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Routine patch testing with the sesquiterpene lactone mix in Europe: a 2-year experience. A multicentre study of the EECDRG.

To test the screening value of the sesquiterpene lactone (SL) mix in Europe today and describe epidemiological and clinical features of Compositae-sensitive patients, the SL mix 0.1% pet. was included in the standard patch test series in 11 European clinics. 10,695 patients were tested, and 106 (1%) had positive reactions, 74% of which were of current or old relevance. The prevalence of positive reactions varied between 0.1 and 2.7% in different centres. The median age of the 66 females was 51.5 years, and 55.2 in the 40 males. The 20 occupationally sensitized had a higher % of males and a median age of 43 years, whereas 7 UV-sensitive patients had a median age of 72 years. Garden plants were the major suspected sensitizers and the clinical patterns were partly, in accordance with plant dermatoses in general, involving hands, forearms and face, and partly widespread eczema in a large proportion of the patients. More than 1/3 were positive to perfume and/or colophony, possibly reflecting cross-reactivity. With only 1 case of active sensitization and no irritant reactions, the SL mix is a safe allergen and the overall prevalence of positive reactions supports its continued use in the standard patch test series.

Adult↗

Facial dermatitis: patch test results and final diagnoses.

BACKGROUND: Facial dermatitis may result from allergic or irritant contact dermatitis, from endogenous conditions such as atopic or seborrheic dermatitis, or a combination of contributing factors. OBJECTIVE: To determine the final diagnoses in patients referred for evaluation of facial dermatitis, and the relevant allergens in those ultimately diagnosed with allergic contact dermatitis (ACD). METHODS: A retrospective chart analysis of all patients patch tested for evaluation of facial dermatitis in an Occupational and Contact Dermatitis referral clinic over a 2-year period from October 1995 to October 1997. RESULTS: Of the 383 patients patch tested, 85 (22%) had facial dermatitis. Of these 85 patients, 55 (65%) had spotty or diffuse facial involvement, 21 (25%) had only eyelid involvement, and in 9 (10%) only the lips were involved. Final diagnoses were relatively equally distributed among three categories: one third had ACD, one third had ACD with other contributing factors, and one third had diagnoses other than ACD. Among patients with ACD, the most common relevant allergens were personal care products, preservatives, and fragrances. CONCLUSION: Allergic contact dermatitis is a frequent cause of facial dermatitis in a referral dermatology clinic. However, in up to two thirds of patients, other diagnoses represent either the primary process or a major component contributing to the eruption. Personal care products, preservatives, and fragrances represent the most common relevant allergens in those diagnosed with ACD. A significant number of relevant reactions would be missed if only the TRUE test standard series were used.

Adolescent↗

Gene rearrangement in positive patch tests.

Lymphoproliferative disorders are usually characterized by lymphoid infiltrates that demonstrate clonality in contrast to inflammatory or reactive infiltrates of the skin that are polyclonal without detectable monoclonal populations of T-cells. Probably the southern blot analysis of TCR gene rearrangement can help to delineate the reactive from the malignant processes. In this study, we applied the technique on benign reactive processes in the skin. We examined biopsies from positive patch tests from patients with a delayed hypersensitivity reaction. We found the same gene rearrangement configuration in 11 of 17 patients with positive patch tests. The extra band revealed in these cases was situated in the EcoR1 digested DNA lane at the 8.0 Kb, between the 2 germline bands at the 11 Kb and the 4 Kb respectively. This observation was not correlated to the degree of the inflammatory response or to the specific hapten induced reaction. This pattern was not found in any of 107 patients with malignant diagnoses, but also in six of 43 patients with benign diseases. The clinical implication may suggest the presence or development of clonality in benign inflammatory disorders.

Biopsy↗

Validity and ethics of the human 4-h patch test as an alternative method to assess acute skin irritation potential.

