Contact sensitization and self-reported eczema in Swedish painters with occupational exposure to isothiazolinones.

BACKGROUND: Due to an increasing occupational usage of isothiazolinone (IT)-containing preservatives, and their potential to cause skin sensitization and allergic contact dermatitis, that is, chronic disease, there is a need for more knowledge on how highly exposed workers are affected. OBJECTIVES: The overall objective was to explore dermatological symptoms of potentially long-lasting or chronic character in Swedish painters. METHODS: Building painters from western and southern Sweden were initially invited to perform a questionnaire on occurrence of skin symptoms. Participants with affirmative responses, and the right inclusion criteria, were further invited to patch testing with four different ITs: benzisothiazolinone (BIT), methylisothiazolinone, methylchloroisothiazolinone and octylisothiazolinone. RESULTS: There was a tendency towards higher occurrence of positive patch test reactions among the painters compared with occupationally unexposed registry patients; however, not statistically significant differences. BIT was the substance most frequently causing positive test results in both groups. The occurrence of adult-onset eczema was higher in painters than in the control group of electricians, and just shy of statistical significance concerning any of several skin locations (face/legs/arms/hands). CONCLUSION: Building painters present with positive patch test reactions to common paint preservatives (ITs), and they report adult-onset eczema more often than do less occupationally exposed groups.

Investigation into Propolis Components Responsible for Inducing Skin Allergy: Air Oxidation of Caffeic Acid and Its Esters Contribute to Hapten Formation.

Propolis is a resin-like material produced by bees from the buds of poplar and cone-bearing trees and is used in beehive construction. Propolis is a common additive in various biocosmetics and health-related products, despite the fact that it is a well-known cause of contact allergy. Caffeic acid and its esters have been the primary suspects behind the sensitization potency of propolis-induced contact allergy. However, the chemical structures of the protein adducts formed between these haptens and skin proteins during the process of skin sensitization remain unknown. In this study, the reactivity of three main contact allergens found in propolis, namely, caffeic acid (CA), caffeic acid 1,1-dimethylallyl ester (CAAE), and caffeic acid phenethyl ester (CAPE), was investigated. These compounds were initially subjected to the kinetic direct peptide reactivity assay to categorize the sensitization potency of CA, CAAE, and CAPE, but the data obtained was deemed too unreliable to confidently classify their skin sensitization potential based on this assay alone. To further investigate the chemistry involved in generating possible skin allergy-inducing protein adducts, model peptide reactions with CA, CAAE, and CAPE were conducted and analyzed via liquid chromatography-high-resolution mass spectrometry. Reactions between CA, CAAE, and CAPE and a cysteine-containing peptide in the presence of oxygen, both in closed and open systems, were monitored at specific time points. These studies revealed the formation of two different adducts, one corresponding to thiol addition to the α,ß-unsaturated carbonyl region of the caffeic structure and the second corresponding to thiol addition to the catechol, after air oxidation to o-quinone. Observation of these peptide adducts classifies these compounds as prehaptens. Interestingly, no adduct formation was observed when the same reactions were performed under oxygen-free conditions, highlighting the importance of air oxidation processes in CA, CAAE, and CAPE adduct formation. Additionally, through NMR analysis, we found that thiol addition occurs at the C-2 position in the aromatic ring of the CA derivatives. Our results emphasize the importance of air oxidation in the sensitization potency of propolis and shed light on the chemical structures of the resultant haptens which could trigger allergic reactions in vivo.

Common fragrance chemicals activate dendritic cells in coculture with keratinocytes.

BACKGROUND: Fragrances are important contact allergens; however, investigation of their skin sensitization potency has been challenging in new approach methods (NAMs). Many fragrance chemicals are susceptible to autoxidation or can be metabolized by enzymes constitutively expressed in skin keratinocytes. Strong sensitizers can be formed in both of these processes. Further, keratinocytes can modulate the dendritic cell (DC) activation and maturation potential, a key event in the acquisition of contact allergy. OBJECTIVES: To evaluate the 2D coculture model consisting of keratinocytes and DCs using different weak to moderate sensitizing fragrance chemicals. Further, to investigate fragrances and related oxidation products in the in vitro model and compare to in vivo data. METHODS: Chemicals were tested in the coculture activation test (COCAT), consisting of HaCaT keratinocytes and THP-1 cells. THP-1 cell surface expression of costimulatory and adhesion molecules (CD86 and CD54) collected after 24 h incubation with the chemicals was analysed using flow cytometry. RESULTS: Twenty-four molecules were tested positive, three were negative (n = 27). Four pairs were evaluated, with aldehydes showing a 6- to 13-fold stronger responses compared to their corresponding alcohols. CONCLUSIONS: Results provide insight into the activation of DC in their natural environment of keratinocytes. α,ß-Unsaturated alcohols were classified as weaker sensitizers compared to their corresponding aldehydes. In sum, testing of fragrances retrieved results in good agreement with in vivo data.

