Contact Dermatitis

Published by Wiley
Online ISSN: 1600-0536
Print ISSN: 0105-1873
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The aim of this study was to evaluate the ability of topical tacrolimus 0.1% under occlusion for 48 h to suppress nickel-elicited allergic contact dermatitis in a randomized, petrolatum- and mometasone furoate 0.1% ointment-controlled double-blind, intra-individual study which included 28 women volunteers. 3 closed patch tests (Finn Chambers on Scanpor, Epitest Ltd Oy, Tuusula, Finland) containing 0.1 ml of 5% nickel sulfate in petrolatum were applied on day 0. After removal on day 2, the study compounds were applied under occlusion for 48 h. The eczema reaction and the degree of erythema were evaluated clinically and by reflectance spectrophotometry at days 4 and 7, respectively. Mean visual scores corresponding to petrolatum-treated sites were significantly higher than those corresponding to both mometasone furoate and tacrolimus at days 4 (P < 0.001) and 7 (P < 0.001). In both tacrolimus- and mometasone furoate-treated sites, there was a significant decrease in visual scores with time (P < 0.001) from day 2 to day 7, and the corresponding mean decreases in scores were 0.73 and 1.04, respectively. The difference between both was 0.30 in favour of tacrolimus (95% confidence intervals, -0.04 and 0.65), although this did not reach statistical significance (P = 0.084). Mean erythema index values were similar at day 2. Significant differences among treatment sites were seen at days 4 (P < 0.001) and 7 (P < 0.001). The decrease was significantly more pronounced on day 7 in patches where tacrolimus had been supplied (P < 0.5). This method might provide useful means to compare different concentrations and/or presentations of tacrolimus or other calcineurin inhibitors and topical anti-inflammatory agents.
 
Thiuram mix is tested in the standard series at a test concentration of 1% pet. The single thiurams (DPTD, TMTD, TMTM, TETD), however, are usually tested at 0.25% pet. in Germany. In other countries, the individual components of thiuram mix are tested at 1% pet. The German Contact Dermatitis Research Group (DKG) compared both patch test concentrations in 530 patients in order to find out if (i) a significant number of positive patch tests are missed by testing at the lower concentration, (ii) problems with irritant test reactions occur by increasing the test concentration to 1%, and (iii) the sensitivity of the thiuram mix rises when the breakdown test is done with the higher concentration. Slightly more positive reactions were seen with the higher concentration, but this increase did not reach statistical significance. The reaction index, as a measure for the relation of positive to irritant and/or questionable reactions, remained unchanged for the individual thiurams. The sensitivity of the mix also did not change when the breakdown test was performed with 1% pet. instead of 0.25% pet. Thus, we conclude that both concentrations are of equal diagnostic value in patch testing.
 
Being a contact allergen of general relevance, p-phenylenediamine (PPD) is patch tested in the baseline series. However, PPD 1% in petrolatum may actively sensitize. Patch testing with PPD at 0.35% pet. proved to be safe, as far as active sensitization is concerned. To determine whether PPD 0.3% pet. reliably detects PPD sensitization. Patch testing with PPD 0.3% pet. and 1% pet. synchronously was performed in consecutive patients in a multicentre study within the Information Network of Departments of Dermatology. Altogether, 2042 patients were patch tested. PPD 1% pet. yielded 6.0% positive reactions (n = 123), and PPD 0.3% pet. yielded 4.7% (n = 95). The synchronous reproducibility of PPD reactions was similar as known from parallel patch tests with identical PPD concentrations. The diagnostic properties of PPD 0.3% pet. expressed as reaction index and positivity ratio were good. Of the 123 patients reacting to PPD 1% pet., 32 (26%) had no positive reaction to PPD 0.3% pet. In 22 of these 32 patients (69%), no clinical relevance could be found. As patch testing with PPD 0.3% pet. is reliable according to our results, we recommend replacing PPD 1% pet. in the baseline series with PPD 0.3% pet.
 
