Corticosteroid contact allergy--the importance of late readings and testing with corticosteroids used by the patients.
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Biomedical subjects
Publications and source records attributed to Marléne Isaksson.
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The elicitation of a positive patch test reaction in a given individual depends upon the dose of the sensitizer applied, the patch test technique and the occlusion time. The dose is determined by the concentration and volume/amount of test preparation applied. If the same amount/volume of a test preparation is applied all the time with the same test technique (same area of skin) and occlusion time, it is appropriate to use concentration as a dose parameter. Most contact sensitizers are incorporated in petrolatum (pet.). With pet. as vehicle, it is impossible to repeatedly apply an exact volume/amount. This study was performed to investigate the inter- and intra-individual variation of pet. preparation applied at patch testing by 3 technicians. Weighing demonstrated that the 3 technicians had about the same precision in their pet. application. The investigation demonstrates that there is both an inter-individual (statistically significant) and intra-individual variation in the amounts of pet. applied at patch testing for the 3 technicians. Presently, there is no recommendation on what amount of pet. preparation to apply, which merits a decision to be taken based on thorough investigations on the appropriate volumes of pet. preparation to be applied in various patch test systems.
We have previously shown that the concentration of diphenylmethane-4,4'-diisocyanate (4,4'-MDI) in commercial test preparations was so low that patch testing with the same was not reliable. The stability of 4,4'-MDI in petrolatum (pet.) was compared with pet. preparations of polymeric diphenylmethane diisocyanate (PMDI), which consists of a complex mixture of monomeric isomers and oligomers of MDI. Preparations of 4,4'-MDI and PMDI were stored under 3 different conditions, i.e. at room temperature, refrigerated and frozen. They were analysed continuously during 1 year with regard to the content of 4,4'-MDI, 3-ring oligomers and 4-ring oligomers using liquid chromatography-mass spectrometry. PMDI preparations kept frozen were stable for a year. All other preparations failed to fulfil the requirements of stability, i.e. +/-20% of the initial concentration. Storage in a freezer prolonged the lifetime for 4,4'-MDI. The decrease in concentration for preparations kept at room temperature and refrigerated was less rapid in PMDI preparations than in 4,4'-MDI preparations. PMDI preparations are better suited for patch testing patients exposed to MDI because they are more stable and homogeneous than 4,4'-MDI preparations. They better reflect possible allergens that workers are exposed to because products used in industry contain both monomers and oligomers.
A topical corticosteroid preparation on the Swedish market, Flutivate cream, contains a fairly high concentration of formaldehyde (FA). In this study, we have investigated the clinical relevance of contact allergy to FA when treating an allergic eczema with Flutivate cream, containing an FA-releasing preservative. In a randomized, double-blind study, 7 patients hypersensitive to both FA and nickel repeatedly applied Flutivate cream containing FA or Betnovate cream not containing FA to areas of experimentally induced nickel dermatitis. 17 controls allergic to nickel, but not FA, went through the same procedure. In 29 per cent of the FA-allergic individuals, the experimental dermatitis healed when treated with Flutivate cream compared with 71 per cent of the controls (P = 0.04). The conclusion to draw from this study is that an individual hypersensitive to FA should not use the corticosteroid preparation Flutivate cream on dermatitis skin.
The aim of this study was to evaluate the validity of a questionnaire and medical anamnesis to identify persons with dermatitis in an occupational setting. The design was a clinical epidemiological cross-sectional study. The study was performed between the second and fourth week of January 2001. A questionnaire was followed a week later by a medical occupational interview and a clinical dermatological examination, including a comprehensive patch test with potential workplace chemicals. The anamnesis and the clinical examination were made independently by occupational and dermatological physicians, and the skin examination was performed blinded to anamnestic data. The setting was the mother plants of a Danish-based international company producing wind turbine systems. The study population was a workplace cohort, highly exposed to epoxy resin systems and other chemicals, and totalled 724 production workers at 4 facilities. The rate of participation was 84.7%. Using enquete questions of current skin rash against the clinical presence of dermatitis, we found a sensitivity of 22% and a specificity of 89%, compared to 45% and 87%, respectively, when the anamnestic work history, taken by an occupational physician, was the screening parameter. Using 'workplace periodic prevalence' of dermatitis, we found sensitivities in the range of 63-76% by a questionnaire and 70-83% by medical anamnesis. Questionnaire screening by skin symptoms gave the highest values for redness, a sensitivity of 33% and a specificity of 76%, and decreasing validity parameters as more symptoms were added to the list of screening questions. We found that the use of a questionnaire and medical anamnesis were problematic, when the purpose was screening for contact dermatitis and allergy, in this industrial cohort manufacturing reinforced plastic products. But these instruments might be useful for epidemiological surveillance, when the questionnaire has been validated in the given occupational setting.
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%.
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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.