For more than 50 years, the Draize rabbit skin irritation test has reigned supreme as the regulatory method of choice for the identification of skin irritant chemicals. To date no in vitro alternative test has been validated as an adequate replacement. However, one potential option, to test the endpoint of concern (skin irritation) in the species of concern (man) has been overlooked. The advent of predictive in vitro tools for the identification of substances corrosive to the skin has opened up the practical possibility of carrying out safe and ethical studies on small panels of humans. The human 4-h patch test has been developed to meet the needs of identifying chemical skin irritation potential, providing data which is inherently superior to that given by a surrogate model, such as the rabbit. This paper reviews in detail the present state of the human 4-h patch test, highlighting its advantages and noting its utility as the 'gold standard' on which to build future in vitro models.

Animal Testing Alternatives↗

Sensitization to azo dyes: negative patch tests to yellow and red azo dyes in printed paper.

An over 2 x fold increase in para-aminoazobenzene allergy was observed in patients with allergic contact dermatitis during the years 1990-1991. Presuming that an increase in colour-printed newspapers might be a new unrecognized source of clinical allergy to azo dyes, patch tests were performed in 32 patients with an established p-aminoazobenzene allergy using a series of important azo dyes used in offset printing ink (Pigment Yellow 12, Pigment Yellow 13, Pigment Red 53, Pigment Red 57), as well as with dye-containing inks and specimens of colour-printed newspaper containing these azo dyes. In 25 out of the 32 patients (78%), positive patch tests were seen to textile azo dyes, in particular to Disperse Orange 3 (24 patients). In none of the 32 patients were reactions observed to the azo dyes used in printing ink, to the inks used or to the colour-printed paper specimens, indicating that these products were apparently not a cause of contact dermatitis in our group of patients with azo dye sensitization.

Adult↗

Patch testing with a new fragrance mix - reactivity to the individual constituents and chemical detection in relevant cosmetic products.

UNLABELLED: A new fragrance mix (FM II), with 6 frequently used chemicals not present in the currently used fragrance mix (FM I), was evaluated in 6 dermatological centres in Europe, as previously reported. In this publication, test results with the individual constituents and after repeated open application test (ROAT) of FM II are described. Furthermore, cosmetic products which had caused a contact dermatitis in patients were analysed for the presence of the individual constituents. In 1701 patients, the individual constituents of the medium (14%) and the highest (28%) concentration of FM II were simultaneously applied with the new mix at 3 concentrations (break-down testing for the lowest concentration of FM II (2.8%) was performed only if the mix was positive). ROAT was performed with the concentration of the FM II which had produced a positive or doubtful (+ or ?+) patch test reaction. Patients' products were analysed for the 6 target compounds by gas chromatography-mass spectrometry (GC-MS). RESULTS: 50 patients (2.9%) showed a positive reaction to 14% FM II and 70 patients (4.1%) to 28% FM II. 24/50 (48%) produced a positive reaction to 1 or more of the individual constituents of 14% FM II and 38/70 (54.3%) to 28% FM II, respectively. If doubtful reactions to individual constituents are included, the break-down testing was positive in 74% and 70%, respectively. Patients with a positive reaction to 14% FM II showed a higher rate of reactions to the individual constituent of the 28% FM II: 36/50 (72%). Positive reactions to individual constituents in patients negative to FM II were exceedingly rare. If doubtful reactions are regarded as negative, the sensitivity, specificity, positive predictive value and negative predictive value for the medium concentration of FM II towards at least 1 individual constituent was 92.3% (exact 95% confidence interval 74.9-99.1%), 98.4% (97.7-99.0%), 48% (33.7-62.6%) and 99.9% (99.6-"100.0%), respectively. For the high concentration, the figures were very similar. The frequency of positive reactions to the individual constituents in descending order was the same for both FM II concentrations: hydroxyisohexyl 3-cyclohexene carboxaldehyde (Lyral) > citral > farnesol > citronellol > alpha-hexyl-cinnamic aldehyde (AHCA). No unequivocally positive reaction to coumarin was observed. Lyral) was the dominant individual constituent, with positive reactions in 36% of patients reacting to 14% FM II and 37.1% to 28% FM II. 5/11 patients developed a positive ROAT after a median of 7 days (range 2-10). The 5 patients with a doubtful or negative reaction to 28% FM II were all ROAT negative except 1. There were 7 patients with a certain fragrance history and a positive reaction to either 28% or 14% FM II but a negative reaction to FM I. Analysis with GC-MS in a total of 24 products obtained from 12 patients showed at least 1-5 individual constituents per product: Lyral (79.2%), citronellol (87.5%), AHCA (58.3%), citral (50%) and coumarin (50%). The patients were patch test positive to Lyral, citral and AHCA. In conclusion, patients with a certain fragrance history and a negative reaction to FM I can be identified by FM II. Testing with individual constituents is positive in about 50% of cases reacting to either 14% or 28% FM II.

