Active sensitization to dimethylthiocarbamylbenzothiazol sulphide: An unexpectedly strong rubber contact allergen.

BACKGROUND: The two dialkylthiocarbamyl benzothiazole sulphides, dimethyl-thiocarbamylbenzothiazole sulphide (DMTBS) and diethylthio-carbamylbenzothiazole sulphide (DETBS) were shown to be good markers of both thiuram and mercaptobenzothiazole sensitivity. OBJECTIVES: To investigate if DMTBS and/or DETBS could be better markers of contact allergy to common rubber additives than the ones currently used. METHODS: Sixty-eight dermatitis patients were patch tested with DMTBS and DETBS, both at 1% in petrolatum (pet). Because of late reactions in 10 patients, these were retested to DMTBS and DETBS in serial dilutions. Tetramethylthiuram monosulphide (TMTM) 1.0% pet was also tested. RESULTS: At the initial reading Days 3 and 7, no reactions were noted to DMTBS or DETBS. At retesting, 10 of the 68 (15%) patients reacted positively to lower concentrations of DMTBS than the initial test concentration. Seven of 8 also reacted to TMTM. Three of them had positive reactions to DEBTS. All 10 patients had reactions to more diluted solutions to DMBTS than to DEBTS (p = 0.0077; Mc-Nemar test, two-sided). CONCLUSIONS: Results speak for patch test sensitization to DMTBS with cross-reactivity to TMTM and also DEBTS. DMTBS and DEBTS could be new markers of rubber allergy but a safe test concentration must be found.

Contact allergy to oxidized linalool and oxidized limonene: Patch testing in consecutive patients with dermatitis.

BACKGROUND: Contact allergy to oxidized (ox.) linalool and ox. limonene has been reported to have a high prevalence, raising the question of inclusion into the baseline series. However, several important issues should be clarified and further investigated before inclusion can be warranted. OBJECTIVES: To report the trends of ox. terpenes allergy in patients with dermatitis, features of the patch test reactions, and clinical characteristics of the patients. METHODS: A retrospective analysis of 5773 patients was performed. All patients were patch tested with baseline series, individual ingredients of fragrance mix I and II, ox. linalool, and ox. limonene from 2013 to 2020. RESULTS: The prevalence rates of contact allergy to ox. linalool and ox. limonene were 7.0% and 5.1%, respectively. Significantly increasing trends of contact allergy were observed. More than 95% of contact allergy cases were identified on Day 3/4. Patients with contact allergy to ox. linalool and ox. limonene were significantly younger than those with contact allergy to other fragrances and were predominantly female. Strong reactions were associated with older age and multiple fragrance allergies. CONCLUSIONS: Contact allergy to ox. linalool and ox. limonene is becoming increasingly important, and findings show intriguing features. More studies concerning the clinical relevance before recommending these substances for screening are required.

Skin Exposures, Hand Eczema and Facial Skin Disease in Healthcare Workers During the COVID-19 Pandemic: A Cross-sectional Study.

The COVID-19 pandemic has led to enhanced hygiene procedures and use of personal protective equipment, but also to increased attention to occupational skin disease in healthcare workers. The occurrence of hand and facial skin disease in > 5,000 Swedish healthcare workers was investigated in a questionnaire survey. Levels of skin exposure related to hygiene procedures and personal protective equipment were recorded. Caring for patients with COVID-19 entailed higher levels of wet work and face mask exposures, and was associated with higher 1-year prevalence of both hand eczema (36%) and facial skin disease (32%) compared with not being directly engaged in COVID-19 care (28% and 22%, respectively). Acne and eczema were the most common facial skin diseases; for both, a dose-dependent association with face mask use was found. Dose-dependent associations could be shown between hand eczema and exposure to soap and gloves, but not to alcohol-based hand disinfectants.

Contact allergy to polyhexamethylene biguanide (polyaminopropyl biguanide).

