Stability of fragrance patch test preparations applied in test chambers.

BACKGROUND: Petrolatum patch test preparations are for practical reasons often applied in test chambers in advance, several hours or even days before the patient is tested. As many fragrance compounds are volatile it may be suspected that petrolatum preparations applied in test chambers are not stable over time. OBJECTIVES: To investigate the stability of petrolatum preparations of the seven chemically defined components in the fragrance mix (FM I) when stored in test chambers. METHODS: Samples of petrolatum preparations applied in test chambers stored at room temperature and in a refrigerator for between 4 and 144 h were analysed using liquid chromatographic methods. RESULTS: The concentration decreased by ≥ 20% within 8 h in four of seven preparations stored in Finn chambers at room temperature. When stored in a refrigerator only the preparation of cinnamal had decreased by ≥ 20% within 24 h. The stability of preparations of cinnamal stored in IQ chambers with a plastic cover was slightly better, but like the preparations applied in Finn chambers, the concentration decreased by ≥ 20% within 4 h at room temperature and within 24 h in a refrigerator. Cinnamal and cinnamyl alcohol were found to be more stable when analysed as ingredients in FM I compared with when analysed in individual preparations. CONCLUSIONS: Within a couple of hours several fragrance allergens evaporate from test chambers to an extent that may affect the outcome of the patch test. Application to the test chambers should be performed as close to the patch test occasion as possible and storage in a refrigerator is recommended.

Concentration variability of potent allergens of p-tert-butylphenol-formaldehyde resin (PTBP-FR) in patch test preparations and commercially available PTBP-FR.

BACKGROUND: p-tert-Butylphenol-formaldehyde resin (PTBP-FR) is a common component of glues used in the manufacturing of many plastic, electronic, rubber, wood and leather products. Two main allergens of PTBP-FR have been described. OBJECTIVES: To determine the concentrations of the two main allergens of PTBP-FR in diagnostic patch testing preparations and PTBP-FR available to glue and adhesive manufacturers. METHODS: Nuclear magnetic resonance spectrometry was used to confirm the identity and determine the purity of reference materials. High-pressure liquid chromatography was used to analyse patch test preparations and commercially available PTBP-FR. RESULTS: In the PTBP-FR in analysed patch test preparations the highest concentration of the allergenic dimer 4-tert-butyl-2-(5-tert-butyl-2-hydroxy-3-hydroxymethyl-benzyloxymethyl)-6-hydroxymethylphenol found was 1·79% and the lowest 0·21%. The highest concentration of the allergenic dimer 4-tert-butyl-2-(5-tert-butyl-2-hydroxy-benzyloxymethyl)-6-hydroxymethylphenol found in PTBP-FR of analysed patch test preparations was 0·50% and the lowest concentration found was 0·04%. In commercially available PTBP-FR the highest concentration of 4-tert-butyl-2-(5-tert-butyl-2-hydroxy-3-hydroxymethyl-benzyloxymethyl)-6-hydroxymethylphenol found was 3·7% and the highest concentration of 4-tert-butyl-2-(5-tert-butyl-2-hydroxy-benzyloxymethyl)-6-hydroxymethylphenol found was 1·1%. In three PTBP-FR samples neither allergen could be detected. CONCLUSIONS: Our data suggest that reporting resin concentration in petrolatum is not predictive of a consistent concentration of the two main allergens of PTBP-FR. The 10-fold difference in allergen concentration between different patch test preparations has significant ramifications for maintaining consistent dose of delivered allergen. The results of this study reinforce the need for patch test product standardization in the contact dermatitis community.

Variation in allergen content over time of acrylates/methacrylates in patch test preparations.

