Skincare products containing low concentrations of formaldehyde detected by the chromotropic acid method cannot be safely used in formaldehyde-allergic patients.

BACKGROUND: Formaldehyde is a well-known contact sensitizer. Formaldehyde releasers are widely used preservatives in skincare products. It has been found that formaldehyde at concentrations allowed by the European Cosmetics Directive can cause allergic contact dermatitis. However, we still lack information on whether formaldehyde at low concentrations affects dermatitis in formaldehyde-allergic individuals. OBJECTIVES: To study the effects of low concentrations of formaldehyde on irritant contact dermatitis in formaldehyde-allergic individuals. METHODS: Fifteen formaldehyde-allergic individuals and a control group of 12 individuals without contact allergy to formaldehyde and formaldehyde releasers were included in the study. The individuals performed the repeated open application test (ROAT) during 4 weeks with four different moisturizers releasing formaldehyde in concentrations that had been determined as > 40, 20-40, 2·5-10 and 0 p.p.m. by the chromotropic acid (CA) spot test. Dimethyloldimethylhydantoin was used as a formaldehyde releaser in the moisturizers. The ROAT was performed on areas of experimentally induced sodium lauryl sulfate dermatitis. The study was double blind, controlled and randomized. RESULTS: Nine of the 15 formaldehyde-allergic individuals had reappearance or worsening of dermatitis on the areas that were treated with moisturizers containing formaldehyde. No such reactions were observed in the control group (P < 0·001) or for the moisturizers without formaldehyde in the formaldehyde-allergic individuals (P < 0·001). CONCLUSIONS: Our results demonstrate that the low concentrations of formaldehyde often found in skincare products by the CA method are sufficient to worsen an existing dermatitis in formaldehyde-allergic individuals.

Clinically relevant contact allergy to formaldehyde may be missed by testing with formaldehyde 1·0%.

BACKGROUND: It has been found that patch testing with 15 µL formaldehyde 2·0% aq. detects twice as many allergies as by testing with 1·0%. The clinical relevance of positive patch test reactions is often difficult to determine. Repeated open application tests are simple to do and help to evaluate the significance of patch test results. OBJECTIVES: To study the clinical relevance of contact allergy to formaldehyde detected by 2·0% formaldehyde (0·60 mg cm(-2) ) but not by 1·0%. METHODS: Eighteen patients positive to formaldehyde 2·0% but negative to 1·0%, and a control group of 19 patients with dermatitis but without allergy to parabens, formaldehyde and formaldehyde releasers were included in the study. Formaldehyde 2000 p.p.m., the maximum concentration permitted in leave-on cosmetics according to the EU Cosmetics Directive, was added to a batch of moisturizer preserved with parabens. The same batch without formaldehyde served as a control. The study was double-blinded and randomized. The patients were provided with both moisturizers and instructed to apply one of them twice a day on a marked-out 5 × 5-cm area on the inside of one upper arm and the other moisturizer on the other arm. Reading of the test sites was done once a week for a maximum of 4 weeks. RESULTS: In the control group there were no allergic reactions to either of the moisturizers. Nine of 17 formaldehyde-allergic patients reacted with an allergic reaction to the moisturizer which contained formaldehyde (P < 0·001). No positive reactions were observed to the moisturizer without formaldehyde. CONCLUSIONS: Our results demonstrate that contact allergy to formaldehyde 2·0% may be clinically relevant.

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.

The lipophilic hapten parthenolide induces interferon-gamma and interleukin-13 production by peripheral blood-derived CD8+ T cells from contact allergic subjects in vitro.

BACKGROUND: Peripheral blood mononuclear cells (PBMC) from persons with contact allergy to nickel react in vitro predominantly with nickel-induced CD4+ T cell-mediated production of both T-cell type 1 and 2 cytokines. OBJECTIVES: The aim of the present study was to investigate if the contact allergen parthenolide, a sesquiterpene lactone of lipophilic character, elicits an immune response which differs from that induced by water-soluble nickel ions. PATIENTS AND METHODS: Ten allergic subjects with strong (n = 6), moderate (n = 2), or weak (n = 2) patch-test reactivity to parthenolide and five patch test-negative control subjects participated in the study. PBMC from the subjects were analysed for in vitro reactivity with parthenolide by an enzyme-linked immunospot (ELISpot) assay, measuring cytokine production at the single-cell level. RESULTS: The allergic group, but not the control group, responded to parthenolide with increased numbers of cells producing interferon (IFN)-gamma, interleukin (IL)-2, IL-4, IL-5 (P < 0.05 for all) and IL-13 (P < 0.01). The responses manifested by T-cell type 1 (IFN-gamma and IL-2) and type 2 (IL-4, IL-5 and IL-13) cytokines were positively correlated between cytokines. Subjects with a strong or moderate, but not weak or negative, patch-test reaction displayed detectable in vitro responses. In contrast to the CD4+ T cell-mediated peripheral reactivity induced by nickel, cell depletion experiments identified the parthenolide-reactive IFN-gamma- and IL-13-producing cells as CD8+ T cells. CONCLUSIONS: The finding that the PBMC reactivity to parthenolide in humans involves a CD8+ T cell-mediated type 1 and 2 cytokine response warrants further studies on the relationship between the chemical nature of a hapten and the resulting immune response.