BACKGROUND: Polyaminopropyl biguanide (INCI name) and polyhexamethylene biguanide (PHMB) are polymeric biguanides. PHMB is a broad-spectrum antimicrobial substance used as a preservative in many products. Due to our limited knowledge on PHMB contact allergy frequency and the fact that cases of allergic contact dermatitis to PHMB might be missed, we have included PHMB as a screening allergen since 2016. OBJECTIVE: To report the prevalence of positive patch test reactions to PHMB as a screening allergen in patients with suspected allergic contact dermatitis. METHODS: A retrospective analysis of 1760 patch tested patients from July 2016 to December 2018 was performed. Polyaminopropyl biguanide 2.0% aqua was included in the extended Malmö baseline series during the study period. RESULTS: Of all patients, 1204 (68.4%) were female. Positive patch test reactions were reported in 19 patients (1.1%). The most common sites of lesions were face, head, and neck (52.6%). There was a significant correlation between concomitant reactions to PHMB and other cosmetic-related allergens. CONCLUSION: The prevalence of positive reactions to PHMB was higher than that previously reported. Patch testing with PHMB should be performed in patients with dermatitis who have lesions on the face, head, and neck.

Patch testing with a textile dye mix with and without Disperse Orange 3.

BACKGROUND: The textile dye mix (TDM) 6.6% pet. 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 p-phenylenediamine (PPD)-allergic dermatitis patients have shown positive patch test reactions to DO 3. There has been a discussion to exclude DO 3 from TDM 6.6% because of frequent, strong reactions to TDM 6.6% and PPD. OBJECTIVES: To study if DO 3 can be omitted from a TDM. METHODS: Patch tests were performed on 2250 dermatitis patients with TDM 6.6%, TDM 5.6% pet., TDM 7.0% pet., and PPD 1.0% pet.; 122 patients were also patch tested with DO 3 1.0% pet. RESULTS: Among the 2250 patients patch tested, contact allergy prevalence to TDM 6.6% was 2.4%, to TDM 5.6% 1.8%, and to TDM 7.0% 2.0%. Of the 54 TDM 6.6%-positive patients, 55.6% reacted to PPD; as much as 42.2% of PPD-allergic women and 50% of PPD-allergic men reacted to TDM 6.6%. Of the 17 DO 3-positive patients, 94.1% showed a positive reaction to PPD. CONCLUSION: Results indicate that DO 3 can probably be omitted from TDM, but patch testing with TDM 6.6%, TDM 7.0%, DO 3 1.0%, and PPD 1.0% simultaneously is needed to finally decide whether it is possible or not.

Prevalence of contact allergy to metals: nickel, palladium, and cobalt in Southern Sweden from 1995-2016.

BACKGROUND: In 2001, the EU nickel directive was introduced to prevent contact allergy to nickel. Contact allergy to palladium and/or cobalt is often seen together with contact allergy to nickel. OBJECTIVES: To compare the contact allergy prevalence of nickel, palladium, and cobalt allergy before and after the introduction of the EU nickel directive in consecutive patients with dermatitis. METHODS: A retrospective analysis of patch test results from 1995-2016 was performed (n = 18 264). Chi-square tests were used to examine trends for nickel, palladium, and cobalt across test years. Logistic regression was used for associations. RESULTS: The prevalence of nickel allergy decreased significantly in the youngest age group (6-30 years) for both female and male patients from 1995-1999 to 2012-2016: females: 33.4% to 19.1% (P < .001); males: 5.9% to 2.1% (P < .05). The concomitant reactions between nickel and palladium and nickel and cobalt among young females, respectively, also decreased significantly. Isolated palladium and cobalt allergy remained stable (1.4% and 2.3%, respectively) during the same time period for both men and women. CONCLUSIONS: The prevalence of nickel has decreased among young females and males suspected of contact allergy in Southern Sweden after the introduction of the EU nickel directive. There has been no change in isolated palladium or cobalt allergy.

Skin exposure to the rubber accelerator diphenylguanidine in medical gloves-An experimental study.

