R. J. G. Rycroft

Textbook of contact dermatitis

The Textbook of Contact Dermatitis covers every conceivable aspect of modern day management of contact dermatitis. Both irritatnt and allergic types of contact dermatitis are dealt with clearly and comprehensively, special emphasis being given to occupational aspects as well as to prevention, diagnosis and treatment. Also covered are epidemiological aspects, computerization of patch test data and patient imformation systems, noninvasive bioengineering measurement techniques, methods of skin testing other than patch testing, histopathology of both irritant and allergic contact dermatitis, and subjective reactions. The editors and contributing authors are all leading practitioners in the field. Their expertise has been brought to bear to

Use of the local lymph node assay for the estimation of relative contact allergenic potency.

The effective toxicological evaluation of skin sensitization demands that potential contact allergens are identified and that the likely risks of sensitization among exposed populations assessed. By definition, chemicals which possess the toxicological property of skin sensitization potentially are capable of causing allergic contact dermatitis (ACD) in humans. However, this hazard is not an all‐or‐none phenomenon; clear dose‐response relationships can be discerned and thresholds identified for both the induction of sensitization and the elicitation of contact dermatitis. Commonly, these parameters are grouped under the heading of potency, determination of which is vital for risk assessment. In the present investigation, the local lymph node assay (LLNA) has been employed to determine the relative potency of a range of 20 chemicals. The parameter used is the estimated concentration required to produce a 3‐fold increase in draining lymph‐node cell proliferative activity, the EC3 value. These measurements have been compared with an assessment of the human sensitizing potency of the 20 selected chemicals, each being assigned to 1 of 5 classes based on their human sensitizing potency. The EC3 value, derived from LLNA work carried out in acetone/olive oil vehicle, correlated well with the human classification, with the strongest sensitizers having low EC3 values (<0.1%), weaker sensitizers having EC3 values generally in the 1–10% range, and non‐sensitizing chemicals having EC3 values in excess of 100%. In conclusion, the derivation of the EC3 for a chemical provides an objective and quantitative estimate of potency that is of considerable utility for skin sensitization risk assessment.

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).

The frequency of fragrance allergy in a patch-test population over a 17-year period

Fragrances are widely encountered in our daily environment and are known to be a common cause of allergic contact dermatitis. We have reviewed our patch test data from 1980 to 1996 to establish whether the pattern of fragrance allergy has changed with time. During this period, 25,545 patients (10,450 male, 15,005 female) were patch tested with the European standard series. The mean annual frequency of positive reactions to the fragrance mix was 8·5% in females (range 6·1–10·9) and 6·7% in males (range 5·1–12·9). Females were 1·3 times more likely to be allergic to fragrance (P < 0·001, 95% confidence interval, CI 1·17–1·41). Males with fragrance allergy were older than females by 5·6 years (mean age 48·2 vs. 42·6 years; P < 0·001, 95% CI 3·9–7·3). The incidence of a concomitant positive patch test to balsam of Peru in fragrance‐sensitive patients showed wide variation, suggesting that it is not a reliable marker of fragrance allergy. There was a positive correlation between the isomers isoeugenol and eugenol. Oak moss remained the most common overall allergen throughout the study, positive in 38·3% of females and 35·6% of males who were tested to the constituents of the fragrance mix. During the period of the study the incidence of positive tests to oak moss increased by 5% yearly (P = 0·001, 95% CI 2·2–8·7). The frequency of allergic reactions to eugenol and geraniol remained relatively constant. Isoeugenol and alpha‐amyl cinnamic aldehyde sensitivity increased and hydroxycitronellal showed a slow decline. There was a striking reduction in the frequency of sensitivity to cinnamic aldehyde (by 18% yearly; P < 0·001, 95% CI 14·3–21·0) and cinnamic alcohol (by 9% yearly; P < 0·001, 95% CI 5·2–12·9); these are now uncommon fragrance allergens. These data show temporal trends which may reflect the frequency of population exposure to individual fragrances.

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.

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.

Variation in response of human skin to irritant challenge

A major obstacle to the establishment of a protocol for in vivo irritant skin testing in humans is the apparent variability of responses between individuals. This study of the threshold response of normal human skin to a standard irritant (sodium lauryl sulfate 0.3–10%), in a group of 22 subjects, revealed a marked interindividual variation in their threshold reaction. The results demonstrate that this phenomenon does exist and that it will have to be allowed for in future human irritant test systems or assays.

Patch testing with preservatives at St John's from 1982 to 1993

We have reviewed our patch test results for preservative allergy from 1982 to W3. 8 preservatives were included: formaldehyde. 2‐bromo‐2‐nitropropane‐1,3‐diol (Bronopol™), quatenium‐15 (Dowicil 200™). Imidazolidinyl urea (Germall 115™). diazolidinyl urea (Germall 11™) and 1,2‐dibromo‐2,4‐dicyanpbutane (one of the constituents of Euxyl K 400™). Whereas the allergy rate to formaldehyde is quite stable, there is a slight increase in the imidazolidinyl urea allergy rate to formaldehyde is quite stable, there is a slight increase in the imidazolidinyl urea allergy rate. Quaternium‐15s rate a rapid rise seems to have stabilized. Although very important constituents of cosmetics, preservatives not only induce allergies on the face but also on the hands, and, as expected, the allergy rate in men and women generally differs. Among the 5 formaldehyde‐releasers, there are some favoured simultaneous reactions quaternium ‐15 and formaldehyde, and diazolidinyl urea or imidazolidinyl urea. Coccomitant reactions between 1‐brome‐2‐nitropropane‐1,3‐diol and formaldehyde are not common, and those between 2‐brome‐2‐nitropropane‐1,3‐diol and disazolidynl urea or imidazolidinyl urea very uncommon. Concomitant reactions between imidazolidinyl urea, diazolidinyl urea, and formaldehyde are not very common. This supports the hypothesis that allergic reactions to the Germalls are directed toward the initial molecule rather than to formaldehyde.

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.

A retrospective analysis of contact allergy to lanolin

Background Lanolin is often stated to be an important sensitizer but some of the available literature is based on the analysis of high‐risk patients.Objectives To analyse the frequency of contact allergy to lanolin (wool alcohols) in a central London teaching hospital patch‐test population.Methods Review of 24,449 patients recorded on our database during 1982–96 who were tested with a standard series containing 30% wool alcohols.Results The mean annual rate of sensitivity to this allergen was 1·7%. The wool alcohols‐allergic group contained a higher proportion of females (P < 0·05), and the mean age of both males and females (48·4 and 49·2 years) was higher than that of non‐wool alcohols‐allergic patients (41·4 and 35·9 years; P < 0·0005). There was no difference in atopic eczema status between these groups. The highest prevalence of allergy to wool alcohols was among patients with lower leg dermatitis (6·0%; 95% confidence interval, CI 4·46–7·54), followed by those with anogenital dermatitis (3·23%; 95% CI 1·81–4·65). There was an unexplained decline in the rate of positive patch tests to Amerchol® L‐101. However, some patients who reacted to this were negative with wool alcohols, so it may be a useful additional test reagent. The mean rates of allergy to Eucerin® (0·65% per annum) and 50% hydrogenated lanolin in petrolatum (1% per annum) were low, and we no longer use these as test reagents.Conclusions This study illustrates that lanolin sensitization has remained at a relatively low and constant rate even in a high‐risk population (i.e. patients with recent or active eczema).