BACKGROUND: Acrylates/methacrylates are volatile substances. There might be a gradual decrease in acrylate/methacrylate allergen content over time in patch test preparations but this has not yet been documented. OBJECTIVES: To determine the allergen content of acrylates/methacrylates in patch test preparations over time under different storage conditions. METHODS: Five acrylate/methacrylate allergens [2-hydroxyethyl methacrylate (2-HEMA), methyl methacrylate (MMA), ethylene glycol dimethacrylate (EGDMA), triethylene glycol diacrylate (TREGDA) and 2-hydroxypropyl acrylate (2-HPA)] in syringes and IQ™ chambers (Chemotechnique Diagnostics, Vellinge, Sweden) were analysed using gel permeation chromatography and high-performance liquid chromatography to measure the allergen content over time in samples stored in the freezer, refrigerator and under room temperature. RESULTS: The concentration of allergens in syringes decreased with time. Those stored at room temperature had the fastest rate of decrease, followed by those in the refrigerator and freezer. In most cases, in syringes or IQ™ chambers under all storage conditions, the MMA decreased most rapidly, followed by 2-HPA, 2-HEMA, EGDMA and TREGDA. The allergens in the IQ™ chambers rapidly disappeared, with almost all samples reaching nondetectable levels by day 8. MMA was the first to reach a nondetectable level--at day 2. CONCLUSIONS: Acrylate/methacrylate allergens are lost rapidly from IQ™ chambers especially if stored at room temperature. Allergens in syringes remain above 80% of their initial concentrations for longer periods compared with IQ™ chambers. In syringes and IQ™ chambers there is a slower rate of decrease in concentration when the storage temperature is lower. Allergens should be stored refrigerated, replaced regularly, and freshly applied on to test patches on the day of use.

An outbreak of furniture related dermatitis ('sofa dermatitis') in Finland and the UK: history and clinical cases.

In February 2007, an epidemic of severe dermatitis from Chinese recliner chairs and sofas started to unfold first in Finland and a few months later in the UK. Some patients reacted in patch tests (PTs) strongly to the material of their furniture, either leather or fabric. There have been hundreds of reports of chair or sofa dermatitis from Finland and the UK, with all cases linked to the same furniture factory in China. Clinical findings in both countries were very similar and unlike any known dermatosis. Many cases have been quite severe, resembling mycosis fungoides or septic infections, requiring hospitalization. Commercial PTs did not reveal the cause but a fungicide was strongly suspected, although such use was denied by the factory. The laboratory of Malmö University Dermatology Clinic has helped in the process by making thin layer chromatograms from sofa or chair materials and test substances of suspected chemicals. Finally, sachets marked with 'mouldproof agent' were found in varying numbers and distribution in the sofas. These contained dimethyl fumarate (DMF) which proved in skin tests to cause strong positive reactions with down to 0.01 dilution. Reports from other countries (Belgium, France, Ireland, Sweden and Spain) have since appeared, and the EU has banned the use of DMF in consumer products.

An epidemic of furniture-related dermatitis: searching for a cause.

Background Sitting in new chairs or sofas has elicited dermatitis in numerous patients in Finland and in the U.K. since autumn 2006. The cause of the dermatitis seemed to be an allergen in the furniture materials. Objectives To determine the cause of the dermatitis in patients with furniture-related dermatitis. Methods Altogether 42 patients with furniture-related dermatitis were studied. First, 14 Finnish patients were patch tested with the standardized series and with the chair textile material. A thin-layer chromatogram (TLC) strip and an extract made from the same textile material were tested in seven Finnish patients. The test positive spot of the TLC and the content of a sachet found inside a sofa in the U.K. were analysed by using gas chromatography-mass spectrometry. All chemicals analysed were patch tested in 37 patients. Results A positive patch test reaction to the chair textile and to its extract was seen in all patients tested, one-third of whom had concurrent reactions to acrylates. Positive reactions to the same spot of the TLC strip were seen in five of seven patients and dimethyl fumarate was analysed from the spot as well as from the sachet contents. Dimethyl fumarate (0.01%) elicited positive reactions in all the patients. The other chemicals analysed did not elicit positive reactions, but one patient in the U.K. had a positive reaction to tributyl phosphate. Conclusions Sensitization to dimethyl fumarate was seen in all the patients with furniture-related dermatitis. Concurrent sensitization or cross-reactions were common among the sensitized patients.

