The methylisothiazolinone epidemic goes along with changing patients' characteristics - After cosmetics, industrial applications are the focus.

BACKGROUND: Sensitization to methylisothiazolinone (MI) has seen an exceptional epidemic, mainly attributed to its use in cosmetics. OBJECTIVES: To trace the epidemic of MI allergy (2009-2018), and to analyze a possible change of patients' characteristics. METHODS: Informationsverbund Dermatologischer Kliniken-data of patients patch tested between 2009 and 2018 with MI (0.05% aq.) were analyzed concerning anamnestic items and sensitization frequencies. RESULTS: Overall, 4.9% reacted positive to MI. Comparing sensitization to MI in three periods (2009, 2013/14, and 2017/18), there was an increase to 7% in 2013 and a decrease to 3.4% in 2018. The MOAHLFA Index (M=Men, O=Occupational Dermatitis, A=Atopic Dermatitis, L=Leg Dermatitis, F=Face Dermatitis, A= Age > 40) for the period 2013/14 is characterized by a lower proportion of occupational dermatitis and a higher proportion of face dermatitis. The period 2017/18 is characterized by increases of occupational dermatitis and hand dermatitis, and a decrease of face dermatitis. Painters, personal care workers, and hairdressers were particularly affected. Sensitization in hairdressers and personal care workers (mostly cosmeticians) decreased after the peak in 2013/14, whereas sensitization to MI in painters continued to increase. CONCLUSIONS: After an unprecedented epidemic of MI allergy, mainly caused by its use in cosmetics, the continuous use of MI in industrial applications, for example, paints, and subsequent sensitization remain a matter of concern.

Factors associated with p-phenylenediamine sensitization: data from the Information Network of Departments of Dermatology, 2008-2013.

BACKGROUND: Risk factors for p-phenylenediamine (PPD) sensitization include the use of hair dyes, the application of temporary black henna tattoos, working as a hairdresser, and, possibly, exposure to hair dye pretests. OBJECTIVES: To quantify the impact of these (putative) risk factors on PPD sensitization. METHODS: Six items related to PPD exposure were added to the routine Information Network of Departments of Dermatology questionnaire from 2008 to 2013. A retrospective analysis of data from 4314 patients tested with PPD 1% pet. was conducted. RESULTS: Of the PPD-positive patients (n = 271), 80% had their hair dyed, and, of these, 57% subsequently developed scalp dermatitis, whereas only 11% had had a henna tattoo. The self-administrated pretest with hair dye was performed by only a few patients, precluding a more detailed analysis. Hair dyeing [odds ratio (OR) 6.0; 95% confidence interval (CI): 3.9-9.4], henna tattoos (OR 2.4; 95%CI: 1.5-3.7) and being a hairdresser (OR 2.1; 95%CI: 1.3-3.2) increased the risk of PPD sensitization. Neither dyeing of own hair nor application of a temporary henna tattoo seemed to affect PPD sensitization in hairdressers. p-Aminoaryl compounds more often gave positive reactions in patients with henna tattoo. CONCLUSIONS: Hair dyeing is the major risk factor for PPD sensitization in this clinical setting, and application of a temporary black henna tattoo may also lead to (strong) PPD sensitization.

Sensitization to reactive diluents and hardeners in epoxy resin systems. IVDK data 2002-2011. Part II: concomitant reactions.

