P. J. Frosch

Monitoring levels of preservative sensitivity in Europe - A 10-year overview (1991-2000)

A 10‐year multicentre analysis of the frequency of sensitivity to common preservatives collected in 16 centres in 11 countries has shown stable but persisting high levels of sensitivity to formaldehyde and 5‐chloro‐2‐methyl‐4‐isothiazolin‐3‐one + 2‐methyl‐4‐isothiazolin‐3‐one (MCI/MI). It has also revealed a significant increase in the level of reactivity to methyldibromoglutaronitrile (MDBGN) from 0.7% in 1991 to 3.5% in 2000. The current high level of sensitivity to MDBGN requires an urgent safety re‐evaluation and risk assessment update along with consideration of immediate lowering of use concentrations, especially in leave‐on products.

Patch testing with fragrances: results of a multicenter study of the European Environmental and Contact Dermatitis Research Group with 48 frequently used constituents of perfumes

The objective of this study was to determine the frequency of reactivity to a series of commonly fragrances in dermatological patients. A total of 48 fragrances (FF) were chosen, based on the publication of Fenn in 1989 in which the lop 25 constituents of 3 types (1. perfumes, 2. household products, 3. soaps) of 400 commercial products on the US market had been determined. In a pilot study on a total of 1069 patients in 11 centres, the appropriate test concentration and vehicle were examined. For most fragrances, 1% and 5% were chosen, and petrolatum proved to be the best vehicle in comparison to isopropyl myristate and diethyl phthalate. In the main study, a set of 5 to 10 fragrances at 2 concentrations was patch tested in each centre on a minimum of 100 consecutive patients seen in the patch test clinic. These patients were also patch tested to a standard series with the 8% fragrance mix (FM) and its 8 constituents. In patients with a positive reaction to any of the 48 FF, a careful history with regard to past or present reactions to perfumed products was taken. A total of 1323 patients were tested in 11 centres. The 8% FM was positive in 89 patients (8.3% of 1072 patients). Allergic reactions to the constituents were most frequent to oak moss (24), isoeugenol (20), eugenol (13), cinnamic aldehyde (10) and geraniol (8). Reactions read as allergic on day 3/4 were observed only 10 × to 7 materials of the new series (Iso L: Super® (2), Lyral® (3), Cyclacet® (1), DMBCA (1), Vertofix® (1), citronellol (1) and amyl salicylate (1)). The remaining 41 fragrances were negative. 28 irritant or doubtful reactions on day 3/4 were observed to a total of 19 FF materials (more than 1 reaction: 5% citronellol (2), 1%amyl salicylate (2), 1%isononyl acetate (3), 0.1% musk xylol (2). 1%citral (2), and 1% ionone beta (2)). Clinical relevance of positive reactions to any of the FF series was not proved in a single case. This included the 4 reactions in patients who were negative to the 8% FM. In conclusion, the top 25 fragrances commonly found in various products caused few reactions in dermatological patients and these few appeared to be clinically irrelevant, with the possible exeption of Lyral®. However, this data should be interpreted in the light of the relatively small number of patients tested (only 100 in most centres).

Further important sensitizers in patients sensitive to fragrances - II. Reactivity to essential oils

The aim of this study was to determine the frequency of responses to selected fragrance materials in consecutive patients patch tested in 6 dermatological centres in Europe. 1855 patients were evaluated with the 8% fragrance mix (FM) and 14 other frequently used well‐defined fragrance chemicals (series I). Each patient was classified regarding a history of adverse reactions to fragrances: certain, probable, questionable, none. Reactions to FM occurred in 11.3% of the subjects. The 6 substances with the highest reactivity following FM were Lyral® (2.7%), citral (1.1%), farnesol P (0.5%), citronellol (0.4%), hexyl cinnamic aldehyde (0.3%), and coumarin (0.3%). 41 (2.2%) of the patients reacted only to materials of series I and not to FM. 6.6% of 1855 patients gave a history of adverse reactions to fragrances which was classified as certain. This group reacted to FM only in 41.1%, to series I and FM in 12.0% and to series I only in 7.2%. 74.3% of the 39 patients reacting to both FM and 1 of the materials of series I had any type of positive fragrance history, which was significantly higher in comparison to those with isolated reactions to series I (53.6% of 41), p = 0.04. The study identified further sensitizers relevant for patch testing of patients with contact dermatitis, of which Lyral® is the most important single chemical.

Deodorants on the European market: quantitative chemical analysis of 21 fragrances

Deodorants are one of the most frequently used types of cosmetics and side‐effects from them are common. Recent studies relate perfume allergy to this type of product. 73 deodorants were analyzed by gas chromatography ‐ mass spectrometry for the determination of the contents of 7 well‐known fragrance allergens from the fragrance mix and 14 other commonly used fragrance materials. The deodorants were purchased at retail outlets in 5 European countries. It was found that in general, fragrance mix ingredients were more frequently present in vapo‐ and aerosol sprays than in roll‐on products. The levels of the fragrance mix substances ranged from 0.0001–0.2355%. The products investigated contained cinnamic aldehyde and isoeugenol less frequently (17% and 29% respectively), and eugenol and geraniol most frequently (57% and 76% respectively). The 14 other fragrance materials were found in 40–97% of the deodorants, with hedione and benzyl acetate the most frequently found substances. The concentration of these 14 substances ranged from 0.0001–2.7%. It is concluded that the levels of cinnamic aldehyde and isoeugenol found in the deodorants could prove to be relevant for elicitation of contact dermatitis. No conclusions could be drawn about the other fragrance mix constituents, as threshold levels in sensitized individuals have not been investigated. Furthermore, all of the fragrance materials investigated were frequently found in deodorants and, apart from the fragrance mix ingredients, the extent of problems with sensitization to these fragrance materials is largely unknown.

