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.

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.

Contact allergy to citral and its constituents geranial and neral, coupled with reactions to the prehapten and prohapten geraniol.

BACKGROUND: Citral is commonly used as a fragrance and flavor material and consists of the aldehydes geranial and neral. Citral is included in fragrance mix (FM) II. Geranial and neral have also been identified in autoxidation of geraniol, a fragrance compound present in FM I. OBJECTIVES: To study contact allergy to citral, geranial, and neral, and concomitant reactivity to oxidized geraniol and fragrance markers of the baseline series. METHODS: A total of 1476 dermatitis patients with suspected allergic contact dermatitis were patch tested using geranial, neral, and citral, all 3.5% petrolatum (pet.) as well as geraniol 6.0% and oxidized geraniol 11% pet. in addition to the Swedish baseline series. RESULTS: Frequencies of positive reactions to citral, geranial, and neral were 2.9%, 3.4% and 1.9%, respectively. Together, citral and geranial gave 4.2% positive patch test reactions in consecutive dermatitis patients. In patients with positive reactions to citral or its components, 25% to 34% reacted to FM II and 61% reacted to oxidized geraniol. CONCLUSIONS: Patch testing with citral, its components, or oxidized geraniol detects contact allergic reactions not detected using the baseline series. Patch testing with pure geraniol was shown to be of little value. Geranial and neral, although closely chemically related, are concluded to be separate haptens.

Contact allergy to oxidized geraniol among Swedish dermatitis patients-A multicentre study by the Swedish Contact Dermatitis Research Group.

BACKGROUND: Geraniol is a widely used fragrance terpene, and is included in fragrance mix I. Geraniol is prone to autoxidation, forming the skin sensitizers geranial, neral, and geraniol-7-hydroperoxide. Oxidized geraniol has previously been patch tested in 1 clinic, giving 1% to 4.6% positive reactions in consecutive patients when tested at 2% to 11%. AIM: To compare test reactions to pure and oxidized geraniol, to compare 2 different test concentrations of oxidized geraniol and to investigate the pattern of concomitant reactions to fragrance markers of the baseline series in a multicentre setting. METHODS: One thousand four hundred and seventy-six consecutive patients referred for patch testing were patch tested with geraniol 6% pet. and oxidized geraniol 6% and 11% pet. RESULTS: Pure geraniol 6% pet., oxidized geraniol 6% pet. and oxidized geraniol 11% pet. gave 1%, 3% and 8% positive patch test reactions and 0.7%, 3% and 5% doubtful reactions, respectively. Approximately 50% of the patients with doubtful reactions to oxidized geraniol 6% pet. had positive reactions to oxidized geraniol 11% pet. CONCLUSIONS: Oxidized geraniol 11% pet. provides better detection than oxidized geraniol 6% pet. As most patients reacted only to oxidized geraniol, it is important to explore further whether oxidized geraniol should be included in a baseline patch test series.

Solvent Orange 60 is a potent contact sensitizer in occupational and everyday life.

BACKGROUND: Solvent Orange (SO) 60 is a perinone-type dye that is often used in plastic materials such as spectacle frames and has been shown to cause contact allergy. The first case of SO 60 allergic contact dermatitis caused by spectacle frames was reported in 1999, and the second in 2011. We have recently seen 10 patients, of whom 6 developed dermatitis in the retroauricular/temporal area after wearing plastic spectacles. OBJECTIVES: To report the cause of the dermatitis in the 10 patients and to describe our first case with occupational SO 60 contact allergy. METHODS: In this retrospective study, patch test results of 10 patients, tested with the Swedish baseline series and our specific spectacle and/or plastic series, including SO 60 1.0% pet., in 2011-2017 were analysed. RESULTS: Ten patients, 2 males and 8 females, aged 43 to 71 years, reacted positively to SO 60 1.0% pet., namely, 4 pensioners, 2 nurses, 1 office worker, 1 teacher, 1 shop assistant, and 1 unemployed person. Four of the patients had an atopic history. Patch test reactions varied from + to +++; some had spread >20 cm outside the test area in terms of erythematous, infiltrated skin with papules. Retesting of patient no. 1 with serial dilutions of SO 60 in acetone showed positive reactions down to 1 ppm. Three patients reacted to the extracts of their earpieces. Gas chromatography-mass spectrometry was used to confirm the presence of SO 60 in 2 earpieces. CONCLUSIONS: SO 60 should be included in any spectacle patch test series that may be used. If there is a strong suspicion of contact allergy to SO 60 before patch testing, lowering the test concentration from 1.0% to 0.01% should be considered.

