Carolyn M. Willis

Oral prednisone suppresses allergic but not irritant patch test reactions in individuals hypersensitive to nickel

A multicentre, randomized, double‐blind, crossover study was designed to investigate the effects of prednisone on allergic and irritant patch test reactions. 24 subjects with known allergy to nickel were recruited and patch tested with a nickel sulfate dilution series in aqueous solution, 5% nickel sulfate in petrolatum and 2 dilution series of the irritants nonanoic acid and sodium lauryl sulfate. The subjects were tested ×2, both during treatment with prednisone 20 mg oral daily and during placebo treatment. The total number of positive nickel patch test reactions decreased significantly in patients during prednisone treatment. The threshold concentration to elicit a patch test reaction increased and the overall degree of reactivity to nickel sulfate shifted towards weaker reactions. The effect of prednisone treatment on the response to irritants was divergent with both increased and decreased numbers of reactions, although there were no statistically significant differences compared with placebo. It is concluded that oral treatment with prednisone suppresses patch test reactivity to nickel, but not to the irritants tested.

Variability in responsiveness to irritants: thoughts on possible underlying mechanisms

Patch testing with chemical irritants almost always produces a striking variability in the intensity of reaction between individuals, even amongst normal, healthy subjects. Whilst there have been many attempts to define factors which predispose to heightened or, conversely, to diminished reactivity, the underlying cellular mechanisms responsible for the variability remain poorly understood. In this review, a number of possible explanations are proposed, with a particular emphasis on those which relate to the influence of pre‐existing disease or to the genetic regulation of certain immunological and inflammatory processes.

Clinical morphology of sodium lauryl sulfate (SLS) and nonanoic acid (NAA) irritant patch test reactions at 48 h and 96 h in 152 subjects

In this study of 152 women, comparison of patch test responses between 2 irritants over 96 h at 2 symmetrical anatomical sites is studied. 2 irritants, each at 4 different concentrations (nonanoic acid (NAA) 80%, 40%, 20%, 10%; sodium lauryl sulfate (SLS) 3%, 2%, 1% and 0.5%) and using propan‐lol and‘water for injection’as the respective controls, were placed as 15 μl aliquots, soaked onto filter paper discs in Finn Chambers, on the volunteers left and right lower back. The patches were removed at 47, and read at 48 and 96 h. Irritant reactions were evaluated for erythema and surface changes by degree and area affected. Statistical analysis of the results showed that erythema decreased with time for all concentrations of NAA, and at higher concentrations for SLS. Surface changes increased with time for SLS and at higher concentrations of NAA. There was no statistically significant difference comparing left and right sides. Traditionally in patch testing, reactions which fade after 48 h have been regarded as irritant rather than allergic. This study refutes that assumption. Data from our left to right comparisons, made in the same individuals at the same time, show that irritant reactions may be more reproducible than previously appreciated.

The inuence of patch test size and design on the distribution of erythema induced by sodium lauryl sulfate

Patch testing is an invaluable tool for the experimental induction of acute irritant contact dermatitis (ICD), with a variety of chamber systems available for use. Ideally, the inammatory reactions produced should be of uniform intensity across the test area, thereby facilitating grading of the response and tissue sampling for histopathological studies. Unfortunately, annular, follicular and/ or blotchy erythema frequently occur. In this study, we set out to compare the performance of 5 patch test systems (8 mm, 12 mm and 18 mm Finn Chambers; 19 mm and 25 mm Hilltop chambers) when testing normal healthy volunteers with sodium lauryl sulfate at concentrations selected to produce mild, moderate and moderately severe reactions. Visual assessment of the patch test sites revealed good dose responses with all 5 chamber types. Uniformity of erythema across the test site was more closely linked to the actual intensity of response than the delivery system itself, mild reactions being far less likely to display homogeneous erythema than moderately severe reactions. Extra large chambers did not perform signicantly better than smaller chambers. Balancing the need for a uniform reaction pattern and adequate tissue sampling area, against the exposure risk, we conclude that 12 mm Finn Chambers represent the optimum patch test system for acute SLS‐induced irritation where histopathological investigations are the ultimate aim.

Keratin 17 is expressed during the course of SLS‐induced irritant contact dermatitis, but unlike keratin 16, the degree of expression is unrelated to the density of dividing keratinocytes

The aims of this study were to utilize quantitative immunocytochemical techniques to determine the densities of keratin 16 (K16) and keratin 17 (K17) expressed by keratinocytes during the course of acute patch test reactions to sodium lauryl sulfate (SLS), and to relate these to the proliferative state of the epidermis, as assessed by Ki‐67 immunolabelling. Significantly increased numbers of dividing keratinocytes were present in 48h and 96h reactions, concurrent with high levels of expression of K16 and more moderate expression of K17. Statistical analysis indicated a good correlation between K16 expression and the density of Ki‐67+ keratinocytes present in the epidermis (r=0.843). This was not the case for K17 (r=0.396). The results demonstrate that both K16 and K17 expression are features of acute irritant contact dermatitis reactions, but suggest that the factors which influence and control their expression differ.

Evaluation of gas chromatography mass spectrometry and pattern recognition for the identification of bladder cancer from urine headspace

Previous studies have indicated that volatile organic compounds specific to bladder cancer may exist in urine headspace, raising the possibility that they may be of diagnostic value for this particular cancer. To further examine this hypothesis, urine samples were collected from patients diagnosed with either bladder cancer or a non-cancerous urological disease/infection, and from healthy volunteers, from which the volatile metabolomes were analysed using gas chromatography mass spectrometry. The acquired data were subjected to a specifically designed pattern recognition algorithm, involving cross-model validation. The best diagnostic performance, achieved with independent test data provided by healthy volunteers and bladder cancer patients, was 89% overall accuracy (90% sensitivity and 88% specificity). Permutation tests showed that these were statistically significant, providing further evidence of the potential for volatile biomarkers to form the basis of a non-invasive diagnostic technique.

Ultrastructure of Irritant and Allergic Contact Dermatitis

The ultrastructural changes seen in acute contact dermatitis vary according to the chemical nature and concentration of the substance applied to the skin, the intensity of the response and the time of biopsy. In general, irritants have a greater impact on the stratum corneum than allergens, and produce a wider variety of morphological changes in the viable layers of the epidermis, a reflection of the heterogeneity in their mechanisms of action. Allergic contact dermatitis reactions are generally more uniform, the predominant ultrastructural changes being spongiosis, vesiculation and exocytosis. Epidermal Langerhans cells within both allergic and irritant patch test reactions show ultrastructural evidence of activation and degeneration, and are frequently seen in apposition to lymphocytes. Oedema and capillary dilation are the most commonly described features within the dermis of allergic and irritant patch test reactions. Our knowledge of the ultrastructure of chronic contact dermatitis remains limited.