High frequency of contact allergy to gold in patients with endovascular coronary stents.

BACKGROUND: Stent implantation is an effective method for treatment of atherosclerotic disease. Factors predisposing to in-stent restenosis are still largely unknown. Contact allergy to metal ions eluted from the stent has been suggested to be a risk factor. OBJECTIVES: To explore whether there is a possible induction of contact allergy to metals used in stents among patients with a stainless steel stent containing nickel (Ni stent) and patients with a gold-plated stent (Au stent). METHODS: Adults (n = 484) treated with coronary stent implantation participated in the study with patch testing. The study design was retrospective and cross-sectional with no assessment of contact allergy before stenting. Age- and sex-matched patch-tested patients with dermatitis (n = 447) served as controls. RESULTS: Of Au-stented patients, 54 of 146 (37%) were allergic to gold compared with 85 of 447 (19%) controls (P < 0.001). Within the stented population there were no statistically significant differences in contact allergy to gold or nickel between Ni-stented and Au-stented patients. In multivariate models where other risk factors for contact allergy to gold were considered, the Au stent showed a trend towards statistical significance (odds ratio 1.43, 95% confidence interval 0.95-2.16; P = 0.09). CONCLUSIONS: As the frequency of contact allergy to gold is higher in stented patients independent of stent type it suggests a previous sensitization. However, several pieces of circumstantial evidence as well as statistical analysis indicate the possibility of sensitization in the coronary vessel by the Au stent. Ni stents and Au stents should not be ruled out as risk factors for induction of contact allergy to these metals.

Contact allergy to sodium cocoamphoacetate present in an eye make-up remover.

This is a case report of a contact allergic reaction on the face due to a skin cleansing product containing the amphoteric surfactant sodium cocoamphoacetate, occurring in an atopic woman with multiple contact sensitivities. Because of its weak irritant properties, this surfactant is widely used in cosmetic products intended to be used for sensitive skin, including products for intimate, and baby hygiene.

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.

Risk of contact allergy and dermatitis at a wind turbine plant using epoxy resin-based plastics.

AIMS: To identify workplace and individual risk factors for occupational contact allergy and dermatitis. METHODS: A cross-sectional study was carried out at an international company producing wind turbine systems in Denmark. A cohort of 724 production workers at four facilities was highly exposed to epoxy resin as well as other chemicals. A screening questionnaire (participation rate 84.7%) was followed by an interview by an occupational physician and a dermatological examination, including patch testing, for a comprehensive list of potential workplace sensitizers. RESULTS: Clinically diagnosed dermatitis was found among 214 workers (35.8%) and contact allergy to materials used in the workplace was found in 66 workers (10.9% of the total population and 20.3% of those who underwent patch testing). Of the 66 workers with a work-related allergy, 40 (60.6%) were allergic to epoxy compounds, 25 (37.9%) to hardeners and ten (15.2%) to other workplace materials, where one person showed an allergy only to these materials. Experiencing contact allergy was related to older age and longer employment in the workplace-however, neither of these risk factors was significant. The main risk factor for current dermatitis was contact allergy to materials used in the workplace, determined by patch testing, OR=5.4 (95% CI 3.9-9.9). Fewer days of absence from work was also related to current dermatitis, OR=2.0 (95% CI 1.2-3.5). CONCLUSIONS: In a cohort of workers with extensive exposure to chemicals related to epoxy-resin systems, contact dermatitis and allergy was prevalent. Older age and longer duration of employment at the workplace were individual risk factors for allergy to workplace materials, whilst work-related allergies and longer duration of employment at the workplace were significant risk factors for current dermatitis.

Patch testing with methyldibromo glutaronitrile, a multicentre study within the EECDRG.

