Para-phenylendiamine (PPD) 1% pet. is an important allergen in the standard series.
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Coloring Agents↗
Biomedical subjects
J P Lepoittevin
Publications and source records attributed to J P Lepoittevin.
Routine patch testing with frullanolide mix: an European Environmental and Contact Dermatitis Research Group multicentre study.
Contact sensitivity to plants containing 1 or more sesquiterpene lactones (SLs) is difficult to diagnose. The mixture of SLs (SL mix) has been shown to detect only about 60% of sensitized individuals. In order to improve the diagnosis of sensitization to plants containing SLs, we have tested a mixture of frullanolides contained in Frullania dilatata and Frullania tamarisci at 3 different concentrations (0.01%, 0.033% and 0.1% in petrolatum). 8605 consecutive eczema patients in 1 North American and 15 European dermatology departments were tested with this mix, and 0.35% of positive cases to the different concentrations were found. Routine use of this mix permitted detection of only a small percentage of extra cases and did not improve the SL mix score. The frullanolide mix should therefore be restricted to investigations in particular geographical zones and/or in particular occupations.
Allergens↗
Further important sensitizers in patients sensitive to fragrances.
In order to find sensitizers additional to the current fragrance mix (FM) a series of fragrance materials (series II) was evaluated in 6 dermatological centres in Europe. 11 of the test materials were essential oils, the remaining 7 being either mixtures of isomers or simple chemicals of frequent usage in the perfume industry. 1606 patients were consecutively tested with series II and 8% FM. Each patient was classified regarding a history of adverse reactions to scented products: certain, probable, questionable, none. Reactions to FM occurred most frequently in 11.4% of the subjects. The 6 materials with the highest reactivity after the FM were ylang-ylang oil (YY) I (2.6%), YY II (2.5%), lemongrass oil (1.6%), narcissus absolute (1.3%), jasmine absolute (1.2%) and sandalwood oil (0.9%). 48 (3.0%) of the patients reacted only to materials of series II and not to FM. 6.0% of 1606 patients gave a history of adverse reactions to fragrances which was classified as certain. This group reacted to FM only in 22.9%, to series II and FM in 15.6% and to series II only in 5.2%. 63.5% of the patients reacting to both FM and 1 of the materials of series II had some type of positive fragrance history, which was higher in comparison to those with isolated reactions to FM (46.2% of 121) or to series II, respectively, (45.8% of 48). However, this difference was not statistically significant. In conclusion, the materials of series II identified a further subset of patients with a fragrance problem, which would have been missed by the current FM as the single screening tool for patch testing.
Dermatitis, Allergic Contact↗
Further important sensitizers in patients sensitive to fragrances.
The aim of this study was to determine the frequency of responses to selected fragrance materials in consecutive patients patch tested in 6 dermatological centres in Europe. 1855 patients were evaluated with the 8% fragrance mix (FM) and 14 other frequently used well-defined fragrance chemicals (series I). Each patient was classified regarding a history of adverse reactions to fragrances: certain, probable, questionable, none. Reactions to FM occurred in 11.3% of the subjects. The 6 substances with the highest reactivity following FM were Lyral (2.7%), citral (1.1%), farnesol P (0.5%), citronellol (0.4%), hexyl cinnamic aldehyde (0.3%), and coumarin (0.3%). 41 (2.2%) of the patients reacted only to materials of series I and not to FM. 6.6% of 1855 patients gave a history of adverse reactions to fragrances which was classified as certain. This group reacted to FM only in 41.1%, to series I and FM in 12.0% and to series I only in 7.2%. 74.3% of the 39 patients reacting to both FM and 1 of the materials of series I had any type of positive fragrance history, which was significantly higher in comparison to those with isolated reactions to series I (53.6% of 41), p = 0.04. The study identified further sensitizers relevant for patch testing of patients with contact dermatitis, of which Lyral is the most important single chemical.
Allergens↗
The time-dose-response relationship for elicitation of contact dermatitis in isoeugenol allergic individuals.