Exclusion of Disperse Orange 3 is possible from the textile dye mix present in the Swedish baseline patch test series. A study by the Swedish Contact Dermatitis Research Group.

BACKGROUND: The textile dye mix (TDM) 6.6% in petrolatum contains Disperse Blue (DB) 35, Disperse Yellow 3, Disperse Orange (DO) 1 and 3, Disperse Red 1 and 17, and DB 106 and 124. The most frequent allergen in TDM-positive patients is DO 3. Around 85% of para-phenylenediamine (PPD)-allergic dermatitis patients have been positive to DO 3. There has been a discussion to exclude DO 3 from TDM 6.6% because of strong simultaneous reactions to TDM and PPD. OBJECTIVES: To study if DO 3 can be excluded from TDM 6.6%. METHODS: Patch tests were performed on 1481 dermatitis patients with TDM 6.6%, TDM 7.0% (without DO 3 but the other disperse dyes at 1.0% each), DO 3 1.0%, and PPD 1.0% pet. RESULTS: Contact allergy to TDM 6.6% was 3.6% and to TDM 7.0% was 3.0%. All 26 DO 3-positive patients were positive to PPD. The 44 patients positive to TDM 7.0% plus the 13 positive to PPD and TDM 6.6% but negative to TDM 7.0% were 57, outnumbering the 53 positive to TDM 6.6%. CONCLUSION: TDM 7.0% can replace TDM 6.6% in the Swedish baseline series, since TDM 7.0% together with PPD 1.0% will detect patients with textile dye allergy.

Contact allergy to haptens in the Swedish baseline series: Results from the Swedish Patch Test Register (2010 to 2017).

BACKGROUND: Allergic contact dermatitis has considerable public health impact and causative haptens vary over time. OBJECTIVES: To report the prevalence of contact allergy to allergens in the Swedish baseline series 2010 to 2017, as registered in the Swedish Patch Test Register. METHODS: Results and demographic information for patients tested with the Swedish baseline series in 2010 to 2017 were analysed. RESULTS: Data for 21 663 individuals (females 69%) were included. Females had significantly more positive patch tests (54% vs 40%). The reaction prevalence rates were highest for nickel sulfate (20.7%), fragrance mix I (7.1%), Myroxylon pereirae (6.9%), potassium dichromate (6.9%), cobalt chloride (6.8%), methylchloroisothiazolinone/methylisothiazolinone (MCI/MI; 6.4%), MI (3.7%), colophonium (3.5%), fragrance mix II (3.2%), and formaldehyde (3.2%). Myroxylon pereirae reaction prevalence increased from 5% in 2010 to 9% in 2017 and that for methyldibromo glutaronitrile from 3.1% to 4.6%. MCI/MI and MI reactions decreased in prevalence after 2014. Nickel reaction prevalence decreased among females aged 10 to 19 years. CONCLUSIONS: Nickel remains the most common sensitizing agent, with reaction prevalence decreasing among females younger than 20 years. The changes in MCI/MI and MI reaction prevalence mirrored those in Europe. The register can reveal changes in contact allergy prevalence over time among patients patch tested in Sweden.

Patch Testing with Propolis of Different Geographical Origins in a Baseline Series.

The chemical composition of propolis varies with geographical origin; however, it is not known whether this affects the frequency of contact allergy to propolis. In order to study the frequency of contact allergy to propolis of different geographical origins and concomitant reactions, 1,470 consecutive patients with dermatitis from Denmark, Lithuania and Spain were patch tested with propolis from China, Lithuania, North America and Sweden, and with a baseline series. Patch test reactions to any type of propolis ranged from 1.3% to 5.8%. There were no statistically significant differences in the frequency of positive reactions between the 4 types of propolis in the respective countries. Testing with a single commercially available type of propolis detects only approximately half of propolis-allergic patients. In patients allergic to propolis, concomitant reactions to Myroxylon pereirae resin, colophonium and Fragrance mix I were common, ranging from 12.5% to 50.0%.

Suitable test concentration of cobalt and concomitant reactivity to nickel and chromium: A multicentre study from the Swedish Contact Dermatitis Research Group.