Contact allergy to and allergic contact dermatitis from methyldibromo glutaronitrile (MDBGN) have frequently been reported. As there has been no agreement on which MDBGN test preparation to use, a study was initiated to help determine the optimal patch test preparation for MDBGN. 2661 consecutively patch tested patients at 11 test clinics representing 9 European countries participated. Petrolatum preparations with MDBGN at 1.0%, 0.5%, 0.3% and 0.1% were inserted in the standard series. Contact allergy rates were noted in the range 4.4-1.1% following decreasing test concentrations. Reactions not fulfilling all criteria to be classified as allergic reactions could represent either weak allergic or irritant reactions, and such reactions were noted in the range 8.2-0.5% with decreasing concentrations. A significant number of these reactions represented weak allergic reactions, as allergic reactions were obtained to higher patch test concentrations in the same individual. Morphologically irritant reactions were noted only for the highest test concentrations. In summary, the contact allergy rates and frequencies of doubtful and irritant reactions vary with the patch test concentration. The final decision on patch test concentration for MDBGN should not only rely on these factors but also include information on patch test concentrations required to diagnose individual cases with allergic contact dermatitis from MDBGN as well as results of repeated open application tests.

Repeated open application test with methyldibromo glutaronitrile, a multicentre study within the EECDRG.

Contact allergy to and allergic contact dermatitis from methyldibromo glutaronitrile (MDBGN) have frequently been reported. This study was initiated to help determine the optimal patch test preparation for MDBGN. In 51 patients with a doubtful or a positive patch test reaction to at least 1 of 4 test preparations with MDBGN in petrolatum at 1.0% w/w, 0.5%, 0.3% and 0.1%, a repeated open application test (ROAT) with moisturizers with and without MDBGN at 0.03% w/w was performed on the upper arms for 2 weeks. 18 of the 51 (35.3%) patients developed a positive ROAT. In all patients, there was a positive ROAT only to the moisturizer with MDBGN (P < 0.001). A statistically significant association was also found between the patch test reactivity (PTRL) and the outcome of the ROAT (P < 0.001). If only considering those with a PTRL above 0.3%, thus with negative or doubtful test reactions to 0.1% and 0.3%, there were still statistically significantly more patients with a positive ROAT to the moisturizer with MDBGN than to the moisturizer without MDBGN. The study demonstrates that patch testing with MDBGN at 0.3% and 0.1% will miss clinically relevant patch test reactions to MDBGN.

Epoxy-based production of wind turbine rotor blades: occupational dermatoses.

Occupational dermatoses were investigated in a factory producing rotor blades for wind turbines by an epoxy-based process. In a blinded study design, 603 workers were first interviewed and thereafter clinically examined. Based on a history of work-related skin disease, clinical findings of dermatitis, or both, 325 (53.9%) of the workers were patch tested with a specially profiled occupational patch-test series and the European standard patch-test series. Calculated on all investigated workers, 17.1% of the workers were diagnosed with occupational dermatoses caused by work. Occupational allergic contact dermatitis was found in 10.9% of the workers. The estimated frequency of irritant contact dermatitis caused by work was 6.1%. Dermatitis on the hands was associated with contact allergy to epoxy resin (P = 0.017). The number of days on leave before the clinical examination was negatively associated with the presence of dermatitis (P = 0.001). Among workers employed 7-12 months, the frequency of occupational contact allergy was higher than that among workers employed for

Methylisothiazolinones elicit increased production of both T helper (Th)1- and Th2-like cytokines by peripheral blood mononuclear cells from contact allergic individuals.

BACKGROUND: Delayed-type hypersensitivity reactions to nickel (Ni2+) in humans are associated with increased production of both T helper (Th) 1- and Th2-like cytokines. Cytokine responses to the major group of contact allergens, i.e. organic compounds, have been less extensively studied. We have investigated here the cytokine production induced by a mixture of methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI), the active ingredients in common preservatives that are capable of eliciting allergic contact dermatitis. OBJECTIVE: To characterize the immune response induced by MCI/MI in terms of the production of Th1- and Th2-like cytokines in peripheral blood mononuclear cells (PBMC) from allergic and non-allergic subjects. METHODS: Ten subjects with a history of contact allergy to MCI/MI and nine age-matched non-allergic volunteers participated. Their actual status was confirmed by patch testing. PBMC were cultured in the presence or absence of MCI/MI; cell proliferation was measured employing [3H]thymidine incorporation; and the number of cytokine-producing cells was determined using the enzyme-linked immunospot (ELISpot) assay and the levels of soluble cytokines in culture media by the enzyme-linked immunosorbent assay (ELISA). RESULTS: The proliferative response of PBMC to MCI/MI was significantly greater in the case of the allergic group than for the non-allergic group, as was the production of interleukin (IL)-2 and IL-13 (as determined by ELISpot and/or ELISA). PBMC from three of the allergic individuals with increased production of IL-2 and IL-13 responded to MCI/MI with elevated numbers of cells producing IL-4 and IL-5. The increases in the production of IL-2, IL-4, IL-5 and IL-13 were positively correlated. CONCLUSION: MCI/MI elicited concomitant production of both Th1- and Th2-like cytokines by PBMC from subjects with contact allergy to these substances. This finding indicates that the organic compounds MCI/MI elicit a mixed Th1- and Th2-type of response, similar to that elicited by the metal ion Ni2+ in Ni2+-sensitized individuals.

