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Patch testing to detect corticosteroid allergy: is it adequate?

Whilst patch testing with corticosteroids in ethanol is more sensitive than either petrolatum or the cream formulation, the frequency of false-negative reactions is not known. We have compared patch testing with corticosteroid at 1% in ethanol with intradermal (i.d.) tests using 1 mg corticosteroid suspended in normal saline. Patch tests with tixocortol pivalate and budesonide detected all patients allergic to hydrocortisone and budesonide, respectively. For other corticosteroids, the use of ethanol as a vehicle resulted in both false-positive and false-negative reactions. In particular, patch tests with hydrocortisone-17-butyrate missed 30% of all positive reactions detected by i.d. testing. There may be a case for advising the avoidance of this steroid in all patients who are positive on patch testing to tixocortol pivalate and budesonide.

Anti-Inflammatory Agents↗

A stronger patch test elicitation reaction to the allergen hydroxycitronellal plus the irritant sodium lauryl sulfate.

Household and cleaning products often contain both allergens and irritants. The aim of this double-blinded, randomized, paired study was to determine whether patch testing with an allergen (hydroxycitronellal) combined with an irritant [sodium lauryl sulfate (SLS)] cause a stronger patch test elicitation reaction than patch testing with the allergen (hydroxycitronellal) alone, in patients previously patch tested positive to hydroxycitronellal. A stronger patch test elicitation reaction was defined as at least 1 day of patch test reading showing more positive patch tests (+, ++ or +++) on the forearm patch tested with 6 concentrations of SLS plus hydroxycitronellal than on the forearm tested with 6 concentrations of hydroxycitronellal alone and no day of patch test readings showing more positive tests on the hydroxycitronellal forearm. 15/20 (75%) had at least 1 day of patch test reading with more positive patch tests on the forearm patch tested with SLS plus hydroxycitronellal and no day of patch test readings with more positive patch tests on the forearm tested with hydroxycitronellal (P = 0.0253). Estimation of the blood flow with laser Doppler supported these findings.

Adult↗

An audit of the value of patch testing: the patient's perspective.

Evaluation of the benefits of patch testing has been difficult. We have attempted to establish patients' views on patch testing and to assess the effectiveness of advice given in the clinic. Postal questionnaires were sent to 135 patients. A total of 105 replies were received (77.8% response rate). 42 patients (40.4%) reported improvement in their skin condition after testing. Of the 43 patients with a final diagnosis of allergic contact dermatitis (ACD), 31 (72%) believed that patch testing had helped. About 1/2 of these were able to avoid the allergens concerned and had made changes in their lifestyle. This contrasts with the group of patients with final diagnoses other than ACD, in whom only 20 of 62 (32%) recorded patch testing as helpful. Similar numbers in both groups had improved sufficiently to be discharged from the clinic. 91 of the patients were entirely correct in their knowledge of the patch test results. 39 felt that the results had not been explained in sufficient detail. This study shows that patch testing is beneficial, especially for those with ACD. Patients' knowledge of the results was good but education could be improved.

Adolescent↗

Gas chromatographic and mass spectrometric purity analysis of acrylates and methacrylates used as patch test substances.

BACKGROUND: To make a correct diagnosis of allergic contact dermatitis, patch testing needs to be performed, and the patch test substances need to be pure. OBJECTIVE: We wanted to study how pure commercial (meth)acrylic patch test substances are. METHODS: The purity of (meth)acrylic patch test substances (diacrylates, dimethacrylates, and triacrylates) dissolved in acetone was determined by gas chromatography. The impurities were identified by mass spectrometry in both electron impact and chemical ionization mode. RESULTS: The analyzed dimethacrylates were very pure (97% to 99%). The purity of the three studied diacrylates were 81% to 91%, but tripropyleneglycol diacrylate (81% pure) contained as much as 13% of tripropyleneglycol monoacrylate. The purities of the triacrylates were 82% to 86%. All diacrylates and triacrylates contained 1% to 13% of the corresponding hydroxyacrylates. CONCLUSION: The impurities may result in false interpretation of the patch test results, and accordingly in wrong diagnosis. If the patch test substance is impure, at least, the chemical impurities that can be detected by gas chromatography should be measured and reported in a certificate of analysis, preferably from each batch.

Acrylates↗

Predictive patch testing of "Medigloves" on humans using the repeated insult technique.

