Patch Test Procedure Research Articles

Allergic contact granuloma due to palladium following ear piercing

Two cases of sarcoidal-type allergic contact granuloma due to metals in ear piercing are presented, the first to palladium (Pd) only, and the second to Pd and possibly also to other metals. Both the patients developed papulonodular lesions at the helices following ear piercing, which after 3-4 weeks, became more granulomatous and very resistant to treatment. Indeed, repeated intralesional injections with corticosteroids produced only a temporary regression of the lesions. Biopsies from the persistent granulomatous lesions from the helices in both the patients and the positive test to Pd in case 2, 3 weeks after the patch-testing procedure, demonstrated epithelioid granulomas, with some multinucleate histiocytes surrounded by a lymphocytic-histiocytic infiltrate. Areas of fibrinoid necrosis were found in both the helix biopsies. An infectious pathology was excluded. Patch testing showed a strong positive reaction to Pd only in case 1 and to Pd and nickel in case 2. Chemical analysis of the earring of patient 1 confirmed the presence of Pd; however, analysis of the earrings of the second patient did not show the presence of Pd, but showed the presence of nickel and copper. Both the clinical and histological findings concur with some rarely reported similar observations in the literature.

Prevalence and relevance of contact dermatitis allergens: A meta-analysis of 15 years of published T.R.U.E. test data

Background The patch test procedure is frequently employed to help determine or confirm the cause of allergic contact dermatitis (ACD). The T.R.U.E. Test has become a global standard and is the commercially available patch test system currently used within the United States. Although many studies report T.R.U.E. Test data, none has measured the overall prevalence and relevance of reactions to the allergens tested by the T.R.U.E. Test. Our objective is to describe the prevalence and relevance of contact dermatitis allergens as tested by the T.R.U.E. Test. Methods We conducted a search of the MEDLINE database from 1966 to June 2000 for all publications on the use of the T.R.U.E. Test in the clinical evaluation of ACD in human subjects. Inclusion and exclusion criteria were applied. For each study, we identified and recorded the number of subjects tested, the number of patients with positive reactions, and the number with relevant reactions. Data were analyzed using the SAS system (Cary, NC). Results Ours is the first study to compile the entire corpus of published T.R.U.E. Test data and to examine these data using meta-analytic techniques. The meta-analysis shows that nickel (14.7% of tested patients), thimerosal (5.0%), cobalt (4.8%), fragrance mix (3.4%), and balsam of Peru (3.0%) are the most prevalent allergens. The 5 least prevalent allergens are paraben mix (0.5%), black rubber mix (0.6%), quaternium-15 (0.6%), quinoline mix (0.7%), and caine mix (0.7%). By contrast, North American Contact Dermatitis Data Group (NACDG) data show that the 5 most prevalent allergens are nickel (14.3%), fragrance mix (14%), neomycin (11.6%), balsam of Peru (10.4%), and thimerosal (10.4%). NACDG data indicate that the prevalence of allergy to cobalt is 9.2%. In order to assess the clinical importance of T.R.U.E. Test allergens, we employ the Significance-Prevalence Index Number (SPIN). Based on SPIN, the most clinically important allergens tested by the T.R.U.E. Test are nickel (SPIN = 894), cobalt (266), fragrance mix (158), colophony (141), and thiuram mix (138). Conclusions Our results identify the prevalence of common contact dermatitis allergens as tested by the T.R.U.E. Test and are in general agreement with previously published reports using other patch test methods. Over 3700 allergens have been identified as causing ACD, of which the T.R.U.E. Test tests only 23. Thus, the T.R.U.E. Test is a screening test at best. Comparison with NACDG data suggests that clinically important allergens may be missed by the T.R.U.E. Test.

FS02.6 Patch test reactivity to nickel sulphate and fragrance mix in unselected children