BACKGROUND: Beside the basic resins, reactive diluents and hardeners are important sensitizers in epoxy resin systems (ERSs). Because of chemical similarities, immunological cross-reactivity may occur. OBJECTIVES: To analyse concomitant reactivity among reactive diluents and hardeners in the patients concerned, as one integral part of a research project on the sensitizing capacity of ERSs (FP-0324). METHODS: A retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK), 2002-2011, was performed. RESULTS: There was close concomitant reactivity to 1,6-hexanediol diglycidyl ether and 1,4-butanediol diglycidyl ether (1,4-BDDGE), and to phenyl glycidyl ether (PGE) and cresyl glycidyl ether (CGE), whereas reactions to p-tert-butylphenyl glycidyl ether occurred more independently from those to PGE and CGE. Concomitant reactions to butyl glycidyl ether and 1,4-BDDGE may point to a common allergenic compound derived from the metabolism of 1,4-BDDGE. Among the structurally more diverse group of hardeners, there was no evidence of immunological cross-reactions. CONCLUSIONS: More detailed knowledge of cross-reactivity among ERS components facilitates the interpretation of patch test results and will allow safer ERSs to be composed in the future.

Sensitization to reactive diluents and hardeners in epoxy resin systems. IVDK data 2002-2011. Part I: reaction frequencies.

BACKGROUND: Epoxy resin systems (ERSs), consisting of resins, reactive diluents, and hardeners, are indispensable in many branches of industry. In order to develop less sensitizing ERS formulations, knowledge of the sensitizing properties of single components is mandatory. OBJECTIVES: To analyse the frequency of sensitization in the patients concerned, as one integral part of a research project on the sensitizing potency of epoxy resin compounds (FP-0324). METHODS: A retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK), 2002-2011, and a comparison of reaction frequencies with (surrogate) exposure data, were performed. RESULTS: Almost half of the patients sensitized to epoxy resin were additionally sensitized to reactive diluents or hardeners. Among the reactive diluents, 1,6-hexanediol diglycidyl ether was the most frequent allergen, followed by 1,4-butanediol diglycidyl ether, phenyl glycidyl ether, and p-tert-butylphenyl glycidyl ether. Among the hardeners, m-xylylene diamine (MXDA) and isophorone diamine (IPDA) were the most frequent allergens. According to the calculated exposure-related frequency of sensitization, MXDA seems to be a far more important sensitizer than IPDA. Up to 60% of the patients sensitized to hardeners and 15-20% of those sensitized to reactive diluents do not react to epoxy resin. CONCLUSIONS: In cases of suspected contact allergy to an ERS, a complete epoxy resin series must be patch tested from the start.

Reactivity to sorbitan sesquioleate affects reactivity to fragrance mix I.

BACKGROUND: Fragrance mix I (FM I) and its single constituents contain 5% and 1% sorbitan sesquioleate (SSO), respectively. SSO is a rare sensitizer and a potential irritant. OBJECTIVES: To determine whether the outcome of the FM I breakdown test is affected by positive patch test reactivity to SSO. METHODS: A retrospective analysis of data from the Information Network of Departments of Dermatology, 1998-2013, was performed. RESULTS: The full FM I breakdown test including SSO was tested in 2952 patients. Of these, 154 (5.2%) had a positive patch test reaction to SSO 20% pet. and 2709 (91.8%) had a negative patch test reaction. Positive reactions to one or more of the single fragrances contained in the mix were significantly more common (82.5% versus 57.3%) in SSO-positive patients, who also had more multiple reactions than FM I-positive patients with negative SSO reactions (61.5% versus 21.3% patients with reactions to two or more fragrances). CONCLUSIONS: Our results indicate that reactivity to SSO markedly affects the outcome of patch testing with FM I and its single constituents. SSO must be an obligatory part of the full FM I breakdown test, and should ideally be included in the baseline series.

Recent increase in allergic reactions to methylchloroisothiazolinone/methylisothiazolinone: is methylisothiazolinone the culprit?