BACKGROUND: In Sweden, cobalt chloride 0.5% has been included in the baseline series since the mid-1980s. A recent study from Stockholm showed that cobalt chloride 1% petrolatum (pet.) was more suitable than 0.5%. Cobalt chloride at 1.0% has been patch tested for decades in many European countries and around the world. OBJECTIVES: To study the suitability of patch testing to cobalt 1.0% vs 0.5% and to analyze the co-occurrence of allergy to cobalt, chromium, and nickel. RESULTS: Contact allergy to cobalt was shown in 90 patients (6.6%). Eighty (5.9%) patients tested positive to cobalt 1.0%. Thirty-seven of the 90 patients (41.1%) with cobalt allergy were missed by cobalt 0.5% and 10 (0.7%) were missed by cobalt 1.0% (P < .001). No case of patch test sensitization was reported. Allergy to chromium was seen in 2.6% and allergy to nickel in 13.3%. Solitary allergy to cobalt without nickel allergy was shown in 61.1% of cobalt-positive individuals. Female patients had larger proportions of positive reactions to cobalt (P = .036) and nickel (P < .001) than males. CONCLUSION: The results speak in favor of replacing cobalt chloride 0.5% with cobalt chloride 1.0% pet. in the Swedish baseline series, which will be done 2021.

Contact Allergy in Western Sweden to Propolis of Four Different Origins.

Propolis, which is produced by honeybees and is used in "natural" products, can cause contact allergy. The composition of propolis varies between regions, but little is known about how this variation affects contact allergenicity. The aims of this study were to investigate the frequency of propolis contact allergy in western Sweden, and whether the frequency varies according to the origin of the propolis. Patch-testing was performed using propolis from China, Lithuania, North America, and Sweden in 722 consecutive patients with dermatitis in western Sweden. Frequencies of positive patch-test reactions ranged from 2.4% to 3.6%. There were some, not statistically significant, differences in frequency of contact allergy to the 4 samples of propolis of different origins, with the highest frequency to the sample from China and the lowest frequency to the sample from Sweden. Concomitant positive patch-test reactions to plant and fragrance substances in the baseline series were common, most frequently to Myroxylon pereirae resin and colophonium.

Patch testing with purified and oxidized citronellol.

BACKGROUND: Citronellol is a commonly used fragrance terpene included in fragrance mix II. As with many other fragrance terpenes, citronellol is susceptible to autoxidation. Citronellol hydroperoxides are formed in large amounts and are the only oxidation products identified as sensitizers in oxidized citronellol. AIM: To compare frequencies of contact allergy to purified and oxidized citronellol and to investigate the pattern of concomitant reactions to fragrance markers of the baseline series, oxidized linalool, and oxidized limonene. METHODS: A total of 658 dermatitis patients were patch tested with purified and oxidized citronellol at 2.0%, 4.0%, 6.0%, and 1.0%, 2.0%, 4.0%, 6.0% petrolatum, respectively. The irritant properties of purified and oxidized citronellol were studied before patch testing. RESULTS: Few irritant reactions were observed in the pretest. Purified citronellol detected positive reactions in 0.15%-0.31% of patients, while oxidized citronellol detected positive reactions in 0.61%-4.5%. Among patients reacting to oxidized citronellol, 34%-50% showed concomitant reactions to fragrance markers of the baseline series and 75%-91% to oxidized linalool or oxidized limonene. CONCLUSION: Oxidized citronellol detects more cases of contact allergy than purified citronellol, and these cases are not all detected using fragrance mix II. Patch testing with oxidized citronellol will add to the tools in the diagnosis of fragrance allergy.

Can patch testing with methylchloroisothiazolinone/methylisothiazolinone be optimized using a new diagnostic mix? - A multicenter study from the Swedish Contact Dermatitis Research Group.

BACKGROUND: Methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) and methylisothiazolinone (MI) are tested to detect contact allergy to these isothiazolinones. OBJECTIVES: To study if an aqueous patch test preparation with MCI and MI in a mix of 0.015% and 0.2%, respectively, detects more contact allergies than the commonly used preparations of MCI/MI in 0.02% aq. and MI in 0.2% aq. METHODS: A total of 1555 patients with dermatitis in five Swedish dermatology departments were tested consecutively with MCI/MI 0.215% aq., MCI/MI 0.02% aq., and MI 0.2% aq. RESULTS: The share of contact allergy to MCI/MI 0.215% aq., MCI/MI 0.02% aq., and MI 0.2% aq. varied in the test centers between 7.9% and 25.9%, 3.2% and 10.3%, and 5.8% and 12.3%, respectively. MCI/MI 0.215% aq. detected significantly more patch-test positive individuals than both MCI/MI 0.02% aq. (P < .001) and MI 0.2% aq. (P < .001), as well as either one of MCI/MI and MI (P < .001). In the patients only reacting to MCI/MI 0.215% aq., 57.7% were recorded as having a dermatitis that was explained or aggravated by exposure to either MCI/MI or MI. CONCLUSION: The results speak in favor of replacing the preparations MCI/MI 0.02% aq. and MI 0.2% aq. with MCI/MI 0.215% aq. as the screening substance in the Swedish baseline series, which has been implemented in 2020.