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Only a few cases of allergic contact dermatitis (ACD) from chlorphenesin have been reported and since 2015 no new cases have been published. We describe two additional cases of ACD from this preservative in cosmetics observed during late 2021. [...]

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In recent years, skin reactions secondary to the use of medical devices (MD), such as allergic contact dermatitis have increasingly been observed (e.g. to continuous blood sugar monitoring systems, insulin pumps, wound dressings, medical gloves, etc.): this is regarded as a developing epidemic. Lack of labelling of the composition of MD, as well as frequent lack of cooperation of manufacturers to disclose this relevant information, even when contacted by the clinician for the individual case of an established adverse reaction, significantly impede patient care. To advocate for full ingredient labelling in the implementation of EU regulation for MD. This position paper reviews the scientific literature, the current regulatory framework adopted for MD to date, and the likely impact, including some costs data in case of the absence of such labelling. Efforts made by several scientific teams, who are trying to identify the culprit of such adverse effects, either via asking for cooperation from companies, or using costly chemical analyses of MD, can only partly, and with considerable delay, compensate for the absence of meaningful information on the composition of MD; hence, patient management is compromised. Indeed, without knowing the chemical substances present, physicians are unable to inform patients about which substances they should avoid, and which alternative MD may be suitable/tolerated. There is an urgent need for full and accurate labelling of the chemical composition of MD in contact with the human body.

In the 2010s an epidemic of allergic contact dermatitis to methylisothiazolinone (MI) occurred in Europe. European authorities banned the use of methylisothiazolinone in leave-on cosmetics in 2017 and limited its use in rinse-off products in 2018. To investigate the sensitization rate to MI in Belgium between January 2014 and December 2019, and to assess cosensitizations to octylisothiazolinone (OIT) and benzisothiazolinone (BIT) in MI-sensitized patients. A retrospective study of patch test results with MI, OIT, and BIT observed in patients attending five Belgian hospitals. Overall, 560 of 10 029 patients (5.58%) had a positive patch test reaction to MI, and its sensitization rate decreased from 7.9% in 2014 to 3.1% in 2019. Rinse-off cosmetics, paints, and detergents were the most prevalent sensitization sources in recent years. Simultaneous reactions readily occurred to OIT, and, surprisingly, and increasingly, also to BIT. Contact allergy to MI in Belgium has reached a pre-epidemic level, reflecting the impact of recent regulatory measures. Leave-on cosmetics, in contrast to rinse-off products, have almost disappeared as sensitization sources in Europe. Paints and detergents also remain problematic. The remarkably high number of patients (co)sensitized to BIT should be a focus of future research.

Preservatives have been used for a long time mainly but not exclusively by cosmetic industries. The aim was obvious, but most companies did not take into account the potential allergenicity of preservatives. Different ones were launched on the market. The most popular were the parabens and the formaldehyde releasers, such as quaternium-15, 2,5-diazolidinyl urea (Germall II®) and imidazolidinyl urea (Germall 115®), and all of them displayed allergenic properties. [...]

BACKGROUND: Limonene and linalool are common fragrance terpenes. Both oxidized R-limonene and oxidized linalool have recently been patch tested in an international setting, showing contact allergy in 5.2% and 6.9% of dermatitis patients, respectively.OBJECTIVE: To investigate concomitant reactions between oxidized R-limonene and oxidized linalool in consecutive dermatitis patients.METHODS: Oxidized R-limonene 3.0% (containing limonene hydroperoxides 0.33%) and oxidized linalool 6% (linalool hydroperoxides 1%) in petrolatum were tested in 2900 consecutive dermatitis patients in Australia, Denmark, Singapore, Spain, Sweden, and the United Kingdom.RESULTS: A total of 281 patients reacted to either oxidized R-limonene or oxidized linalool. Of these, 25% had concomitant reactions to both compounds, whereas 29% reacted only to oxidized R-limonene and 46% only to oxidized linalool. Of the 152 patients reacting to oxidized R-limonene, 46% reacted to oxidized linalool, whereas 35% of the 200 patients reacting to oxidized linalool also reacted to oxidized R-limonene.CONCLUSIONS: The majority of the patients (75%) reacted to only one of the oxidation mixtures, thus supporting the specificity of the reactions. The concomitant reactions to the two fragrance allergens suggest multiple sensitizations, which most likely reflect the exposure to the different fragrance materials in various types of consumer products. This is in accordance with what is generally seen for patch test reactions to fragrance materials.