Is contact allergy to disperse dyes and related substances associated with textile dermatitis?

BACKGROUND: Disperse dyes (DDs) are the most common sensitizers among textile dyes, but there is little knowledge of the clinical relevance of positive patch test reactions. OBJECTIVE: To investigate if patient-reported textile-related skin problems can be explained by contact allergy to eight different DDs and/or to chemically related substances, by occupation or by atopic constitution, and if the skin problems are influenced by age or sex. METHODS: A questionnaire on textile-related skin problems was answered by 858 of 982 consecutively patch tested patients in Malmö, Sweden and in Leuven, Belgium. The baseline series used for patch testing was supplemented with a textile dye mix (TDM) consisting of the eight DDs and with the separate dyes. The association between textile-related skin problems and contact allergy to the DDs and other risk factors was investigated using multiple logistic regression analysis. RESULTS: Eighteen per cent of the patients suspected textiles as a cause of their skin problems. Atopic constitution and female sex were risk factors for skin reactions. Synthetic materials were the most common textiles to give skin problems. A significant association was found between self-reported textile-related skin problems and contact allergy to para-phenylenediamine (PPD) [adjusted odds ratio (OR) 2.1; 95% confidence interval (CI) 1.0-4.3]. A similar, but more imprecise, adjusted OR was found for TDM (OR 1.9; 95% CI 0.57-5.6). Contact allergy to black rubber mix was too rare to be evaluated. CONCLUSIONS: Contact allergy to PPD was a more prevalent indicator for skin reactions to textiles than the TDM used in this study.

Contact allergy to textile dyes in southern Sweden.

Contact allergy to disperse dyes in textiles is documented in prevalence studies from southern Europe. To evaluate the prevalence of allergic patch test reactions to different textile dyes in southern Sweden, and to look at the sites of dermatitis in individuals hypersensitive to textile dyes, we retrospectively investigated 3325 consecutively patch-tested patients. They had all been patch tested with the standard test series supplemented with a textile dye mix (TDM) consisting of 8 disperse dyes, i.e. Disperse (D) Blue 35, 106 and 124, D Yellow 3, D Orange 1 and 3 and D Red 1 and 17. All but 3 of the TDM-positive patients were additionally tested with the separate dyes included in the mix. The frequency of contact allergy to TDM was 1.5%, which is comparable with studies from southern Europe. The most common dye allergen was D Orange 1. The high prevalence of allergic reactions to D Orange 1 was unexpected, whereas test reactions to D Blue 106 and 124 were lower than expected from other studies. Compared to all tested patients, the TDM-positive patients more often had dermatitis on their arms, face, neck and axillary folds, and women also had a higher frequency of hand dermatitis.

Chemical analysis of monomers in epoxy resins based on bisphenols F and A.

Diglycidyl ether of bisphenol A (DGEBA) is the monomer and most important contact allergen in epoxy resin(s) based on bisphenol A (DGEBA-R). Both thin-layer chromatography (TLC) and high-pressure liquid chromatography (HPLC) methods are available for the analysis of products containing DGEBA-R. With respect to detection and quantification, epoxy resins of the bisphenol F-type, i.e. epoxy resins containing the isomers of diglycidyl ethers of bisphenol F (DGEBF), are not as well investigated as DGEBA-R. The isomers of DGEBF are p,p'-DGEBF, o,p'-DGEBF and o,o'-DGEBF. Both p,p'-DGEBF and o,p'-DGEBF have been shown to be contact allergens in humans, and all 3 isomers are sensitizers in the guinea pig maximization test. We aimed (i). to develop HPLC methods for separation and purification of the individual DGEBF isomers, (ii). to detect and quantify the DGEBF isomers in epoxy resins of the bisphenol F-type and (iii). to evaluate and develop the TLC as a method for the detection of the DGEBF monomers. We found the total content of the DGEBF isomers in the investigated epoxy resins of the bisphenol F-type to vary from 17.0 to 81.7% w/w. Some of them also contained 0.1-2.4% w/w DGEBA. The HPLC method showed a sensitivity that was 2000-20 000x higher than that obtained with the TLC method for the DGEBF monomers. We concluded that the range of the DGEBF isomer content in epoxy resins of the bisphenol F-type is approximately the same as the monomer content in liquid compared to solid DGEBA-R. The relevance of contact allergy to DGEBA-R can remain unrecognized if the suspected product is an epoxy resin of the bisphenol F-type, which is analysed with the TLC method.