Acrolein↗

Differential patterns of epidermal leukocyte infiltration in patch test reactions to structurally unrelated chemical irritants.

In previous studies, we showed that a number of aspects of the histopathology of irritant contact dermatitis are profoundly influenced by the chemical nature of the irritant applied. We report here that this phenomenon also extends to the infiltration of leukocytes into the epidermis. Healthy volunteers were patch tested with the following irritants and their appropriate controls: benzalkonium chloride, sodium lauryl sulphate, croton oil, dithranol, nonanoic acid, and propylene glycol. After visually grading the intensity of the resulting inflammation, biopsies were removed and the major phenotypic classes of leukocytes identified immunocytochemically. Dermal and epidermal cell densities were determined, and the expression of several activation/proliferation antigens studied. We found a similar pattern of cellular infiltration in the dermis of all irritant groups; the densities of most of the cell types rising in line with the intensity of inflammation. Within the epidermis, however, there were marked differences in the patterns of cellular infiltration between the irritant groups, leading to poorer correlations between leukocyte density and visual grading. The greatest disparity occurred between croton oil and nonanoic acid biopsies, the former being characterized by the influx of large numbers of leukocytes, the latter showing remarkably little exocytosis. Infiltration of neutrophils occurred to varying degrees with all irritants, but a disproportionately large number were present in sodium lauryl sulphate biopsies. All control groups showed a rise in CD4+ cells, with distilled water also producing increases in CD11c+ cells and neutrophils. A selective influx of CD25+ cells occurred in the epidermis of both irritant and control groups. Our observations further highlight the heterogeneous nature of irritant contact dermatitis, and confirm previous findings that visually negative control patch tests show marked cellular reactivity.

Anthralin↗

Atopy patch test reactions are associated with T lymphocyte-mediated allergen-specific immune responses in atopic dermatitis.

BACKGROUND: Positive test reactions to epicutaneous application of aeroallergens served as a model of 'early' eczema in atopic dermatitis (AD) in a number of dermato-immunological studies. However, no quantitative evaluation has been performed so far comparing specific T-cell activation parameters in the peripheral blood of AD patients with positive or negative atopy patch tests (APT). OBJECTIVE: The purpose of this study was to investigate specific immunological parameters in patients with atopic dermatitis showing positive or negative atopy patch tests reactions. METHODS: APT results (n = 96) were compared with allergen-specific IgE, specific lymphocyte proliferation, and the expression of 'activation' markers on peripheral blood T-cells upon in vitro stimulation with house dust mite, cat or grass pollen allergens. RESULTS: Only a subpopulation (48%) of patients sensitized to aeroallergens (i.e. specific IgE > 0.7 kU/L) developed APT-reactions to the corresponding allergen. APT reactions were, however, significantly associated with allergen specific lymphocyte proliferation (p < 0.0001), and a higher number of CD54+ or CD30+ T-cells (p < 0.05) upon in vitro stimulation. CONCLUSION: The association of delayed skin reactions with allergen specific T-cell parameters in the blood points to an immunologically mediated mechanism leading to positive reactions in the APT.