Differentiation of allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD) is important because of different management requirements. Various non-invasive tests have been used in an attempt to improve diagnosis. In irritant dermatitis, thickening of the epidermis has been a constant finding. High-Definition Optical Coherence Tomography (HD-OCT) is a non-invasive real-time three-dimensional imaging technique with cellular resolution for which an adapted algorithmic method for pattern analysis discriminating inflammatory skin diseases has been proposed. The aim of this study was threefold. (1) To evaluate the correlation between HD-OCT features and clinical scores of allergic and irritant patch test reactions. (2) To explore the potential of HD-OCT in optimizing the visual patch test scoring. (3) To assess in vivo the cytological and 3-D micro-architectural differences in skin reaction types between doubtful positive ACD and ICD. Twenty-two volunteers were patch tested using potassium(VI)dichromate, cobalt(II)chloride, nickel(II) sulfate and palladium(II)chloride. Visual patch test scoring and HD-OCT assisted patch test scoring were performed at 48 and 96 h after patch test application according to ECDRG guidelines. Selected HD-OCT features correlated well with clinical severity scores. HD-OCT assessment improved the visual patch test scoring although not significantly. Increased epidermal thickness observed in ICD at first reading was a significant finding useful in differentiating doubtful (+?) ACD from irritant (IR) ICD reactions. In conclusion, HD-OCT might be a unique tool for in vivo non-invasive real-time three-dimensional epidermal thickness measurements helping to differentiate IR from doubtful (+?) reactions in patch testing. Selected HD-OCT features corresponded well with severity of visual scoring. These features might help to quantify the degree of inflammation in inflammatory skin conditions. HD-OCT might help in optimizing visual patc

The present guideline summarizes all aspects of patch testing for the diagnosis of contact allergy in patients suspected of suffering, or having been suffering, from allergic contact dermatitis or other delayed-type hypersensitivity skin and mucosal conditions. Sections with brief descriptions and discussions of different pertinent topics are followed by a highlighted short practical recommendation. Topics comprise, after an introduction with important definitions, materials, technique, modifications of epicutaneous testing, individual factors influencing the patch test outcome or necessitating special considerations, children, patients with occupational contact dermatitis and drug eruptions as special groups, patch testing of materials brought in by the patient, adverse effects of patch testing, and the final evaluation and patient counselling based on this judgement. Finally, short reference is made to aspects of (continuing) medical education and to electronic collection of data for epidemiological surveillance.

BACKGROUND: In view of the current and unprecedented increase in contact allergy to methylisothiazolinone (MI), we characterized and evaluated two recent epidemics of contact allergy to preservatives used in cosmetic products to address failures in risk assessment and risk management.OBJECTIVE: To evaluate temporal trends of preservative contact allergy.METHODS: The study population included consecutive patch tested eczema patients seen at a university hospital between 1985 and 2013. A total of 23 138 patients were investigated for a contact allergy.RESULTS: The overall prevalence of contact allergy to at least one preservative increased significantly over the study period, from 6.7% in 1985 to 11.8% in 2013 (p < 0.001). Importantly, the preservatives methyldibromo glutaronitrile and MI rapidly resulted in high sensitization prevalence rates, which reached epidemic proportions. Although the proportion of patients with current clinical disease attributable to methyldibromo glutaronitrile contact allergy decreased significantly following the ban on its use in cosmetic products (p < 0.001), the sudden and high proportion of current sensitization to MI requires immediate attention (p < 0.001).CONCLUSIONS: The introduction of new preservatives in Europe with inadequate pre-market risk assessment has rapidly increased the overall burden of cutaneous disease caused by preservatives. We suggest that the cosmetic industry has a responsibility to react faster and replace troublesome preservatives when a preservative contact allergy epidemic is recognized, but the European Commission has the ultimate responsibility for failures in risk management after new, major sensitizing preservatives are introduced onto the market.

Flexural eczema and atopic dermatitis are frequently synonymized. As respiratory atopy is rarely tested for and found in these patients, systematically equating a flexural distribution of dermatitis with atopic dermatitis may too frequently result in misclassified diagnoses and potentially missed opportunity for intervention toward improving patients' symptoms and quality of life. We present a critical review of the available evidence for the atopic dermatitis diagnosis and discuss the similarities between atopic dermatitis and allergic contact dermatitis. Because neither flexural predilection nor atopy is specific for atopic dermatitis, we conclude that the term atopic dermatitis is a misnomer and propose an etymologic reclassification of atopic dermatitis to "atopy-related" dermatitis. Allergic contact dermatitis can induce an atopic dermatitis-like phenotype, and thus, flexural dermatitis cannot be assumed as atopic without further testing. Patch testing should at least be considered in cases of chronic or recurrent eczema regardless of the working diagnosis.

BACKGROUND: Contact allergy to fragrances is common, and impairs quality of life, particularly in young women.OBJECTIVE: To provide current results on the prevalences of sensitization to fragrance allergens used as markers in the baseline series of most European countries.METHODS: Data of patients consecutively patch tested between 2009 and 2012 in 12 European countries with fragrance allergens contained in the baseline series were collected by the European Surveillance System on Contact Allergies network and descriptively analysed. Four departments used the TRUE Test(®) system.RESULTS: The 'basic markers' were tested on 51 477 [fragrance mix II (FM II)] to 57 123 [Myroxylon pereirae, balsam of Peru] patients, and yielded positive reactions as follows: fragrance mix I 6.9%, Myroxylon pereirae 5.4%, FM II 3.8%, colophonium 2.6%, and hydroxyisohexyl 3-cyclohexene carboxaldehyde 1.7%, with some regional differences. Prevalences with TRUE Test(®) allergens were lower. Additional fragrances were tested on 3643 (trimethylbenzenepropanol) to 14 071 (oil of turpentine) patients, and yielded between 2.6% (Cananga odorata) and 0.7% (trimethylbenzenepropanol) positive reactions.CONCLUSIONS: Contact allergy to fragrances is common throughout Europe, with regional variation probably being explained by patch test technique, and differences in exposure and referral patterns. The current basic markers of fragrance sensitivity in the baseline series should be supplemented with additional fragrance allergens.

