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Background: Naturally derived cosmetic product ingredients of both plant and animal origin are being included increasingly in product formulations in order to cater to consumer preferences. They may be an overlooked cause of reactions to cosmetic products in some patients with dermatitis., Objectives: To identify naturally derived cosmetic product ingredients with allergenic potential (type I and type IV) and propose a cosmetic screening test series., Methods: The study was conducted in two steps. The first step was a market survey using a nonprofit application helping consumers avoid problematic substances in cosmetic products. The application contained 10 067 cosmetic products that were label checked for naturally derived cosmetic product ingredients. The second step was a literature search to examine how frequently the naturally derived ingredients were described and related to allergic reactions in cosmetics or other topically administered products., Results: We identified 121 different naturally derived cosmetic product ingredients that were included in at least 30 cosmetic products. In total, 22 ingredients were selected for a screening test series., Conclusions: We propose a supplemental patch test and a prick test screening series with naturally derived cosmetic product ingredients for patients with skin reactions to cosmetic products, aiming to identify a cause in more patients than is currently possible., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Contact allergy to oxidized limonene, with hydroperoxides of limonene (Lim-OOHs) as the main allergens, is common. However, high proportions of weak positive and doubtful patch test reactions have been reported., Objectives: To determine the clinical relevance, elicitation threshold and dose-response relationship of Lim-OOHs in individuals with a positive or doubtful patch test reaction to standard Lim-OOHs 0.3% pet., Methods: A multicentre 3-week double-blind vehicle-controlled repeated open application test (ROAT) study with a simulated fine fragrance containing Lim-OOHs at 1260, 420 and 140 ppm, equal to a dose/area per application of Lim-OOHs of 3.0, 0.99 and 0.33 μg/cm 2 , was performed., Results: Among 11 subjects allergic to Lim-OOHs, 11 (100%), 7 (64%), and 3 (27%), respectively, reacted to the applied doses. No reactions were seen in 17 healthy controls exposed to the highest dose. This difference in reactivity was statistically significant (P < 0.0001). Among 13 subjects with doubtful patch test reactions to Lim-OOHs, two (15%) had positive ROAT reactions to the highest Lim-OOH dose applied (P = 0.36 as compared with controls)., Conclusions: Contact allergy to Lim-OOHs is of clinical relevance in patients with positive patch test reactions. A doubtful patch test reaction to Lim-OOHs 0.3% pet. can be of clinical relevance., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: For cosmetics, it is mandatory to label 26 fragrance substances, including all constituents of fragrance mix I (FM I) and fragrance mix II (FM II). Earlier reports have not included oxidized R-limonene [hydroperoxides of R-limonene (Lim-OOH)] and oxidized linalool [hydroperoxides of linalool (Lin-OOH)], and breakdown testing of FM I and FM II has mainly been performed in selected, mix-positive patients., Objectives: To report the prevalence of sensitization to the 26 fragrances, and to assess concomitant reactivity to FM I and/or FM II., Methods: A cross-sectional study on consecutive dermatitis patients patch tested with the 26 fragrances and the European baseline series from 2010 to 2015 at a single university clinic was performed., Results: Of 6004 patients, 940 (15.7%, 95%CI: 14.7-16.6%) were fragrance-sensitized. Regarding the single fragrances, most patients were sensitized to Lin-OOH (3.9%), Evernia furfuracea (3.0%), Lim-OOH (2.5%), and hydroxyisohexyl 3-cyclohexene carboxaldehyde (2.1%). Significantly fewer patients were 'FM I-positive and constituent-positive' than 'FM II-positive and constituent-positive' (32.7% versus 57.0%, p < 0.0001). Additionally, significantly more patients were 'FM II-negative but constituent-positive' than 'FM I-negative but constituent-positive' (12.4% versus 3.2%, p = 0.0008)., Conclusions: Non-mix fragrances are the most important single fragrance allergens among consecutive patients. The test concentration of the single FM I constituents should be increased when possible., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Contact dermatitis in healthcare workers is a world wide problem. We conducted a retrospective observational study of the patch-test results of 1402 healthcare workers and 1402 matched controls with contact dermatitis who were treated at 3 hospitals departments in Denmark between 2007 and 2014. The primary objective was to determine whether healthcare work was associated with contact allergy to thiuram mix. Unadjusted univariate analyses revealed that healthcare work was significantly associated with occupational contact dermatitis and hand dermatitis. Contact allergy to thiuram mix was more common in healthcare workers was significantly associated with having occupational contact dermatitis, hand dermatitis and older age. In conclusion, we report here a potential problem of contact allergy to thiurams in healthcare workers with contact dermatitis. Legislative authorities may in the future focus on the use of rubber accelerators in, for example, protective gloves, which are widely used by healthcare professionals.