Allergens↗

[Dental materials--problem substances in allergologic diagnosis? II: Patch test diagnosis and relevance evaluation of selected dental material groups].

The problems in patch testing and relevance evaluation as well as the practical consequences are discussed for the most important groups of dental materials (DM). These include metal alloys: amalgam with a low allergy prevalence; palladium salts showing a high correlation with nickel allergy but a low one with metallic palladium or alloys; the widespread allergen nickel is most relevant when dealing with nickel containing DM-alloys that are not corrosionresistant; gold salts with widely differing test results and limited benefit to detect genuine gold intolerance. Among synthetic resins methylmethacrylate is the most important allergen because of the high frequency of exposition. With composite materials and other methacrylates, both cross reactions and active sensitization should be kept in mind. Relevant reactions due to additives are rare; positive benzoylperoxide tests should be interpreted very critically. A number of DM may contain allergens of the etheric oils-colophonium - Perubalsam group. DM should be tested with standardized methods only. As the dental consequences may be expensive, interpretation of such test results demands utmost care and special experience.

Adult↗

Allergic contact dermatitis from cosmetics. Retrospective analysis of 819 patch-tested patients.

BACKGROUND: Cosmetics have been used since the oldest known civilisations, and nowadays almost everybody resorts to beauty products. OBJECTIVE: Considering the increasing incidence of contact dermatitis, the aim of the study is to determine the impact of allergy to cosmetics. METHODS: From January 1998 to December 1999, 819 patients were subjected to epicutaneous tests for suspicion of allergic contact dermatitis (ACD). The results were analysed retrospectively in the total population and in that of children under 16: the interest has been focused on cosmetics. RESULTS: 297 patients (36.3%) with ACD to 1 or more cosmetic ingredients have been detected. 34 (48.6%) out of 70 children patch tested showed an ACD: cosmetics represented the first cause. CONCLUSION: For two decades, the incidence of ACD has been rising; two main reasons can be put forward: a rising product consumption and a more exhaustive allergen research in patch testing.

Adolescent↗

Release of nickel ions from stainless steel alloys used in dental braces and their patch test reactivity in nickel-sensitive individuals.

Nickel ions leached in sufficient quantities from nickel-containing alloys may induce nickel sensitization or elicit allergic contact dermatitis. Nickel-containing stainless steel alloys are generally considered safe for nickel-sensitive individuals to use. The study summarized in this paper investigated 3 parameters. First, the release of nickel was estimated in artificial saliva and sweat from 4 different stainless steel alloys frequently used in dental braces. Second, in a pilot study, oral mucosa cells harvested from 3 dental patients before and after the attachment of dental braces were analysed for possible nickel content. Third, patch test reactivity of the 4 stainless steel alloys was tested on 31 nickel-sensitive subjects. All 4 stainless steel alloys released small amounts of nickel ions into artificial saliva (<0.13 micro g/cm2/week) and artificial sweat (<0.05 micro g/cm2/week), but no measurable amounts of nickel were found in any of the oral mucosa samples. None of the 31 nickel-sensitive subjects reacted to patch testing with the 4 stainless steel alloys, indicating that these stainless steel alloys would be safe to use in direct and prolonged contact with the skin.

Dental Alloys↗

Expression of adhesion molecules in early allergic patch test reactions.