Patch testing with hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) - a multicentre study of the Swedish Contact Dermatitis Research Group.

BACKGROUND: In 2014, the fragrance hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) was excluded from the Swedish baseline series. OBJECTIVES: To study (i) whether fragrance mix (FM) II with 5% HICC detects more positive reactions than usual FM II with 2.5% HICC, and (ii) the reproducibility of patch testing with HICC. METHODS: Two thousand one hundred and eighteen dermatitis patients at five Swedish dermatology departments were consecutively tested with FM II 14% pet., FM II 16.5% pet., and duplicate preparations of HICC 5% pet. RESULTS: Of the patients, 3.2% reacted to FM II 14%, and 1.5% reacted to HICC. Separate testing with HICC detected 0.3% reactions without concomitant reactivity to FM II. FM II with 5% HICC did not give rise to more irritant reactions or signs of active sensitization than FM II with 2.5% HICC. Patch testing with duplicate applications of HICC increased the overall prevalence of HICC contact allergy to 1.9%. CONCLUSION: FM II with 5% HICC does not detect more positive reactions than FM II with 2.5% HICC. Separate testing with HICC does not detect a sufficient proportion of patients who react only to HICC, without concomitant reactions to FM II, to warrant its inclusion in a baseline series.

Recommendation to include a textile dye mix in the European baseline series.

BACKGROUND: Disperse dyes are common sensitizers, but are not currently included in the European baseline series. OBJECTIVES: To justify the inclusion of a textile dye mix in the European baseline patch test series. METHODS: A survey of the reported frequencies of contact allergy to textile dyes and textile dye mixes was performed by searching PubMed (http://www.ncbi.nlm.gov.ludwig.lub.lu.se/pubmed, last accessed 14 December 2014). The results from a multicentre study performed within the European Environmental Contact Dermatitis Research Group (EECDRG) and published in 2014 formed the final basis for the recommendation. RESULTS: The EECDRG study performed in Europe and the United States showed that 2.1-6.9% of consecutively tested dermatitis patients reacted to a 6.6% wt/wt textile dye mix consisting of eight disperse dyes. The clinical relevance was ascertained in >30% of the positive cases. A high frequency of simultaneous sensitivity to Disperse Orange 3 (DO 3) and p-phenylenediamine (PPD) was seen. Active sensitization to the mix was not noted. CONCLUSIONS: It is recommended to include a 6.6% textile dye mix consisting of eight disperse dyes in the European baseline series, even though one component, DO 3, may be superfluous, owing to its frequent cross-reactivity with PPD. Removal of DO 3 from the mix would need further study.

Patch testing with a textile dye mix in two concentrations - a multicentre study by the Swedish contact dermatitis research group.

UNLABELLED: Disperse dyes, which are used for colouring synthetic textile fibres, are well-known contact sensitisers. To investigate the outcome of patch-testing with a textile dye mix (TDM) at 7 dermatology clinics in Sweden, a TDM tested at 2 concentrations was included into the baseline series during one year. The mix consisted of Disperse (D) Blue 35, D Yellow 3, D Orange 1 and 3, D Red 1 and 17, all 1.0%, and D Blue 106 and D Blue 124, each 0.3% in the mix 6.6% and 1.0% each in the mix 8.0%. In 2,122 tested patients, contact allergy to the TDM at the concentration 8.0% was found in 2.8% and to the TDM at 6.6% in 2.5% of the patients. The contact allergy to the TDM could explain or contribute to the dermatitis in about 35% of the patients. CONCLUSION: contact allergy to the TDM is common and inclusion into the Swedish baseline series should be considered.