The number of doubtful reactions to 1.0% (wt/vol) formaldehyde in patients who were read both at days 2–4 and 5–8 that were diagnosed as positive and doubtful/negative to 2.0% (wt/vol) formaldehyde.
Background.The currently used patch test concentration for formaldehyde is 1.0% (wt/vol) in water. However, clinical experience and previous studies suggest that 1.0% might be insufficient for detecting an optimized number of clinically relevant cases of contact allergy to formaldehyde. Objectives.To validate earlier patch test results for comparison of 1% (wt/vol) and 2% (wt/vol) formaldehyde in water, and to investigate co-reactivity with quaternium-15. Materials and methods.In 12 dermatology clinics, 3591 patients were routinely patch tested simultaneously with 2.0% (wt/vol) (0.60 mg/cm2) and 1.0% (wt/vol) (0.30 mg/cm2) formaldehyde. Micropipettes were used for delivering the exact dosage of the allergen. Results.Significantly more patients reacted to 2.0% formaldehyde than to 1.0% (3.4% versus 1.8%, p < 0.001). Overall, there were no sex differences between those reacting positively to 2.0% and 1.0%. Of 25 quaternium-15-positive patients, 4 (0.1%) reacted positively without reacting to formaldehyde. Conclusion.On the basis of the results of this multicentre study, as well as of previous studies, it can be suggested that 2.0% (wt/vol) in water formaldehyde should be used in routine patch testing in the baseline series.
 
Recently, the preservative methyldibromo glutaronitrile (MDBGN) at 0.5% w/w in petrolatum was included in the European standard patch test series based on the studies on chemical stability and consideration of rates of contact allergy, doubtful and irritant reactions as well as information on clinical relevance represented by results of a repeated open application test (ROAT) and patch test concentrations required to diagnose allergic contact dermatitis from MDBGN in individual cases. In this report, a case with a clinically relevant contact allergy to MDBGN, which on the mandatory reading occasion on D3 only was traced by a patch test with MDBGN at 1.0% (0.32 mg/cm2), is presented. The patient suffered from a chronic hand dermatitis, and when the patient stopped using a liquid soap containing MDBGN, the hand dermatitis substantially improved. A ROAT performed in a blinded and controlled way with applications twice daily on the hands with 2 moisturizers with and without MDBGN resulted in a deterioration of the hand dermatitis on the hand to which the MDBGN-preserved moisturizer had been applied.
 
Patch testing was performed with phosphorus sesquisulfide P4S3 in 2 groups containing equal numbers of patients using different concentrations (0.5% P4S3 in pet. and 1% P4S3 in pet., the usual suggested test concentration as recommended by the International Contact Dermatitis Research Group). We found that there was a statistically significant increase in the number of clinically irrelevant irritant reactions in the group tested with the concentration (chi 2 = 16, p < 0.0004). We recommend that patch testing with phosphorous sesquisulfide should be at a reduced concentration of 0.5% pet.
 
Unlabelled: Sporadic cases of contact allergy to white petrolatum, which is used as a vehicle in patch test preparations, have been reported. The quantitative relevance of the phenomenon remains yet to be elucidated. Methods: Retrospective analysis of patch test data of the Information Network of Departments of Dermatology (IVDK, http://www.ivdk.org) between 1992 and 2004. Results: Analysis of 79 365 patients patch tested with pure petrolatum yielded 27 '+' (0.03%) and 2 '+++' (0.003%) reactions. The majority of non-negative reactions (0.3%) was interpreted as doubtful (235) or mild irritant (32). The negative reaction index (RI) (-0.8), and the high positivity ratio (PR) (93%) especially a lack of concordance with patch test preparations containing > or=99% petrolatum indicate that many of the 'positive' (+) reactions have to be considered as irritant. There were 2 '+++' reactions. In 1 case, an 'angry back reaction' was confirmed. The other case is probably a reading or documentation error, as the majority of patch test reactions to preparations containing petrolatum remained negative in this case also. Conclusions: True allergic patch test reactions to white petrolatum are extremely rare and probably due to an individually increased susceptibility to allergens and/or irritants. This is in agreement with considering petrolatum as a non-sensitizer.
 
As shown in the preceding paper, propolis or bee-glue is the cause of an increasing number of allergic reactions in persons using it in external preparations and cosmetics. Propolis and its main contact allergen, 1,1-dimethylallyl caffeic acid ester, designated LB-1, show strong sensitizing properties in patients as well as in guinea pig experiments. 9 patients have been patch tested with this compound, 8 of whom reacted strongly. Chemical separation of different propolis samples and poplar bud extracts reveal that LB-1 is always present. Poplar bud secretion is the bee's major source for propolis and hence the origin of LB-1. A warning is indicated, in agreement with several other authors, that propolis should not be used in topical products because of its strong sensitizing properties.
 