Contact dermatitis from electrocardiograph-monitoring electrodes: role of p-tert-butylphenol-formaldehyde resin.

Three cases of allergic contact dermatitis localized to the sites of electrocardiograph-monitoring electrodes are reported. All patients had positive patch tests to both the gel and the adhesive part of the Red Dot 2239 3M monitoring electrode used and to the p-tert-butylphenol-formaldehyde resin (PTBP-F-R) of the standard series. Two patients had a history of possible exposition to the resin previously but there was no explanation for the third. No information about the presence of PTBP-F-R in the electrodes could be obtained from the manufacturers. Chemical analysis of samples of the electrode, using a gas chromatography-mass spectrometry (GC-MS) and high pressure liquid chromatography (HPLC) analytical system, demonstrated the presence of several PTBP-F-R derivatives in both the gel and the adhesive part.

Sensitizing capacity and cross-reaction pattern of the isomers of diglycidyl ether of bisphenol F in the guinea pig.

In this study, the sensitizing capacities of the 3 main low-molecular-weight isomers of epoxy resins based on diglycidyl ether of biphenol F (DGEBF) were investigated in a guinea pig maximization test (GPMT). The isomers are p,p'-DGEBF, o,p'-DGEBF, and o,o'-DGEBF. The sensitization capacities were compared to diglycidyl ether of bisphenol A (DGEBA), which is the main constituent in the most common epoxy resin. The cross-reaction pattern between all 4 compounds was also investigated. It was found that all 3 DGEBF isomers were potent sensitizers. It was also found that p,p'-DGEBF, o,p'-DGEBF, and DGEBA cross-reacted with one another, and that animals induced with o,o'-DGEBF reacted significantly only to o,p'-DGEBF, but not to the other 2 DGEBF isomers or DGEBA.

Sensitizing capacity of 5,5'-di-tert-butyl-2,2'-dihydorxy-(hydroxymethyl)-dibenzyl ethers in the guinea pig.

In patients hypersensitive to p-tert-butylphenol-formaldehyde resin (PTBP-F-R), it is for diagnostic, therapeutic and preventive reasons necessary to know the identity of the primary sensitizing substances, their sensitizing capacities as well as their cross-reaction patterns. We have recently shown that the 2 dimers in PTBP-F-R, 5,5'-di-tert-butyl-2,2'-dihydroxy-3-hydroxymethyl-dibenzyl ether (X) and 5,5'-di-tert-butyl-2,2'-dihydroxy-3,3'-dihydroxymethyl-dibenzyl ether (IX) are contact sensitizers in man. The aim of this study was to investigate the sensitizing capacities of these dimers in PTBP-F-R and potential cross-reacting substances in the guinea pig with the guinea pig maximization test. IX, X, 2,6-dimethylol-p-tert-butylphenol (2,6-MPTBP), 2-methylol-p-tert-butylphenol (2-MPTBP), p-tert-butylcatechol (PTBC), 5,5'-di-tert-butyl-2,2'-dihydroxy-dibenzyl ether (XI) were used as possible cross reacting substances. IX and X were shown to be sensitizers. When compared to the sensitizers in phenol-formaldehyde resin, IX is a strong sensitizer (p= 0.00052) and X a moderate sensitizer (p=0.0053). Animals sensitized to IX showed cross-reactions to X (p=0.010), 2,6-MPTBP (p=0.0011) and PTBC (p=0.0498). Animals sensitized to X showed no cross-reactions to the substances that were tested. The results indicate that IX is a main allergen in PTBP-F-R, with possibly also X.