Swedish Experiences From Patch Testing Methylisothiazolinone Separately.

The preservative methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) is a well-known sensitiser and present in the Swedish baseline series since the 1980s. The proportions of MCI/MI are 3:1. MI alone has been used as a preservative since less than 10 years. This study was conducted on behalf of the Swedish Contact Dermatitis Research Group to evaluate inclusion of MI in the Swedish baseline series since the preparation of MCI/MI might fail to detect contact-allergic reactions to MI alone. Patients with suspected allergic contact dermatitis at 5 Swedish dermatology departments were consecutively patch tested with MI 2,000 ppm aq and MCI/MI 200 ppm aq. The number of cases with exclusive contact allergy to MI varied between 0.8-4.2%. In total, 1.9% reacted exclusively to MI and not to MCI/MI. Due to the considerable frequency of contact allergy to MI not traced by MCI/MI, MI 2,000 ppm aq is included in the Swedish baseline series from January 2014. This corresponds to a dose of 60 µg/cm2.

Patch testing with a textile dye mix--a multicentre study.

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.

Patch testing with formaldehyde 2.0% in parallel with 1.0% by the Swedish contact dermatitis research group.

In a multicentre study consecutively patch-tested dermatitis patients were tested simultaneously with 1.0% and 2.0% (w/v) formaldehyde in aqua applied with a micropipette (15 µl) to the filter paper disc in Finn Chambers (0.30 mg/cm(2) and 0.60 mg/cm(2), respectively). A total of 2,122 dermatitis patients were patch-tested. In all, 77 (3.6%) patients reacted positively to formaldehyde; 37 reacted only to 2.0%, 35 reacted to both concentrations and 5 patients reacted only to 1.0%. Significantly more patients were thus diagnosed with contact allergy to formaldehyde with 2.0% compared to 1.0% (p < 0.001) without causing more irritant reactions. The detected number of isolated allergic reactions to the 2 formaldehyde-releasers in the Swedish baseline series and not to formaldehyde itself raises the question whether quaternium-15 1.0% and diazolidinyl urea 2.0% should be present in the Swedish baseline series.

Sensitizing capacity of Disperse Orange 1 and its potential metabolites from azo reduction and their cross-reactivity pattern.

BACKGROUND: Simultaneous contact allergies to Disperse Orange 1, 4-nitroaniline and p-aminodiphenylamine (PADPA), as well as to other disperse azo dyes and to p-phenylenediamine (PPD), have been reported. Cross-reactivity is one of the possible explanations for simultaneous reactions between PPD and disperse azo dyes. Some metabolites from the azo reduction of these disperse azo dyes could be sensitizers, as human skin bacteria produce azo reductases. OBJECTIVES: To investigate the sensitizing capacity of Disperse Orange 1, PADPA and 4-nitroaniline, and the cross-reactivity between these substances and Disperse Yellow 3, its potential metabolites from azo reduction (4-aminoacetanilide and 2-amino-p-cresol), and PPD. METHOD: The guinea-pig maximization test was used. RESULTS: It was found that both Disperse Orange 1 and PADPA are strong sensitizers and cross-react with each other. We were unable to sensitize guinea-pigs with 4-nitroaniline tested in equimolar concentrations to Disperse Orange 1. CONCLUSIONS: The results indicate that patients sensitized primarily to Disperse Orange 1 will also react to PADPA, which can be found mainly in hair dyes. PPD, 4-nitroaniline, 4-aminoacetanilide, 2-amino-p-cresol and Disperse Yellow 3 did not show any cross-reactivity with Disperse Orange 1 or PADPA.

Contact allergy from disperse dyes in textiles: a review.