BACKGROUND: The frequency of sensitization to methylchloroisothiazolinone (MCI)/ methylisothiazolinone (MI) observed in the Information Network of Departments of Dermatology (IVDK) was constantly around 2.1% from 1998 to 2009. After that, it increased to 3.9% in 2011, paralleled by an increase in the frequency of allergic reactions to MI in the preservative series from 1.9% in 2009 to 4.4% in 2011. MI without MCI has increasingly been used as a preservative in cosmetics and skin care products in recent years. OBJECTIVES: To epidemiologically investigate the possible reasons for this development and to analyse concomitant reactions to MCI/MI and MI. METHODS: A retrospective analysis of IVDK data from 2009 to 2011 was performed. RESULTS: Stratified data analysis revealed pronounced increases in reactivity to MCI/MI and MI in females, face dermatitis patients, and patients tested because of suspected cosmetic intolerance. The proportion of MI-positive patients among those reacting to MCI/MI increased from 43% to 59% between 2009 and 2011. CONCLUSION: More widespread consumer exposure has most likely led to the increase in primary sensitization to MI and subsequently to a rise in MCI/MI reactions resulting from immunological cross-reactions. A reduction in the maximum use concentration of MI seems advisable. MI should be patch tested in the baseline series.

Contact sensitization to tree moss (Evernia furfuracea extract, INCI) is heterogeneous.

BACKGROUND: Evernia prunastri (oak moss) and Evernia furfuracea (tree moss) are lichens from which natural extracts are obtained. OBJECTIVES: To identify possible subgroups of E. furfuracea-sensitized patients according to whether these are allergic to lichen components or to contaminants. METHODS: A retrospective analysis was performed of surveillance data collected by the Information Network of Departments of Dermatology (www.ivkd.org) in 2003-2010 with oak moss absolute (1% pet.), tree moss absolute (1% pet.), and colophonium (colophony, 20% pet.). RESULTS: In total, 3030 patients had been tested with all three allergens. Positive reactions to E. furfuracea were observed in 6.37%, to E. prunastri in 5.71%, and to colophonium in 4.82%. Concordance between positive reactions to E. prunastri and E. furfuracea was good only in patients not co-sensitized to colophonium (Cohen's κ = 0.681, 95% confidence interval 0.615-0.746). Moreover, E. furfuracea-sensitized patients showed (strong or extreme) concomitant reactions to colophonium significantly more often if not co-sensitized to E. prunastri. CONCLUSIONS: Two subgroups of E. furfuracea-sensitized patients are identifiable: (i) those with sensitization to (oxidized) resin acids, as indicated by positive patch test reactions also to colophonium, and (ii) those non-sensitized to resin acids, but sensitized to common constituents of E. prunastri and E. furfuracea.

Occupational contact allergy caused by rubber gloves--nothing has changed.

BACKGROUND: Allergic contact dermatitis caused by rubber gloves is not infrequent, and has almost exclusively been attributed to contact sensitization to accelerators. Thiurams have been the most frequent allergens, followed by dithiocarbamates. OBJECTIVES: To describe the current allergen pattern in patients with occupational allergic contact dermatitis caused by rubber gloves. METHODS: This study was a retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK), 2002-2010. RESULTS: Of 93 615 patients patch tested in the IVDK, 3448 both suffered from occupational dermatitis and were tested because of suspected glove allergy. Among these, healthcare workers were the largest group (n = 1058). Of all occupational dermatitis patients, 13% were sensitized to thiurams, 3.5% to dithiocarbamates, 3% to mercaptobenzothiazole and/or its derivatives, and 0.4% to thioureas. Positive test reactions to 1,3-diphenylguanidine were seen in 3.0%. Reaction frequencies varied with the years, but showed no uniform time trend. CONCLUSIONS: As compared with a former IVDK data analysis (1995-2001), there was no change in sensitization pattern and no decline in sensitization frequencies. This is in line with data from the literature. Particularly in healthcare, there is a need for (i) allergen declaration on the glove package, and (ii) gloves with reduced accelerator content.

Occupational contact allergy in the building trade in Germany: influence of preventive measures and changing exposure.