Background: Cobalt is a strong skin sensitizer and a prevalent contact allergen. Recent studies have recognized exposure to leather articles as a potential cause of cobalt allergy., Objectives: To examine the association between contact allergy to cobalt and a history of dermatitis resulting from exposure to leather., Methods: A questionnaire case-control study was performed: the case group consisted of 183 dermatitis patients with a positive patch test reaction to cobalt chloride and a negative patch test reaction to potassium dichromate; the control group consisted of 621 dermatitis patients who did not react to either cobalt or chromium in patch testing. Comparisons were made by use of a χ(2) -test, Fisher's exact, and the Mann-Whitney test. Logistic regression analyses were used to test for associations while taking confounding factors into consideration., Results: Leather was observed as the most frequent exposure source causing dermatitis in the case group. Although the case group significantly more often reported non-occupational dermatitis caused by leather exposure (p < 0.001), no association was found between cobalt allergy and dermatitis caused by work-related exposure to leather., Conclusions: Our study suggests a positive association between cobalt allergy and a history of dermatitis caused by non-occupational exposure to leather articles., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: A patient who had suffered from persistent generalized dermatitis for 7 years was diagnosed with cobalt sensitization, and his leather couch was suspected as the culprit, owing to the clinical presentation mimicking allergic chromium dermatitis resulting from leather furniture exposure., Materials and Methods: The cobalt spot test, X-ray fluorescence, inductively coupled plasma mass spectrometry and scanning electron microscopy were used to determine cobalt content and release from the leather couch that caused the dermatitis and from 14 randomly collected samples of furniture leather., Results: The sample from the patient's leather couch, but none of the 14 random leather samples, released cobalt in high concentrations. Dermatitis cleared when the patient stopped using his couch., Conclusions: Cobalt is used in the so-called pre-metallized dyeing of leather products. Repeated studies have found high levels of cobalt sensitization, but not nickel sensitization, in patients with foot dermatitis. We raise the possibility that cobalt may be widely released from leather items, and advise dermatologists to consider this in patients with positive cobalt patch test reactions., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Painters are among the occupational groups that most commonly experience occupational contact dermatitis, but few investigations exist concerning this occupation., Objectives: To characterize painters with contact dermatitis and identify the most common allergens associated with the occupation. Materials and methods. All patch test results of 219 painters and 1095 matched controls registered by the Danish Contact Dermatitis Group between 2001 and 2010 were analysed., Results: Hand eczema (p < 0.0001) and occupational contact dermatitis (p < 0.0001) were observed significantly more often in the painters than in the group of controls. Sensitizations to the following allergens from the European baseline series were associated with the occupation and were statistically significant: methylchloroisothiazolinone/methylisothiazolinone, epoxy resin, formaldehyde, and quaternium-15. Three different isothiazolinones emerged as the most frequent sensitizers of the allergens tested in addition to the baseline series., Conclusions: The results indicate that painters have an increased risk of developing occupational hand eczema. Isothiazolinones and epoxy resin proved to be the two most frequent sensitizers in painters., (© 2012 John Wiley & Sons A/S.)

Primin was included in the European standard series (ESS) in 1984. In 2000, a primin-free variant of Primula obconica, the main source of contact allergy to primin, was introduced in the market. The aim of this study was to analyse the trends of primin allergy in 13 986 consecutively patch-tested eczema patients over a 20-year period from 1985 to 2004. 151 patients gave a positive patch test to primin. The majority were women, in two-third of patients the patch test was relevant and most presented with hand eczema. Only few of the cases (4.7%) were occupational. A significant decline of contact allergy to primin was seen (P < 0.001) over the years affecting all age groups. The frequency was 0.5% during 2000-2004. Contact allergy has been rare since 2000. The low frequency of positive patch test to primin does not support inclusion in the ESS in our region.