The elicitation response in allergic contact dermatitis is dose dependent, but the time-concentration relationship for elicitation has not previously been described. In this study 27 isoeugenol-sensitive patients participated in serial dilution patch tests with isoeugenol and a double-blinded Repeated Open Application Test (ROAT) using two concentrations of isoeugenol, 0.2 and 0.05%. Seven controls without isoeugenol allergy were also included. The participants applied 3.72 +/- 1.57 (mean +/- SD) mg/cm(2) of coded isoeugenol solutions twice a day to a 3 x 3 cm(2) area on the volar aspect of the right and left arm, respectively. For each test site the applications continued until a reaction appeared or for a maximum of 28 days. The minimal criteria for a positive reaction regarded as allergic contact dermatitis was persistent erythema at the ROAT test site. All controls were negative and 16/24 (66.7%) of the included isoeugenol-sensitive subjects showed a positive ROAT to the 0.2% solution within the study period (Fisher's test, p = 0.0024). Ten of the positive patients also reacted to the 0.05% solution. The median number of days until a positive reaction to the 0.2% solution was 7 days and was 15 days for the 0.05% solution. There was a highly significant correlation between the patients' patch test threshold and the number of days until a positive ROAT. In conclusion, the time until an isoeugenol allergic individual reacts in a ROAT depends on the individual sensitivity as well as the exposure concentrations; for low concentrations of the allergen or low degree of sensitivity, the allergic contact dermatitis may develop after several weeks of exposure. Therefore, a negative ROAT after 7 days may be a false negative.
Administration, Topical↗
Clothing dermatitis from Naphthol AS.
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Adult↗
Tixocortol pivalate contact allergy in the GPMT: frequency and cross-reactivity.
In spite of their intrinsic anti-inflammatory properties, corticosteroids can induce contact allergy. When studying the allergenic properties of corticosteroids it has to be considered that both the allergenic and anti-inflammatory effect may influence the induction phase as well as the elicitation phase and that such effects may be dose-dependent. A multiple dose guinea pig maximization test (GPMT) was therefore used to study the dose-response relationship of tixocortol pivalate. The GPMT was conducted according to OECD guideline #406, using a multiple-dose design and test results were analysed with logistic regression analysis. There was a significant tixocortol pivalate sensitization of the test animals compared to the control group (p<0.05), after both challenge and re-challenge. The challenge with 1% tixocortol pivalate gave more positive reactions than the challenge with 3%. The highest frequency of positive animals was observed when the animals were treated with low to intermediate induction concentrations and intermediate to high challenge concentrations with tixocortol pivalate in the TRUE Test. Cross-reactivity was found between tixocortol pivalate and hydrocortisone, which was expected from their close molecular resemblance, whereas no cross-reactivity was seen between tixocortol pivalate and the 3 other corticosteroids: amcinonide, budesonide, and hydrocortisone-17-butyrate.
Allergens↗
Occupational erythema-multiforme-like dermatitis from sensitization to costus resinoid, followed by flare-up and systemic contact dermatitis from beta-cyclocostunolide in a chemistry student.
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Adult↗
Patch testing with serial dilutions of budesonide, its R and S diastereomers, and potentially cross-reacting substances.
BACKGROUND: Budesonide, a marker for corticosteroid allergy, is a 1:1 mixture of 2 diastereomers, the R and S, present in all commercial formulations. Budesonide is said to cross-react with group B substances through the R and S diastereomer and some group D substances only through the S diastereomer. OBJECTIVE: To investigate the cross-reactivity pattern between the R and S diastereomers and 4 potentially cross-reacting substances, 2 from group B and 2 from group D. METHODS: By patch testing 10 patients hypersensitive to budesonide with a serial dilution of budesonide, the R and S diastereomer, triamcinolone acetonide, amcinonide, prednicarbate, and hydrocortisone-17-butyrate. RESULTS: Nine of 10 patients reacted to budesonide and the S diastereomer. Seven of 9 to the R diastereomer. Each of the 9 patients with S diastereomer allergy reacted to the group B and/or group D substances. Five patients reacted to triamcinolone acetonide, not to 1.0% but only to 0.0010% and 0.00010%. CONCLUSION: The R and S diastereomers can induce positive patch test reactions in budesonide-hypersensitive individuals. The potential of budesonide to cross-react with substances from group B and D might be explained by the presence of the 2 diastereomers. When patch testing with triamcinolone acetonide, much lower concentrations than recommended should be used.
Allergens↗
Identification of Lilial as a fragrance sensitizer in a perfume by bioassay-guided chemical fractionation and structure-activity relationships.
