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Biomedical subjects

P J Frosch

Publications and source records attributed to P J Frosch.

At least 19 recordsLinked to original sources
PubMed2001

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↗
PubMed2001

Testing with fine fragrances in eczema patients: results and test methods.

The frequencies of contact allergic reactions to 2 fine fragrances were studied by patch testing. Further, a comparison was made of test results before and after evaporation of the solvent. A total of 480 consecutive eczema patients were included, 100 in the Dortmund clinic and 380 in the Gentofte clinic. Patch testing was done with 2 international brand prestige fragrances. Each fragrance was tested in duplicate. One was applied immediately and the other was allowed to dry for 5 min before application. Testing procedures and assessment of reactions followed the international recommendations. In Dortmund 11% (11/100) and in Gentofte 5.8% (22/380) gave a positive patch test reaction to one or both of the fine fragrances. Assessments done in Gentofte showed that in 73% of the cases the positive reaction indicated a clinically relevant fragrance allergy. More irritant reactions were found to the wet, non-evaporated form of the fragrances compared with the dried form, while the method of testing did not significantly influence the number of positive reactions. It is recommended that patch testing be performed with hydro-alcoholic fragrance products after evaporation of the solvent.

Adolescent↗
PubMed2000

Patch testing with corticosteroid mixes in Europe. A multicentre study of the EECDRG.

This study investigated whether a corticosteroid mix containing tixocortol pivalate, budesonide, and hydrocortisone-17-butyrate could detect contact allergy to corticosteroids. 2 corticosteroid mixes, 1 with a high (mix I) and 1 with a low (mix II) concentration and the 3 individual constituents, each at 2 concentrations, were inserted into the standard series of 16 participating clinics. Tests were read on day (D) 3 or 4. 5432 patients were tested, and 110 (2.0%) had positive reactions to at least 1 of the 8 test preparations. Of the 8 preparations, mix I identified most allergic patients, followed by mix II, budesonide 0.10%, budesonide 0.002%, and tixocortol pivalate, both concentrations (1.0 and 0.10%) tracing the same number. With the mixes, 53.2-59.6% of tixocortol pivalate allergy was missed. 47 patients were allergic to either concentration of tixocortol pivalate, 25% of these only to 1.0% and another 25% only to 0.10%. Testing with mix I and tixocortol pivalate 0.10% picked up 98/110, testing with tixocortol pivalate 1.0% and 0.10% and budesonide 0.10% picked up 105/110. 3379 patients were read on both D3 or D4 as well as on D7. Without a late reading (D7), up to 30% of contact allergy to corticosteroid markers was missed.

Administration, Topical↗
PubMed2000

Multicentre study for the development of an in vivo model to evaluate the influence of topical formulations on irritation.

Although skin protective products to prevent irritant skin reactions are in wide use, neither standardized test models to prove differences in efficacy exist, nor has the quality or the reproducibility of results been evaluated in a multicentre approach. This should be mandatory when developing or testing skin care products. Therefore, we have designed a multicentre study in an approach to find a standardized test procedure for the evaluation of skin protective products. In this irritation study, a repeated short-time occlusive irritation test (ROIT) with a standardized protocol has been evaluated in 2 phases (12 days and 5 days protocol) in 4 (n=20) respectively 6 (n=33) skilled centres. The skin reaction was induced by 2 irritants (0.5% aq. SLS and toluene, 2x a day for 30 min). Its modification by 3 different cream bases with different hydrophilicity was analyzed. The irritation was monitored by bioengineering methods (TEWL measurement, colorimetry) and by clinical scoring. The evaluation showed that significant results could already be achieved with the 5-day protocol. Furthermore, in spite of the expected inter-centre variations due to heterogeneity of the individual threshold of irritation, interpretation of clinical score, and inter-instrumental variability, the ranking of the vehicles regarding reduction of the irritant reaction was consistent in all centres.

Administration, Topical↗
PubMed2000

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↗
PubMed2000

VEGF production, cell proliferation and apoptosis of human IGR 1 melanoma cells under nIFN-alpha/beta and rIFN-gamma treatment.

