts attracted attention. The present evaluation of literature data confirms that this is also true for cellulases. These enzymes--mostly of fungal origin--are frequently used in biotechnology. Several cases of specific airway sensitization caused by cellulases are verified by a number of studies. As symptoms, results of skin prick tests, detection of specific IgE-antibodies and results of specific bronchoprovocation tests are consistent, an immunologic mechanism seems to be confirmed.

[Decrease in nickel sensitization in young patients--successful intervention through nickel exposure regulation? Results of IVDK, 1992-2001]. / Rückgang der Nickelkontaktallergie in den letzten Jahren. Eine Folge der "Nickel-Verordnung"? Auswertungen der Daten des IVDK der Jahre 1992-2001.

BACKGROUND: In the early 1990s, the prevalence of nickel contact allergy was high-almost 20% on a population level, and some 40% in contact dermatitis patients. Around that time, nickel exposure was starting to be regulated. PATIENTS/METHODS: Descriptive and bivariate analyses of patch test results of all patients tested with nickel sulfate (5% pet.) in the departments joining the Network of Departments of Dermatology (IVDK) 1992-2001 (n=82,991, women: 52,709; men: 30,282). The annual frequency of sensitization to nickel was analyzed in women and men in four age subgroups (<31/31 to <44/44 to 58= or >58). RESULTS: In young women less than 31 (n=13.909) the prevalence of contact allergy to nickel decreased significantly from 36.7% in 1992 to 25.8% in 2001. In young men in the same age group (n=7087), the prevalence dropped from 8.9% in 1992 to 5.2% in 2001. CONCLUSIONS: The observed decline indicates that measures to limit the release of nickel from costume jewelry helped reduce the prevalence of nickel allergy. In general term, allergen elimination or reduction is an effective primary prevention strategy which does not depend on individual behavior modifications.

When should a substance be designated as sensitizing for the skin ('Sh') or for the airways ('Sa')?

In the List of MAK and BAT Values compounds are designated with 'Sa' ('sensitizing for the airways') or 'Sh' ('sensitizing for the skin') if, according to scientific evidence, they are allergens. Mainly based on suggestions by a WHO working group and based on our own experience, extended criteria have been elaborated by the working group 'skin and allergy' of the Commission of the Deutsche Forschungsgemeinschaft for the Investigation of Health Hazards of Chemical Compounds in the Work Area, which are presented in this article. They serve as guidelines for deciding which substances have to be labelled 'Sa' and 'Sh', respectively, for the prevention of sensitization and subsequent allergic diseases in workers. Although in some special cases their strict application may not be deemed necessary or possible, the proposed new criteria should be used to make the procedure of classification of substances: 1) more rational, 2) more consistent, 3) more comprehensible, and 4) more transparent. This paper informs readers working scientifically or administratively in this field and invites a critical discussion of the issue.