PURPOSE: Since 1993, assiduous efforts have been made in Germany to lower the incidence of allergic cement dermatitis by reducing the content of hexavalent chromium (Cr VI). Usage of epoxy resin systems has considerably increased in the building trade in the same period. We analysed data of the Information Network of Departments of Dermatology (IVDK) to evaluate the influence of these changing occupational exposures on frequencies of sensitization. METHODS: IVDK data of 1,153 men working in the building trade (bricklayers, tile setters etc.) presenting with occupational skin disease in the years 1994-2008 were analysed, taking into consideration not only the year of patch testing, but also beginning and duration of work in the building trade. RESULTS: While contact sensitization to chromate decreased from 43.1 to 29.0%, sensitization to epoxy resin increased from 8.4 to 12.4%. Logistic regression analysis revealed that, compared to those who had already worked before 1994, patients having started to work in building trade after 1999 had a significantly decreased risk of chromate sensitization (odds ratio 0.42) and a significantly increased risk of sensitization to epoxy resin (odds ratio 2.79). Additionally, risk of thiuram sensitization increased with the duration of employment. CONCLUSION: Our data confirm that reducing Cr VI content of cement is useful in preventing allergic cement eczema, as previously found in Scandinavia. In contrast, the increasing prevalence of contact sensitization to epoxy resin components in the building trade is alarming. Preventive measures, which have already been implemented, have to be enforced.

Is cocamidopropyl betaine a contact allergen? Analysis of network data and short review of the literature.

BACKGROUND: There is no general agreement on whether cocamidopropyl betaine (CAPB) is a skin sensitizer. OBJECTIVE: To examine the evidence for CAPB being a (non-)sensitizer. METHODS: This was a retrospective analysis of data on patch testing with CAPB 1% aqua collected by the Information Network of Departments of Dermatology from 1996 to 2009, with a focus on the patch test reaction profile, and demographic and clinical features of CAPB positives, supplemented by a literature review. RESULTS: Eighty-three thousand eight hundred and sixty-four patients were patch tested with CAPB 1% aqua, yielding 2.16% [95% confidence interval (CI) 2.06-2.26%] positive (2.03% + and 0.13% + + /+ + + ) and 4.6% non-allergic reactions. Thus, the reaction index was-0.368 and the positivity ratio was 94.2%. Reproducibility on synchronous patch testing (n = 6534) was poor [Cohen's kappa: 0.29 (95% CI 0.25-0.32)] and results upon retesting (n = 1157) were almost non-reproducible [kappa: 0.12 (95% CI 0.05-0.19]. Multifactorial logistic regression analysis revealed an increased risk associated with being male and aged ≥40 years, with atopic dermatitis, with scalp dermatitis, with being a hairdresser, and with a 48-hr patch test application. When only + + or + + + reactions were used as a conservative outcome, only the elevated risk in males and in patients with atopic dermatitis remained significant. CONCLUSION: The vast majority of positive reactions to CAPB are presumably false positive. Allergic reactions are very rare. This would support the notion of CAPB being 'not a significant skin sensitizer', in line with current classification systems.

Contact allergy to thiurams: multifactorial analysis of clinical surveillance data collected by the IVDK network.

PURPOSE: To analyse the association between occupation (represented by job title) and contact allergy to thiuram vulcanising agents based on data of a clinical registry (IVDK, www.ivdk.org ). METHODS: Clinical, demographic and allergy patch test data of all patients tested between 1992 and 2006 with the thiuram mix (1% in petrolatum) as part of the baseline series was analysed (n = 121,051). Poisson regression analysis was used to quantify the association between different occupations (and other relevant factors) and a positive patch test reaction to the thiuram mix. Furthermore, the time trend of sensitisation prevalence was analysed in high-risk occupational subgroups identified. RESULTS: In comparison to a largely unexposed reference group (office workers and teachers), rubber manufacturers had a significantly elevated risk (prevalence ratio (PR): 5.1, 95% confidence interval (CI) 2.0-10.5). However, health care workers such as physicians and dentists (PR: 3.8, 95% CI: 3.0-4.8) or nursing staff (PR: 3.0, 95% CI: 2.5-3.6) as well as meat and fish processors (PR 3.5, 95% CI: 2.2-5.3) and cleaners (PR 3.1, 95% CI: 2.5-3.8) were found to have a high sensitisation risk as well. In case of health care workers, a significant downward trend during the study period was observed; while in food processors and cleaners, sensitisation prevalence remained largely stable. CONCLUSION: The adjusted multifactorial analysis identified occupations yet unknown to be associated with elevated thiuram contact allergy risk, e.g., food processors and cleaners. Thus, (i) further in-depth research can be targeted and (ii) efforts to prevent sensitisation to thiurams focussed, e.g., by limiting thiuram concentrations in products to a residual level which is technically inevitable.

