Marléne Isaksson

Contact allergy to (meth)acrylates in the dental series in southern Sweden: simultaneous positive patch test reaction patterns and possible screening allergens

Contact allergy to dental allergens is a well‐studied subject, more so among dental professionals than dental patients. 1632 subjects had been patch tested to either the dental patient series or dental personnel series at the department of Occupational and Environmental Dermatology, Malmö, Sweden. Positive patch tests to (meth)acrylate allergens were seen in 2.3% (30/1322) of the dental patients and 5.8% (18/310) of the dental personnel. The most common allergen for both groups was 2‐hydroxyethyl methacrylate (2‐HEMA), followed by ethyleneglycol dimethacrylate (EGDMA), triethyleneglycol dimethacrylate, and methyl methacrylate. 47 (29 dental patients and 18 dental personnel) out of these 48 had positive patch tests to 2‐HEMA. All 30 subjects who had a positive reaction to EGDMA had a simultaneous positive reaction to 2‐HEMA. One dental patient reacted only to 2,2‐bis[4‐(2‐hydroxy‐3‐methacryloxypropoxy) phenyl]propane (bis‐GMA). From our data, screening for (meth)acrylate contact allergy with 2‐HEMA alone would have picked up 96.7% (29/30) of our (meth)acrylate‐allergic dental patients and 100% (18/18) of our (meth)acrylate‐allergic dental personnel. The addition of bis‐GMA in dental patients would increase the pick‐up rate to 100%.

Patch testing with corticosteroid mixes in Europe A Multicentre Study of the EECDRG

This study investigated whether a corticosteroid mix containing tixocortol pivalate, budesonide, and hydrocortisone‐17‐butyrate could detect contact allergy to corticosteroids. 2 corticosteroid mixes, 1 with a high (mix I) and 1 with a low (mix II) concentration and the 3 individual constituents, each at 2 concentrations, were inserted into the standard series of 16 participating clinics. Tests were read on day (D) 3 or 4. 5432 patients were tested, and 110 (2.0%) had positive reactions to at least 1 of the 8 test preparations. Of the 8 preparations, mix I identified most allergic patients, followed by mix II, budesonide 0.10%, budesonide 0.002%, and tixocortol pivalate, both concentrations (1.0 and 0.10%) tracing the same number. With the mixes, 53.2–59.6% of tixocortol pivalate allergy was missed. 47 patients were allergic to either concentration of tixocortol pivalate, 25% of these only to 1.0% and another 25% only to 0.10%. Testing with mix I and tixocortol pivalate 0.10% picked up 98/110, testing with tixocortol pivalate 1.0% and 0.10% and budesonide 0.10% picked up 105/110. 3379 patients were read on both D3 or D4 as well as on D7. Without a late reading (D7), up to 30% of contact allergy to corticosteroid markers was missed.

Oral prednisone suppresses allergic but not irritant patch test reactions in individuals hypersensitive to nickel

A multicentre, randomized, double‐blind, crossover study was designed to investigate the effects of prednisone on allergic and irritant patch test reactions. 24 subjects with known allergy to nickel were recruited and patch tested with a nickel sulfate dilution series in aqueous solution, 5% nickel sulfate in petrolatum and 2 dilution series of the irritants nonanoic acid and sodium lauryl sulfate. The subjects were tested ×2, both during treatment with prednisone 20u2003mg oral daily and during placebo treatment. The total number of positive nickel patch test reactions decreased significantly in patients during prednisone treatment. The threshold concentration to elicit a patch test reaction increased and the overall degree of reactivity to nickel sulfate shifted towards weaker reactions. The effect of prednisone treatment on the response to irritants was divergent with both increased and decreased numbers of reactions, although there were no statistically significant differences compared with placebo. It is concluded that oral treatment with prednisone suppresses patch test reactivity to nickel, but not to the irritants tested.

Poor correlation between stated and found concentrations of diphenylmethane-4,4′-diisocyanate (4,4′-MDI) in petrolatum patch-test preparations

Diphenylmethane diisocyanate (MDI) is widely used in its polymeric form in the manufacturing of polyurethane products. Previous reports on MDI‐related contact allergy have shown a pattern, where patients seem to react to their own MDI‐based work material but not to commercial patch‐test preparations, which contain 4,4′‐MDI. Therefore, we performed chemical analyses of 14 commercial test preparations of 4,4′‐MDI obtained from 8 European and 4 American dermatology departments as well as 2 preparations from 2 major European suppliers of patch‐test allergens. A new method for monitoring 4,4′‐MDI in petrolatum preparations was developed and the determination of 4,4′‐MDI as the MDI‐dibutylamine derivative using liquid chromatography‐mass spectrometry was performed. None of the preparations obtained from the dermatology departments contained more than 12% of the concentration stated on the label. In most cases, 4,4′‐MDI content was only a few percentages or less of the concentration stated. 7 of the 14 preparations were analysed before the expiry date. Yet, only 1 of them, a preparation directly obtained from the supplier, came close to the concentration stated on the label. Thus, using these preparations, patients will be tested with a lower concentration than intended, leading to possible false‐negative reactions.