Keywords:1,1,1-trichloroethane;methyl chloroform;allergic contact dermatitis;occupational;organic solvents;lumber company;machine cleaning
 
Keywords:occupational;allergic contact dermatitis;painters;laboratory worker;1,2-diaminocyclohexane;m-xylenediamine;cross-sensitivity;epoxy hardeners
 
Using a modified FCA (Freund's complete adjuvant) procedure, the sensitizing capacity of Euxyl K 400 and its ingredients, 1,2-dibromo-2,4-dicyanobutane and 2-phenoxyethanol, has been studied in guinea pigs. The experiments demonstrate that a distinct but weak sensitizing potency exists for Euxyl K 400 and dibromodicyanobutane. Phenoxyethanol remained almost negative. These results are in good accordance with the low number of cases of allergic contact dermatitis due to Euxyl K 400 and dibromodicyanobutane described since their introduction on the market. Cases of phenoxyethanol contact allergy have been published hitherto only 4x in the medical literature.
 
Occupational contact allergy to 1,2-benzisothiazolin-3-one (1,2-BIT, Proxel) is analysed. This compound is widely used in industry as a preservative in water-based solutions such as pastes, paints and cutting oils. The optimal concentration for patch testing proved to be 0.4 g/l (0.04%) in water. In 4 out of 17 patients (23%) at occupational risk (painters, paper-hangers), contact allergy to 1,2-BIT was found. Of 556 consecutive dermatological patients without clear occupational risk, 10 (1.8%) showed positive patch tests to 1,2-BIT; in 3 patients 1,2-BIT contact allergy was related to domestic paper-hanging. Although the chemical structure of 1,2-BIT shows some analogy with the preservative Kathon CG, true cross-sensitivity was found to be unlikely.
 
The isothiazolinone, 1,2-benzisothiazolin-3-one (Proxel), is a popular preservative, as well as a skin sensitizer and irritant. Patch test studies have been performed with different concentrations and vehicles. The current suggested patch test concentration is 0.1% BIT in petrolatum (pet). This article evaluates the effects of patch testing at this concentration and reviews the current literature. An irritancy patch test was performed on 56 controls, using BIT in concentrations of 0.002% and 0.05% in aqueous dipropylene glycol (Proxel GXL) and 0.1% in pet. 10 had positive readings at 4 days with 0.1% BIT in petrolatum, 9 of which were negative at retest. 0.1% BIT is, therefore, irritant and not a suitable concentration for patch testing. Literature review revealed 15 patch test studies, with varying testing techniques. Additional studies with adequate controls and experimental tests should be invaluable in furthering our insight into BIT sensitization and irritation.
 
The recent negative publicity about the widely used cosmetic preservative methylisothiazolinone and methylchloroisothiazolinone (Kathon CG) has made many cosmetic manufacturers look for safer alternatives. One such candidate is Euxyl K 400 (Schulke and Mayr, Hamburg, Germany), a preservative containing 2 active ingredients: methyldibromoglutaronitrile (synonym 1,2-dibromo-2, 4-dicyanobutane) and phenoxyethanol, in a 1:4 ratio. Several cases of contact allergy to methyldibromoglutaronitrile in Euxyl K 400 have been described. Of 107 cosmetic products (including shampoos, bath foams, shower gels, body milks and creams), analyzed for the presence of methyldibromoglutaronitrile, 14 (13%) proved to contain the preservative. We therefore decided to study the frequency of contact allergy to methyldibromoglutaronitrile in The Netherlands.
 
An investigation was conducted as follows in 9 farmers with contact allergy due to rubber boots: (i) patch tests with 19 rubber additives; (ii) chemical analysis of additives in 6 pairs of rubber boots; (iii) use tests on a hypoallergenic trial product in 5 patients. The following results were obtained: (i) in the patch tests, all 9 patients showed positive reactions to 1 or more of the nitrogen(N)-containing antioxidants (IPPD, DMBPPD, ETMDQ); (ii) ETMDQ was detected in 1 pair of rubber boots, and IPPD and DMBPPD in another pair; (iii) no patient using hypoallergenic boots during rice-planting had recurrent dermatitis. N-containing antioxidants, such as IPPD, DMBPPD and ETMDQ, were thus considered as the main causative agents and the trial product was found useful for managing contact dermatitis. Contact allergy due to ETMDQ in rubber is reported here for the 1st time.
 
Two male employees in an industry producing plastic emulsions acquired contact dermatitis from preservatives. One was sensitized to both components in a preservative, i.e. 1,2-benzisothiazolin-3-one and ethylene diamine. The other man acquired a contact allergy to 1,2-benzisothiazolin-3-one and to another preservative, formaldehyde.
 
Three men working as mouldmakers in the pottery industry acquired a contact allergic dermatitis to a releasing oil. All three were shown to be sensitized to the biocide (1,2-benzisothiazolin-3-one) in the oil.
 