Several disperse dyes (DDs) are still considered to be the most important allergens in textile dermatitis, but there are sparse data about their current use in textiles. The aim of this review was to evaluate published studies and reports on contact allergy to DDs published in PubMed during the last 22 years (1990-2012). Prevalence data are provided by study and by dye, as well as by the described clinical peculiarities of DD dermatitis. We reviewed 54 studies. In total, 26 DDs were tested. The average prevalence in screening studies was >1% for Disperse Blue 106, Disperse Blue 124, and Disperse Orange 3. There is a lack of data on patch testing with Disperse Blue 26, Disperse Blue 102, Disperse Orange 37, Disperse Orange 149, Disperse Yellow 23 and Disperse Yellow 49, which are listed as allergens by the EU Commission. It is necessary to check the purity and identity of dyes used for patch testing, confirm the clinical relevance of positive reactions by patch testing with suspected textiles, and, if the results are positive, determine the culprit dye.

Are allergenic disperse dyes used for dyeing textiles?

BACKGROUND: There are no data showing that disperse dyes, used to patch test patients, are currently being used for dyeing synthetic garments. It is unknown whether disperse dyes, which are currently routinely patch tested, are in fact present in synthetic textiles on the market. OBJECTIVES: To determine whether eight disperse dyes, hitherto most widely cited as allergenic, are still used in textiles that are sold in various countries. METHODS: Textiles from 13 countries in Europe, Asia and the United States were analysed. The procedure used for dye identification was thin-layer chromatography. When there were matching spots from the textile extract and reference dye, high-performance liquid chromatography was performed. RESULTS: Of 121 analysed items, three showed positive results for some of the investigated disperse dyes. Four dyes in these items could be detected and confirmed by the use of high-performance liquid chromatography. A pair of light brown ladies' tights manufactured and purchased in Italy contained Disperse Yellow 3, Disperse Blue 124, and Disperse Blue 106, and a set of black bra and panties purchased in India contained Disperse Orange 1. CONCLUSIONS: The eight disperse dyes that are most frequently incriminated in textile dye dermatitis are very rarely used in textiles nowadays.

Patch testing with the textile dyes Disperse Orange 1 and Disperse Yellow 3 and some of their potential metabolites, and simultaneous reactions to para-amino compounds.

BACKGROUND: It is known that, in vitro, human skin bacteria are able to split disperse azo dyes into the corresponding aromatic amines, some of which are sensitizers in the local lymph node assay. We hypothesize that the molecules of disperse dyes migrate onto the skin while garments are worn, and are metabolized and degraded by commensal skin bacteria. These molecules penetrate the skin and induce sensitization. OBJECTIVES: To evaluate the elicitation capacities of the possible azo-degradation products of the selected azo disperse dyes in patients allergic to them and to compare it with the elicitation capacities of other para-compounds. METHODS: Ten patients allergic to Disperse Yellow 3 (DY3) and/or Disperse Orange 1 (DO1) were patch tested with a dilution series of the purified dyes 4-nitroaniline and p-aminodiphenylamine in concentrations equimolar to those of purified DO1 in the dilution series, as well as 4-aminoacetanilide and 2-amino-p-cresol in concentrations equimolar to those of purified DY3 in the dilution series. Results. Three patterns of patch test reactions could be seen. The 6 patients who were positive to DO1 and DY3 also reacted to p-aminodiphenylamine and 2-amino-p-cresol. Two patients were positive to DO1 only, and both reacted to p-aminodiphenylamine, but to neither 4-aminoacetanilide or 2-amino-p-cresol. Two patients did not react to DO1 or DY3 on this occasion. CONCLUSION: We show that it is possible that the major sensitizers in contact allergy to DO1 and DY3 are their metabolites, p-aminodiphenylamine and 2-amino-p-cresol, respectively, which might be formed by the azoreductase pathway of skin bacteria.

Patch testing with a textile dye mix in a baseline series in two countries.

Disperse dyes are the most common contact sensitizers among textile dyes. The main aim of this study was to investigate the outcome of patch testing with a textile dye mix 6.6%. A total of 2,049 patients from Sweden and 497 from Belgium were tested with the mix, consisting of Disperse (D) Blue 35, D Yellow 3, D Orange 1 and 3, D Red 1 and 17, 1.0% each, and D Blue 106 and D Blue 124, 0.3% each. Of the total number, 65 patients, 2.6%, tested positively to the mix, 4.2% of the Belgian patients and 2.1% of the Swedish patients. Patch testing with the mix 6.6% revealed significantly more patients with contact allergy compared with testing with a previous mix 3.2% (p < 0.01). Contact allergy to the mix was significantly more common in the Belgian than in the Swedish patients.