The effect of natural and recombinant interferons (nIFN, rIFN) on cell growth, apoptosis and the production of vascular endothelial growth factor (VEGF) was investigated in the human melanoma cell line IGR 1. We determined cell proliferation, cell vitality, DNA synthesis, apoptosis, intracellular oxygen radicals (ROS) and VEGF-mRNA as well as VEGF-protein levels. rIFN-gamma significantly inhibited growth by decreasing DNA synthesis and increasing apoptosis. Less pronounced was the growth inhibitory effect of nIFN-beta because an increased rate of apoptosis was outweighed by enhanced DNA synthesis. nIFN-alpha only had minor effects on cell growth parameters. Under long-term incubation (144 h) nIFN-beta decreased, but rIFN-gamma increased production of the angiogen VEGF. Our data underscore the multiple effects of IFNs on melanoma cells and may contribute to the understanding of ambivalent results of melanoma therapy by IFNs. Particularly, the increased VEGF production under long-term treatment with serum IFN levels between 100 and 1,200 IU/ml should be kept in mind.

Apoptosis↗
PubMed1999

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↗
PubMed1999

Human T lymphocyte priming in vitro by haptenated autologous dendritic cells.

Dendritic cells (DC), generated from adherent peripheral blood mononuclear cells (PBMC) by culturing with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4, were used to study in vitro sensitization of naive, hapten-specific T cells and to analyse cross-reactivities to related compounds. DC were hapten-derivatized with nickel sulphate (Ni) or 2-hydroxyethyl-methacrylate (HEMA), followed by tumour necrosis factor-alpha (TNF-alpha)-induced maturation, before autologous T cells and a cytokine cocktail of IL-1beta, IL-2 and IL-7 were added. After T cell priming for 7 days, wells were split and challenged for another 7 days with Ni or HEMA, and potentially cross-reactive haptens. Hapten-specificity of in vitro priming was demonstrated by proliferative responses to the haptens used for priming but not to the unrelated haptens. Highest priming efficiencies were obtained when both IL-4 and IL-12 were added to the cytokine supplement. Marked interferon-gamma (IFN-gamma) release (up to 4 ng/ml) was found when IL-12 was included in the cultures, whereas IL-5 release (up to 500 pg/ml) was observed after addition of IL-4 alone, or in combination with IL-12. Nickel-primed T cells showed frequent cross-reactivities with other metals closely positioned in the periodic table, i.e. palladium and copper, whereas HEMA-primed T cells showed distinct cross-reactivities with selected methacrylate congeners. Similar cross-reactivities are known to occur in allergic patients. Thus, in vitro T cell priming provides a promising tool for studying factors regulating cytokine synthesis, and cross-reactivity patterns of hapten-specific T cells.

Cells, Cultured↗
PubMed1999

Contact allergy to calcipotriol does exist. Report of an unequivocal case and review of the literature.

A 64-year-old woman developed an itchy papulovesicular dermatitis at the periphery of psoriatic plaques on the lower legs after the daily application of calcipotriol ointment (Psorcutan Salbe) for 2 weeks. She had used the same ointment for 4 weeks 6 months before. Patch testing revealed strongly positive reactions to the marketed product and to the active ingredient calcipotriol in a concentration series (2.0, 10.0 and 50.0 microg/ml in isopropyl alcohol). A repeated open application test (ROAT) on the forearms showed a vesicular dermatitis after 4 days on the side that received the calcipotriol ointment, whereas the control with the placebo ointment remained completely negative. Histologic examination of the + + patch test reaction was in line with the picture of contact allergy. Retesting after 6 months confirmed the hypersensitivity, with a positive reaction even at 0.4 microg/ml. For comparison, the ROAT with calcipotriol ointment was performed for 2 weeks on both forearms of 15 volunteers never exposed to calcipotriol before. Only 2 subjects developed a slight reaction on days 5 and 11, respectively. Based on this case and on previous reports in the literature, calcipotriol must now be regarded as both a contact allergen and an irritant. For patch testing, a concentration of 2 microg/ml in isopropyl alcohol is the most suitable. If the reaction is only weakly positive and not reproducible after some time, it might be of the irritant type. In unclear cases, a ROAT should be performed. A severe papulovesicular dermatitis within 1 week will confirm the presence of contact allergy.

