J. D. Wilkinson

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).

Reduced frequency of nickel allergy upon oral nickel contact at an early age.

From animal studies we know that oral administration of T‐dcpcndcnt antigens before sensitization effectively induces systemic immune unresponsiveness. Such ‘oral tolerance’ is persistent, dose‐dependent, antigen‐specific and presumably T suppressor cell‐mediated. Oral tolerance induction could be an effective way to prevent undesired T cell‐mediated immune functions, such as playing a role in allograft reaction, autoimmune and allergic diseases. In the present study allergic contact hypersensitivity (ACH) to nickel, currently presenting the most frequent contact allergy in man, was chosen to establish the feasibility of oral prevention of undesired T cell‐mediated immunity in man. Potentially tolerizing (oral nickel contacts via orthodontic braces) as well as sensitizing (ear piercing) events were studied retrospectively in 2176 patients attending nine European patch test clinics. Patients were interviewed by means of a confidential questionnaire. The results show that ear piercing strongly favoured development of nickel ACH. More importantly, patients having had oral contacts with nickel‐releasing appliances (dental braces) at an early age, but only if prior to ear piercing, showed a reduced frequency of nickel hypersensitivity. Frequencies of other hypersensitivities, in particular to fragrance, were not affected. These results support our view that induction of specific systemic immunologic tolerance by timely oral administration of antigens is feasible in man.

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.

Testing with fragrance mix. Is the addition of sorbitan sesquioleate to the constituents useful

In a multicentre study, the value of adding sorbitan sesquioleate (SSO) to the constituents of the 8% fragrance mix (FM) was investigated. In 7 centres, 709 consecutive patients were tested with 2 types of FM from different sources, its 8 constituents with 1% SSO, its 8 constituents without SSO, and 20% SSO. 5 patients (0.71%) reacted to the emulsifier SSO itself, read as definitely allergic on day 3/4. 53 patients reacted to either one of the mixes with an allergic type of reaction. When tested with the constituents without SSO, 41.5% showed an allergic reaction versus 54.7% with SSO. If both types of reactions were considered (allergic and irritant) 38.3% of 73 patients showed a positive “breakdown” result without SSO, versus 54.8% with SSO. The differences were statistically significant. Reactivity to FM constituents was changed in a specific pattern by addition of SSO‐irritant reactions increased, particularly for cinnamic alcohol, eugenol, geraniol, oak moss and hydroxycitronellal, whereas others showed only a slight change. Allergic reactions were also increased by SSO, but the rank order of the top 3 sensitizers (isoeugenol, oak moss and eugenol) did not change. Cinnamic alcohol was the only constituent with decreased reactivity after addition of SSO. A positive history of fragrance sensitivity (HFS) was clearly associated with a positive allergic reaction to either the mix or 1 of its constituents (51% versus 28.6% with a negative HFS). Irritant reactions were linked to a negative HFS in a high proportion (64.3%). In 17 patients, a repeated open application test (ROAT) was performed with a total of 43 patch‐test‐positive materials. The ROAT was positive in 20/31 (64.5%) tests in 11 patients with a positive HFS, but negative in all 6 patients with a negative HFS (0/12 tests). In conclusion, addition of SSO to the constituents of FM increases both irritant and allergic reactions, though the difference from the results obtained without SSO is not as high as previously reported. The ROAT is a valuable tool in validating such patch test results.

Patch testing with corticosteroid mixes in Europe A Multicentre Study of the EECDRG

