Oral provocation of patients allergic to sesquiterpene lactones with German chamomile tea to demonstrate possible systemic allergic dermatitis.

BACKGROUND: Most patients with contact allergy to Asteraceae plants are patch test positive to sesquiterpene lactone mix (SLM). There are several reports among these patients of a flare-up of hand eczema after ingestion of food and beverages originating from Asteraceae plants. AIM: To investigate whether German chamomile tea can elicit systemic allergic dermatitis. PATIENTS AND METHODS: Individuals with or without contact allergy to SLM were patch tested with an extract of German chamomile tea. Six weeks later, they were provoked with capsules containing either freeze-dried German chamomile tea or placebo capsules containing lactose, in a double-blind, randomized study. A numerical rating scale (NRS) was used to ascertain the volunteers' opinion of their hand eczema status. The study individuals were examined to detect a possible flare-up of healed patch test reactions to chamomile. RESULTS: None of the subjects had a flare-up of healed patch test reactions. According to the NRS, SLM-positive individuals experienced a significant worsening of hand eczema, independently of whether they received chamomile or lactose capsules. CONCLUSION: No evidence suggestive of systemic allergic dermatitis was found.

Patch testing with methylchloroisothiazolinone/methylisothiazolinone 200 ppm aq. detects significantly more contact allergy than 100 ppm. A multicentre study within the European Environmental and Contact Dermatitis Research Group.

BACKGROUND: Methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) are the active ingredients in commonly used preservative systems (e.g. Kathon CG(®)). MCI/MI is present in the European baseline patch test series at 100 ppm aq. Since 1986, 200 ppm (dose 0.006 mg/cm(2)) has been used in Sweden without causing skin irritation. Centres in Spain, the United Kingdom and Ireland have also used 200 ppm in their baseline series. OBJECTIVES: To find the optimal patch test concentration for MCI/MI. MATERIALS AND METHODS: MCI/MI 100 ppm aq. and MCI/MI 200 ppm aq. were simultaneously patch tested in 3300 consecutively tested dermatitis patients at eight European patch test clinics and one US patch test clinic. With the Finn Chambers(®) technique (diameter 8 mm), 15 µl was micropipetted on to the filter paper in the chamber. The corresponding volume for Van der Bend(®) chambers was 20 µl, and that for IQ Chambers(®) was 25 µl. RESULTS: Contact allergy to MCI/MI at 100 and 200 ppm was found in 1.2% and 2.1% of patients, respectively (p < 0.001). CONCLUSIONS: MCI/MI 200 ppm aq. (dose 0.006 mg/cm(2) ) diagnoses significantly more contact allergy than the presently used concentration of 100 ppm (dose 0.003 mg/cm(2)), without resulting in more adverse reactions. MCI/MI at 200 ppm should therefore be considered for inclusion in the European baseline test series.

Implants and contact allergy: are sensitizing metals released as haptens from coronary stents?

BACKGROUND: The possible impact of metal release from coronary artery stents has, with their increased use, become a concern. OBJECTIVES: To study in vitro metal release in biologically relevant milieu from coronary stents made of different alloys. MATERIALS AND METHOD: Coronary stents in common use in a department of cardiology at the time of the study were tested. A previously described in vitro technique was used, whereby the stents were kept in the extraction media for a week. Two different extraction media were used to show the necessity of studying the actual biological surrounding of the implant when metal release is investigated. Metal release was determined with atomic absorption spectrometry. RESULTS: In this study, we show metal release from stents after immersion in extraction media of artificial sweat and cysteine solution, as illustrative media. CONCLUSION: Metal release from coronary stents is shown. The magnitude of release is influenced by several factors. The extent to which metal release in vitro has potential biological effects, in terms of elicitation of an allergic reaction or induction of sensitization, in vivo needs to be explored. However, as metal release from an implant in a biologically appropriate medium has been established, better risk assessments in relation to delayed hypersensitivity may be undertaken.

Patch testing with serial dilutions of various isothiazolinones in patients hypersensitive to methylchloroisothiazolinone/methylisothiazolinone.