Methylchloroisothiazolinone and methylisothiazolinone (MCI/MI) contact allergy affects 1-3% of patch-tested patients in European centres. The aim of the present study was to evaluate the importance of the factors--time and concentration (dose/per unit area)--in the elicitation capacity by means of a repeated open application test (ROAT) experimental design. The study was designed as a double-blind, placebo-controlled, dose-response ROAT preceded by a diagnostic patch testing. 25 subjects with confirmed MCI/MI allergy and 10 healthy, non-MCI/MI allergic control subjects were exposed to 0.025 microg/cm2 (2 p.p.m.) of MCI/MI/unit area of the skin for 4 weeks. After a wash-out period of at least 4 weeks, the subjects were exposed to 0.094 microg/cm2 (7.5 p.p.m.) of MCI/MI/unit area of the skin for 4 weeks. The study showed the importance of both time and exposure in the elicitation process. It demonstrated that the elicitation threshold for MCI/MI is expected to be in the proximity of 0.025 microg/cm2 although it was not possible to establish a definitive elicitation threshold for MCI/MI in this study.

The morphology of early allergic contact dermatitis reactions was studied in formaldehyde allergic individuals exposed to a cream product preserved with 4 different concentrations of diazolidinyl urea. The study was made using a dose-escalating design in 3 different anatomical regions, the upper arm, neck and face. On the arm and neck, the dominant initial morphology was an eczematous papular eruption. In the face, the initial skin changes were more homogeneous and infiltrated erythema.

In the year 2000, the level of methyldibromo glutaronitrile (MDGN) allergy in dermatology clinics in Europe exceeded the level of allergies to all other preservatives, with a prevalence of 3.5%. In the present study, cases of primary sensitization and elicitation to MDGN due to cosmetic products were collected over an 8-month period at the Department of Dermatology, Gentofte University Hospital. The aim was to identify the products related to hand eczema, assess exposure to MDGN in these products and relate the findings to results from a newly developed updated risk assessment model for contact allergy. Out of 24 patients with a positive patch test to MDGN, 17 patients with hand eczema were identified. In 11 of these patients, cosmetic products used in relation to the onset of the disease were shown to contain MDGN (65%). In 8 of these 11 cases, primary sensitization was probable, 5 due to hand/body lotions and 3 due to lotions and/or liquid hand soap. Chemical analysis of 12 products showed that lotions contained 149-390 ppm of MDGN, liquid hand soap 144-399 ppm, a rinsing cream 293 ppm and shampoos 78-79 ppm. The shampoo exposure was not of certain relevance to the eczema. Applying the newly developed updated risk assessment model showed that the concentrations of MDGN in lotions of 149-390 ppm exceeded the calculated maximum acceptable exposure level for MDGN, which would be expected to lead to sensitization in consumers using such products, as seen in the current study. The present cases and updated exposure-based risk assessment process add to the evidence and need for re-defining safe-use concentrations of MDGN in cosmetic products.

The aim of this study was to evaluate whether a moisturizer used on normal skin can increase skin response to allergens. Twelve nickel-allergic volunteers applied a lipid-rich moisturizer on the upper arm 3 times daily for 7 days, while the other upper arm served as a control. A control group followed the same treatment protocol. Following treatment with moisturizer, patch tests with 1% NiCl2 aqueous solution were applied on each upper arm. After 24 and 72 h, skin reactions were evaluated blinded by clinical scoring, and by bioengineering methods measuring transepidermal water loss, skin colour and skin thickness. In the nickel-allergic group the strength of patch-test reactions was increased on the moisturizer-treated arm as evaluated by clinical scoring after 24 h and by measurement of transepidermal water loss and skin thickness after 72 h. In the control group, no significant differences were found. Our findings show that threshold values for elicitation of allergic reactions in already sensitized individuals may be influenced by use of lipid-rich moisturizers.