Objectives: Study patch test reactivity to nickel sulphate and fragrance mix in a population of unselected infants with focus on reproducibility, clinical relevance, and nickel patch test concentration.Method: The data presented is part of a clinical epidemiological study of allergic diseases in newborns followed prospectively with questionnaire, clinical examination and testing at 0, 3, 6, 12 and 18 months of age. TRUE Test patches were used with nickel sulphate in 3 concentrations: 200, 66, 22 ìg/cm2 and fragrance mix 430 ìg/cm2. A positive reaction suggesting sensitisation was defined as at least palpable erythema present at both the 12 and 18 months follow‐up visits.Results: A total of 543 children (268 girls, 275 boys) were patch tested at least once, 304 children were tested at both 12 and 18 months. The prevalence of a reproducible positive reaction to nickel sulphate 200 ìg/cm2 was 8.6%(20 girls, 6 boys). A transient reactivity was observed in 111 children (53 girls, 58 boys). A clinical relevance to nickel was found in only one child. There was no association between number of patch test procedures performed and reactions to nickel sulphate. Reproducible reactivity to fragrance mix was not found.Conclusion: A high proportion of transient patch test reactivity to nickel sulphate 200 ìg/cm2 was found. Patch testing with nickel in concentrations used for adults cannot be recommended in infants. The interpretation of a singular positive nickel patch test in small children must be assessed with caution. Allergic reactions to fragrance mix were not found in this age group.

Evidence-based diagnosis in patch testing.

Evidence-based medicine (EBM) is defined as the integration of the best research evidence with clinical expertise and patient values. Based on the principles of EBM, we can conclude that patch testing is cost-effective only if patients are selected on the basis of a clear-cut clinical suspicion of contact allergy and only if patients are tested with chemicals relevant to the problem (high pretest probability). Random patch testing (low pretest probability) should be discouraged. Proper pretest probability assessment can only be done in expert centres, because problem-based testing requires both a thorough knowledge of the patch-test procedure and knowledge about potential sensitizers in a specific environment.

Patch-Test-Induced Subjective Complaints

Background: Many patients report subjective complaints during epicutaneous patch testing. Objective: To demonstrate the possible relationship between the occurrence of subjective complaints and patch testing. Methods: All consecutive patients who were referred to our clinic for patch testing, during 1 year, were investigated to study a possible association of the patch test procedure and subjective complaints like tiredness, shakiness or feeling unwell. The patients were asked to fill in a form concerning subjective complaints on the days of the investigation. Only those without complaints on the day the patches were applied were included in the study (n = 102). Results: Of the 102 patients, 17 had complaints on both days 2 and 3, 14 only on day 2, 6 only on day 3 and 65 did not develop any complaints at all. The number of patients with complaints on both days 2 and 3 (n = 17) was larger than was to be expected from chance (n = 4.6; p < 0.01). There was a significant correlation between the number of positive patch test reactions and the number of complaints on day 2 (r = 0.19; p << 0.001) and on day 3 (r = 0.15; p < 0.001). Positive patch tests were found in 72.2% of the patients who reported the complaint of shakiness; this proportion is significantly higher than expected from chance (p < 0.05). Conclusion: The results confirm those of our earlier study and demonstrate that patch testing can cause subjective complaints, especially when positive patch tests are present.

Principles and methodology for identification of fragrance allergens in consumer products.

Fragrances contain several hundreds of different chemicals, a few major and many minor, which are responsible for the complexity of the odour. Fragrances are a major cause of allergic contact dermatitis. As a diagnostic tool, the current fragrance mix is very useful though not ideal. A 50-year-old woman presented with a pruriginous, erythematous eruption, characterized by papules, vesicles, exudation and crusting over the neck and chest. With the suspicion of fragrance allergy, patch testing was performed. Initially, the only positive reaction observed was with her own eau de toilette named Woman. The TRUE Test fragrance mix patch test was negative. Chemical fractionation of Woman perfume concentrate was combined with a sequenced patch testing procedure and with structure-activity relationship studies. Ingredients supplied by the manufacturer were also included in the study. Benzophenone-2, Lyral, alpha-hexyl cinnamic aldehyde and alpha-damascone were found to be responsible for the patient's contact allergy to the commercial product. These substances contain chemical structural alerts giving them antigenic ability. The common use of new chemicals to manufacture fragrances, and the increased number of patients sensitive to them but with negative fragrance mix reactions, makes it necessary to identify new potential fragrance sensitizers in commercial products.

EXPRESSION OF HEAT SHOCK PROTEINS IN HEAVY METAL-PROVOKED INFLAMED HUMAN SKIN

ABSTRACTThe expression of heat shock protein (hsp) 65, 72 and 90 was studied in human inflamed skin after heavy metal salt treatment, by using epicutaneous patch-testing procedure and immunohistochemistry. There was a slight immunoreactivity to hsp 65 and hsp 72, but not to hsp 90 in keratinocytes in normal skin. An increased immunoreactivity to hsp 72 was obtained in apically located keratinocytes in a statistically signific ant (p<0.01) increased number of reactions to cobalt chloride and gold chloride compared to control skin. These metal salts also induced the highest degree of expression of keratinocyte intercellular adhesion molecule (ICAM)-1. There were epidermal dendritic cells as well as macrophage-like cells in the dermis, which expressed hsp 65 and hsp 90, in biopsies from metal salt-treated and control skin, while expression of hsp 72 in macrophage -like cells was found only in the dermis.