The predictive patch tests using the repeated insult technique with pieces of ETO sterilized "Medigloves" on 200 human subjects showed negative allergic reactions in all cases. Therefore, the sensitizing potential of "Medigloves" is quite low, if any. Mild to severe forms of miliaria rubra were occasionally observed in about one fourth of the subjects during the induction and challenge periods since the weather was quite warm and humid. However, three subjects who developed more pronounced miliaria rubra on the skin underneath rubber-glove squares were selected for provocative use tests. The results were negative in all cases. A subject who showed a false-positive allergic reaction also showed negative results in a provocative use test and in patch tests with standard rubber chemicals and pieces of "Medigloves" from various batches. Occlusive patch tests for 72 hours with Mediglove pieces from the same batch used in the initial test challenge phase were repeatedly negative when performed during the cool time of the year. In tropical countries, predictive closed patch tests employing solid occlusive materials should be done during cool weather in order to prevent or minimize the occurrence of miliaria. In hot weather, this is a common source of false positive reactions.

Adult↗

Optimizing the patch-test concentration of para-tertiary-butylcatechol: results of a prospective study with a dilution series.

Para-tertiary-butylcatechol (PTBC), which has long been patch tested internationally at 1% and 0.5% concentrations, was recently shown to induce patch-test sensitization at the 1% patch-test concentration. In order to determine a safe patch-test concentration, we performed a prospective study with lowered patch-test concentrations. A dilution series of PTBC 0.25%, 0.1%, 0.01% and 0.001% (petrolatum, pet.) was tested on the upper back. Additionally, 0.25% PTBC was tested on the left upper arm to allow patients to carry out self-examination daily. Patch tests were read on D1-3, D7, D14 and D21 after patch-test application. Patients who were not able to return for all scheduled readings were telephoned and asked to report any reaction at the patch-test sites. 65 out of the 101 patients included completed the study. A positive patch-test reaction was observed in 4 patients during D1-D3, indicating previous sensitization. 1 patient had a doubtful reaction at D3 reading. Negative patch-test results were noted in 60 patients. None of the patients developed a positive patch-test reaction during the late readings (D7-D21). Thus, patch-test sensitization was not observed in any case. Para-tertiary-butylcatechol 0.25% pet. is recommended for patch testing internationally.

Adult↗

Patch testing with metalworking fluids from the patient's workplace.

In view of the wide variety of components currently used in metalworking fluids (MWF), relevant contact sensitizations may be overlooked, because commercially available MWF test series cannot cover the full spectrum. Hence, patch testing with MWF from the patient's workplace is an important additional diagnostic tool. However, recommendations on how to perform such patch tests vary. We retrospectively analyzed patch test data of the Department of Dermatology in Dortmund, 1992-2003. In 141 metalworkers tested because of suspected occupational contact dermatitis due to MWF, 829 patch tests with 306 samples of MWF were performed. Water-based MWF (wb MWF) were mainly tested in 2 dilution series, i.e. pure (workplace concentration), 10% aq. and 1% aq., and pure, 50% aq. and 10% aq. Positive reactions to wb MWF occurred in 27 patients. Patch testing with wb MWF at workplace concentration resulted in 16.1% (39/242) positive reactions, with a positivity ratio of 69% and a reaction index of 0. From the analysis of reaction patterns and concomitant reactions, we conclude that most of these positive reactions indicated true contact allergy. With lower concentrations, relevant allergic reactions may be missed. Neat oils were tested as is or diluted from 1 to 50% in olive oil, but no reactions at all were observed. For optimum benefit of patch testing with MWF from the patient's workplace, breakdown testing is recommended. To overcome the time-consuming difficulties associated with this procedure, we propose a centre for information and documentation of contact allergies due to occupational exposure. Furthermore, full declaration of MWF ingredients is desirable.

Adult↗

In situ immunological characterization of the infiltrating cells in positive patch tests.