BACKGROUND: Isocyanates with the general formula R-(N=C=O) are theoretically contact sensitizers. However, allergic contact dermatitis (ACD) from isocyanates is seldom reported. In previous reports, patients reacted to their isocyanate-based work materials but not to commercial patch-test preparations of isocyanates. Therefore, we suspected that the low frequency of reported ACD from isocyanates was partly due to inadequate commercial preparations. A past study also showed the concentrations of diphenylmethane-4,4'-diisocyanate (4,4'-MDI) in petrolatum preparations to be much lower than declared. OBJECTIVE: In this study, 2,4-toluene diisocyanate (2,4-TDI), 1,6-hexamethylene diisocyanate (1,6-HDI), and isophorone diisocyanate (IPDI) were investigated in a similar fashion. METHODS: In preparations from 12 dermatology departments and two suppliers of patch-test allergens, we determined the isocyanate content as the isocyanate-dibutylamine derivative, using liquid chromatography and mass spectrometry. The preparations were considered stable if the ratio between the stated and found concentrations was within the range of 0.8 to 1.2. RESULTS: Although 28 of 36 investigated preparations had ratios outside of the stable range, they were in its vicinity, which indicates that preparations of 2,4-TDI, 1,6-HDI, and IPDI are more stable than are preparations of 4,4'-MDI where previously reported results showed ratios far outside of stable range. CONCLUSION: As opposed to preparations of 4,4'-MDI, preparations of 2,4-TDI, 1,6-HDI, and IPDI can be considered to be stable.
BACKGROUND: Photoallergic contact dermatitis from ketoprofen has been recognized since the mid-1980s. Skin reactions have been reported to continue weeks after discontinuation of ketoprofen. One reason for this could be residual ketoprofen in the skin, which has been shown in a skin biopsy specimen. OBJECTIVE: We sought to report on 3 cases of photoallergic contact dermatitis from ketoprofen in topical anti-inflammatory gels and on relapses of dermatitis appearing after use of ketoprofen-contaminated objects. METHODS: We patch and photopatch tested, with standard series, the anti-inflammatory gel, ketoprofen, and its ingredients in serial dilutions and extracts of personal objects. We performed chemical investigations of personal objects with thin-layer chromatography, high-pressure liquid chromatography, and gas chromatography-mass spectrometry. RESULTS: Photoallergy was demonstrated to ketoprofen, which was detected in personal objects. CONCLUSION: Relapses of photoallergic contact dermatitis in patients photoallergic to ketoprofen can be induced by ketoprofen-contaminated objects such as bandages and slippers.
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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 x2, both during treatment with prednisone 20 mg 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.
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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.
Up to 5% of dermatitis patients are allergic to corticosteroids. Because such allergy may be difficult to suspect due to the anti-inflammatory action of the corticosteroid, markers for corticosteroid allergy should be present in any standard series. Budesonide and tixocortol pivalate are two such markers, and they seem to detect a majority of corticosteroid allergy. The patch test concentration for a given corticosteroid may be crucial. A false-negative reaction may follow despite the patient being allergic, if too high a test concentration is used, because of the anti-inflammatory action of the corticosteroid. Patch test readings must be performed not only on Day 3 or Day 4 but also on a late occasion, i.e., Day 7 after test application, also because the anti-inflammatory action may suppress an allergic reaction at an early reading. Once a patient has reacted to a corticosteroid, an extended corticosteroid series should be tested, so that information may be given on which corticosteroids to use and, above all, which corticosteroids to avoid.
BACKGROUND: Contact allergy to grease is rare and often not even suspected. We investigated such a case in which the detected allergen was the stabilizer in the grease, which is rarely found as an allergen. OBJECTIVE: Thin-layer chromatography (TLC) was used in a novel way and helped detect the allergen. METHODS: Patch testing with our standard series, a metal-working series, the different substances individually, the grease in serial dilution and extracts of personal objects, the TLC plate. Gas chromatography-mass spectrometry was also used. RESULTS: Test results indicated contact allergy to grease containing N-phenyl-1-naphthylamine and contact allergy to Disperse Orange 1, N-cyclohexyl-N'-phenyl-4-phenylenediamine, N-isopropyl-N'-phenyl-4-phenylenediamine, and N,N'-diphenyl-4-phenylenediamine. CONCLUSION: N-phenyl-1-naphthylamine was the main cause of the patient's dermatitis. This case report underlines the importance of testing the patient's own products and also underlines the benefit of using TLC strips for patch testing and of visiting the workplace to get correct information about exposure conditions.
BACKGROUND: An industry producing rotor blades for wind turbines with an epoxy-based technology had experienced an increasing number of workers with dermatitis, among whom the frequency of occupational contact allergy (OCA) was suspected to be underestimated. OBJECTIVE: To investigate the frequency of OCA by patch-testing with a specially profiled occupational patch test series. METHODS: 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 an occupational patch test series and the European Standard patch test series. RESULTS: Of the 603 investigated workers, 10.9% had OCA and 5.6% had contact allergy to epoxy resin in the standard test series. Contact allergy to amine hardeners/catalysts was found in 4.1% of the workers. Among the workers with OCA, 48.5% reacted to work material other than epoxy resin in the European Standard patch test series. CONCLUSION: Approximately 50% of the workers with OCA would not have been detected if only the European Standard patch test series had been used.
Skin exposure to biocides containing high concentrations of methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) may cause severe chemical burns and may also induce sensitization. We report two cases in which skin exposure to a newly launched biocide containing 2-methyl-4-isothiazolin-3-one (MI) and 1,2-benzisothiazolin-3-one led to sensitization to Ml, which in the second case was preceded by a chemical burn. A study was performed to investigate the pattern of reactivity to MCI and Ml in two patients who presumably had a primary sensitization to Ml and in one patient who had been sensitized to MCI/MI by being patch-tested. The patients were patch-tested with serial dilutions of MCI/MI, MCI, MI, and 2-n-octyl-4-isothiazolin-3-one. The first two patients reacted to both MCI/MI and the separate active ingredients, with a higher level of reactivity to Ml than to MCI. The third patient reacted to MCI/MI and MCI only. A biocide containing Ml caused sensitization and occupational contact dermatitis in the first two patients, through contact with wallpaper glue in one case and after a chemical burn in the other case.