BACKGROUND: In recent years, the prevalence of contact allergy to the preservative methylisothiazolinone (MI) has increased dramatically. Cosmetic products are one of the major sources of exposure.OBJECTIVES: To examine whether allowed concentrations of MI in cosmetic rinse-off products have the potential to cause allergic contact dermatitis.METHODS: Nineteen MI-allergic subjects and 19 controls without MI allergy applied two liquid hand soaps five times per day on areas of 5 × 10 cm(2) on the ventral side of their forearms. One soap contained 100 ppm MI, the maximum allowed concentration in cosmetics, and was used by 10 allergic subjects and all controls. Another liquid soap with 50 ppm MI was used by nine allergic subjects. As the negative control, all subjects used a similar soap that did not contain MI. The repeated open applications proceeded until a positive reaction occurred or up to 21 days. The study was conducted in a randomized and blinded fashion.RESULTS: Ten out of 10 MI-allergic subjects developed positive reactions to the soap with 100 ppm and seven out of nine reacted to the 50 ppm soap, while none of the 19 controls had a positive reaction during 21 days of application. No reactivity was seen to the soap without MI. The difference in reactivity to MI between MI-allergic subjects and controls was statistically significant (Fisher's exact test, P ˂ 0.0001).CONCLUSIONS: Rinse-off products preserved with 50 ppm MI or more are not safe for consumers. No safe level has yet been identified.

BACKGROUND: In view of the current epidemic of contact allergy to methylisothiazolinone (MI), it is important to clarify the extent of use of MI and related isothiazolinones in paints currently available for the consumer and worker in Europe.OBJECTIVES: To elucidate the use and concentrations of MI, methylchloroisothiazolinone (MCI) and benzisothiazolinone (BIT) in paints on the European retail market.METHODS: Wall paints (n = 71) were randomly purchased in retail outlets in five European countries. The paints were quantitatively analysed for their contents of MI, MCI and BIT by high-performance liquid chromatography coupled to tandem mass spectrometry.RESULTS: MI was found in 93.0% (n = 66) of the paints, with concentrations ranging from 0.7 to 180.9 ppm, MCI in 23.9% (n = 17), ranging from 0.26 to 11.4 ppm, and BIT in 95.8% (n = 68), ranging from 0.1 to 462.5 ppm. High concentrations of MI were found in paints from all five countries. Paints purchased in Denmark and Sweden contained especially high concentrations of BIT.CONCLUSION: The use of MI across European countries is extensive. In view of the ongoing epidemic of MI contact allergy, an evaluation of the safety of MI in paints is needed.

Many key ingredients of hair cosmetics (in particular, dyes, bleaches, and hair-styling agents) are potent (strong to extreme) contact allergens. Some heterogeneity is apparent from published results concerning the range of allergens for which patch testing is important. The objective of the present review was to collect information on the current practice of using ‘hair cosmetic series’, and discuss this against the background of evidence concerning consumer/professional exposure and regulatory aspects to finally derive a recommendation for a ‘European hair cosmetic series’. The methods involved (i) a survey targeting all members of the COST action ‘StanDerm’ (TD1206) consortium, (ii) analysis of data in the database of the European Surveillance System on Contact Allergies (ESSCA), and (iii) literature review. Information from 19 European countries was available, partly from national networks, and partly from one or several departments of dermatology or, occasionally, occupational medicine. Apart from some substances being tested only in single departments, a broad overlap regarding ‘important’ allergens was evident. Some of the substances are no longer permitted for use in cosmetics (Annex II of the Cosmetics Regulation). An up-to-date ‘European hair cosmetics series’, as recommended in the present article, should (i) include broadly used and/or potent contact allergens, (ii) eliminate substances of only historical concern, and (iii) be continually updated as new evidence emerges., Many key ingredients of hair cosmetics (in particular, dyes, bleaches, and hair-styling agents) are potent (strong to extreme) contact allergens. Some heterogeneity is apparent from published results concerning the range of allergens for which patch testing is important. The objective of the present review was to collect information on the current practice of using 'hair cosmetic series', and discuss this against the background of evidence concerning consumer/professional exposure and regulatory aspects to finally derive a recommendation for a 'European hair cosmetic series'. The methods involved (i) a survey targeting all members of the COST action 'StanDerm' (TD1206) consortium, (ii) analysis of data in the database of the European Surveillance System on Contact Allergies (ESSCA), and (iii) literature review. Information from 19 European countries was available, partly from national networks, and partly from one or several departments of dermatology or, occasionally, occupational medicine. Apart from some substances being tested only in single departments, a broad overlap regarding 'important' allergens was evident. Some of the substances are no longer permitted for use in cosmetics (Annex II of the Cosmetics Regulation). An up-to-date 'European hair cosmetics series', as recommended in the present article, should (i) include broadly used and/or potent contact allergens, (ii) eliminate substances of only historical concern, and (iii) be continually updated as new evidence emerges.