Skin biopsies from positive allergic patch tests were analysed by immunoenzymatic labelling of frozen sections with monoclonal antibodies. In seventeen patients the cellular infiltrate consisted of T cells admixed with Langerhans cells/indeterminate cells, but in two patients there were also many B lymphocytes. The B cells were accompanied by dendritic reticulum cells forming B-cell follicles, indistinguishable from those of normal and hyperplastic lymph nodes. There was no correlation between these two immunohistological staining patterns and the sensitizing antigen, the extent of local reaction or the time from epicutaneous application of allergen to examination (2 to 16 days). The ratio between T-helper and T-suppressor cells varied considerably, and showed no correlation with these variables. In all patients the infiltrating T cells expressed HLA-DR antigen. Transferrin receptors were identified on the infiltrating T cells in biopsies from nine patients. These data indicate activation of T cells in the infiltrate from positive patch tests, and support the functional significance of Langerhans cells in the initiation and maintenance of cutaneous contact allergy. An involvement of B cells and B-cell accessory cells in the pathogenesis of contact allergic reactions is also suggested. The presence of dendritic reticulum cells in skin infiltrates from positive patch tests may reflect a functional implication of the skin in the development of B-cell memory.

Adult↗

The "edge effect" with patch test materials.

A positive "edge effect", i.e., the accumulation on the skin of a chemical solution (such as fluorescein 0.01% in a 50/50 water-ethanol solution) at the periphery of the patch test sites has been demonstrated. It occurs with different test materials (Finn Chamber; Silver Patch Test; Patch Test Chamber). Practical implications are discussed: this observation could be important when discussing results of laboratory investigations. In clinical practice, it could explain the occurrence of "ring-shaped" positive allergic patch test reactions to chemicals used in solution, i.e., Kathon CG or hydrocortisone.

Humans↗

Patch test reactions at D4, D5 and D6.

In this retrospective study, patch test reactions in 3 groups of patients were analysed, in order to obtain information on the best day for the 2nd patch-test reading after day 2 (D2), on the usefulness of additional readings after D3, and on the dependence of patch-test reactions at D4, D5, or D6 on allergen and/or patient characteristics. In the years 1990 to 1995, patch tests were routinely read at D3 and D4 in 1096 patients, at D3 and D5 in 1243 patients, and at D3 and D6 in 1136 patients. In all of the 3 groups, significantly more positive reactions diminished than appeared de novo from D3 to the later reading. Virtually identical results were observed in subgroups of patients formed by sex, age or atopy. However, men might possibly react more slowly than women on patch testing, showing more increasing than diminishing reactions in the D3/D4- and the D3/D5-comparison. Reactions to individual allergens showed wide differences in this connection. Neomycin sulfate, cobalt salts, and p-phenylenediamine can be characterized as slow allergens, with more reactions increasing than diminishing from D3 to the later readings. With fragrance mix and balsam of Peru, the opposite pattern occurred. In all subgroups of patients, and with most allergens, the gain in positive reactions was biggest when an additional reading was performed at D5. We conclude that for a single 2nd patch test reading after D2, D3 is the best day, and especially better than D4. If a 3rd reading is performed, it should be done at D5 to get the maximum information out of patch testing. However, this extends the test procedure to at least 1 day of the weekend.

Adult↗

Patch testing in occupational hand dermatitis.

Patch testing is valuable for the management of most forms of hand eczema; it tends to be diagnostically useful, however, only in the nonendogenous forms. Historical and morphologic clues that distinguish hand eczema of endogenous from that of exogenous causes can increase the yield of valuable information from patch testing. Knowledge of the occupations at risk for skin disease and the time required for irritant and allergic contact dermatitis to develop will improve history taking--the key to suspecting an occupational component.

Allergens↗

The use of decision-analytical modelling in economic evaluation of patch testing in allergic contact dermatitis.

OBJECTIVE: The objective of this observational prospective study was to demonstrate the cost effectiveness of patch testing in patients suspected of allergic contact dermatitis (ACD) and to determine the order in which different severity groups rank in terms of cost effectiveness. DESIGN AND SETTING: This observational study was conducted on 567 patients from 10 investigator sites in the US over a period of 1 year. All patients with a suspicion of contact allergy who exhibited at least moderate disease activity were included in the study and were stratified according to disease severity and whether or not they were patch tested. In each severity category, the cost effectiveness of patch testing was evaluated. Patients who were ruled out for contact allergy (without the use of patch test) by the first 6 months after admission were excluded. A validated dermatology-specific quality of life (DSQL) instrument was administered to all patients at the start of the study, and at 6 and 12 months thereafter. The cost-effectiveness analysis is demonstrated using a decision-analytical model. Costs included office visits and prescription costs without generic substitution. The cost of patch testing was not included due to the large variation in price among commercially available products. MAIN OUTCOME MEASURES AND RESULTS: Patch testing was performed on 22% of patients with mild disease, 41% of patients with moderate disease and 50% of those with severe disease. There was a significant difference between the patch-tested and non-patch-tested groups in terms of the time to obtain a confirmed diagnosis (medians = 8 and 175 days, respectively) and a significant difference in the ratio of patients who had a confirmed diagnosis (88 and 69%, respectively). As a result of changes made in their lifestyle, 66% of patients in the patch-tested group and 51% in the non-patch-tested group reported 75% or more improvement in their disease symptoms after 6 months. Early confirmation of diagnosis helped reduce the prediagnosis cost of treatment which was mostly based on preliminary diagnosis. The greatest quality-of-life (QOL) benefits from patch testing relative to nonpatch testing occurred in patients with recurrent/chronic ACD. CONCLUSIONS: Patch testing is most cost effective and reduces the cost of therapy in patients with severe ACD. Greater improvements in quality of life were seen in patients with recurrent/chronic ACD who were patch tested than patients who were not patch tested within the same group. Results were not sensitive to changes due to the addition of indirect costs or costs using generic substitution.