Contact allergy to essential oils: current patch test results (2000-2008) from the Information Network of Departments of Dermatology (IVDK).

BACKGROUND: Essential oils are used in perfumery and in products for aromatherapy or balneotherapy. Previous studies have shown some to be important contact sensitizers. A practical diagnostic approach, based on the results of a large, central European network and other evidence, is needed. METHODS: Data of the Information Network of Departments of Dermatology (IVDK; www.ivdk.org) on all patients patch tested between January 2000 and December 2008 with essential oils were retrospectively analysed. RESULTS: 15 682 patients of 84 716 consulting in the period had been tested with at least one essential oil, and 637 reacted positively to at least one of the essential oils, most commonly to ylang-ylang oil (I and II) (3.1% as weighted mean of positive tests in special series and consecutive testing), lemongrass oil (1.8%), jasmine absolute (1.6%), sandalwood oil and clove oil (1.5% each). Cross-reactivity between distillate and main allergen, if available, was marked. CONCLUSIONS: Patch testing the important essential oils should be considered in patients with a suggestive history. Additionally, culprit products brought in by the patient should be tested, closing a diagnostic gap by (i) including those other essential oils not included in the commercial test series and (ii) providing a means of testing with the oxidized substances to which the patient had actually been exposed.

Skin sensitizing properties of the ethanolamines mono-, di-, and triethanolamine. Data analysis of a multicentre surveillance network (IVDK) and review of the literature.

Numerous publications address the skin sensitizing potential of the short chain alkanolamines triethanolamine (TEA), diethanolamine (DEA), monoethanolamine (MEA), which are not skin sensitizing according to animal studies. Regarding TEA, we analysed patch test data of 85,098 patients who had been tested with TEA 2.5% petrolatum by Information Network of Departments of Dermatology (IVDK) to identify particular exposures possibly associated with an elevated risk of sensitization. Altogether, 323 patients (0.4%) tested positive. The profile of patch test reactions indicates a slightly irritant potential rather than a true allergic response in many cases. Although used widely, no exposure associated with an increased risk of TEA sensitization was identified. Therefore, the risk of sensitization to TEA seems to be very low. MEA and DEA were patch tested in a much more aimed fashion in 9602 and 8791 patients, respectively when prevalence of contact allergy was 3.8% and 1.8%. MEA is the prominent allergen in metalworkers with exposure to water-based metalworking fluids (wbMWFs); DEA is probably used in cutting fluids less frequently nowadays. Chronic damage to the skin barrier resulting from wbMWF, the alkalinity of ethanolamines (increasing from TEA to MEA), and other cofactors may contribute to a notable sensitization risk.

Patch testing with benzoyl peroxide: reaction profile and interpretation of positive patch test reactions.