Administration, Cutaneous↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

Isoeugenol is an important contact allergen: can it be safely replaced with isoeugenyl acetate?

The prevalence of contact allergy to the fragrance mix in individuals with eczema is up to 10%. Within the mix, isoeugenol (CAS 97-54-1) is an important individual allergen. Until May 1998, the IFRA (International Fragrance Association) guidelines suggested that isoeugenol could safely be used at a level of 0.2% in consumer products. In May 1998, IFRA recommended that isoeugenol should not be used at a level that exceeds 0.02% in consumer products, but did not provide guidance on allergen substitution. An alternative to isoeugenol, based on aroma and absence of guidelines on use, is isoeugenyl acetate (CAS 93-29-8). 155 consecutive subjects were patch tested to isoeugenyl acetate (1.2%, 0.4%, 0.13% eth.) and isoeugenol 1% pet. 6 (3.9%) had an allergic reaction to 1.2% isoeugenyl acetate at D4. The reactions to the other 2 dilutions tended to be graded. 8 individuals had at least a palpable erythema by D4 to isoeugenol 1% pet. The majority of individuals allergic to isoeugenol were also intolerant of isoeugenyl acetate. Effective labelling of fragrance substances on consumer products will facilitate monitoring of exposure.

Allergens↗
PubMed1998

Cross-reactivity patterns of contact-sensitizing methacrylates.

Methacrylates are well-known contact sensitizers with increasing frequency of contact leading to occupational skin disease. Here, we developed an animal model to facilitate studies on the sensitizing capacities and cross-reactivity patterns between four clinically most important allergens: methacrylate (MMA), 2-hydroxyethyl methacrylate (2-HEMA), 2-hydroxypropyl methacrylate (2-HPMA) and ethyleneglycol dimethacrylate (EGDMA). Inbred guinea pigs were immunized by ic injections of 300 microliters of 1.0 M methacrylate solutions in Freund's complete adjuvant into both flanks, both ears, and the neck. After 14 days open skin tests were performed with 50% MMA, 2-HEMA, or 2-HPMA or 10% EGDMA solutions in 40% DMSO in ethanol. Cross-reactivities were investigated 14 days later by skin testing with all four methacrylates. Using this newly developed protocol, strongly positive skin tests for methacrylates could be induced in almost all guinea pigs (MMA 26/26, 2-HEMA 16/18, 2-HPMA 15/16 and EGDMA 11/11). Whereas EGDMA induced only weak or infrequent cross-reactivities, 2-HEMA sensitization led to strong cross-reactions to all other methacrylates. Both MMA and 2-HPMA induced strong cross-reactivity to EGDMA but only weak to moderate reactivities to the other methacrylates. The absence of strong cross-reactions with monomethacrylates in EGDMA (dimethacrylate)-sensitized animals may be explained by the predominance of highly EGDMA-specific T-cells in these animals. In contrast, sensitization with MMA, 2-HEMA, and 2-HPMA would lead to recruitment of T-cells cross-reactive to the other monomethacrylates, according to their molecular similarities. The strong skin hypersensitivities observed for EGDMA in these latter groups are ascribed to enzymatic degradation into monomethacrylate compounds, notably 2-HEMA, at a rate sufficient to elicit cognate effector T-cells. The results of this study offer new insights in the development of methacrylate hypersensitivities and common cross-sensitization patterns in clinical practice.

Allergens↗
PubMed1998

["Windmill-plasty" for coverage of large defects of the scalp].