Anti-Allergic Agents↗

Interference of the position of substances in an epicutaneous patch test battery with the occurrence of false-positive results.

BACKGROUND: Epicutaneous patch tests represent a practical and objective method that help in the etiologic diagnosis of allergic contact dermatitis. The technique of patch test application is an important factor in obtaining good results. OBJECTIVES: The aims of this study were (1) to determine whether the substances that form the test battery interfere with the patch test result and (2) to establish a rule for positioning the substances during patch test application. METHODS: Two hundred patients were studied. The standard patch test battery was applied in 3 versions. The original, with the substances applied in alphabetical order was called version 1 (V1) and tested on the left back in all patients In 100 patients, on the right side, the same substances were tested but applied at different positions, avoiding the proximity of elements with a tendency to cross reaction and/or cosensitizing. This version of the battery was named version 2 (V2). Another 100 patients had V1 applied to the left back, and, on the right side, the version 3 of the battery (V3) was applied, consisting of the same allergens but placed close to those with a tendency for cross reaction and/or cosensitization. RESULTS: In the group V1-V2, 163 results were positive in V1 and 124 in V2, with the difference being statistically significant (P <.05). In the group V1-V3, 134 results were positive in V1 and 207 in V3, with the difference also being significant (P <.005). The substances with the largest number of positive results, when tested close to other elements with a tendency for chemical affinity, were parabens, fragrance-mix, thimerosal, balsam of Peru, potassium dichromate, cobalt chloride, mercapto mix, and propylene glycol. CONCLUSIONS: (1) The substances of a patch test battery eliciting positive responses may interfere with test positivity to neighboring substances. (2) In addition to the already established techniques, the position of the substances forming the test battery needs to be determined; substances with a tendency to cross reaction or cosensitizing substances should be tested distant from one another, thus preventing the occurrence of false-positive results.

Allergens↗

The classification of skin irritants by human patch test.

The human 4 hour patch test provides an opportunity to identify substances with significant skin irritation potential without recourse to the use of animals. The protocol is designed to avoid the production of more than mild irritant reactions and meets the highest ethical standards. This paper provides the background to the development of the method and comments on its performance in the light of recent intra- and inter-laboratory investigations. In particular, the value of the method in providing 'gold standard' data for the identification of those substances (or preparations) which should, or should not, be classified as irritant to skin in European legislation is discussed. On the basis of the published data and supplementary investigations, recommendations are made on both the conduct and interpretation of the human 4 hour patch test. Finally, the lack of any necessity for formal validation of this assay is addressed.

Health Planning Guidelines↗

[Atopy patch testing with aeroallergens and food].

The atopy patch test (APT), a patch test employing allergens known to elicit IgE-mediated reactions which is assessed by evaluating eczematous skin lesions after 24 h to 72 h, was developed as a diagnostic tool for characterizing patients with aeroallergen-triggered atopic eczema (AE, atopic dermatitis). Positive APT reactions are associated with allergen-specific T-cell responses. The specificity of APT is higher than the specificity of skin prick tests or RAST. More studies for the standardization of APT methods are necessary, especially with regard to food APT.

Adult↗

Late reactions to the patch-test preparations para-phenylenediamine and epoxy resin: a prospective multicentre investigation of the German Contact Dermatitis Research Group.