BACKGROUND: Dermatitis caused by occupational contact allergy to rubber additives such as diphenylguanidine (DPG) in medical gloves is a hazard for healthcare workers. Both the duration of exposure to medical gloves and the number of gloves used per day vary. The use of alcoholic skin disinfectants before glove donning is mandatory. OBJECTIVES: To assess whether skin exposure to the rubber accelerator DPG released from glove material is influenced by alcoholic hand disinfectants, time, and pH. METHODS: With the use of ethanol washes, the amount of DPG left on the hands after wearing of gloves for 60 minutes was measured, and comparisons between hands exposed and not exposed to alcoholic disinfectant before glove donning were made. With the use of artificial sweat buffered at pH 4, 5, and 6, DPG release from the insides of gloves at different times was measured. RESULTS: The use of alcoholic disinfectant prior to polyisoprene glove donning increased the amount of DPG recovered from the hands. Of the DPG released from polyisoprene gloves into artificial sweat, almost 84% was released within 10 minutes. pH did not influence the rate of release. CONCLUSIONS: The use of alcoholic disinfectant increased skin exposure to the rubber accelerator DPG. Even a short duration of use of gloves results in substantial exposure to DPG.

N,N-dimethylacrylamide-A new sensitizer in the FreeStyle Libre glucose sensor.

BACKGROUND: Isobornyl acrylate (IBOA) has recently been identified as one sensitizer in the FreeStyle Libre glucose sensor. Analyses with gas chromatography-mass spectrometry (GC-MS) have indicated the presence of N,N-dimethylacrylamide (DMAA) in the sensor. MATERIAL AND METHODS: Seven patients were referred for patch testing after developing skin reactions when using FreeStyle Libre. All patients were patch tested with IBOA and DMAA. Two patients were tested with adhesive patches that had been removed from the sensors "as is," and two patients were tested with acetone extracts of materials from the sensor. The extracts were analysed with GC-MS. RESULTS: Six patients reacted to both IBOA and DMAA, and one patient reacted only to DMAA. Positive reactions were also observed in both patients tested with the adhesive patch "as is". One patient reacted to both an extract of the adhesive patch and an extract of the sensor itself. When analysed with GC-MS, IBOA was found in both extracts and DMAA was found in the extract of the sensor. CONCLUSION: Both IBOA and DMAA may be present in adhesives used in medical devices such as glucose sensors or insulin pumps, and should be patch tested when suspected contact allergic reactions to these products are investigated.

Hand eczema and occupational contact allergies in healthcare workers with a focus on rubber additives.

BACKGROUND: Hand eczema (HE) in healthcare workers (HCWs) is common. Besides wet work, healthcare work also implies exposure to contact allergens. OBJECTIVES: To assess HE and contact allergy related to occupational exposures in HCWs. METHODS: In a cross-sectional study, 311 HCWs with HE within the preceding 12 months and a control group of 114 HCWs without HE were investigated with the baseline series and a special patch test series based on substances found in the gloves, soaps, alcoholic hand disinfectants and hand creams provided at the hospitals. RESULTS: Contact allergy to rubber additives was significantly more common in HCWs with HE (6%) than in HCWs without HE (1%, P = .02). The corresponding percentages for fragrances were 11% and 3%, respectively (P = .004). Occupational HE was found in 193 of 311 (62%) HCWs. Of these, 22 of 193 (11%) had occupational allergic contact dermatitis, including 17 with glove-related rubber contact allergy. Contact allergy to diphenylguanidine was as common as contact allergy to thiurams. Occupational contact allergy to rubber additives was significantly associated with sick-leave related to HE. CONCLUSION: Contact allergy to rubber additives in medical gloves is the most common cause of occupational allergic contact dermatitis in HCWs. Aimed patch testing with relevant rubber additives is mandatory when HE in HCWs is investigated.

A retrospective investigation of hexavalent chromium allergy in southern Sweden.