The closure of large circular defects on the scalp is technically difficult and cosmetically often not satisfying, if a free transplant is necessary. Following the technique of Tillmann described first in 1908, several flaps shaped like a windmill can be combined. We report on 14 patients (ages 41-88 years) where large defects resulting from the excision of various tumors (5 melanomas, 5 basal cell carcinomas, 1 keratoacanthoma, 1 trichilemmal cyst, 1 squamous cell carcinoma, 1 skin metastasis) were successfully closed by this method. The diameter of the defect ranged between 4 and 8 cm (mean 5.7 cm). Size and number of the rotating flaps (3 or 4) was varied according to the size of the defect and the mobility of the surrounding tissue. The procedure was performed with local anesthesia in all cases. Wound healing occurred without complications except in 3 cases. 2 patients (63 years, 70 years) developed small necrotic areas on the tips of the flaps. In a 74 year old man with a very large defect of 8 cm diameter, one flap of four underwent total necrosis. The cosmetic result was rated "very good" in 71.4% and "good" in 14.3%. The preservation of the terminal hair turned out to be of special advantage. The "windmill procedure" is an important addition to the surgical approaches for closure of large defects on the scalp, particularly in young patients.

Adult↗
PubMed1998

Patch testing with preservatives, antimicrobials and industrial biocides. Results from a multicentre study.

Preservatives are biologically reactive substances, and their allergenic potential has been known for a long time. This study examined the role of different preservatives in a large number of patients with suspected allergic contact dermatitis. Patch test data and data from the patients' history were collected from the 24 departments participating in the Information Network of Departments of Dermatology from 1 January 1990 to 31 December 1994. Patch test data from 28,349 patients tested with preservatives of the standard series (SS), from 11,485 patients tested additionally with a preservative series (PS), and from 1787 patients tested with an industrial biocide tray (IB) were evaluated. Sensitization rates (standardized) of the SS preservatives were all > 1%, with thiomersal rating highest (5.3%), the parabens lowest (1.6%), and the remainder (chlormethylisothiazolinone/methylisothiazolinone, formaldehyde and methyldibromoglutaronitrile/phenoxyethanol (MDBGN/PE)) in the range of 2%. The most important allergens of the PS were, in women, alkylaminobenzoate (contained in milking fat) (2.5%), MDBGN/PE (2.2%), benzalkonium chloride (1.8%), chloracetamide (1.4%), diazolidinyl urea (1.3%), octylgallate (1.2%) and Bronopol (1.1%). In men rates differed only with regard to alkylaminobenzoate (0.9%). Patients tested with the IB series reacted most often to methylene-bis-thiocyanate (5%), but with a reaction index of -0.7, many reactions were most probably false positives. A further seven preservatives, mostly formaldehyde-releasers used in cutting fluids, gave sensitization rates of between 1% and 3%. Glutaraldehyde, not contained in the series but often tested additionally, showed a remarkable increase in sensitization during the study period. Health care personnel were frequently affected. Altogether, this study identified areas of concern within the different groups of preservatives. The overall impact of most of the preservatives on public health seems to be low, but for diagnostic reasons preservatives must be included in patch test series.

Adult↗
PubMed1998

Contact allergies in healthcare workers. Results from the IVDK.

Healthcare workers often suffer from occupational skin disease frequently caused by allergic sensitization. Therefore the patch-test results and important patient history items of 31,849 patients recorded between 1992 and 1995 in the 24 allergy departments participating in the Information Network of Departments of Dermatology (IVDK) were evaluated. Significantly increased sensitization rates common to the healthcare sector as a whole were found for the vaccine preservative thiomersal (12.6% vs. 4.9%), the surface and instrument disinfectants glutardialdehyde (9.9% vs. 2.6%), formaldehyde (3.6% vs. 2.1%) and glyoxal (4.2% vs. 1.4%), and for the compounds of the thiuram mix (6.7% vs. 2.6%) present in protective gloves. Formaldehyde seems to lose its importance, but glyoxal must be added to the list of occupational allergens in the healthcare sector. In addition, occupation-specific sensitization was observed, with fragrances in massage therapists (16.1% vs. 10.6%) and nurses (13.8% vs. 11.4%), as well as with methacrylates in dental technicians. The often assumed importance of drugs as type-IV allergens was not confirmed, at least in terms of quantity. The identification of subgroups of increased risk and of occupation-specific allergens could be the basis of targeted preventive action in the healthcare sector.

Adult↗