Textile dyes Disperse Orange 1 and Yellow 3 contain more than one allergen as shown by patch testing with thin-layer chromatograms.

BACKGROUND: It is known that some patch-test preparations containing disperse dyes contain impurities with unknown relevance for the development or elicitation of contact allergy. OBJECTIVE: To evaluate the significance of the impurities found in the commercial dyes Disperse Orange 1 (DO1) and Disperse Yellow 3 (DY3) regarding contact allergy in patients with known sensitivity to them. METHODS: Ten patients allergic to DY3 and/or DO1 were tested with a dilution series of commercial and purified DY3 and DO1 (with water-soluble parts prepared from the commercial dyes) and with naphthalene sulfonate. Nine patients were additionally tested with thin-layer chromatograms (TLCs) made from the commercial DO1 and DY3 and with paper chromatograms made from the water-soluble part of these dyes. RESULTS: Eight of nine and three of six patients tested positively to the TLCs of DO1 and DY3, respectively. Among them, 4 of 8 and 2 of 3 patients, respectively, were positive also to another spot on the TLCs. One patient was positive to the paper chromatogram from the water-soluble part of DO1. None of the tested patients reacted to naphthalene sulfonate. CONCLUSION: The results of our study suggest that there are more relevant allergens in the fat-soluble and water-soluble fractions of the commercial disperse dyes.

Patch testing with a textile dye mix and its constituents in a baseline series.

BACKGROUND: Among the textile dyes, disperse dyes are common sensitizers. OBJECTIVE: To investigate whether patch testing with a textile dye mix consisting of eight disperse dyes would be equivalent to testing with the separate ingredients of the mix at the concentrations used in the mix. METHODS: Researchers tested 1,780 consecutive patients with a mix consisting of Disperse Blue 35, Disperse Yellow 3, Disperse Orange 1, Disperse Orange 31 (mislabeled as Disperse Orange 3), Disperse Red 1 and 17, all at 0.5%, and Disperse Blue 106 and 124, both at 0.1%, and with the ingredients at these concentrations. Testing with the labeled dyes at 1.0% was done on 500 of the patients and additionally on the remaining patients who reacted positively to the mix, any of the ingredients, p-phenylenediamine, or black rubber mix. RESULTS: Thirty-five patients (2%) reacted to the mix, and 34 patients were allergic to at least one ingredient tested at the lower concentration. CONCLUSION: The textile dye mix was as good a detector of contact allergy to the disperse dyes as was testing with any combination of the ingredients at the concentration in the mix. Increasing the concentration of the ingredients of the textile dye mix might increase the sensitivity of the mix.

Patch testing of patients allergic to Disperse Blue 106 and Disperse Blue 124 with thin-layer chromatograms and purified dyes.

BACKGROUND: Former investigations have demonstrated that patch test preparations containing Disperse Blue (DB) 106 and DB 124 are impure. OBJECTIVE: To investigate the significance of impurities in preparations of disperse dyes with regard to contact allergy. MATERIALS/METHODS: 21 patients allergic to DB 106 and/or DB 124 were tested with dilution series of commercial and purified DB 106 and DB 124. All patients were additionally tested with thin-layer chromatography (TLC) strips made from the commercial preparations containing DB 106 and 18 of them also with TLC strips containing DB 124. RESULTS: 13 of 21 and 12/18 patients tested positively to the strips of DB 106 and DB 124, respectively. Among these patients, 4/13 and 5/12, respectively, did not react to the main spot but reacted to other spots. Dilution series of purified DB 106 and DB 124 were positive in 10 patients each, while 16 and 15 patients, respectively, tested positively to the dilution series of the corresponding commercial disperse dye. CONCLUSION: Approximately 25% of the patients, diagnosed as contact allergic to DB 106 and DB 124, only reacted to impurities in the patch test preparations. This has implications for diagnosis and prevention.