Background: We observed an increasing number of patients who presented with facial or retro‐auricular dermatitis after skin contact with plastic spectacles or plastic covered temples. Objectives: To identify the allergens in plastic spectacles that may cause allergic contact dermatitis. Methods: All patients with suspected allergic contact dermatitis to eyewear were tested with Solvent Orange 60 (SO60), four additionally with Solvent Yellow 14 (SY14), and five with scrapings from their own spectacles. In one case, a chemical analysis of the spectacles was performed to uncover the causative allergen. Results: Three patients were allergic to SO60, two patients to SY14, and two patients were allergic to both SO60 and SY14. Conclusion: Patients with suspected allergic contact dermatitis from spectacles should be tested with SO60 and SY14, and based on findings from previous reports, also with Solvent Red 179. [ABSTRACT FROM AUTHOR]

Background: In 2005, methylisothiazolinone (MI) was allowed as a stand‐alone preservative in cosmetics. This resulted in an epidemic of allergic contact dermatitis to MI, mainly affecting women exposed to leave‐on cosmetics. Consequently, a regulation of Annex V in the European Union in 2017 banned the use of MI in leave‐on cosmetics and reduced the allowed concentration in rinse‐off products. Objective: To analyze the temporal trends in contact allergy to MI in Danish patients in relation to key events including European regulations over time. Methods: A retrospective study of consecutive patients patch tested with methylisothiazolinone from 2005 to 2019. Demographics and clinical characteristics in terms of MOAHLFA (male, occupational, atopic dermatitis, hand dermatitis, leg dermatitis, facial dermatitis and age >40 years), sources of exposure, and clinical relevance were analyzed in relation to key historical events. Results: Three hundred eighty of 12 494 patients (3.0%, 95CI: 2.7–3.4%) tested from 2005 to 2019 were sensitized to MI. An increasing trend in the prevalence of MI contact allergy from 2005 to 2019 (P <.01) was observed, although a decline in the absolute number of patch‐test positive patients was seen from 2013 and onward. A reduction in leave‐on cosmetics as a source of exposure was observed following the legislative ban in 2017, from 24.8% from in 2010 to 2013 to 6.2% in 2017 to 2019 (P <.01). Conclusion: The epidemic of MI contact allergy is declining in absolute terms, although the prevalence in the patch‐tested population has not returned to its pre‐epidemic levels. The legislative regulation of MI in 2017 has been effective in terms of leave‐on cosmetics as a source of exposure in MI allergic patients. The process of post‐marketing risk assessment of contact allergens in the European Union needs improvement. [ABSTRACT FROM AUTHOR]

Background Chromium is an important skin sensitizer. Exposure to it has been regulated in cement, and recently in leather. Studies on the deposition of chromium ions on the skin as a result of handling different chromium-containing materials are sparse, but could improve the risk assessment of contact sensitization and allergic contact dermatitis caused by chromium. Objectives To determine whether the handling of chromium-containing samples of leather and metal results in the deposition of chromium onto the skin. Methods Five healthy volunteers participated. For 30 min, they handled samples of leather and metal known to contain and release chromium. Skin deposition of chromium was assessed with the acid wipe sampling technique. Results Acid wipe sampling of the participants' fingers showed chromium deposition on the skin in all participants who had been exposed to leather (range 0.01-0.20 µg/cm2) and in 3 of 5 participants after they had manually handled metal discs (range 0.02-0.04 µg/cm2). Conclusions We found that samples of leather and metal had the ability to deposit chromium on the skin at significant levels, in spite of a short duration of exposure. [ABSTRACT FROM AUTHOR]

The history of chromium as an allergen goes back more than a century, and includes an interventional success with national legislation that led to significant changes in the epidemiology of chromium allergy in construction workers. The 2015 EU Leather Regulation once again put a focus on chromium allergy, emphasizing that the investigation of chromium allergy is still far from complete. Our review article on chromium focuses on the allergen's chemical properties, its potential exposure sources, and the allergen's interaction with the skin, and also provides an overview of the regulations, and analyses the epidemiological pattern between nations and across continents. We provide an update on the allergen from a dermatological point of view, and conclude that much still remains to be discovered about the allergen, and that continued surveillance of exposure sources and prevalence rates is necessary. [ABSTRACT FROM AUTHOR]