Fragrance materials are among the most common causes of allergic contact dermatitis. The aim of this study was to identify in a perfume fragrance allergens not included in the fragrance mix, by use of bioassay-guided chemical fractionation and chemical analysis/structure-activity relationships (SARs). The basis for the investigation was a 45-year-old woman allergic to her own perfume. She had a negative patch test to the fragrance mix and agreed to participate in the study. Chemical fractionation of the perfume concentrate was used for repeated patch testing and/or repeated open application test on the pre-sensitized patient. The chemical composition of the fractions giving a positive patch-test response and repeated open application test reactions was obtained by gas chromatography-mass spectrometry. From the compounds identified, those that contained a "structural alert" in their chemical structure, indicating an ability to modify skin proteins and thus behave as a skin sensitizer, were tested on the patient. The patient reacted positively to the synthetic fragrance p-t-butyl-alpha-methylhydrocinnamic aldehyde (Lilial), a widely used fragrance compound not present in the fragrance mix. The combination of bioassay-guided chemical fractionation and chemical analysis/structure-activity relationships seems to be a valuable tool for the investigation of contact allergy to fragrance materials.
Aldehydes↗
Presence of resin acids in "Oakmoss" patch test material: a source of misdiagnosis?
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Dermatitis, Allergic Contact↗
Synthesis of a water-soluble analog of 6-methyl-3-N-alkyl catechol labeled with carbon 13: NMR approach to the reactivity of poison ivy/oak sensitizers toward proteins.
A 13-C labeled water soluble derivative of alkylcatechol was synthesized and reacted with human serum albumin in phosphate buffer at pH 7.4 in air to allow a slow oxidation of the catechol into orthoquinone. The formation of several adducts was evidenced by a combination of 13C and 1H-13C correlation NMR. Although some adducts could result from a classical o-quinone formation - Michael type addition, our results suggest that a second pathway, involving a direct reaction of a carbon centered radical with proteins could be an important mechanism in the formation of modified proteins.
Carbon Isotopes↗
Regulation of the contact sensitivity response to urushiol with anti-urushiol monoclonal antibody ALG 991.
The objective of the studies was to demonstrate that the contact sensitivity (CS) response to poison ivy/oak could be downregulated following treatment with a monoclonal antibody (mAb) reacting with the allergen urushiol. Conjugation of urushiol and its synthetic analogue 3-n-pentadecylcatechol (PDC) to N-acetylcysteine yielded hydrosoluble derivatives which induced humoral immune responses in BALB/c mice. Hybridomas secreting monoclonal antibodies (mAbs) reacting with urushiol and PDC were generated by fusion of B lymphocytes from immunized mice with mouse myeloma P3NS0 cells. The specificity of mAb ALG 991 (IgM isotype) was defined by inhibition of antibody binding by PDC analogues. This demonstrated that mAb ALG 991 reacted with the catechol moiety of urushiol, the region of the allergen being critically important in the induction of contact dermatitis. The CS response to urushiol in BALB/c mice was suppressed by stimulation with mAb ALG 991 and the role of sensitized T cells, including suppressor T cells, has been considered. Suppression of CS was most effective with low doses (1 microg) of mAb incorporated into a vaccine with Freund's adjuvant. This treatment suppressed CS responses in BALB/c mice already sensitized to urushiol.
Allergens↗
Development of structure-activity relationships (SARs) in allergic contact dermatitis.
One of the major objectives at the end of this century is the development of "alternative" tests for the evaluation of the pharmacological and/or toxicological activity of newly developed molecules. Contact allergy is no exception to the rule and many research programs have been started to develop in vitro techniques for the detection of allergizing compounds. In parallel with these biological studies, another approach is becoming important and will no doubt become more so, namely, the study of structure activity relationships (SARs). This consists of using molecular or physicochemical properties to predict and, in certain cases, quantify the allergizing potential of a new molecule without using any biological test. Three main approaches are currently under study: the creation of allergy databases, the design of "expert" computerized systems, and the development of quantitative SARs. These three often complementary approaches are still at the development stage, but we can begin to see their potential and limitations. The aim of this article is not to give an exhaustive description of all the systems developed worldwide, but to illustrate each approach by giving some important examples.
Allergens↗
Lyral is an important sensitizer in patients sensitive to fragrances.