Background Patch test results often vary between departments, and also between countries. Such variation may be partly attributable to systematic effects introduced by patient characteristics, differing exposures, patient selection, or methodological differences. Objective To examine the amount of variation of patient characteristics in terms of the MOAHLFA index and of the proportion of patients with at least one positive reaction to the (European) baseline series (‘P’ measure), and to examine potential reasons for the variation. Methods A retrospective analysis was performed of patch test data from 63 530 consultations collected by 53 departments from 12 countries participating in the European Surveillance System on Contact Allergies (ESSCA) ( www.essca-dc.org) between 2009 and 2012. Results Considerable variation in the prevalence of the MOAHLFA factors between departments was found, caused, for example, by differing specializations (e.g. occupational dermatology) or patient characteristics. Notable variation concerning the ‘P’ measure was observed; however, larger national networks (contributing to the ESSCA) tend to have quite similar ranges of this measure. Conclusions Data from one department per country give valuable insights into the spectrum of contact allergy prevalence rates in that country, but are not as representative as national data pooled from several departments., BACKGROUND: Patch test results often vary between departments, and also between countries. Such variation may be partly attributable to systematic effects introduced by patient characteristics, differing exposures, patient selection, or methodological differences.OBJECTIVE: To examine the amount of variation of patient characteristics in terms of the MOAHLFA index and of the proportion of patients with at least one positive reaction to the (European) baseline series ('P' measure), and to examine potential reasons for the variation.METHODS: A retrospective analysis was performed of patch test data from 63 530 consultations collected by 53 departments from 12 countries participating in the European Surveillance System on Contact Allergies (ESSCA) ( www.essca-dc.org) between 2009 and 2012.RESULTS: Considerable variation in the prevalence of the MOAHLFA factors between departments was found, caused, for example, by differing specializations (e.g. occupational dermatology) or patient characteristics. Notable variation concerning the 'P' measure was observed; however, larger national networks (contributing to the ESSCA) tend to have quite similar ranges of this measure.CONCLUSIONS: Data from one department per country give valuable insights into the spectrum of contact allergy prevalence rates in that country, but are not as representative as national data pooled from several departments.

Children are patch tested in the same manner as adults, but little has been done to establish whether positive or negative findings influence the course of skin symptoms. To uncover the course of skin symptoms and the impact of persistent eczema on life quality in paediatric patients referred for patch testing, a retrospective questionnaire was sent to children and adolescents referred for patch testing during a 9-year period. Persistent eczema at follow-up was strongly associated to atopic dermatitis, but was not explained by gender, age, contact allergy or time span from patch testing to follow-up. Among patients without atopic dermatitis, 23.5% reported to suffer from chronic eczema. Persistent eczema increased the risk of severe impairment of life quality. Our findings indicate a significant risk of childhood eczema becoming chronic and affecting life quality considerably. Patch testing did not affect the course of eczema, highlighting the difficulties of avoidance behaviour.

p-Phenylenediamine (PPD) and Diphenylcyclopropenone (DPCP) are two potent haptens. Both haptens are known to cause delayed-type hypersensitivity, involving a cytokine response and local infiltration of T-cell subpopulations, resulting in contact dermatitis. We investigated the systemic immune effects of PPD and DPCP, two relatively unexplored skin allergens. The dorsal sides of the ears of BALB/c mice were exposed to PPD or DPCP (0.1% w/v or 0.01% w/v), or vehicle alone. Mice were treated once daily for 3 days (induction period) and subsequently twice per week for 8 weeks. Local and systemic immune responses in the auricular and pancreatic lymph nodes, spleen, liver, serum, and ears were analyzed with cytokine profiling MSD, flow cytometry, and qPCR. Ear swelling increased significantly in mice treated with 1% PPD, 0.01% DPCP or 0.1% DPCP, compared with vehicle treatment, indicating that the mice were sensitized and that there was a local inflammation. Auricular lymph nodes, pancreatic lymph nodes, spleen, and liver showed changes in regulatory T-cell, B-cell, and NKT-cell frequencies, and increased activation of CD8(+) T cells and B cells. Intracellular cytokine profiling revealed an increase in the IFN-γ- and IL-4-positive NKT cells present in the liver following treatment with both haptens. Moreover, we saw a tendency toward a systemic increase in IL-17A. We observed systemic immunological effects of PPD and DPCP. Furthermore, concentrations too low to increase ear thickness and cause clinical symptoms may still prime the immune system. These systemic immunological effects may potentially predispose individuals to certain diseases.