BACKGROUND: In 2005, methylisothiazolinone (MI) on its own came into use as a preservative. Prior to that, MI was always present together with methylchloroisothiazolinone (MCI). Can the pattern of reactivity to the separate active ingredients in allergic patients tell us something about the primary sensitizer? OBJECTIVES: To investigate the potential pattern of cross-reactivity between the isothiazolinones tested, and to find the minimal elicitation concentration for each chemical, in order to determine whether the primary sensitizer is MCI or MI. METHODS: Patients reacting to MCI/MI and/or MI were additionally patch tested with MCI/MI, MCI, MI, 2-n-octyl-4-isothiazolin-3-one (OIT) and 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (dichloro-OIT) in serial dilutions. RESULTS: Three different groups of reactors were seen. One group did not react to MI; another group reacted to both MCI and MI, but had higher patch test reactivity to MCI; and a third group reacted to both MCI and MI with very similar patch test reactivity, but reacted more often to OIT and dichloro-OIT. CONCLUSIONS: Patch testing with the active ingredients of MCI/MI in serial dilutions could give information on the primary sensitizer.

Does the new standard for eugenol designed to protect against contact sensitization protect those sensitized from elicitation of the reaction?

BACKGROUND: Potential fragrance allergens used in daily products should have a concentration limited to levels that are at, or below, acceptable exposure levels based on the quantitative risk assessment for the induction of dermal sensitization. To date, there are insufficient data to discern any quantitative relationship between induction and elicitation concentrations for fragrance ingredients that have a potential for dermal sensitization. When available, these data should be used to confirm the effectiveness of quantitative risk assessment-based risk management procedures. OBJECTIVE: In this study, the relationship between the allergen concentration and the time to elicit allergic contact dermatitis in eugenol-sensitized patients was studied. The products used to elicit allergic contact dermatitis had a concentration of eugenol that was equal to, or below, the International Fragrance Association standard. METHODS: Volunteers with and without known sensitization to eugenol were patch tested with various concentrations of eugenol (dilution series) and also underwent repeated open application tests (ROATs). This study model has previously been successfully used with stronger sensitizers. RESULTS: In this study, allergic contact dermatitis, as evidenced by a positive ROAT, could not be elicited by any of the concentrations studied, including in those patients where the patch tests were positive. CONCLUSIONS: When tested in a 3-week ROAT at, or below, its current International Fragrance Association Standard, eugenol did not induce reactions even in those known to be sensitized. Whether this represents a false-negative result for a weak allergen is unknown.

Contact allergy to gold in patients with oral lichen lesions.

The aetiology of oral lichen lesions is obscure. In this study the frequency of contact allergy to gold in 83 patients with oral lichen lesions was compared with that in two control groups, comprising 319 age- and gender-matched patients with dermatitis selected from files and 83 clinically examined dermatitis patients. All patients were tested epicutaneously with gold sodium thiosulphate. The two control groups tested were under examination for a tentative diagnosis of allergic dermatitis not related to oral problems. The frequency of contact allergy to gold was 28.9% in the patients with oral lichen lesions, 18.2% in patients selected from files, and 22.9% in the clinically examined control patients. The difference in frequency between patients with oral lichen lesions and those taken from files was statistically significant.

Patch testing with a textile dye mix in a baseline series in two countries.

Disperse dyes are the most common contact sensitizers among textile dyes. The main aim of this study was to investigate the outcome of patch testing with a textile dye mix 6.6%. A total of 2,049 patients from Sweden and 497 from Belgium were tested with the mix, consisting of Disperse (D) Blue 35, D Yellow 3, D Orange 1 and 3, D Red 1 and 17, 1.0% each, and D Blue 106 and D Blue 124, 0.3% each. Of the total number, 65 patients, 2.6%, tested positively to the mix, 4.2% of the Belgian patients and 2.1% of the Swedish patients. Patch testing with the mix 6.6% revealed significantly more patients with contact allergy compared with testing with a previous mix 3.2% (p < 0.01). Contact allergy to the mix was significantly more common in the Belgian than in the Swedish patients.

Comparison of three different techniques for application of water solutions to Finn Chambers®.

BACKGROUND: With regard to contact allergy, the dose of a sensitizer per unit skin area is an important factor for both sensitization and elicitation, and therefore a known amount/volume of test preparation should be applied at patch testing. OBJECTIVES: To compare three different techniques for the application of aqueous solutions to Finn Chambers, in order to determine the precision and accuracy of each technique when the recommended 15 µl volume is applied. METHODS: Four technicians applied formaldehyde 1.0% aq. (wt/vol) and methylchloroisothiazolinone/methylisothiazolinone 200 ppm (wt/vol) in sets of 10 onto Finn Chambers, with three different techniques: (i) micro-pipetting; (ii) dripping the solutions; and (iii) dripping the solutions followed by removal of excess solution with a soft tissue. Assessment of the variations was performed with the use of descriptive data. The ability to apply the exact amount was assessed by Fisher's exact test by categorizing each application as in or out of the range 12-18 µl. RESULTS/CONCLUSIONS: The micro-pipette technique had the best accuracy and precision, as well as the lowest inter-individual variation. The technique in which excess solution was removed had good precision, but failed in the application of the defined amount, i.e. 15 µl.