Contact allergy to fragrances is a common problem world-wide. The currently used fragrance mix (FM) for patch testing has only eight constituents and does not identify all fragrance-allergic patients. As perfumes may contain 100 or more substances, the search for markers for allergy continues. The synthetic fragrance 4-(4-hydroxy-4-methylpentyl)-3-cyclohexene carboxaldehyde (Lyral) was tested together with the FM and 11 other fragrance substances on consecutive patients in six European departments of dermatology. All patients were carefully questioned regarding a history of reactions to scented products in the past and were grouped into four categories: 'certain', 'probable', 'questionable' and 'none'. Lyral (5% in petrolatum) gave a positive reaction in 2.7% of 1855 patients (range 1.2-17%) and ranked next to 11.3% with FM allergy. Twenty-four patients reacted to both Lyral and FM, but 21 (1.1%) reacted positively only to Lyral. Of 124 patients with a 'certain' history, 53.2% reacted to the FM and a further 7.2% to Lyral only. If any kind of history of fragrance intolerance was given, 80% (40 of 50) of Lyral positive patients had a 'positive' history while only 58.6% (123 of 210) of FM positive patients had such a history; this difference was significant at P < 0.01. Lyral was identified by gas chromatography-mass spectrometry in some products which had caused an allergic contact dermatitis in four typical patients who showed a patch test positive to Lyral and negative or doubtful to FM. In conclusion, we recommend the testing of 5% Lyral (in petrolatum) in patients suspected of contact dermatitis.
Adult↗
Patch testing with budesonide in serial dilutions: the significance of dose, occlusion time and reading time.
Budesonide is advocated as a marker molecule for corticosteroid contact allergy. When patch testing corticosteroids, one must consider their sensitizing potential but also their anti-inflammatory properties, as well as the possibility of different time courses for such properties. The dose-response relationship for budesonide was therefore investigated with regard to dose, occlusion time, and reading time. 10 patients were patch tested with budesonide in ethanol in serial dilutions from 2.0% down to 0.0002% with occlusion times of 48, 24, and 5 h. Readings were on D2, D4, and D7. The 48-h occlusion picked up most positive reactors, 8/10. The D4 reading (48-h occlusion) detected most positive reactors, 8/10, and here 0.002% picked up most contact allergies. Late readings favoured high concentrations. The "edge effect" was noted for several concentrations at early readings. Due to the individual corticosteroid reactivity, the dose-response relationship and the time courses of the elicitation and the anti-inflammatory capacity, several features may be explained, i.e., that lower concentrations may detect budesonide allergy better at early readings, that patients with an "edge reaction" can have positive reactions to lower concentrations.
Administration, Topical↗
Regulatory classification of substances oxidized to skin sensitizers on exposure to air.
Regulatory classification of substances in the European Union (EU) is intended to identify their hazardous toxicological properties in a formal and harmonized manner. In the regulatory work, a specific chemical with its molecular structure is classified as a skin sensitizer. This implies that the compound is stable throughout its lifetime. The purpose of the present paper is to discuss the problem of skin sensitizing oxidation/degradation products formed by air exposure of various materials or substances with very low allergenic activity. In regulatory classification work on skin sensitizers, the intrinsic suspectibility of a chemical to air oxidation (autoxidation) should be taken into consideration. We give examples of natural terpenoid materials, but the concept of allergens formed by air oxidation can apply to other materials widely used in industrial products. If a positive classification is made for a substance with a known chemical structure, a note should indicate that the primary chemical structure of the notified substance is not a skin sensitizer, but that (some of) its oxidation products are. Complex mixtures which inevitably contain sensitizing oxidation products should (on the basis of sufficient evidence) be classified as skin sensitizing.
Allergens↗
Identification of coumarin as the sensitizer in a patient sensitive to her own perfume but negative to the fragrance mix.
The aim of this study was to identify the chemicals responsible for the sensitivity of a 44-year-old woman to her own perfume, but showing negative patch test results to the fragrance mix. For this purpose, the perfume concentrate from the eau de toilette was chemically fractionated. Each fraction obtained was afterwards tested on the patient using a ROAT and/or a patch test. Only 1 fraction gave a positive ROAT result. This fraction was analyzed and found to contain coumarin and ethyl vanillin. Coumarin, one of the most widely used fragrance compounds that is not present in the fragrance mix, was confirmed as being the sensitizer.
Adult↗