BACKGROUND: Psoriasis is a common immune-mediated inflammatory disease that affects the skin and joints. The interleukin (IL)-23/IL-17A axis and IL-22 play key roles in the pathogenesis of psoriasis. IL-23-responsive innate lymphoid cells (ILCs) with a high capacity to produce IL-17 and/or IL-22 have recently been identified and associated with inflammatory bowel diseases. The occurrence and role of ILCs in human skin are poorly understood.OBJECTIVES: To describe the prevalence of the different ILC subpopulations in skin from healthy controls and patients with psoriasis or allergy to nickel.METHODS: Skin biopsies were taken from healthy skin, nonlesional and lesional psoriatic skin, and nickel- and petrolatum-exposed skin from patients with contact allergy to nickel, and lymphocytes were isolated. The cells were stained and characterized by flow cytometry. Cytokine and ligand mRNA expression were measured by quantitative polymerase chain reaction.RESULTS: We found that members of the three groups of ILCs were present in human skin. Remarkably, the number and frequency of RORγt(+) CD56(+) ILC3s, which are known to produce IL-22, were elevated in both nonlesional and lesional skin from patients with psoriasis compared with healthy skin and skin from patients with contact allergy to nickel. Furthermore, skin ILCs expressed high levels of the natural killer receptor NKG2D. NKG2D binds to stress-induced ligands, including major histocompatibility complex class I-related chain A, which we found to be strongly upregulated in lesional skin from patients with psoriasis.CONCLUSION: These results show that ILCs are present in human skin and indicate that RORγt(+) CD56(+) ILC3 may be involved in the pathogenesis of psoriasis.

BACKGROUND: Atranol and chloroatranol are the main allergens of oakmoss absolute. However, the immune responses induced by these substances are poorly characterized.OBJECTIVES: To characterize immune responses induced by atranol, chloroatranol and oakmoss absolute in mice.METHODS: Mice were sensitized and challenged with various concentrations of atranol, chloroatranol, and oakmoss absolute. The immune responses were analysed as B cell infiltration, T cell proliferation in the draining lymph nodes, and expression of interleukin (IL)-18, IL-1β and tumour necrosis factor-α in skin. The cytotoxicity of atranol and chloroatranol against keratinocytes was determined.RESULTS: Sensitization experiments showed that atranol, chloroatranol and oakmoss induced sensitization when applied in high concentrations. Challenge experiments showed that even low concentrations of atranol and chloroatranol induced sensitization. In parallel, atranol and chloroatranol elicited challenge reactions following sensitization with oakmoss. The magnitude of the immune response to the three allergens increased in the following order: atranol, chloroatranol, and oakmoss. The expression of proinflammatory cytokines was induced by chloroatranol and oakmoss, but not by atranol. Chloroatranol was found to be more cytotoxic than atranol against keratinocytes.CONCLUSIONS: Atranol and chloroatranol can elicit both sensitization and challenge reactions, but the mixture of allergens in oakmoss absolute is more potent than atranol and chloroatranol alone.

Background: The rate of contact allergy and allergic contact dermatitis caused by methylisothiazolinone (MI) is dramatically increasing throughout Europe. Objectives: To report on methylchloroisothiazolinone (MCI)/MI and MI allergy in Belgium. Patients and methods Between January 2010 and December 2012, the medical charts of 6599 patients of the Belgian Contact and Environmental Dermatitis Group were retrospectively reviewed for MCI/MI and MI sensitization by use of a standardized questionnaire. Available data on sensitization in 2081 patients tested in 2013 were also included. Results: In 2012, the sensitization rate for MCI/MI had increased to 4.5% and that for MI to 6.0%; the latter showed a further increase to 7.2% in 2013. The people mainly affected were women with a median age of 49 years with hand and/or facial dermatitis, most often resulting from the use of cosmetics. Simultaneous reactions to octylisothiazolinone were observed. Conclusion: A dramatic increase in the rate of contact allergy caused by MI in cosmetics is occurring in Belgium. Notwithstanding the recent recommendation to discontinue the use of MI in leave-on cosmetics, safer use concentrations should also be determined for rinse-off products. Close monitoring of MI sensitization in the near future will be necessary, and the highest test concentrations reported for MI and MCI/MI should be included in the baseline series.

BACKGROUND: Skin diseases are the most commonly recognized occupational diseases in Denmark, and occupational contact dermatitis (OCD) comprises ∼95% of all cases.OBJECTIVES: To prevent occupational contact dermatitis, it is important to specifically identify exposures and work routines related to outbreak of the disease. The aim of this study was to give an overview of exposures for patients with occupational contact dermatitis in Denmark in 2010, and relate this to line of work and disease severity.MATERIAL AND METHODS: The study was a descriptive, register-based study including patients with recognized occupational contact dermatitis in Denmark in 2010. Data were obtained from the National Board of Industrial Injuries in Denmark, and comprised information about the skin disease as well as the occupation/industry of employment and exposures.RESULTS: One thousand five hundred and four patients, 1020 women and 484 men, were included in the study. Irritant contact dermatitis accounted for 70% of all cases; 68% of these were caused by wet work. Forty-six per cent of all patients were employed either in the healthcare sector, in cleaning, or as kitchen workers. Among contact allergies, the most common were to rubber additives from gloves and epoxy in patients employed in the windmill industry.CONCLUSION: The data are important for planning preventive efforts in the future. The workers in the healthcare sector, kitchen workers and cleaners constitute almost half of all cases, and future preventive efforts should be directed at these occupations.

