The effect of repeated open exposure to low levels of nickel on compromised hand skin of nickel-allergic subjects.

Nickel is a very common contact allergen, with some reports showing that more than 10% of women are affected. It is therefore important to be able to assess the risk of elicitation of nickel dermatitis in such individuals, particularly in relation to repeated exposure to low levels of this metal. It has been shown previously that under the conditions of a 48-h occluded patch test, some subjects will react to as little as 0.5 ppm nickel on compromised skin. In the present study, the effect of repeated open nickel application combined with repeated treatment with the anionic surfactant sodium dodecyl sulphate has been evaluated on the hand skin of 4 nickel-allergic subjects. Despite 2 of these being known to be particularly sensitive, there was no evidence of a nickel-allergic reaction following 2x daily immersion of hand skin sites in up to 1 ppm nickel over a period of 23 days.

PERINAL--a new no-touch spray to relieve the symptoms of pruritus ani.

A new no-touch aqueous spray has been developed for the topical treatment of pruritus ani. It contains 0.2% hydrocortisone and 1.0% lignocaine hydrochloride, and has been shown in studies involving 83 patients to constitute a most convenient and clinically effective preparation for alleviating the symptoms of this distressing chronic condition.

An arm immersion model of compromised skin (II). Influence on minimal eliciting patch test concentrations of nickel.

The transition metal nickel is a very common cause of allergic contact dermatitis (ACD). In the general population, adults with hand eczema have a high incidence of allergy to nickel, and nickel allergy is high in occupational dermatoses and is often linked to wet work. Nickel may be found as a trace contaminant in some consumer products, e.g., household cleaning agents. It has therefore been debated whether these levels, whilst not a primary cause, might be sufficient to maintain ACD. The minimal concentration of nickel in patch tests on normal skin that will elicit an allergic reaction in highly sensitised subjects is 1-10 ppm. This trial assessed whether reactivity to nickel was altered on compromised dorsal forearm skin and compared this to normal skin on the contralateral dorsal forearm and on the back. Skin damage consequent upon arm immersion in sodium dodecyl sulphate (SDS) greatly enhanced reactivity to nickel on the forearm, with the dorsal aspect reacting most both in number of reactions at each concentration and in the minimal eliciting concentration, which was 0.5 ppm in 2/20 under the conditions of a 48 h occluded patch.

An arm immersion model of compromised skin (I). Influence on irritation reactions.

Patch testing and safety evaluation processes to assess the allergic or irritant potential of substances are usually performed on normal skin. However, the reactivity of compromised skin may be different. Consequently, it is important to have a test procedure which acts as a model for compromised skin and which reproduces on the target sites the cumulative insult which results from repeated exposure, working temperatures, hydration and the action of surfactants. The procedure described uses regular immersion of forearm skin in an aqueous solution of sodium dodecyl sulphate until an identifiable alteration of skin condition is produced. In this first report, the model system has been described in detail and the influence of skin compromise on the response to 3 irritants, citral, sodium dodecyl sulphate and nonanoic acid, has been assessed. The irritation potential of the materials varied, but each irritant produced a greater degree of reaction on skin compromised to be within the normal clinical range one might expect from housework.

Studies of the quenching phenomenon in delayed contact hypersensitivity reactions.

Studies in guinea pig and man have shown that eugenol can quench non-specifically contact urticarial responses, whereas limonene seems largely ineffective. In a comprehensive series of studies, there was little evidence of quenching of delayed contact hypersensitivity reactions to cinnamic aldehyde or citral, including in 'pre-quenched' material supplied by a perfume/flavour company, and in a similar mixture prepared in this laboratory, in the guinea pig model. In addition, there was no evidence of the quenching by eugenol of allergic reactions to cinnamic aldehyde in a panel of human subjects with a proven history of cinnamic-aldehyde-induced allergic contact dermatitis. Overall, the results lend little credibility to earlier literature reports of quenching phenomena in delayed contact hypersensitivity responses.

Immediate contact reactions to chemicals in the fragrance mix and a study of the quenching action of eugenol.