This study investigated whether a corticosteroid mix containing tixocortol pivalate, budesonide, and hydrocortisone‐17‐butyrate could detect contact allergy to corticosteroids. 2 corticosteroid mixes, 1 with a high (mix I) and 1 with a low (mix II) concentration and the 3 individual constituents, each at 2 concentrations, were inserted into the standard series of 16 participating clinics. Tests were read on day (D) 3 or 4. 5432 patients were tested, and 110 (2.0%) had positive reactions to at least 1 of the 8 test preparations. Of the 8 preparations, mix I identified most allergic patients, followed by mix II, budesonide 0.10%, budesonide 0.002%, and tixocortol pivalate, both concentrations (1.0 and 0.10%) tracing the same number. With the mixes, 53.2–59.6% of tixocortol pivalate allergy was missed. 47 patients were allergic to either concentration of tixocortol pivalate, 25% of these only to 1.0% and another 25% only to 0.10%. Testing with mix I and tixocortol pivalate 0.10% picked up 98/110, testing with tixocortol pivalate 1.0% and 0.10% and budesonide 0.10% picked up 105/110. 3379 patients were read on both D3 or D4 as well as on D7. Without a late reading (D7), up to 30% of contact allergy to corticosteroid markers was missed.

Contact sensitization to 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one (MCI/MI). A European multicentre study.

The frequency of positive reactions to 5‐chloro‐2‐methyl‐4‐isothiazolin‐3‐one (MCI/MI) were studied at 22 European cntact dermatitis clinics over a period of 1 year. A total of 4713 patients participated. All the patients were patch tested with nickel sulphate, formaldehyde, paraben‐mix, and MCI/MI 19.4% of the patients had positive patch tests to nickel, making this the most common allergen, 3% of the patients reacted to 100 ppm MCI/MI, while 2.6% reacted to formaldchyde and 1.1% to parabens. There was great variation in the frequency of MCI/MI sensitivity among the 22 centres. MCI/MI contact allergy was most common among women and in patients with facial dermatitis, while it was rarely seen in patients with dermatitis on the lower legs. There were no fluctuations in the number of positive patch tests to MCI/MI on a monthly basis when the results from all centres were combined. 117 of the 141 MCI/MI sensitized patients included in the study were retested 88% had positive patch tests when retested. 101 of the MCI/MI‐sensitive patients participated in a double ‐blind, placebo‐controlled product use test. This test showed that 31% of the MCI/MI‐sensitive patients had a positive reaction to a MCI/MI‐preserved product. Only a few patients reacted to a control product. It is concluded that the preservative MCI/MI is an important new contact allergen.

Routine patch testing with the sesquiterpene lactone mix in Europe: a 2-year experience A multicentre study of the EECDRG

To test the screening value of the sesquiterpene lactone (SL) mix in Europe today and describe epidemiological and clinical features of Compositae‐sensitive patients, the SL mix 0.1% pet. was included in the standard patch test series in 11 European clinics. 10,695 patients were tested, and 106 (1%) had positive reactions, 74% of which were of current or old relevance. The prevalence of positive reactions varied between 0.1 and 2.7% in different centres. The median age of the 66 females was 51.5 years, and 55.2 in the 40 males. The 20 occupationally sensitized had a higher % of males and a median age of 43 years, whereas 7 UV‐sensitive patients had a median age of 72 years. Garden plants were the major suspected sensitizers and the clinical patterns were partly, in accordance with plant dermatoses in general, involving hands, forearms and face, and partly widespread eczema in a large proportion of the patients. More than 1/3 were positive to perfume and/ or colophony, possibly reflecting cross‐reactivity. With only 1 case of active sensitization and no irritant reactions, the SL mix is a safe allergen and the overall prevalence of positive reactions supports its continued use in the standard patch test series.

Routine patch testing with frullanolide mix: An European Environmental and Contact Dermatitis Research Group multicentre study

Contact sensitivity to plants containing 1 or more sesquiterpene lactones (SLs) is difficult to diagnose. The mixture of SLs (SL mix) has been shown to detect only about 60% of sensitized individuals. In order to improve the diagnosis of sensitization to plants containing SLs, we have tested a mixture of frullanolides contained in Frullania dilatata and Frullania tamarisci at 3 different concentrations (0·01%, 0·033% and 0·1% in petrolatum). 8605 consecutive eczema patients in 1 North American and 15 European dermatology departments were tested with this mix, and 0·35% of positive cases to the different concentrations were found. Routine use of this mix permitted detection of only a small percentage of extra cases and did not improve the SL mix score. The frullanolide mix should therefore be restricted to investigations in particular geographical zones and/or in particular occupations.