BACKGROUND: In recent years, a steep increase in the frequency of occupational contact allergy to isothiazolinones has been reported from several European countries.OBJECTIVE: To examine the extent and occurrence of isothiazolinones in different types of product at Danish workplaces.METHODS: Seven different isothiazolinones were identified in the Dictionary of Contact Allergens: Chemical Structures, Sources, and References from Kanerva's Occupational Dermatitis. By use of the chemical names and Chemical Abstracts Service numbers for these chemicals, information on products registered in the Danish Product Register Database (PROBAS) was obtained.RESULTS: All seven isothiazolinones were registered in PROBAS. The top three isothiazolinones registered were: benzisothiazolinone (BIT), registered in 985 products, methylisothiazolinone (MI), registered in 884 products, and methylchloroisothiazolinone (MCI)/MI, registered in 611 products. The concentration ranges were 0.01 ppm to 45% for BIT, 0.01 ppm to 10% for MI, and 0.01 ppm to 14.1% for MCI/MI. The most common product type was 'paint and varnish'; five of the seven isothiazolinones were registered in this type of product.CONCLUSION: Isothiazolinones are present in multiple products registered for use at workplaces, and may occur in high concentrations.

BACKGROUND: Although contact allergy among children was previously considered to be rare, data from the past decade have shown that it is common among children and that the prevalence may be increasing.OBJECTIVES: To describe the demographics of all children referred for patch testing in Denmark during 2003-2011, to examine the frequency and relevance of positive patch test reactions, and to assess the most common allergens.METHODS: A retrospective analysis of the patch test data from the Danish National Database of Contact Allergy was performed.RESULTS: Of 2594 children and adolescents aged 1-17 years, 25.1% had one or more positive patch test reactions. The associated relevance was 66.4%. The most common sensitizers were metals, fragrances, and hair dyes. The frequency of positive patch test reactions and allergic contact dermatitis was significantly higher among girls.CONCLUSIONS: Allergic contact dermatitis in children is a significant clinical problem. Contact allergy should always be considered when children with recalcitrant eczema are encountered, and special attention should be paid to girls. Patch testing is important, and children may be tested with the same patch test concentrations as adults.

BACKGROUND: Methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) are the active ingredients in commonly used preservative systems (e.g. Kathon CG(®)). MCI/MI is present in the European baseline patch test series at 100 ppm aq. Since 1986, 200 ppm (dose 0.006 mg/cm(2)) has been used in Sweden without causing skin irritation. Centres in Spain, the United Kingdom and Ireland have also used 200 ppm in their baseline series.OBJECTIVES: To find the optimal patch test concentration for MCI/MI.MATERIALS AND METHODS: MCI/MI 100 ppm aq. and MCI/MI 200 ppm aq. were simultaneously patch tested in 3300 consecutively tested dermatitis patients at eight European patch test clinics and one US patch test clinic. With the Finn Chambers(®) technique (diameter 8 mm), 15 µl was micropipetted on to the filter paper in the chamber. The corresponding volume for Van der Bend(®) chambers was 20 µl, and that for IQ Chambers(®) was 25 µl.RESULTS: Contact allergy to MCI/MI at 100 and 200 ppm was found in 1.2% and 2.1% of patients, respectively (p < 0.001).CONCLUSIONS: MCI/MI 200 ppm aq. (dose 0.006 mg/cm(2) ) diagnoses significantly more contact allergy than the presently used concentration of 100 ppm (dose 0.003 mg/cm(2)), without resulting in more adverse reactions. MCI/MI at 200 ppm should therefore be considered for inclusion in the European baseline test series.

BACKGROUND: Contact dermatitis is a frequent occupational and non-occupational skin disease.OBJECTIVES: To investigate the effects of contact dermatitis on labour market affiliation and societal costs in terms of healthcare costs and production loss.METHODS: A total of 21 441 patients patch tested either in hospital departments or at dermatological clinics in the period 2004-2009 were included in the study. The analyses were stratified by children (age 0-15 years), occupational contact dermatitis (age 16-65 years), and non-occupational dermatitis (age ≥ 16 years). Controls were selected from a 30% random sample of the population. Individual encrypted data were retrieved on healthcare utilization, socio-demographics, education, labour market affiliation and transfer payments from public registers in Denmark for cases and controls.RESULTS: Attributable healthcare costs for 4 years prior to patch testing (1 year for children) and the year after patch testing were €959 for children, €724 for occupational contact dermatitis, and €1794 for non-occupational dermatitis. Productivity costs for the same period were €10 722 for occupational contact dermatitis and €3074 for non-occupational contact dermatitis.CONCLUSIONS: The main findings of this study were that there were statistically significant attributable healthcare costs for both children and adults, and statistically significant productivity loss for adults.