Contact allergy to 5,5'-di-tert-butyl-2,2'-dihydroxy-(hydroxymethyl)-dibenzyl ethers, sensitizers, in p-tert-butylphenol-formaldehyde resin.

Allergy to p-tert-butylphenol-formaldehyde resin (PTBP-F-R) is not rare. This resin consists of a large number of substances, most of which are still unknown. More knowledge about the sensitizers in the resin is a good basis for development of diagnosis, treatment and prevention. The aim of this investigation was to study allergens in PTBP-F-R by isolation of some medium molecular weight substances from the resin and patch testing these in individuals hypersensitive to PTBP-F-R. 2 isolated substances were shown to be allergens in PTBP-F-R, 5,5'-di-tert-butyl-2,2'-dihydroxy-3,3'-dihydroxymethyl-dibenzyl ether and 5,5'-di-tert-butyl-2,2'-dihydroxy-3-hydroxymethyl-dibenzyl ether. 13 patients hypersensitive to PTBP-F-R were patch tested with serial dilutions of 5,5'-di-tert-butyl-2,2'-dihydroxy-3,3'-dihydroxymethyl-dibenzyl ether and 12 of them reacted positively. 12 patients hypersensitive to PTBP-F-R were patch tested with serial dilutions of 5,5'-di-tert-butyl-2,2'-dihydroxy-3-hydroxymethyl-dibenzyl ether and 11 of them reacted positively. Positive patch test reactions were seen down to 0.0000025 mmole x 1(-1) (approximately 0.01 ppm) for both 5,5'-di-tert-butyl-2,2'-dihydroxy-3,3'-dihydroxymethyl-dibenzyl ether and 5,5'-di-tert-butyl-2,2'-dihydroxy-3-hydroxymethyl-dibenzyl ether in the most sensitive patient. HPLC analysis of 2 PTBP-F-Rs showed the presence of 1.0-1.7% w/w 5,5'-di-tert-butyl-2,2'-dihydroxy-3,3'-dihydroxymethyl-dibenzyl ether and 0.75-0.90% w/w 5,5'-di-tert-butyl-2,2'-dihydroxy-3-hydroxymethyl-dibenzyl ether in the resins.

Skin disorders in amputees.

BACKGROUND: Dermatologic problems restrict the normal use of a prosthetic limb. The importance of contact dermatitis to skin morbidity in a population of amputees and the selection criteria for patch testing have not been clearly defined. OBJECTIVE: We describe the range of dermatoses seen in a population of amputees and examine the incidence, causes, and patterns of contact dermatitis. METHODS: This is a questionnaire-based, cross-sectional study of 210 amputees. Those with a skin problem were assessed by a dermatologist. Patch testing was undertaken in patients with persistent dermatitis. RESULTS: A total of 34% of amputees experienced a skin problem. Lesions resulting from friction, pressure, and occlusion are common. Allergic contact dermatitis is seen in a third of patients with stump dermatitis. There are no features that distinguish allergic from irritant (chemical or physical) dermatitis. CONCLUSION: Dermatologic problems are common in prosthetic limb users. Allergic contact dermatitis is a significant problem, and all patients with dermatitis on the residual limb should be patch tested.

Occupational dermatoses in composite production.

In a plant that produces fiber-resin composite by impregnation of cellulose fibers with phenol-formaldehyde and melamine-formaldehyde resins, a new technique was introduced that resulted in problems in the handling of uncured products. Many workers suffered dermatitis on areas of exposed skin. A primary investigation found that some workers had an occupationally related skin disease with contact allergy to work materials. We undertook a survey of occupational dermatoses, based on a questionnaire, clinical examination, and patch test with a standard series and a series of products and chemicals representing the work environment. Eighty-eight workers participated in the clinical investigation. In six workers, contact allergy to phenol-formaldehyde resin was seen, and in five workers, contact allergy to melamine-formaldehyde resin was noted. Two workers were allergic to both resins. Occupational dermatitis was diagnosed in nine of 88 (10.2%) workers. In this article, we discuss possible preventive measures for avoiding occupational dermatitis.

