Cecilia Svedman

Selected oxidized fragrance terpenes are common contact allergens

Terpenes are widely used fragrance compounds in fine fragrances, but also in domestic and occupational products. Terpenes oxidize easily due to autoxidation on air exposure. Previous studies have shown that limonene, linalool and caryophyllene are not allergenic themselves but readily form allergenic products on air‐exposure. This study aimed to determine the frequency and characteristics of allergic reactions to selected oxidized fragrance terpenes other than limonene. In total 1511 consecutive dermatitis patients in 6 European dermatology centres were patch tested with oxidized fragrance terpenes and some oxidation fractions and compounds. Oxidized linalool and its hydroperoxide fraction were found to be common contact allergens. Of the patients tested, 1.3% showed a positive reaction to oxidized linalool and 1.1% to the hydroperoxide fraction. About 0.5% of the patients reacted to oxidized caryophyllene whereas 1 patient reacted to oxidized myrcene. Of the patients reacting to the oxidized terpenes, 58% had fragrance‐related contact allergy and/or a positive history for adverse reaction to fragrances. Autoxidation of fragrance terpenes contributes greatly to fragrance allergy, which emphasizes the need of testing with compounds that patients are actually exposed to and not only with the ingredients originally applied in commercial formulations.

Not only oxidized R-(+)- but also S-(-)-limonene is a common cause of contact allergy in dermatitis patients in Europe

Limonene, one of the most often used fragrance terpenes in any kind of scented products, is prone to air‐oxidation. The oxidation products formed have a considerable sensitizing potential. In previous patch test studies on consecutively tested dermatitis patients, oxidized R‐limonene has been proven to be a good and frequent indicator of fragrance‐related contact allergy. The current study extends these investigations to 6 European clinics of dermatology, where the oxidation mixture of both enantiomers of limonene (R and S) have been tested in 2411 dermatitis patients. Altogether, 63 out of 2411 patients tested (2.6%) reacted to 1 or both the oxidized limonene preparations. Only 2.3% reacted to the oxidized R‐limonene and 2.0% to the oxidized S‐limonene. In 57% of the cases, simultaneous reactions were observed to both oxidation mixtures. Concomitant reactions to the fragrance mix, colophonium, Myroxylon pereirae, and fragrance‐related contact allergy were common in patients reacting to 1 or both the oxidized limonene enantiomers. Our study provides clinical evidence for the importance of oxidation products of limonene in contact allergy. It seems advisable to screen consecutive dermatitis patients with oxidized limonene 3% petrolatum, although this patch test material is not yet commercially available.

Chloroatranol, an extremely potent allergen hidden in perfumes: a dose-response elicitation study

Oak moss absolute is a long‐known, popular natural extract widely used in perfumes. It is reported as the cause of allergic reactions in a significant number of those with perfume allergy. Oak moss absolute has been the target of recent research to identify its allergenic components. Recently, chloroatranol, a hitherto unknown fragrance allergen, was identified in oak moss absolute. The objective was to assess the clinical importance of chloroatranol as a fragrance allergen by characterizing its elicitation profile. 13 patients previously showing a positive patch test to oak moss absolute and chloroatranol were included, together with a control group of 10 patients without sensitization to either of the 2 materials. A serial dilution patch test was performed on the upper back with concentrations ranging from 200 to 0.0063 p.p.m. of chloroatranol in ethanol. Simultaneously, the participant performed an open test simulating the use of perfumes on the volar aspect of the forearms in a randomized and double‐blinded design. A solution with 5 p.p.m. chloroatranol was used for 14 days, and, in case of no reaction, the applications were continued for another 14 days with a solution containing 25 p.p.m. All test subjects (13/13) developed an allergic reaction at the site of application of the solution containing chloroatranol. Among them, 12/13 (92%) gave a positive reaction to the 5 p.p.m. solution and 1 to 25 p.p.m. None of the controls reacted (P < 0.001). The use test was terminated at median day 4. The dose eliciting a reaction in 50% of the test subjects at patch testing was 0.2 p.p.m. In conclusion, the hidden exposure to a potent allergen widely used in perfumes has caused a highly sensitized cohort of individuals. Judged from the elicitation profile, chloroatranol is the most potent allergen present in consumer products today.

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.

Deodorants: an experimental provocation study with hydroxycitronellal

Axillary dermatitis is a common problem, particularly in individuals with contact allergy to fragrances. Many individuals suspect their deodorant to be the causal product of their fragrance allergy. It has been shown that deodorants containing cinnamic aldehyde (cinnamal) can elicit axillary dermatitis in patients sensitized to this substance. The aim of the present investigation was to evaluate the importance of hydroxycitronellal used in deodorants for the development of axillary dermatitis, when applied by individuals with and without contact allergy to this fragrance chemical. Patch tests with deodorants and ethanolic solutions containing hydroxycitronellal, as well as repeated open application tests (ROAT) with roll‐on deodorants with and without hydroxycitronellal at different concentrations, were performed in 14 dermatitis patients, 7 with and 7 without contact allergy to hydroxycitronellal. A positive ROAT was noted only in the patients hypersensitive to hydroxycitronellal (P < 0·001) and only in the axilla to which the deodorants containing hydroxycitronellal had been applied (P < 0·001). Deodorants containing hydroxycitronellal in the concentration range of 0·032–0·32% used twice daily on healthy skin in individuals hypersensitive to hydroxycitronellal can elicit axillary dermatitis in a few weeks.