BACKGROUND: Historically, allergic contact dermatitis caused by hexavalent chromium [Cr(VI)] in cement was the most common cause of invalidity attributable to skin disease in Sweden. Since the legislation to reduce Cr(VI) in cement was introduced in 1989, we rarely see allergic contact dermatitis caused by cement. OBJECTIVES: To examine the frequency of contact allergy to Cr(VI) in southern Sweden in 2005-2014. METHODS: We investigated the occurrence of positive reactions to potassium dichromate 0.5% pet. in consecutively tested dermatitis patients, and compared the occurrence of atopic dermatitis, localization of dermatitis and simultaneous positive reactions to cobalt chloride and nickel sulfate in the Cr(VI)-positive patients with those in a group of patients with a similar age and sex distribution. RESULTS: In total, 6482 patients were tested, and 233 Cr(VI)-allergic individuals were found (3.6%). A significantly higher proportion of atopic dermatitis was found among Cr(VI)-allergic patients, and a significantly higher share of foot dermatitis was found among Cr(VI)-allergic women, than among controls. Cr(VI) allergy was less likely when both nickel allergy and cobalt allergy were present. CONCLUSION: A relatively high frequency of contact allergy to Cr(VI) was found. The cause has shifted from cement exposure to other exposures, probably mainly leather.

Simultaneous patch testing with fragrance mix I, fragrance mix II and their ingredients in southern Sweden between 2009 and 2015.

BACKGROUND: Fragrance mix I (FM I) and fragrance mix II (FM II) are included in the European baseline series as screening substances for fragrance contact allergy. OBJECTIVES: To investigate the frequency of allergic reactions to FM I, FM II and their ingredients in consecutively patch tested patients. MATERIALS AND METHODS: A retrospective analysis of data from 4430 patients patch tested between 2009 and 2015 was performed. RESULTS: Of the patients, 6.5% were FM I-positive and 3.2% were FM II-positive. Forty-five per cent of FM I-positive patients did not have positive reactions to FM I ingredients. Thirty-five per cent of those who were FM II-positive did not have positive reactions to FM II ingredients. Twenty-seven per cent of those with positive reactions to one or more of the FM I ingredients were FM I-negative, and 36% of those who had positive reactions to one or more of the FM II ingredients were FM II-negative. The allergens with the highest pick-up rates were Evernia prunastri (1.8%), cinnamal (1.3%), citral (1.2%), and hydroxyisohexyl 3-cyclohexene carboxaldehyde (1.2%). Significant differences were observed in the proportions of positive reactions to FM I, FM II, eugenol, isoeugenol, and farnesol when results from patch testing with materials from different suppliers were compared. CONCLUSIONS: There is a risk of missing fragrance contact allergy when testing with only the fragrance mixes is performed. The use of preparations from different suppliers may affect the patch test results.

Chromate and amine contact allergies in workers manufacturing precast concrete elements.

BACKGROUND: Five workers from a plant manufacturing concrete wall panels and beams were referred to our department because of suspected occupational dermatitis. When patch tested, 3 workers reacted to potassium dichromate. Four workers reacted to ethylenediamine dihydrochloride, without any obvious exposure. Owing to the high proportion of workers with recent-onset skin disease, an investigation of all workers at the plant was initiated. OBJECTIVES: To investigate the prevalence of occupational dermatitis and contact allergy in the workers at the plant. METHODS: All 24 workers at the plant underwent a clinical investigation and were patch tested. RESULTS: Four cases of allergic occupational contact dermatitis and 3 cases of irritant occupational contact dermatitis were diagnosed. Contact allergy to potassium dichromate was found in 4 workers. All 4 also reacted to ethylenediamine dihydrochloride and/or amines that were present as additives in the cement. CONCLUSIONS: Chromate contact allergy can still be found in concrete workers, despite the legislation regulating the amount of hexavalent chromium (chromate) in cement. Occupational contact allergy to amines can be found in workers exposed to cement and concrete, so amines should be tested in these workers.

Concomitant contact allergies to formaldehyde, methylchloroisothiazolinone/methylisothiazolinone, methylisothiazolinone, and fragrance mixes I and II.