BACKGROUND: Late patch-test reactions, developing at day (D) 7 or later have been described for several allergens. Late reactions may reflect patch-test sensitization. Para-phenylenediamine (PPD) and epoxy resins (ER) are potent allergens and therefore may potentially induce patch-test sensitization. Up to now, there has been no prospective study on the frequency of late reactions in routine patch testing with these allergens. OBJECTIVES: To assess the frequency of late reactions to PPD and ER. PATIENTS/METHODS: In 1748 patients PPD (PPD-base, 1% pet.) and ER [based on diglycidylether of bisphenol A (DGEBA, 1% pet.)], and in 812 patients, nickel sulphate (5% pet.) were removed from the test panel of the standard series and applied on the medial side of the upper arm. Patch-test occlusion time was 24 h in 588 (PPD and ER) and 241 patients (nickel sulphate), respectively, and 48 h in 1160 (PPD and ER) and 571 (nickel sulphate) patients, respectively. Patch tests were read on D1-3 and D2-3, respectively; additional late readings were performed on D7, D14 and D21 after patch-test application. Patients who were not able to return for all scheduled late readings were telephoned on D7, D14 or D21, and questioned about a reaction at the test sites. Patients were instructed to perform daily self-examination from D4 onwards and to return immediately to the clinic if a reaction at the upper arm became visible. RESULTS: Data of 1428 patients (ER and PPD) and 638 patients (nickel) were evaluable. In 25 patients (1.8%), patch tests became positive not before D7, among them 21 reactions to PPD (1.5%) and four reactions to ER (0.3%). In five of seven patients, repeated patch tests with PPD disclosed patch-test sensitization as the cause of the late reaction. All late reactions, except for one, occurred in patients in whom patch tests were applied for 48 h. No late reactions were seen with nickel sulphate. CONCLUSIONS: PPD (1% pet.) elicited late reactions in 1.5% of routine patch tests, the majority of them probably being caused by patch-test sensitization. Therefore, the German Contact Dermatitis Research Group decided to remove PPD 1% pet. from the German standard series and to take efforts to optimize the patch-test conditions of PPD. One way to optimize PPD testing could be to reduce the exposure of PPD 1% to 24 h. Alternatively the patch-test concentration of PPD might be reduced.

Adolescent↗

Course of contact allergy in consecutive eczema patients patch tested with TRUE Test panels 1 and 2 at least twice over a 12-year period.

Non-reproducibility of positive patch test reactions is common. In this retrospective study, we investigated the reproducibility of previously positive patch test reactions and the appearance of new positive reactions in a consecutive series of 264 eczema patients tested at least twice over a 12-year period using the TRUE Test standardized patch test system. Out of 297 positive reactions, 66% remained positive in a 2nd test, 10% were scored as doubtful and 24% as negative. Among the previously recorded doubtful reactions, 13% were positive in the 2nd test, 13% were again doubtful and 74% negative. In relation to the degree of patch test reactivity, 48% of the + reactions were reproducible, compared to 87% of ++ and +++ reactions. No difference in reproducibility was observed between patients tested with a short or a long-time interval between tests. With the use of the TRUE Test panels 1 and 2, methodological factors are minimized. The variation in patch test positivity may then be attributed to biological variation, which depends on several individual factors such as patch test reading, patient-related factors such as changed immunological sensitivity, regional variation of the skin on the back and the presence of more or less active dermatitis.

Allergens↗

Nickel patch test reactivity and the menstrual cycle.

Premenstrual exacerbation of allergic contact dermatitis and varying allergic patch test responses have been reported at different points of the period. Using a dilution series of nickel sulphate, we studied the variation in patch test reactivity in nickel allergic women in relation to the menstrual cycle. Twenty women with regular periods were tested on day 7-10 and on day 20-24. Ten nickel patch tests with different concentrations were applied using the TRUE test assay, and the threshold concentration of nickel sulphate eliciting an erythematous reaction was determined. Half of the women were tested first on day 7-10 and the other half first on day 20-24. There was no difference in the degree of patch test reactivity, when the results from day 7-10 and day 20-24 were compared (p > 0.4). However, when we compared the patch test results from the first and second test procedure, we found an increased nickel sensitivity at the second patch test (0.02 < p < 0.05), suggesting a booster effect from the first patch test procedure. In conclusion, we could not demonstrate an increased sensitivity to nickel sulphate patch tests premenstrually in 20 nickel allergic women, but we found that elicitation of positive patch tests led to an increased skin reactivity towards the same allergen, when the patients were retested weeks later.

Adolescent↗