Citral a fragrance allergen and irritant

Citral is a well known contact allergen and a contact irritant. Routine patch testing in the past may have been restricted because of possible irritant (IR) patch test responses. 586 consecutive patients, with hand eczema, were patch tested with a selection of fragrances including citral 2% petrolatum and the European standard series. 28 of the patients showed a positive patch test reaction (+ to +++) to citral and 82 at least 1 IR patch test reaction and no positive patch test reaction to citral. A statistically significant association between a positive patch test reaction to citral and positive patch test reactions to other fragrances compared with IR reactions (n = 82) was established. The difference regarding fragrance history found between those with IR and positive reactions to citral was not significant. Citral could be an allergen and/or irritant, worthy of further more extensive studies.

LASER DOPPLER IMAGING OF SKIN MICROCIRCULATION

Laser Doppler imaging (LDI), a new technique which allows measurement of skin blood perfusion at a distance from the skin surface, was assessed methodologically in healthy volunteers. Each skin LDI value was based on virtually real-time measurements obtained from a number of discrete measuring sites. In scans made along the circumference of the lower arm, valid figures for LDI (as distinct from no output at all) were obtained in 8/8 measurements at 0 degrees inclination, and in 16/16 measurements at 7 degrees, 14 degrees, 22 degrees, 30 degrees and 38 degrees, respectively. Beyond this inclination a numerical output was obtained in only 9/16 of measurements at an inclination of 48 degrees, in 7/16 at 69 degrees, and in no more than 1/16 at 90 degrees. Values obtained at angles of inclination greater than 38 degrees fell within the relatively narrow range of values obtained at lesser angles of inclination. The findings are of interest since measuring sites of clinical importance may not be flat. Variability of measurement (coefficient of variation in per cent) was studied in the lower leg by performing LDI and conventional laser Doppler flowmetry (LDF) concomitantly. The coefficient of variation for measurements in one subject at rest was 13% for LDI vs. 19% for LDF, the corresponding interindividual coefficient of variation values being 25% vs. 28%. In response to heating, finger pulp perfusion increased by 55% as measured by LDI (p = 0.0051) and by 44% (p = 0.0756) as measured by LDF. In summary, the findings contribute to the validation of LDI for skin perfusion measurement.

Follow-up of the monitored levels of preservative sensitivity in Europe. Overview of the years 2001-2008

Cecilia Svedman1, Klaus E. Andersen2, F. M. Brandao3, Derk P. Bruynzeel4, Thomas L. Diepgen5, Peter J. Frosch6, Thomas Rustemeyer4, Ana Gimenez-Arnau7, Margarida Goncalo8, An Goossens9, Jeanne Duus Johansen10, Arto Lahti11, Torkil Menne10, Stefania Seidenari12, Antonella Tosti13, Jan E. Wahlberg14, Ian R. White15, John D. Wilkinson15, Martin Mowitz1 and Magnus Bruze1 1Department of Occupational and Environmental Dermatology, SUS, University of Lund, Malmo 205 02, Sweden, 2Department of Dermatology and Allergy Centre, Odense University Hospital, Odense 5000, Denmark, 3Department of Dermatology, Hospital Garcia de Orta, Almada 2805-267, Portugal, 4Department of Dermatology, Free University Hospital, Amsterdam NL-1081 HV, The Netherlands, 5Department of Social Medicine, Centre of Dermato-Epidemiology, Occupational and Environmental Dermatology, University Hospital Heidelberg, Heidelberg 69115, Germany, 6Department of Dermatology, University of Witten/Herdecke, Dortmund 44137, Germany, 7Department of Dermatology, Hospital del Mar, Universitat Automa de Barcelona, Barcelona 08003, Spain, 8Faculty of Medicine, Department of Dermatology, University Hospital, Coimbra P3000-175, Portugal, 9Contact Allergy Unit, Department of Dermatology, U.Z.K.U., Leuven 3000, Belgium, 10Department of Dermato-Allergology, National Research Centre, Gentofte Hospital, University of Copenhagen, Hellerup 2900, Denmark, 11Department of Dermatology, University of Oulu, Oulu FI-90014, Finland, 12Department of Dermatology, University of Modena, Modena 41100, Italy, 13Department of Dermatology, University of Bologna, Bologna I-40138, Italy, 14Norrbacka, Stockholm 171 76, Sweden, and 15Department of Cutaneous Allergy, St John’s Institute of Dermatology, London SEI 7EH, UK

Contact allergy to gold in patients with gold-plated intracoronary stents

An increasingly common and effective method for the treatment of atherosclerotic disease in the coronary arteries is percutaneous transluminal coronary angioplasty (PTCA) and stenting. The stents are made of different metals. An increased rate of restenosis when using gold‐plated stents has been shown. Contact allergy to gold is common in many countries. Recently, a study has shown an increased rate of contact allergy to nickel among patients with restenosis and a nickel‐containing stent. The aims of our study were to investigate whether there was an increased rate of contact allergy to gold among patients with gold‐plated stents and if this increased the risk of restenosis. 22 patients who had received a gold‐plated stent were patch tested. An age‐ and sex‐matched population of 88 patients, previously patch tested because of a suspected contact dermatitis, served as controls. In the stent group, 10/22 (45.5%) had a contact allergy to gold, in the control group 18/88 (20.5%); the difference is statistically significant (P = 0.04). There was no significant difference regarding frequency of restenosis. Our study indicates that there is a risk of sensitizing the patient when implanting a gold‐plated stent. Further studies are needed to confirm these results and to evaluate whether there is an increased risk of restenosis.

High frequency of contact allergy to gold in patients with endovascular coronary stents

Background  Stent implantation is an effective method for treatment of atherosclerotic disease. Factors predisposing to in‐stent restenosis are still largely unknown. Contact allergy to metal ions eluted from the stent has been suggested to be a risk factor.