BACKGROUND: Disperse dyes are well-known contact sensitizers. However, they are not included in the majority of commercially available baseline patch test series.OBJECTIVES: To investigate the outcome of patch testing with a textile dye mix (TDM) consisting of eight disperse dyes at dermatology clinics in various countries.PATIENTS/MATERIALS/METHODS: Two thousand nine hundred and seven consecutive dermatitis patients at 12 dermatology clinics representing nine countries were tested with a TDM at 6.6%, consisting of Disperse Blue 35, Disperse Yellow 3, Disperse Orange 1 and 3, and Disperse Red 1 and 17, all at 1.0%, and Disperse Blue 106 and Disperse Blue 124, each at 0.3%, provisionally included in the baseline series. Eighty-seven per cent of the patients allergic to the TDM were also tested with the eight separate dyes.RESULTS: Contact allergy to TDM was found in 108 patients (3.7%). The frequency of contact allergy varied from 2.1% to 6.9% in different centres. Simultaneous reactivity to p-phenylenediamine was found in 57 of the TDM-positive patients (53%). The most frequent dye allergen among the TDM-positive patients was Disperse Orange 3. The contact allergy could have explained or contributed to the dermatitis in approximately one-third of the patients for whom clinical relevance of the TDM contact allergy was recorded.CONCLUSIONS: The TDM should be considered for inclusion in the European baseline series.

BACKGROUND: Skin diseases are the most frequently recognized occupational diseases in Denmark. The prognosis for occupational contact dermatitis is often poor.OBJECTIVES: To investigate the prognosis, assessed by eczema, job status and skin-related quality of life, among patients allergic to rubber chemicals and latex (ubiquitous allergens) and epoxy (nonubiquitous allergen), 2 years after recognition of occupational allergic contact dermatitis.METHODS: From a cohort of all patients recognized as having occupational dermatitis by the Danish National Board of Industrial Injuries in 2010, 199 patients with relevant rubber allergy (contact allergy to rubber chemicals or contact urticaria from latex) or epoxy allergy were identified. Follow-up consisted of a questionnaire covering current severity of eczema, employment, exposure and quality of life.RESULTS: The response rate was 75%. Clearance of eczema was reported by 11% of patients and 67% reported improvement. Overall 22% of patients with allergy to a nonubiquitous allergen had total clearance of eczema compared with 10% of cases allergic to ubiquitous allergens and 0% of those with contact urticaria (P = 0·116). Improvement was significantly more frequent in those who had changed jobs compared with those who had not (P = 0·01).CONCLUSIONS: At follow-up, patients with contact urticaria had significantly poorer prognosis than those with contact allergy, and there was a trend towards a poorer prognosis for those with contact allergy to rubber chemicals than those with allergy to epoxy. A significant positive association between job change and improvement was found.

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.

BACKGROUND: Fragrance allergy is a lifelong condition that may give rise to permanent or recurrent contact dermatitis and may affect quality of life (QoL). The effect on QoL has not yet been investigated, and no disease-specific QoL instrument for fragrance allergy exists.OBJECTIVE: To develop and validate a disease-specific instrument to investigate QoL among fragrance-allergic subjects.METHOD: A fragrance QoL instrument (FQL index) was developed on the basis of narratives from 68 fragrance-allergic subjects, and consisted of 13 items. It was tested in a postal survey among 1650 participants patch tested at Gentofte University Hospital (2000–2010). The survey included other QoL instruments [Dermatology Life Quality Index (DLQI) and Short Form 36 (SF36) version 2] and questions on eczema severity (response rate of 66%). A retest was conducted after 3–6 months (response rate of 72.5%).RESULTS: The FQL index showed a significant and strong correlation with the DLQI (rS = 0.70), and disease severity, but a weak correlation with SF36 [mental component summary score, rS = − 0.22; physical component summary score, rS = − 0.31]. Good reliability and responsiveness to changes in disease severity were seen.CONCLUSION: The FQL index is a good instrument with which to investigate QoL in subjects with fragrance allergy. Good correlations with the DLQI and self-estimated disease severity were seen, and it showed good reliability, reproducibility and ability to distinguish changes in disease severity.

BACKGROUND: Fragrance ingredients can cause contact allergy, which may affect quality of life (QoL). However, few studies have investigated this topic.OBJECTIVES: To investigate QoL life among subjects with a fragrance allergy as compared with other eczema patients.METHODS: A case-control survey was sent to subjects with a positive patch test reaction to a fragrance ingredient/marker (n = 550) and to a control group (n = 1100). It contained questions on eczema and the newly developed fragrance QoL index. Participants had been consecutively patch tested at Gentofte University Hospital (2000-2010). The response rate was 65.7%. Information on patch test data was retrieved from the National Contact Dermatitis Database.RESULTS: An increase in impairment of QoL was observed in women with fragrance allergy as compared with the control group (p = 0.042), which was not found among men. Several factors played a significant role in impairment of QoL in women: (i) number of fragrance allergies, (ii) severity of the patch test reaction, (iii) age combined with recent diagnosis; and (iv) allergy to specific fragrance ingredients/markers.CONCLUSION: Fragrance-allergic subjects are just as affected in their QoL as other eczema patients. However, women, and in particular recently diagnosed young women, seem to be more impaired in their QoL than other eczema patients.