Experimental Validation of a Structure–Activity Relationship Model of Skin Irritation by Esters

SAR model development should be a continuous process involving formulation then experimental testing of the model, incorporation of test results into the database, then refinement of the model using the expanded database. The larger database affords greater confidence in its ability to predict the biological response. This iterative procedure was employed with a recently developed structure-activity relationship (SAR) model of human skin irritation. Based on a “leave-one-out” cross validation, the mean sensitivity of the initial model was 0.89, the mean specificity was 0.74. A clinical validation study was conducted to assess the ability of the model to predict human skin irritation by esters commonly used as fragrance ingredients. Esters that were found to cause irritation in rabbits, and that were within the predictive space of the SAR model, were selected for human testing using the patch test procedure. Of the 34 rabbit irritants selected, 16 were predicted by the model to be positive and 18 were predicted to be negative. Patch testing yielded two positive esters, allyl heptanoate and allyl cyclohexanepropionate. These test results were incorporated into the database to refine the SAR model. Best subsets regression and linear discriminant analysis were used to generate 10 submodels consisting of 10 irritants and 50 non-irritants randomly selected from the new database. Physicochemical parameters associated with irritant esters, when compared with non-irritant esters, differed somewhat from those identified in the original model. Irritant esters had lower solubility parameter and water solubility, higher Hansen dispersion and Hansen hydrogen bonding, and lower sum of partial positive charges, when compared with non-irritant esters. The sensitivity of the new model is 0.69 and specificity is 0.67. The results of this study indicate that SAR models based on limited data may not accurately predict the activity of unknown chemicals even though the computationally-derived sensitivity and specificity of the models are high. This finding emphasizes the need for experimental validation of models and their refinement as new data become available.

Skin irritation from air‐oxidized ethoxylated surfactants

Surfactants are known to be skin irritants, but change in their irritant potential due to change in composition during handling and storage has not previously been investigated. The aim of this study was to investigate the influence of oxidation products on the irritant potential of a non-ionic ethoxylated alcohol, C12E5. Pure and oxidized C12E5 were tested, using 2 different patch test procedures; 1 with a single 24 h exposure and 1 with repeated exposures. 18 healthy volunteers participated in each of these studies. Evaluations were made by visual scoring and by measurement of transepidermal water loss and skin blood flow. In the single exposure study, no significant difference in skin irritation was observed between pure C12E5 and a sample of oxidized C12E5 at the concentrations tested (1, 3, 9 and 27%). After repeated exposures, however, the oxidized C12E5 was significantly more irritant than pure C12E5 at the concentrations 9% and 27% (p<0.05). Non-ionic ethoxylated surfactants are known for their weak skin irritant effect and are, due to this, often included in products with prolonged contact with the skin, i.e., skin care products. An increased irritant potential after oxidation might be of importance due to the conditions of use.

Delayed-type hypersensitivity to contact allergens in psoriasis. A clinical evaluation.

The possibility for patch testing procedures to detect contact allergy was examined in 85 hospitalized patients with forms of psoriasis. Exclusion criteria were active lesions on the back, the use of strong topical corticosteroids, methotrexate, cyclosporin and UV therapy. After screening, a group of 47 patients with different forms of psoriasis were selected for patch testing. Personal history, including topical treatment, occupation and domestic circumstances, were reasons to extend the standard series of allergens. Tars, nickel sulfate, perfume and balsam of Peru scored high. The overall positive rate was 68%. This is higher than that observed in earlier studies. The unexpected results are discussed in the light of the possible mechanism of action.

Corneometiy measurements to evaluate skin dryness in the modified soap chamber test.