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 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.

How to optimize patch testing with diphenylmethane diisocyanate

We have previously shown that patch test preparations of polymeric diphenylmethane diisocyanate (PMDI) are more stable than preparations of diphenylmethane‐4,4’‐diisocyanate (4,4’‐MDI). This study was conducted to (i) investigate whether PMDIs yield as many positive reactions as 4,4’‐MDI, (ii) study concurrent reactions to 4,4’‐MDI and 4,4’‐diaminodiphenylmethane (4,4’‐MDA), and (iii) follow the course of positive reactions during 4 weeks. It was shown that PMDIs detect as many positive reactions as 4,4’‐MDI. Thus, they are better patch test agents being more stable than preparations of 4,4’‐MDI. We recommend that PMDIs with a monomer content of at least 35% is used in 2.0% petrolatum (pet.) (i.e. monomer patch test concentration approximately 0.7%). It was shown that reactions to 4,4’‐MDI and PMDIs appear late and we recommend readings on both day (D) 3/4 and D7. 4,4’‐MDA was shown to be a good marker for 4,4’‐MDI and patch testing with 4,4’‐MDA in 0.25% pet. can be used instead of PMDI. Concomitant reactions to 4,4’‐MDI and 4,4’‐MDA are probably not caused by conversion of 4,4’‐MDI into 4,4’‐MDA by reaction with water. Another explanation is a path of reactions leading to ureas and MDI conjugates with skin constituents, which are hydrolysed into 4,4’‐MDA. This complex process depends upon several factors and might explain why positive MDI reactions appear after D7.

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.

Contact allergy to acrylates/methacrylates in the acrylate and nail acrylics series in southern Sweden: simultaneous positive patch test reaction patterns and possible screening allergens.

In a recent study we showed that all our dental personnel/patients were detected with 2‐hydroxyethyl methacrylate (2‐HEMA) and 2,2‐bis[4‐(2‐hydroxy‐3‐methacryloxypropoxy)phenyl]propane (bis‐GMA). We studied 90 patients tested to the acrylate and nail acrylics series at our department over a 10 year period to see whether screening allergens could be found. Patch testing with an acrylate and nail acrylics series was performed. Among the 10 acrylate/methacrylate‐allergic occupational dermatitis patients tested to the acrylate series, the most common allergens were triethyleneglycol diacrylate (TREGDA, 8), diethyleneglycol diacrylate (5), and 1,4‐butanediol diacrylate (BUDA, 5). All 10 of these patients would have been picked up by a short screening series combining TREGDA, 2‐hydroxypropyl methacrylate (2‐HPMA), and BUDA or 1,6‐hexanediol diacrylate (HDDA). Among the 14 acrylate/methacrylate‐allergic nail patients, the most common allergens were ethylene glycol dimethacrylate (EGDMA, 11), 2‐HEMA, (9), and triethyleneglycol dimethacrylate (9). Screening for 3 allergens i.e. 2‐HEMA plus EGDMA plus TREGDA, would have detected all 14 nail patients. A short screening series combining 2‐HEMA, EGDMA, TREGDA, 2‐HPMA, bis‐GMA, and BUDA or HDDA would have picked up all our past study patients (dental, industrial, and nail) with suspected allergy to acrylate/methacrylate allergens.

The development and course of patch-test reactions to 2-hydroxyethyl methacrylate and ethyleneglycol dimethacrylate

Because Methacrylic monomers are used in dental work, dental personnel, technicians, and patients are at risk of being sensitized. 2‐hydroxyethyl methacrylate (2‐HEMA) and ethyleneglycol dimethacrylate (EGDMA) are commonly used. Allergic test reactions to them sometimes appear beyond D7. This study was designed to study the development and course of positive test reactions to 2‐HEMA and EGDMA in allergic patients as a mean to elucidate the issue of patch‐test sensitization. 12 patients with contact allergy to 2‐HEMA and EGDMA were retested with dilution series. The clinical course was followed for 1 month. During the study, 25 positive test reactions to 2‐HEMA and 19 to EGDMA were diagnosed. Within the 1st week, 21 were noted for 2‐HEMA and 18 for EGDMA. After 10 days, another 2 reactions appeared for 2‐HEMA and 1 for EGDMA. All but 1 patient with the latter reactions also had positive reactions within the 1st week. After 1 month, 12 reactions for 2‐HEMA and 10 for EGDMA remained. Patch‐test reactions to 2‐HEMA and EGDMA are long‐lasting. The patch‐test concentrations of 2.0% for 2‐HEMA and EGDMA may be continually used. Positive test reactions emerging after 10 days do not automatically imply active sensitization.

Chemical investigations of disperse dyes in patch test preparations

Background:u2002 Contact allergy to textile dyes is not uncommon. The allergy is detected by patch testing patients with commercial patch test preparations.