BACKGROUND: Both atopic dermatitis and contact sensitization are common conditions; however, a definite understanding of the relationship between contact sensitization and atopic dermatitis has not been reached.OBJECTIVES: In this descriptive study, we investigated the differences between positive patch test reactions in patients with and without atopic dermatitis in a patch test cohort, and explored the influence of disease severity.PATIENTS/MATERIALS/METHODS: Patch test results, information on atopic dermatitis and demographic variables were taken from a database, including all patients patch tested at Bispebjerg and Roskilde Hospitals from January 2009 to January 2013. Severe atopic dermatitis was defined as systemic therapy or hospitalization resulting from atopic dermatitis. All other patients with atopic dermatitis were defined as having mild/moderate disease.RESULTS: The study included 2221 patients: 293 patients with atopic dermatitis and 1928 without. Forty-one per cent of patients with and 46.2% of patients without atopic dermatitis had at least one positive patch test reaction (p = 0.092). More patients with severe atopic dermatitis than patients with non-severe atopic dermatitis had multiple positive patch test reactions (19.4% versus 10.0%, p = 0.046).CONCLUSIONS: Overall, we found similar frequencies of positive patch test reactions in patients with and without atopic dermatitis. However, a higher frequency of multiple sensitizations was found in patients with severe atopic dermatitis.

BACKGROUND: Skin diseases are the most frequently recognized occupational diseases in Denmark. The prognosis for occupational contact dermatitis is often poor.OBJECTIVES: To investigate the prognosis, assessed by eczema, job status and skin-related quality of life, among patients allergic to rubber chemicals and latex (ubiquitous allergens) and epoxy (nonubiquitous allergen), 2 years after recognition of occupational allergic contact dermatitis.METHODS: From a cohort of all patients recognized as having occupational dermatitis by the Danish National Board of Industrial Injuries in 2010, 199 patients with relevant rubber allergy (contact allergy to rubber chemicals or contact urticaria from latex) or epoxy allergy were identified. Follow-up consisted of a questionnaire covering current severity of eczema, employment, exposure and quality of life.RESULTS: The response rate was 75%. Clearance of eczema was reported by 11% of patients and 67% reported improvement. Overall 22% of patients with allergy to a nonubiquitous allergen had total clearance of eczema compared with 10% of cases allergic to ubiquitous allergens and 0% of those with contact urticaria (P = 0·116). Improvement was significantly more frequent in those who had changed jobs compared with those who had not (P = 0·01).CONCLUSIONS: At follow-up, patients with contact urticaria had significantly poorer prognosis than those with contact allergy, and there was a trend towards a poorer prognosis for those with contact allergy to rubber chemicals than those with allergy to epoxy. A significant positive association between job change and improvement was found.

BACKGROUND: Skin diseases are the most commonly recognized occupational diseases in Denmark, and occupational contact dermatitis (OCD) comprises ∼95% of all cases.OBJECTIVES: To prevent occupational contact dermatitis, it is important to specifically identify exposures and work routines related to outbreak of the disease. The aim of this study was to give an overview of exposures for patients with occupational contact dermatitis in Denmark in 2010, and relate this to line of work and disease severity.MATERIAL AND METHODS: The study was a descriptive, register-based study including patients with recognized occupational contact dermatitis in Denmark in 2010. Data were obtained from the National Board of Industrial Injuries in Denmark, and comprised information about the skin disease as well as the occupation/industry of employment and exposures.RESULTS: One thousand five hundred and four patients, 1020 women and 484 men, were included in the study. Irritant contact dermatitis accounted for 70% of all cases; 68% of these were caused by wet work. Forty-six per cent of all patients were employed either in the healthcare sector, in cleaning, or as kitchen workers. Among contact allergies, the most common were to rubber additives from gloves and epoxy in patients employed in the windmill industry.CONCLUSION: The data are important for planning preventive efforts in the future. The workers in the healthcare sector, kitchen workers and cleaners constitute almost half of all cases, and future preventive efforts should be directed at these occupations.

BACKGROUND: Although contact allergy among children was previously considered to be rare, data from the past decade have shown that it is common among children and that the prevalence may be increasing.OBJECTIVES: To describe the demographics of all children referred for patch testing in Denmark during 2003-2011, to examine the frequency and relevance of positive patch test reactions, and to assess the most common allergens.METHODS: A retrospective analysis of the patch test data from the Danish National Database of Contact Allergy was performed.RESULTS: Of 2594 children and adolescents aged 1-17 years, 25.1% had one or more positive patch test reactions. The associated relevance was 66.4%. The most common sensitizers were metals, fragrances, and hair dyes. The frequency of positive patch test reactions and allergic contact dermatitis was significantly higher among girls.CONCLUSIONS: Allergic contact dermatitis in children is a significant clinical problem. Contact allergy should always be considered when children with recalcitrant eczema are encountered, and special attention should be paid to girls. Patch testing is important, and children may be tested with the same patch test concentrations as adults.