BACKGROUND: Patch testing with benzoyl peroxide 1% pet. frequently leads to (weak) positive reactions, often with uncertain clinical relevance. OBJECTIVES: To describe the pattern of patch tests reactions to benzoyl peroxide and to identify patients at risk of a positive reaction. METHODS: Retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK), 1992-2007. RESULTS: Benzoyl peroxide 1% pet. was tested in 29 758 patients. Weak positive reactions (erythema, infiltration, possibly papules) occurred in 6.5%, and strong positive reactions (erythema, infiltration, vesicles) in 1.3%. According to logistic regression analysis, strong positive reactions to benzoyl peroxide were associated with leg or face dermatitis, work as dental technicians, young age and being female. Patients with atopic dermatitis had a significantly increased risk of weak positive reactions only. CONCLUSIONS: Our analysis confirms that benzoyl peroxide 1% pet. is a problematic patch test preparation. Hence, clinical relevance of reactions to benzoyl peroxide has to be assessed very carefully. Patients with atopic dermatitis are particularly prone to irritant reactions to benzoyl peroxide. True allergic reactions may occur in dental technicians and following the treatment of leg ulcers with highly concentrated benzoyl peroxide in past. In contrast, widely used acne treatments with benzoyl peroxide seems to sensitize only rarely.

Chromated metal products may be hazardous to patients with chromate allergy.

BACKGROUND: Hidden allergen exposure may contribute to persistence and relapse of chromate dermatitis. According to case reports, chromated metal products, such as screws, fittings, etc., may be relevant allergen sources for patients sensitized to chromate. OBJECTIVES: To examine concomitant patch test reactivity to potassium dichromate 0.5% petrolatum (pet.) and three different types of chromated metal rings. PATIENTS/METHODS: Patients with proven or suspected chromate allergy were patch tested with potassium dichromate 0.5% pet. and three different types of chromated metal rings (yellow, olive, and black). Hexavalent chromium Cr(VI) release from the patch tested rings was chemically analysed. RESULTS: Ninety-five patients were tested: 49/95 (52%) reacted to potassium dichromate and 25/95 (26%) reacted to black chromated rings. Reactions to chromated rings exclusively occurred in patients reacting to potassium dichromate. Of 20 patients with a strong reaction to potassium dichromate, 14 reacted to black chromated rings. These were shown to have a high Cr(VI) release. Only two patients reacted to the other chromated rings, which had a very low Cr(VI) release. CONCLUSIONS: Handling chromated metal products must be regarded a hazard to chromate-sensitive patients, in particular those with a strong sensitization.

Contact allergy to topical corticosteroids--results from the IVDK and epidemiological risk assessment.

BACKGROUND: Contact allergy (CA) to topical corticosteroids (CS) is relatively rare; however, current data from Germany are not available. Furthermore, valid risk assessment needs to take into account of the actual exposure to CS in the population. PATIENTS AND METHODS: The reaction profile of 9 CS included in a "CS test battery" of the German Contact Dermatitis Research Group (DKG) in patients seen in German clinics belonging to the Information Network of Departments of Dermatology (IVDK; http://www.ivdk.org) between 01/1995 and 12/2004 was analyzed. Applying the "Clinical Epidemiology/Drug Utilization Research" approach, annual incidences of CA to CS in Germany were extrapolated. These estimates were used as numerator for a relative incidence (RI) estimate which used exposure in terms of "defined daily doses" (DDD) to the respective CS as denominator, the latter information collected by the AOK Research Institute (WIdO). RESULTS: On average, 7.4% of all patients were patch tested with the CS series, mostly yielding < 1% positive reactions. Exceptions included hydrocortisone 17-butyrate (1.5%), amcinonide (1.6%) and budesonide (2.6%). With a RI of 10.7, 23.6 and 4.9 per 100,000 DDD, respectively, the three CS mentioned classify as moderate topical drug allergens. Clobetasol 17-propionate and triamcinolone acetonide both yielded a RI of 1.4/100,000 DDD, indicating low sensitization risk. For hydrocortisone, betamethasone, prednisolone and dexamethasone (RI < 1/100,000 DDD) the risk of sensitization appears minute. CONCLUSIONS: The results support and extend previous evidence on the CA risk of CS, adding to a therapeutic index and risk assessment.