Background Along with chromium, nickel and cobalt are the clinically most important metal allergens. However, unlike for nickel and cobalt, there is no validated colorimetric spot test that detects chromium. Such a test could help both clinicians and their patients with chromium dermatitis to identify culprit exposures. Objectives To evaluate the use of diphenylcarbazide ( DPC) as a spot test reagent for the identification of chromium( VI) release. Methods A colorimetric chromium( VI) spot test based on DPC was prepared and used on different items from small market surveys. Results The DPC spot test was able to identify chromium( VI) release at 0.5 ppm without interference from other pure metals, alloys, or leather. A market survey using the test showed no chromium( VI) release from work tools (0/100). However, chromium( VI) release from metal screws (7/60), one earring (1/50), leather shoes (4/100) and leather gloves (6/11) was observed. We found no false-positive test reactions. Confirmatory testing was performed with X-ray fluorescence ( XRF) and spectrophotometrically on extraction fluids. Conclusions The use of DPC as a colorimetric spot test reagent appears to be a good and valid test method for detecting the release of chromium( VI) ions from leather and metal articles. The spot test has the potential to become a valuable screening tool. [ABSTRACT FROM AUTHOR]

Background Chromium-tanned leather articles currently constitute the most important cause of contact allergy to chromium in Denmark. A regulation on the content of hexavalent chromium in leather was adopted in November 2013 by the EU member states. Objectives To characterize patients with chromium allergy and their disease, to serve as a baseline for future studies on the potential effect of the new regulation on chromium in leather. Methods A questionnaire case-control study was performed on 155 dermatitis patients with positive patch test reactions to potassium dichromate and a matched control group of 621 dermatitis patients. Comparisons were made by use of a χ2-test and the Mann- Whitney U-test. Logistic regression analyses were used to test for associations. Results Sixty-six per cent of chromium-allergic patients had a positive history of contact dermatitis caused by leather exposure. They had a significantly lower quality of life ( p < 0.001), a higher prevalence of dermatitis during the last year ( p = 0.008), a higher use of medication during the past 12 months ( p = 0.001) and a higher prevalence of sick leave ( p = 0.007) than patients in the control group. Conclusions Chromium-allergic patients have more severe and more chronic contact dermatitis. Their primary chromium exposure comes from leather articles. [ABSTRACT FROM AUTHOR]

Methylisothiazolinone (MI) used alone is a new preservative causing a high prevalence of contact allergy. The eliciting threshold of MI is unknown. The combination of MI and phenoxyethanol enhances the antimicrobial efficacy of MI. The eliciting doses of MI contact allergy in a patch test and a repeated open application test (ROAT) were investigated. In the patch test, it was determined whether phenoxyethanol influenced the reactivity to MI. Eleven MI-allergic individuals were patch tested with two dilution series of 12 doses of MI and the same 12 doses with phenoxyethanol. The ROAT mimicked the use of a cream preserved with 100, 50 and 5 ppm MI (corresponding to 0.21, 0.105 and 0.0105 µg MI/cm). Phenoxyethanol had no influence on the reactions to MI. The lowest eliciting dose in the patch test was 1.47 µg MI/cm. In the ROAT, 7 patients (64%) reacted to 0.21 and 0.105 µg MI/cm and 2 patients (18%) reacted to 0.0105 µg MI/cm, corresponding to a cream preserved with 5 ppm MI. A maximum of 100 ppm MI is permitted in cosmetic products. Eighteen per cent of MI-allergic patients reacted to a concentration 20 times lower in a ROAT. The amounts used in cosmetics should be reduced, and the development of MI contact allergy should be monitored closely. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 28-year-old woman with a history of atopic dermatitis presented with a one-year history of hand eczema involving the second to fourth fingers on both hands. Topics discussed include occupational exposure to methylisothiazolinone in adhesive labels; diagnostic patch testing for allergens; and exposure assessment of methylisothiazolinone in consumer products.