BACKGROUND: Contact allergies to the preservatives formaldehyde and methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI) have been reported to appear together at a statistically significant level. Recently, revisions concerning the patch test preparations of MCI/MI, MI and formaldehyde have been recommended for the European baseline series. AIM: To investigate (i) the number of concomitant contact allergies to the preservatives, (ii) the number of concomitant contact allergies to the preservatives and the fragrance mixes (FM I and FM II) and (iii) gender differences. METHODS: Patients tested with the Swedish baseline series during the period 2012-2014 at the Department of Occupational and Environmental Dermatology in Malmö, Sweden were investigated. RESULTS: 2165 patients were patch tested with the baseline series (34% males and 66% females). Contact allergies to formaldehyde and MCI/MI and/or MI were significantly associated (p < 0.001). The associations between contact allergy to MCI/MI and/or MI and FM I and/or FM II, and between formaldehyde and FM I and/or FM II as well as, were statistically significant (p < 0.001). CONCLUSION: Contact allergies to formaldehyde and MCI/MI and/or MI are significantly associated, as well as contact allergies to these preservatives and fragrance allergy. Males and females do not differ significantly concerning contact allergy to fragrances.

Formaldehyde in cosmetics in patch tested dermatitis patients with and without contact allergy to formaldehyde.

BACKGROUND: Formaldehyde is a well-known contact sensitizer. Formaldehyde releasers are widely used preservatives in cosmetics. OBJECTIVES: To survey the release of formaldehyde in cosmetics brought by patients investigated because of suspected allergic contact dermatitis, to compare it with information given by the manufacturers on the packages, and to investigate whether formaldehyde-allergic patients are potentially exposed to more cosmetics releasing formaldehyde than dermatitis patients without contact allergy to formaldehyde. PATIENTS/METHODS: Cosmetics from 10 formaldehyde-allergic and 30 non-allergic patients (controls) matched for age and sex were investigated with the chromotropic acid spot test, which is a semiquantitative method measuring the release of formaldehyde. RESULTS: Formaldehyde was found in 58 of 245 (23.7%) products. Twenty-six of 126 (20.6%) leave-on products released formaldehyde, and 17 of 26 (65.4%) of these were not declared to contain formaldehyde or formaldehyde releasers. Among the rinse-off products, there were 32 of 119 (26.8%) formaldehyde-releasing products, and nine of 32 (28.0%) of these were not labelled as containing formaldehyde or formaldehyde releasers. Five of 10 formaldehyde-allergic patients brought leave-on products with ≥ 40 ppm formaldehyde, as compared with 4 of 30 in the control group (p = 0.029). CONCLUSIONS: Cosmetic products used by formaldehyde-allergic patients that are not declared to contain formaldehyde or formaldehyde-releasing preservatives should be analysed.

Methylisothiazolinone contact allergy is rising to alarming heights also in southern Sweden.

The preservative methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) is a well-known sensitiser and present in most baseline series since at least 20 years. The proportions of MCI/MI are 3:1. MI alone has been used as a preservative in occupational and household products, and cosmetics since less than 10 years. MCI/MI tested at 100 ppm fails to detect a significant percentage of contact-allergic reactions to MI. Our aim was to investigate whether a separate test preparation with MI picks up additional cases of contact allergy to MI not detected with MCI/MI 200 ppm. MI was inserted into the baseline series of the Malmö clinic in 2003 starting at 475 ppm, then 900 ppm, then 1,000 ppm, 1,500 ppm and finally 2,000 ppm. In 5,881 consecutively tested dermatitis patients the contact allergy rate for MI varied between 0.5 and 6.5%, with a marked increase in recent years. The contact allergy rate to MI 2,000 ppm alone, not traced by MCI/MI 200 ppm, varied between 0 and 1.9 %. In conclusion, due to the increase of contact allergy to MI not traced by MCI/MI 200 ppm, MI in water at 2,000 ppm should be tested in a baseline series. Independent of patch test technique a dose of 60 µg/cm should not be exceeded to avoid adverse reactions and particularly patch test sensitisation.

Reaction profile in patch testing with allergens formed during vulcanization of rubber.