Mechanism of the antigen formation of carvone and related alpha, beta-unsaturated ketones.

In the present study, the mechanism for the antigen formation of alpha, beta-unsaturated ketones was investigated. A series of analogues of carvone ((5R)-5-isopropenyl-2-methyl-2-cyclohexenone) with altered chemical reactivity and with retained overall structure or with retained reactivity and altered three-dimensional structure were synthesized. These analogues were tested for cross-reactivity in carvone-sensitized animals. Cross-reactivity was observed for analogue 3 ((5R)-5-isopropyl-2-methyl-2-cyclohexen-1-one). No cross-reactions were observed for analogues 1 ((2R,5R)-5-isopropenyl-2-methyl cyclohexanone) and 4 ((5R)-2,3-dimethyl-5-isopropenyl-2-cyclohexene-1-one). Both those compounds also failed to induce sensitization. These findings demonstrate that alpha, beta-unsaturated ketones form antigens after a nucleophilic attack at the beta-carbon with soft nucleophiles such as thiol in cysteine and not with the formation of a Schiff's base after a nucleophilic attack at the carbonyl carbon with nitrogen nucleophiles. Furthermore, no cross-reactivity was observed between R- and S-carvone indicating the importance of the 3-dimensional structure of haptens (and antigens) in T-cell recognition. The analogues were also tested for cross-reactivity on patients allergic to carvone. The results from the animal study were confirmed.

Standardization of the TRUE Test imidazolidinyl urea and diazolidinyl urea patches.

The preservatives imidazolidinyl urea (IMID, Germall 115) and diazolidinyl urea (DU, Germall II) are commonly used in cosmetic products and are well-known sensitizers. The aim of the present study was to establish the optimal patch test concentration in hydrophilic dried-in vehicle (TRUE Test) for IMID and DU. 181 patients were included in the study. Of these, 150 were patients referred for patch testing, 12 were patients with known allergy to IMID and 19 were patients with known allergy to DU. 76 consecutive patients and the 12 IMID-allergic patients were patch tested with a dilution series IMID (0 to 600 microg/cm(2)), formaldehyde (180 microg/cm(2)) and DU (200 microg/cm(2)). 74 consecutive patients and the 19 DU-allergic patients were patch tested with a dilution series of DU (0 to 600 microg/cm(2)), formaldehyde (180 microg/cm) and IMID (200 microg/cm(2)). A positive dose-response relationship was found. The number of doubtful reactions decreased with increasing test concentrations. No late reactions were observed. A patch test concentration in hydrophilic dried-in vehicle (TRUE Test) of 600 microg/cm(2) was found to be adequate and safe for both IMID and DU.

Stability of corticosteroid patch test preparations.

This study investigated the stability of tixocortol pivalate, budesonide, and hydrocortisone-17-butyrate (Hc-17-B) when present in a mix with petrolatum and when the corticosteroids were kept separately in petrolatum. The concentrations chosen for the corticosteroids were the same as those used in a study within the European Environmental Contact Dermatitis Research Group (EECDRG), in which 2 corticosteroid mixes (1 with a high concentration and 1 with a low concentration) and the 3 individual constituents, each at 2 concentrations, were patch tested. Ethanolic solutions of each corticosteroid, as well as 2 mixtures of these 3 corticosteroids, were also made up at corresponding concentrations. The preparations were kept at room temperature, refrigerated, and deep frozen, and repeatedly for 1 year, investigations to check stability by high performance liquid chromatography were carried out. A decrease of < or =20% of the initial value at time 0 was used as the threshold for stability. The petrolatum preparations and the ethanolic solutions of budesonide and tixocortol pivalate were stable for at least the whole investigative period, irrespective of storage conditions, while Hc-17-B 1.0% in ethanol kept deep frozen was stable at least during the same period. The latter corticosteroid when kept at room temperature was stable for 3 months only.