Routine diagnostic patch-testing with formaldehyde 2.0% (0.6 mg/cm2) may be an advantage compared to 1.0%.

Our clinical experience has suggested that the presently recommended patch-test concentration (1.0%) for formaldehyde in the baseline series might be too low. Therefore, consecutively patch-tested dermatitis patients were tested simultaneously with formaldehyde 1.0% and 2.0% (w/v) in aqua. Formaldehyde 1.0% and 2.0% were applied with a micro-pipette (15 microl) to filter paper discs in Finn Chambers (0.30 mg/cm(2) and 0.60 mg/cm(2), respectively). A total of 1397 patients with dermatitis were patch-tested. In all, 68 (4.9%) patients reacted positively to formaldehyde; 37 reacted only to 2.0%, 29 reacted to both concentrations, and 2 reacted only to 1.0%. Significantly more patients were thus diagnosed with contact allergy to formaldehyde 2.0% compared with 1.0% (p < 0.001). We detected 0.1%, 0.4%, and 29.6% irritant reactions to 1.0%, 2.0%, and 3.0% formaldehyde, respectively. We conclude that, with an optimized patch-test technique, doubling the dose per area detects significantly more contact allergies to formaldehyde, but an even higher test concentration causes too many irritant reactions to be usable.

Linalool--a significant contact sensitizer after air exposure.

BACKGROUND: Linalool is a widely used fragrance terpene. Pure linalool is not allergenic or a very weak allergen, but autoxidizes on air exposure and the oxidation products can cause contact allergy. Oxidized (ox.) linalool has previously been patch tested at a concentration of 2.0% in petrolatum (pet.) in 1511 patients, and 1.3% positive patch test reactions were observed. OBJECTIVE: To investigate the optimal patch test concentration for detection of contact allergy to ox. linalool. METHODS: Four concentrations of ox. linalool (2.0%, 4.0%, 6.0%, 11.0% pet.) were tested in 3418 consecutive dermatitis patients. RESULTS: Ox. linalool 2.0%, 4.0%, 6.0%, and 11.0% pet. detected positive patch test reactions in 0.83%, 3.2%, 5.3%, and 7.2% of the tested patients, respectively. The doubtful reactions increased with rising concentrations but relatively less, giving 5.1%, 6.4%, and 7.3% doubtful reactions, respectively, for ox. linalool 4.0%, 6.0%, and 11.0% pet. Few irritative reactions were seen. CONCLUSIONS: Raising the patch test concentration for ox. linalool gave a better detection of contact allergy, as many as 5-7% positive patch test reactions were detected. We suggest a patch test concentration of ox. linalool 6.0% pet. for future patch testing, giving a dose per unit area of 2.4 mg/cm(2) when 20 mg test substance is tested in small Finn Chambers.

Sensitization to dimethyl fumarate with multiple concurrent patch test reactions.

BACKGROUND: Chairs and sofas imported from China to Europe were shown to contain dimethyl fumarate (DMF), a sensitizing, volatile chemical. Many of the sensitized patients also had positive patch test reactions to acrylates. OBJECTIVES: To analyse the occurrence and strength of DMF sensitization and the appearance of concomitant reactions. METHODS: Patch testing with DMF in concentrations of 0.1-0.00001% was carried out in 37 patients. Diethyl fumarate (DEF), diethyl maleate (DEM), dimethyl maleate (DMM), ethyl acrylate (EA), methyl acrylate (MA), and methyl methacrylate (MMA) were also tested with a dilution series at equimolar concentrations. RESULTS: The lowest concentration of DMF eliciting a reaction varied between 0.0001% and 0.1% and all but four patients reacted concurrently to DEF. DEM elicited positive patch test reactions in 21/37 patients and DMM reactions were seen in all 9 patients tested. EA elicited positive reactions in 13/37 patients and a positive MA reaction was seen in 7/37 patients, 2 of whom also reacted to MMA. CONCLUSIONS: The strength of the sensitization to DMF showed variation and concurrent reactions were common. Concurrent reactions to (meth)acrylates were seen in patients, who reacted to lower (0.001% or less) DMF concentration probably elicited by cross-reactivity.

Patch testing with a textile dye mix and its constituents in a baseline series.

