Klaus Ejner Andersen

European Society of Contact Dermatitis guideline for diagnostic patch testing – recommendations on best practice

The present guideline summarizes all aspects of patch testing for the diagnosis of contact allergy in patients suspected of suffering, or having been suffering, from allergic contact dermatitis or other delayed‐type hypersensitivity skin and mucosal conditions. Sections with brief descriptions and discussions of different pertinent topics are followed by a highlighted short practical recommendation. Topics comprise, after an introduction with important definitions, materials, technique, modifications of epicutaneous testing, individual factors influencing the patch test outcome or necessitating special considerations, children, patients with occupational contact dermatitis and drug eruptions as special groups, patch testing of materials brought in by the patient, adverse effects of patch testing, and the final evaluation and patient counselling based on this judgement. Finally, short reference is made to aspects of (continuing) medical education and to electronic collection of data for epidemiological surveillance.

Prevalence of atopic dermatitis, asthma, allergic rhinitis, and hand and contact dermatitis in adolescents. The Odense Adolescence Cohort Study on Atopic Diseases and Dermatitis

Background  Atopic diseases are common in children and adolescents. However, epidemiological knowledge is sparse for hand eczema and allergic contact dermatitis in this age group. Furthermore, no population‐based studies have evaluated the prevalence of atopic diseases and hand and contact dermatitis in the same group of adolescents.

The baboon syndrome: systemically-induced allergic contact dermatitis*

The catchword “baboon syndrome” is used to denote a characteristic distribution pattern of systemic allergic contact dermatitis. Diffuse erythema of the buttocks, upper inner surface of the thighs, and axillae are characteristic features. We describe 3 cases provoked by ampicillin, nickel and mercury. The condition may be overlooked and suspected of being a textile dermatitis or seborrhoeie dermatitis of the elderly.

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).

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.

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.

Hand eczema severity and quality of life: a cross-sectional, multicentre study of hand eczema patients

Background and Objectives:  Hand eczema is a chronic disease with negative impact on quality of life (QoL). In this study, QoL in hand eczema patients is assessed and related to age, sex, severity, and diagnostic subgroups.

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.