Patch test procedures have been developed to compare the irritation potential of surfactant-based products. Skin changes due to product application are usually assessed visually by a trained evaluator using standard scoring scales or instrumentally. This study has been carried out to optimize the assessment of skin dryness in the Modified Soap Chamber Test both by visual scoring and Comeometer measurement, with transepidermal water loss as an additional measure. Products were applied, under occlusion, to the skin, for 2 successive periods of 24 and 21 h; skin reactions were evaluated 3 h after removal of each series of patches, and followed up to 7 days after patches had been removed. Skin dryness progressively develops after patch removal, and reaches a maximum 3 to 5 days later. Capacitance measurements correlate the best with visual scoring of dryness when waiting 5 days after patch removal before assessment. Comeometer is an useful instrument to quantify observed dryness only when transepidermal water loss has recovered a value close to its baseline value. For both visual and instrumental assessments of skin dryness, waiting 3 to 5 days after patch removal in the Modified Soap Chamber Test will provide the most valuable results.

Gamma/delta T cells and human skin reactivity to heavy metals.

Gamma/delta T cells may act as a first line of defence and respond to stress signals from the surrounding tissue. In the present investigation the occurrence of gamma/delta T cells was studied in the human skin after application of heavy metal salts by a routine epicutaneous patch-testing procedure. Gamma/delta cells were not found in normal skin. They were observed in all 14 allergic or irritant patch-test reactions to gold chloride and in 6/8 such reactions to mercuric chloride, where they comprised 16 +/- 6% and 15 +/- 6%, respectively, of the CD3+ cells in the dermis. They were also epidermotropic. Very few of these cells were found in reactions to salts of nickel and silver, except that they were increased in hair follicle epithelium in a reaction to silver nitrate. The gamma/delta cells expressed the V delta 2 and the V gamma 2 gene segments and were CD4-8-, indicating that they had the same phenotype as gamma/delta lymphocytes in the peripheral blood. Moreover, they were 'memory' T cells. These results indicate that gamma/delta lymphocytes play a role in the skin defence against highly reactive heavy metals.

Patch test results of the Dermatology Clinic Zurich in 1989: personal computer-aided statistical evaluation.

The patch test results of 921 consecutively tested patients were registered on an IBM personal computer. A computer program based on the dBase III plus database software, especially designed for this purpose, was used. The statistical evaluation was performed with dBase III plus. 59% of the probands were females and 41% males. The average age was 42.8 years. 26% of the probands were inpatients and 74% outpatients. A majority of the patients presented with eczema of the hands, face or the lower legs. The largest occupational groups were houseworkers and cleaning personnel, office workers and pensioners. To 450 of the 921 patients, at least 4 test series were applied simultaneously. These included European standard, vehicles and emulgators, topical medications, and preservatives and biocides. The other 20 test series available were employed only by 2-81 patients each. The highest sensitization rates were found with: nickel, 18.7%; cobalt, 10.2%; balsam of Peru, 8.8%; framycetin, 8.0%; neomycin, 6.8%; potassium dichromate, 6.1%; p-phenylene diamine, 5.4%; paramix, 4.9%; formaldehyde, 4.8%, and (chlor)methylisothiazolinone, 4.7%. The critical evaluation of the data showed two kinds of problems: first, test-specific aspects led to optimization of the patch test procedures; second, the crucial importance of an adequate statistical analysis for epidemiological investigation was revealed.

Methylchloroisothiazolinone-methylisothiazolinone reactions in patients screened for vehicle and preservative hypersensitivity

More than 1100 patients were tested with methylchloroisothiazolinone-methylisothiazolinone, 100 ppm, in aqueous and petrolatum-based patch test materials from 1985 to 1987 by members of the North American Contact Dermatitis Group. Thirteen reactions to the aqueous materials and 10 to the petrolatum-based materials were observed. Irritant reactions were infrequent, and about half the reactions were deemed relevant. From 1984 to 1985, patch tests with this substance at a concentration of 250 ppm in petrolatum were conducted. Thirteen persons were identified as allergic, but three others were sensitized by the patch test procedure. Sensitization as not observed in tests with aqueous or petrolatum-based substance at a concentration of 100 ppm, and this concentration appears to be the best compromise between safety and sensitive detection of allergy. Use tests are helpful but not infallible as a guide in establishing relevance with methylchloroisothiazolinone-methylisothiazolinone. Wash-off products are frequently well tolerated by patients with positive reactions to this substance.

Potential for irritation increases from the wrist to the cubital fossa.