BACKGROUND: Among the textile dyes, disperse dyes are common sensitizers. OBJECTIVE: To investigate whether patch testing with a textile dye mix consisting of eight disperse dyes would be equivalent to testing with the separate ingredients of the mix at the concentrations used in the mix. METHODS: Researchers tested 1,780 consecutive patients with a mix consisting of Disperse Blue 35, Disperse Yellow 3, Disperse Orange 1, Disperse Orange 31 (mislabeled as Disperse Orange 3), Disperse Red 1 and 17, all at 0.5%, and Disperse Blue 106 and 124, both at 0.1%, and with the ingredients at these concentrations. Testing with the labeled dyes at 1.0% was done on 500 of the patients and additionally on the remaining patients who reacted positively to the mix, any of the ingredients, p-phenylenediamine, or black rubber mix. RESULTS: Thirty-five patients (2%) reacted to the mix, and 34 patients were allergic to at least one ingredient tested at the lower concentration. CONCLUSION: The textile dye mix was as good a detector of contact allergy to the disperse dyes as was testing with any combination of the ingredients at the concentration in the mix. Increasing the concentration of the ingredients of the textile dye mix might increase the sensitivity of the mix.

Patch testing of patients allergic to Disperse Blue 106 and Disperse Blue 124 with thin-layer chromatograms and purified dyes.

BACKGROUND: Former investigations have demonstrated that patch test preparations containing Disperse Blue (DB) 106 and DB 124 are impure. OBJECTIVE: To investigate the significance of impurities in preparations of disperse dyes with regard to contact allergy. MATERIALS/METHODS: 21 patients allergic to DB 106 and/or DB 124 were tested with dilution series of commercial and purified DB 106 and DB 124. All patients were additionally tested with thin-layer chromatography (TLC) strips made from the commercial preparations containing DB 106 and 18 of them also with TLC strips containing DB 124. RESULTS: 13 of 21 and 12/18 patients tested positively to the strips of DB 106 and DB 124, respectively. Among these patients, 4/13 and 5/12, respectively, did not react to the main spot but reacted to other spots. Dilution series of purified DB 106 and DB 124 were positive in 10 patients each, while 16 and 15 patients, respectively, tested positively to the dilution series of the corresponding commercial disperse dye. CONCLUSION: Approximately 25% of the patients, diagnosed as contact allergic to DB 106 and DB 124, only reacted to impurities in the patch test preparations. This has implications for diagnosis and prevention.

A correlation found between contact allergy to stent material and restenosis of the coronary arteries.

BACKGROUND: Metallic implants, stents, are increasingly being used especially in patients with stenosis of the cardiac vessels. Ten to thirty per cent of the patients suffer from restenosis regardless of aetiology. We have shown increased frequency of contact allergy to stent metals in stented patients. OBJECTIVES: To we evaluate whether contact allergy to stent material is a risk factor for restenosis. METHODS: Patients with stainless steel stents, with or without gold plating, were epicutaneously tested and answered a questionnaire. The restenosis rate was evaluated. RESULTS: We found a correlation between contact allergy to gold, gold stent, and restenosis (OR 2.3, CI 1.0-5.1, P = 0.04). The risk for restenosis was threefold increased when the patient was gold allergic and stented with a gold-plated stent. An increased degree of chest pain in gold-allergic patients stented with gold-plated stent was found. CONCLUSIONS: We found a correlation between contact allergy to gold, gold-stent, and restenosis. It may be of importance to consider contact allergy when developing new materials for stenting.

Chemical investigations of disperse dyes in patch test preparations.

BACKGROUND: Contact allergy to textile dyes is not uncommon. The allergy is detected by patch testing patients with commercial patch test preparations. OBJECTIVE: To investigate 8 disperse dyes (DDs) used for patch testing in the departments in Malmö and in Leuven and to compare them with test preparations used at various dermatology departments. MATERIALS/METHODS: The investigated DDs were Disperse Blue (DB) 35, 106, and 124, Disperse Yellow (DY) 3, Disperse Orange (DO) 1 and 3, and Disperse Red (DR) 1 and 17. From 13 clinics, 107 petrolatum preparations were analysed using high-performance liquid chromatography and thin-layer chromatography (TLC), and compared with reference substances obtained at the Malmö laboratory. Concerning DB 35, no reference substance could be identified. RESULTS: TLC visualized impurities in all DDs. For each DD, except DB 35, the mean concentration in the preparations labelled to contain 1.0% (w/w) were DB 106: 0.30%, DB 124: 0.25%, DY 3: 0.44%, DO 1: 0.40%, DO 3: 0.68%, DR 1: 0.49%, and DR 17: 0.35%; there were variations between the samples also with regard to the number of impurities. DO 3 could not be demonstrated in 4/15 preparations labelled DO 3. CONCLUSION: The results may have implications for individual diagnosis and prevention and when comparing test results from various centres.