Hand eczema classification: a cross-sectional, multicentre study of the aetiology and morphology of hand eczema.

Background  Hand eczema is a long‐lasting disease with a high prevalence in the background population. The disease has severe, negative effects on quality of life and sometimes on social status. Epidemiological studies have identified risk factors for onset and prognosis, but treatment of the disease is rarely evidence based, and a classification system for different subdiagnoses of hand eczema is not agreed upon. Randomized controlled trials investigating the treatment of hand eczema are called for. For this, as well as for clinical purposes, a generally accepted classification system for hand eczema is needed.

Allergic reactions to a hairdressers’series: results from 9 European centres

To obtain data on the frequency of sensitization among European hairdressers, the patch test results from 9 centres were evaluated. 8 allergens recommended by the ICDRG and EECDRG in the hairdressing series and PPD from the standard series were used to patch test 809 hairdressers and 104 clients suspected of contact sensitization. Among hairdressers, the mean frequencies of sensitization ranked as follows: GMT 19%, PPD 15%, APS 8%, PTD 8%, ONPPD 4%, and PADH 4%. In contrast to GMT in acid permanent waves, the frequency of sensitization to AMT in alkaline permanent waves was only 4%. Frequencies of sensitization to pyrogallol and resorcinol were 0.8% and 0.6%, respectively. The frequencies of sensitization showed marked regional variations, particularly that to GMT, which was highest in Germany (51%), followed by Spain (22%) and London (19%). Clients of hairdressers showed a similar rank order of sensitization frequency, with the exception of APS, which was completely negative in this (small) series.

Lyral® is an important sensitizer in patients sensitive to fragrances

Contact allergy to fragrances is a common problem world‐wide. The currently used fragrance mix (FM) for patch testing has only eight constituents and does not identify all fragrance‐allergic patients. As perfumes may contain 100 or more substances, the search for markers for allergy continues. The synthetic fragrance 4‐(4‐hydroxy‐4‐methylpentyl)‐3‐cyclohexene carboxaldehyde (Lyral®) was tested together with the FM and 11 other fragrance substances on consecutive patients in six European departments of dermatology. All patients were carefully questioned regarding a history of reactions to scented products in the past and were grouped into four categories: ‘certain’, ‘probable’, ‘questionable’ and ‘none’. Lyral® (5% in petrolatum) gave a positive reaction in 2·7% of 1855 patients (range 1·2–17%) and ranked next to 11·3% with FM allergy. Twenty‐four patients reacted to both Lyral® and FM, but 21 (1·1%) reacted positively only to Lyral®. Of 124 patients with a ‘certain’ history, 53·2% reacted to the FM and a further 7·2% to Lyral® only. If any kind of history of fragrance intolerance was given, 80% (40 of 50) of Lyral® positive patients had a ‘positive’ history while only 58·6% (123 of 210) of FM positive patients had such a history; this difference was significant at P < 0·01. Lyral® was identified by gas chromatography–mass spectrometry in some products which had caused an allergic contact dermatitis in four typical patients who showed a patch test positive to Lyral® and negative or doubtful to FM. In conclusion, we recommend the testing of 5% Lyral® (in petrolatum) in patients suspected of contact dermatitis.

Corticosteroid contact allergy: an EECDRG multicentre study

This article describes the results of an EECDRG multicentre study on contact allergy to corticosteroids. A total of 7238 patients were investigated: 6238 in 13 centres in the course of 1993, and 1000 patients in 1 centre in 1993 and 1994. The 5 corticosteroids tested were budesonide 0.1% pet., betamethasone‐17‐valerate 1% pet., clobetasol‐17‐propionate 1% pet., hydrocortisone‐17‐butyrate 1% eth., and tixoeortol‐21‐pivalate 1%., pet.; 189 (2.6%) gave a positive patehtest reaction (+, ++, +++)to at least 1 of the corticosieroids. The data regarding the corticosteroid‐sensitive patients, as well as the patchtest results, were recorded on a standardized form.

Contact dermatitis. A review.

In recent years, there has been a dramatic rise in our understanding of contact dermatitis. This paper is a review of our knowledge of the mechanisms involved in contact dermatitis and related phenomena, the investigation of these events and the emergence of significant new allergens during the last 5 years.

Contents of fragrance allergens in children's cosmetics and cosmetic-toys

Fragrances are one of the major causes of allergic contact dermatitis from use of cosmetics. The aim of the current study was to assess the possible exposure of infants and children to fragrance allergens from cosmetic products and “toy‐cosmetics”. 25 childrens cosmetics or toy‐cosmetic products were analysed by gas chromatography ‐ mass spectrometry. Target substances were the fragrance allergens from the fragrance mix and 14 other fragrance substances, most of which have been described as contact allergens. The fragrance mix ingredients were either not present in childrens shampoos/shower gels and cream/lotions, or they were present in fairly low concentrations. In hydro‐alcoholic products, such as eau de parfum, eau de toilette, several ingredients of the fragrance mix were found: geraniol was present in 7/7 products, hydroxycitronellal in 6/7 and isoeugenol in 2/7 products. Isoeugenol was present in a maximum concentration of 0.07%. In one cosmetic‐toy, cinnamic alcohol was present at 3.7% which exceeds the current industry guideline for safe products by a factor of 5. In all types of products other fragrance allergens were frequently found. In conclusion, children are already exposed at an early age to well‐known allergens, sometimes at concentrations which are considered to be unsafe. As contact allergy usually persists for life, manufacturers of childrens cosmetics should be aware of their special responsibility and apply the highest possible safety standards.