The effect of site on the irritant dermatitis potential was studied in 10 subjects using the volar surface of the forearm. Erythema scoring and transepidermal water loss (TEWL) measurements were used to assess irritation at different levels on the forearm. A sodium lauryl sulphate (SLS 2 g/v%) solution was used as a standard irritant in a patch test procedure and on open tests. Both the erythema scores and measurements of the TEWL of exposed skin showed significant localization differences, and demonstrated that the same sites on the forearm should be used for irritancy tests and possibly physiological studies.

Contact Dermatitis and Diagnostic Techniques

Proper use of patch testing to identify the causes of contact dermatitis requires that the physician use the test where it will have the highest likelihood of benefit. Identifying endogenous dermatoses by morphologic and historical criteria and distinguishing these from likely cases of exogenous dermatoses prior to testing will enhance the number of people helped by applying the patch test procedure. Knowledge of the technical aspects of patch testing and how to instruct patients with positive and negative tests is an essential part of solving complex contact dermatitis problems.

The development of the patch testing procedure and working for consistency

Patch testing is a necessary tool to investigate contact dermatitis, which has developed alongside the increased knowledge of contact sensitivity in the past 100 years. The history of patch testing, the current state of the art with its problems, and future prospects are discussed.

Prevalence of mercury hypersensitivity in dental students

F or approximately 150 years, mercury in amalgam has been used as a dental restorative material. Throughout this time the potential toxicity of this metal to patients’” and dental professionals4-9 has been studied and debated. In these reports and many others, problems with mercury contamination and toxicity were uncovered. Although the extent of the problems may be controversial, the overall impact has led to increased emphasis on mercury hygiene in dental schools and in private practice.‘0,1’ Most studies on mercury contamination have concentrated on patients and dentists, with considerably less attention to dental students. This is unfortunate because students, in a sense, serve as a bridge between the two major groups, practicing dentists and their patients. Certainly, problems with mercruy contamination in first-year dental students should be similar to problems in patients. Conversely, problems with mercury contamination or toxicity in fourth-year dental students should reflect problems in practicing dentists. Some attempts have been made to study this unique group. In most of these experiments, however, the number of students screened for different forms of mercury contamination or toxicity has been small, with numbers ranging from 8 to 29 students.‘2-‘6 For this reason, there is little agreement between the results of these pilot studies. In a study by White and Brandt,” however, 298 dental students were screened for allergic responses to mercury. Through the use of epicutaneous patch-test procedures, they showed that the rate of hypersensitivity to mercuric chloride increased as students progressed through the dental curriculum. This observation linking hypersensitivity to mercury to the preparation of alloy restorations suggested that mercury as an allergen was an additional occupational hazard for the dental profession. With increased emphasis on mercury hygiene and the development of improved techniques for preparing amalgam, a second study of this phenomenom was

Result of patch test and allergic contact dermatitis--statistics over the past six years

Over the past six years we have practised the examination of standard allergen patch test for patients with allergic contact dermatitis or other contact skin diseases and report the data in this paper. Three hundred and ninety-four patients, who complained of itching and skin legion due to contact with chemical agents were examined. Following the widespread use of the patch test procedure, we used eighteen standard allergenic agents and about eighty percent of these patients showed positive reaction. Furthermore, over fifty percent of the patients manifested positive reaction to the plural allergenic agents. The highest percentage of positive reaction was found in the 30-40 years old patients. Of the series of allergenic agents, urushiol caused the highest positive reaction. Among other agents, metal group, e.g., cobalt chloride, and formalin were also high. Many positive patients to paraphenylendiamine (PPI) were engaged in the occupations associated with PPD. This evidence indicates that the materials that are frequently treated at the place of work or homelife play a major role in the pathogenesis of allergic contact skin diseases.

Quantitation of contact allergy in guinea pigs by measuring changes in skin blood flow and skin fold thickness

Skin blood flow determined by laser Doppler flowmetry (LDF) and skin fold thickness (SFT) have been used to quantitate allergic contact dermatitis in the guinea pig maximization test (GPMT) using chlorocresol as the allergen. The closed patch test procedure itself influenced both LDF and SFT measurements when determined in 12 sham-treated guinea pigs. The LDF was maximal at 24 hours and the SFT at 48 hours. Before correlating the quantitative measurements with the conventional visual scoring in test and control animals the value from a nearby control site was subtracted from the test site values. The correlations were highly significant (p less than 0.001-0.05) indicating that the quantitative methods were useful supplements to the visual scoring as a measure of interobserver and interlaboratory differences.