BACKGROUND: Vulcanization of rubber changes its allergen pattern. OBJECTIVES: To estimate the contact allergic reactivity profile of users of finished rubber products. METHODS: Twenty-four patients with known contact allergy to rubber accelerators were patch tested with 21 compounds found in chemical analyses of vulcanized rubber products. No diphenylguanidine, p-phenylenediamine antioxidants or thioureas were included in the study. RESULTS: Thiuram monosulfides formed during vulcanization showed generally stronger test reactions than the corresponding thiuram disulfides. We also obtained more positive thiuram reactions to the monosulfides than to the disulfides. A positive reaction to a dithiocarbamate was accompanied by a positive reaction to the corresponding thiuram, except for 1 patient. The nitrogen substituents showed only minor differences between the methyl, ethyl and pentamethylene groups, but the butyl derivatives gave, in most cases, a negative response. Dialkylthiocarbamyl benzothiazole sulfides, formed between thiurams and mercaptobenzothiazoles during vulcanization, showed strong test reactions in almost all patients who were sensitive to dithiocarbamates, thiurams, or mercaptobenzothiazoles. CONCLUSIONS: We found thiuram monosulfides to be better markers of thiuram sensitivity than the corresponding disulfides or dithiocarbamates. Surprisingly, the dialkylthiocarbamyl benzothiazole sulfides were good markers of both thiuram and mercaptobenzothiazole sensitivity. This is an unexpected finding that needs to be confirmed in a larger study.

Prevalence, incidence and predictive factors for hand eczema in young adults - a follow-up study.

BACKGROUND: Hand eczema is common in the general population and affects women twice as often as men. It is also the most frequent occupational skin disease. The economic consequences are considerable for society and for the affected individuals. METHODS: To investigate the prevalence and incidence of hand eczema and to evaluate risk factors for development of hand eczema in young adults. Subjects and methods; This is a prospective follow-up study of 2,403 young adults, 16 - 19 years old in 1995 and aged 29 - 32 years, 13 years later, in 2008. They completed a postal questionnaire that included questions regarding one-year prevalence of hand eczema, childhood eczema, asthma, rhino-conjunctivitis and factors considered to affect hand eczema such as hand-washing, washing and cleaning, cooking, taking care of small children and usage of moisturisers. These factors were evaluated with the multinominal logistic regression analysis. RESULTS: The one-year prevalence of hand eczema was 15.8% (females 20.3% and males 10.0%, p < 0.001). The incidence was 11.6 cases per 1000 person-years (females 14.3 and males 5.2, p < 0.001). Childhood eczema was the most important risk factor for hand eczema. The odds ratios were 13.17 when having hand eczema 1995 and 2008 compared to 5.17 in 2008 (p < 0.001). A high frequency of hand washing was important in predicting hand eczema only when having 1-year prevalence 2008, OR 1.02 (p = 0.038). CONCLUSIONS: After 13 years an increased 1-year prevalence of hand eczema was found. The significant risk factors for hand eczema changed over time from endogenous to exogenous factors.

Recommendation to include formaldehyde 2.0% aqua in the European baseline patch test series.

BACKGROUND: The currently used patch test concentration of formaldehyde (1.0% aqua; 0.30 mg/cm(2)) has been shown to fail to detect ~ 50% of contact allergies to formaldehyde. OBJECTIVES: To justify the inclusion of formaldehyde 2.0% aqua (0.60 mg/cm(2)) in the European baseline patch test series. METHODS: A survey of the reported frequencies of contact allergy to formaldehyde found with formaldehyde 2.0% aqua as compared with 1.0% aqua was performed. Studies that describe a standardized patch test technique for obtaining a correct dose per unit area were included. Experimental provocation tests in patients with contact allergy to formaldehyde detected only with 2.0% aqua were also surveyed. RESULTS: In a multicentre study performed in 12 dermatology clinics among 3591 individuals, 3.4% reacted to 2.0%, and 1.8% reacted to 1.0% (p < 0.001). A randomized double-blind repeated open application test performed in individuals reacting only to 2.0% but not to 1.0% showed that 9 of 17 formaldehyde-allergic individuals reacted to a moisturizer that contained formaldehyde (p < 0.001). CONCLUSIONS: It is recommended that formaldehyde 2.0% aqua (0.60 mg/cm(2)) should replace formaldehyde 1.0% in the European baseline series from 2014. With the Finn Chamber(®) technique, a standardized amount of 15 µl of the solution obtained by using a micropipette should be used.