Benzisothiazolinone is used as a slimicide in the manufacture of disposable powder-free polyvinyl chloride (PVC) gloves. We recently reported 6 patients from dentistry and health care probably sensitized to benzisothiazolinone in PVC gloves. The study aimed to investigate how widely disposable PVC gloves for medical use on the Finnish market in 2006 contain benzisothiazolinone and to report new cases from 2 clinics in Helsinki. 31 brands of disposable PVC gloves were analysed for their benzisothiazolinone content. We looked through the patient material of Helsinki University Central Hospital to find benzisothiazolinone allergic patients. We also described 3 previously unpublished benzisothiazolinone allergic patients from Finnish Institute of Occupational Health. 9 (30%) of the 31 glove brands contained 3-26 p.p.m. benzisothiazolinone. From the 2 clinics, we found 5 new benzisothiazolinone allergic patients who had used PVC gloves containing benzisothiazolinone. In addition, 3 patients had used disposable PVC gloves whose benzisothiazolinone content remained unknown. In Finland, benzisothiazolinone in powder-free PVC gloves has caused a small epidemic of allergic contact dermatitis in dental personnel and other health care workers. 1/3 of the disposable PVC gloves contained some benzisothiazolinone. A concentration of 20 p.p.m. benzisothiazolinone in a glove seems to be enough for sensitization.
 
This study examines in detail the human skin sensitization potential of Bronopol. A total of 120 subjects began the study. Many subjects showed irritation reactions from the 5% concentration used in the induction phase. There was no score other than zero obtained from the 93 subjects on whom the challenge tests were conducted. This work suggests that false positives may have occurred in the earlier study, caused by the use of concentrations of Bronopol above the irritancy threshold or uneven trituration of the agent in the vehicle. It can be concluded that, under the conditions of this test, no evidence of sensitization was observed.
 
The clinical efficiency of mitigating contact dermatitis with a Ginkgo biloba extract and carboxymethyl-beta-1,3-glucan formulation was investigated in a double-blind versus placebo study using 22 subjects (Caucasian women aged 22-55 years) with allergic contact dermatitis from various substances in the European standard series. The formulation was applied to intact skin 2X a day for 2 weeks ("in use" application) prior to a single application of a selected contact allergen under a Finn Chamber for 24 h. Readings were carried out in a blind study by a dermatologist 2 and 3 days after patch removal. Representative photographs were taken of treated, placebo and untreated test areas. 68.2% of the panelists showed significantly reduced skin reactivity (p = 0.037*) on the treated site 2 days after patch removal, versus untreated and/or placebo sites. This finding indicates that the Ginkgo biloba/carboxymethyl-beta-1,3-glucan formulation can mitigate against allergic contact dermatitis.
 
Forty-two cases of contact sensitivity to N-isopropyl-N'-phenylparaphenylenediamine (IPPD), an amine antiozonant used in rubber manufacture, were collated from several firms and plants dealing with tyres. Ten motor car tyres manufactured by eight different firms all induce sensitivity reactions in seven subjects allergic to IPPD. Clinical cross-reaction tests show that 100% of the subjects sensitive to IPPD are also sensitive to N-phenyl-N'-cyclohexy-paraphenylenediamine (CPPD), another amine antiozonant, and 37% to paraphenylenediamine (PPD). The various types of tyres were analyzed by gas chromatography and then by infra-red and thin-layer chromatography where necessary. None of the 12 tyres examined was found to be free from aromatic amines. Test reactions carried out with various automobile accessories on subjects allergic to IPPD in tyres gave positive results precisely in those cases where the articles contained IPPD. The authors then studied occupational sensitivity to N-dimethyl-1,3 butyl-N'-phenylparaphenylenediamine (DMPPD), a rubber antiozonant purported to be non-sensitizing and marketed in the United States. The The DMPPD tests were positive for all the IPPD-allergic patients tested; there is no doubt as to the allergenic nature of DMPPD. The irritant and sensitizing potentials of the four amines in question were tested in laboratory animals: PPD proved to be the most allergenic product, IPPD the least allergenic, and DMPPD and CPPD seem to give identical results. All these products produce positive cross-reactions in varying degrees of severity.
 
Top-cited authors
Jacob P Thyssen
  • Copenhagen University Hospital Herlev-Gentofte
An Goossens
  • Universitair Ziekenhuis Leuven
Magnus Bruze
  • Lund University
Klaus Ejner Andersen
  • University of Southern Denmark
Wolfgang Uter
  • Friedrich-Alexander-University of Erlangen-Nürnberg