In order to study the relevance of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and endothelial leukocyte adhesion molecule 1 (ELAM-1) for lymphocyte extravasation in the early phase of allergic contact dermatitis, the time courses of lymphocyte infiltration and adhesion molecule expression during initiation of this disorder were determined. Sequential biopsies of positive allergic patch test reactions were obtained 4, 8, 16 and 24 h after antigen application, cryostat sectioned and stained with monoclonal antibodies for ICAM-1, VCAM-1, ELAM-1 and lymphocytes by use of an immunoperoxidase technique. The slides were evaluated semiquantitatively according to appropriate gradation scales that had been defined separately for the staining with each antibody. Our results show that there is a significant upregulation of VCAM-1 and ELAM-1 expression within the first 8 h after antigen application, when lymphocyte extravasation is just beginning. In contrast, ICAM-1 is already expressed in higher levels in normal skin and is hardly enhanced during the first 8 h of patch test reactions. The main influx of lymphocytes occurs 16-24 h after antigen application and is accompanied by a further increase in all three adhesion molecules. We conclude that VCAM-1 and ELAM-1 rather than ICAM-1 may be of particular importance for the start phase of allergic contact dermatitis and that all three of them contribute to an amplification of this inflammation.

Cell Adhesion Molecules↗

Patch testing in children: a study of 562 schoolchildren.

562 schoolchildren from Oporto were patch tested with the standard series of the Portuguese Contact Dermatitis Group (GPEDC). 13.3% of the children had positive reactions, the most common being to neomycin, thimerosal, para-tertiary-butylphenol-formaldehyde (PTBPF) resin and fragrance-mix. Thus contact allergy in children seems not to be as unusual as previously thought.

Adolescent↗

Persistence of patch test reactions to clioquinol (Vioform) and cross-sensitization.

Ten patients with positive patch test reactions to clioquinol were retested in 1979 after an average interval of 6 years. On subsequent testing we also examined test reactions to other quinoline derivatives (including antimalarial drugs) and potassium iodide. All patients showed a positive reaction to clioquinol at retesting. Many cross-reactions of hydroxyquinolines included reactions to quinoline-based antimalarial drugs, and a few allergic reactions to potassium iodide. The consequences of these findings are discussed.

Adult↗

A proposed relevance scoring system for positive allergic patch test reactions: practical implications and limitations.

A relevance scoring system for positive allergic patch test reactions is proposed. It refers to current relevance (CR) as well as past relevance (PR). The system was evaluated in adult patients between January 1 and June 30, 1996, and limited to 4 allergens: nickel sulfate, neomycin sulfate, epoxy resin and colophony. Certain methods available for increasing the accuracy of relevance were used in the present study. Practical implications and limitations of using a relevance scoring system are discussed.

Adolescent↗

The case for patch test readings beyond day 2. Notes from the lost and found department.

Additional patch test readings taken after 2 days (48 hours) are valuable in distinguishing false-positive reactions, which may occur up to 22% of the time. Second readings taken on days 3 through 7 may detect an additional 34% positive reactivity. Those reactions, both lost (initially positive, later negative) and found (initially negative, later positive) by delayed readings, require clinical correlation for relevance as do the readings that persist at and beyond day 2 (positive at both readings).

Allergens↗

Histologic aspects of patch test reactions in allergic contact dermatitis.

Twenty subjects with allergic contact dermatitis were patch tested with the responsible allergen applied to four fixed points on the back. Skin biopsies of the four sites were obtained after 6, 12, 24 and 48 hours, fixed in neutral formalin and stained with hematoxylin-eosin, Giemsa and toluidine blue. Sections were examined and lymphomonocytes, mast cells, eosinophils and basophils counted. In all cases the infiltrate consisted mainly of lymphomonocytes (80-82%); mast cells (5%) and basophils (0.2%) do not present clear variations within the given time. Eosinophils showed a definite numerical increase in six cases out of 20.

Adult↗

Comparative study of the density of particles in suspensions for patch testing.

A simple and reliable method to evaluate the density of particles in patch test suspensions is described. The number of particles per unit volume has been found to vary significantly within a wide range of values. These variations have no relation to the concentration or the molecular weight of the substance, as far as particles larger than 10 micron are concerned. Because the presence of particles is one of the factors which can influence percutaneous penetration and since physical manipulations are able to modify the size of these particles, it is suggested that the kinetics of penetration of haptens through the skin should be revaluated with regard to this special point.

Absorption↗