José G. Camarasa

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).

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.

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.

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.

Patch testing with the "sesquiterpene lactone mix": a marker for contact allergy to Compositae and other sesquiterpene-lactone-containing plants. A multicentre study of the EECDRG

6278 patients were patch tested with a sesquiterpene lactone mix (SL‐mix) in 10 European clinics. 4011 patients were tested only with 0.1% SL‐mix. 63 (approximately 1.5%) of whom were positive, with 26 (41%) of these cases being considered clinically relevant. There were no cases of active sensitization occurred though 5 eases of irritation were reported. 22 irritant reactions and 22 cases of active sensitization occurred when testing also with 1% and 0.33% concentrations of SL‐mix. SL‐mix 0.1% pet is shown to be an important patch test and many relevant sensitizations will be missed without routine screening with such a mix. Most patients with SL‐mix sensitivity presented with hand and/or face dermatitis, apparent photodermatitis or more generalised eczema.

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.

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.

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.

Allergic contact dermatitis from triphenyl phosphate

A 29-year-old man, with no previous allergic or atopic history, had a 6-month history of an itchy fissured psoriasiform dermatitis of both palms. He was a carpenter but tolerated woods well. Asked about hobbies, he described making special figures, such as animals, that would participate in festivals at carnival time. For the last few months, he had been constructing a big bird, the feathers of which were applied meticulously one by one. He used natural feathers of different colours, which he attached carefully with a plastic glue. Positive patch test results of a standard series, balsams, plastics and lacquers (Henna!-Trolab®) were as follows at 4 days. paraben-mix 15% pet. + + cobalt chloride 1% pet. + potassium dichromate 0.5% pet. + + formaldehyde 1% aq. + triphenyl phosphate 5% pet. + + Discussion