In this study, the nature of non-immune immediate contact reactions (NIICR) produced by cinnamic aldehyde, benzoic acid and sorbic acid were investigated, with particular interest in the 'quenching' ability of eugenol. Three groups of human subjects were studied, and the guinea-pig ear was also used as a model of NIICR. Cinnamic aldehyde, benzoic acid and sorbic acid were all able to produce NIICR in the majority of subjects studied. There was a strong correlation between the susceptibility of each subject to each urticant, but no correlation between the susceptibility to NIICR and age, atopic status or tanning ability. Eugenol caused a reduction in NIICR induced by all three urticants. This 'quenching' effect was apparent even when the eugenol was applied up to 60 min prior to application of cinnamic aldehyde, and its effect was not eliminated by washing. In the guinea-pig-ear model, ear thickening was induced by all three urticants, and this response was inhibited by eugenol.

Minimum eliciting patch test concentrations of cobalt.

In sensitized subjects, minimum eliciting levels of cobalt were estimated using patch tests with aqueous cobalt chloride on both normal skin and on skin pretreated in various ways to enhance penetration and reactivity. 6 reacted to 10,000 ppm and 1 gave an equivocal reaction to 1000 ppm aq. cobalt. Pretreatment of the patch test site for 24 h with surfactant enhanced reactivity, reducing the minimum eliciting concentration to 1000 ppm cobalt chloride in 1 subject, to 100 ppm in 2 subjects, and in 3 subjects to 10 ppm aqueous cobalt chloride. No reactions were obtained at 1 ppm. EDTA was effective in reducing the response to aqueous cobalt.

Influence of detergent washing powders on minimal eliciting patch test concentrations of nickel and chromium.

Minimum eliciting levels of nickel have been estimated in 25 nickel-sensitive subjects, and of chromium in 14 chromium-sensitive subjects by patch tests with aqueous solutions of the respective metals. The minimum level of each metal required to provoke a patch test reaction was considerably greater than that found in fabric washing powder solutions and was in the majority of patients tested of the order of 112 ppm nickel (0.05% nickel sulphate) or 885 ppm hexavalent chromium (0.25% potassium dichromate). One nickel-sensitive subject and one chromium-sensitive subject reacted to 1 ppm of the respective metal. Fabric washing powder did not significantly alter the patch test reaction to nickel sulphate or provoke reactions in nickel- or chromium-sensitive subjects. EDTA significantly reduced the number and severity of patch test reactions to nickel sulphate but not those to potassium dichromate or trivalent chromium.

Halogenation and topical corticosteroids: a comparison between the 17-butyrate esters of hydrocortisone and clobetasone in ointment bases.

Clobetasone butyrate 0.05% (Eumovate), a halogenated topical steroid, was compared with hydrocortison butyrate 0.1% (Locoid) which does not contain any halogen atoms. In the treatment of eczema there was not difference between the preparations, but in that of psoriasis the halogen-containing steriod was significantly more effective. Under normal circumstances neither preparation had any detectable effect on adrenal function, but with large doses under total-body polythene occlusion, circulating cortisol levels were reduced less by the halogenated than by the non-halogenated preparation. Corticosteroids which contain a halogen atom are often considered to cause more adverse effects than the non-halogenated preparations with similar clinical efficacy. This study shows that this cannot be assumed for their ability to suppress cortisol levels.

Effect on adrenal function of topically applied clobetasol propionate (Dermovate).

Thirty-nine patients (15 outpatients and 24 inpatients) with a variety of skin diseases affecting variable areas of the body surface were treated with clobetasol propionate ointment (Dermovate). Before and after treatment the adrenal response to an intramuscular injection of tetracosactrin was rested and additional 9 am plasma cortisol levels were measured at intervals during treatment. A satisfactory initial therapeutic response was achieved in almost all cases during the trial period. When more than 50 g of ointment a week was used a significant number of patients developed adrenal suppression. WHen less than 50 g per week was used any suppression tended to be transtion. These cysts may be the cause of this condition, producing abnormal amounts of ovarian steroids which modify the pituitary response. Futher studies are needed, however, to determine this possibility.