Demonstration of the contact sensitizer p-tert-butylcatechol in p-tert-butylphenol formaldehyde resin.

BACKGROUND: In regard to patients hypersensitive to p-tert-butylphenol formaldehyde resin (PTBP-F-R), it is for diagnostic, therapeutic, and preventive reasons necessary to know the identity of the primary sensitizing substances and their sensitizing capacities, as well as their cross-reaction patterns. In patients hypersensitive to PTBP-F-R, we have demonstrated a statistically significant overrepresentation of simultaneous reactions to p-tert-butylcatechol (PTBC). In the guinea pig, we have shown that PTBC is a strong sensitizer, giving cross reactions to p-tert-butylphenol. Furthermore, PTBC cross reacts to the PTBP-F-R monomer 2,6-methylol p-tert-butylphenol, which is a strong sensitizer in the guinea pig. OBJECTIVE: The aim of this study was to investigate the background to the observed simultaneous reactions to PTBP-F-R and PTBC and to see if these could be explained by the presence of PTBC in PTBP-F-R. METHODS: High pressure liquid chromatography (HPLC), nuclear magnetic resonance spectrometry (NMR), mass spectrometry (MS). RESULTS: PTBC was isolated and identified; the concentrations in two resins were determined. HPLC analyses showed the presence of 0.099% and 0.020% wt/wt PTBC, respectively. CONCLUSION: This study shows that PTBC can be present in at least in some brands of PTBP-F-R. The study also indicates that a positive patch test reaction to PTBP-F-R could be an indication of allergy to PTBC, at least in patients with high sensitivity to PTBC. When detecting contact allergies to PTBP-F-R in a patient for whom no clinically relevant exposure to this resin can be found, the possibility of PTBC as the eliciting factor should be considered.

Simultaneous p-tert-butylphenol-formaldehyde resin and p-tert-butylcatechol contact allergies in man and sensitizing capacities of p-tert-butylphenol and p-tert-butylcatechol in guinea pigs.

In patients who are hypersensitive to p-tert-butylphenol-formaldehyde resin (PTBP-F-R), it is necessary, for diagnostic, therapeutic, and preventive reasons, to know the identity of the primary sensitizing substances, their sensitizing capacities, and their crossreaction patterns. The aims of this study were to investigate the presence of a simultaneous p-tert-butylcatechol (PTBC) contact allergy in individuals who were hypersensitive to PTBP-F-R, to investigate the sensitizing capacity of PTBC and p-tert-butylphenol (PTBP) in guinea pigs, and to study any crossreaction patterns. In 294 dermatitis patients tested with PTBP-F-R and PTBC, there was a statistically significant over-representation of simultaneous test reactions. Use of the guinea pig maximization test demonstrated that PTBC is a strong sensitizer giving crossreactions to PTBP. PTBP, however, failed to induce sensitization.

Contact allergy to the monomers of p-tert-butylphenol-formaldehyde resin in the guinea pig.

In patients hypersensitive to p-tert-butylphenol-formaldehyde resin (PTBP-F-R), and butylphenol derivatives therein, it is for diagnostic, therapeutic and preventive reasons necessary to know the identity of the primary sensitizing substances, their sensitizing capacities as well as their cross-reaction patterns. The monomers in PTBP-F-R, 2-methylol p-tert-butylphenol (2-MPTBP) and 2,6-dimethylol p-tert-butylphenol (2,6-MPTBP), have been shown to be contact sensitizers in man. The aim of this study was to investigate the sensitizing capacities of the monomers and establish cross-reacting patterns in the guinea pig with the guinea pig maximization test. 2,6-MPTBP was shown to be a strong sensitizer while it was indicated that 2-MPTBP was a sensitizer. Animals sensitized to 2,6-MPTBP showed cross-reactions to 2-MPTBP and p-tert-butylcatechol. No cross-reactions were shown to p-tert-butylphenol, tert-butyl 4-hydroxyanisole (BHA) and 3,5-di-tert-butyl 4-hydroxytoluene (BHT).