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Biomedical subjects

Peter J Frosch

Publications and source records attributed to Peter J Frosch.

29 records · Page 2Linked to original sources

Patch testing with components of water-based metalworking fluids.

Water-based metalworking fluids (MWFs) may cause both irritant and allergic contact dermatitis. Several well-known MWF allergens are available for patch testing, but considering the wide variety of possible components used in MWF, our diagnostic arsenal covers only a small part of potential allergens. We therefore selected 13 frequently used MWF components that might be sensitizers and had not yet been tested routinely. In 5 centres, 233 dermatitis patients with present or past occupational exposure to MWF were patch tested with this and other panels. Only 7 patients showed positive reactions to the study panel. Allergic reactions to the emulsifier diglycolamine [syn. 2-(2-aminoethoxy) ethanol] were seen in 5 patients, and 1 patient each reacted positively to 2-amino-2-ethyl-1,3-propanediol (AEPD) and methyldiethanolamine (MDEA). Clinical relevance of the reactions to diglycolamine was unequivocally proven by its presence in the MWF from the patients' workplace in 3 cases. Diglycolamine seems to be an important MWF allergen, independently from monoethanolamine and diethanolamine. A test concentration of 1% petrolatum (pet.) appears to be appropriate. The importance of AEPD and MDEA as MWF allergens still remains to be established. The lack of positive test reactions to the other MWF components tested may be due to their low-sensitizing potential or too low a patch test concentration being used.

Adult↗

Contact sensitization to N-(cyclohexylthio)phthalimide.

Previous reports revealed relative high sensitization rates to the rubber chemical N-(cyclohexylthio)phthalimide (CTP; CAS-No. 17796-82-6), but the relevance of positive reactions remained unknown. It was discussed whether the test concentration of 1% pet. needed to be changed. The German Contact Dermatitis Research Group (DKG) added CTP in 3 concentrations, i.e. 0.25% pet., 0.5% pet, 1% pet., to the rubber series. From June 1999 to December 2000, 1936 patients in 30 departments of dermatology were tested with CTP. Of the 56 patients with a positive test reaction (2.9%), 52 reacted to CTP 1% pet., 21 to CTP 0.5% pet., and 9 to CTP 0.25% pet. The reaction indices were about the same with all concentrations. 34 patients with a positive reaction to CTP 1% pet. did not react to the lower concentrations. The majority of these reactions are probably false-positive. With CTP 0.25% pet., however, the majority of true allergic reactions to CTP were missed. Analysis of population characteristics and concomitant sensitizations to other rubber chemicals led to the conclusion that a positive reaction to CTP 0.5% pet. was a good indicator of contact allergy to CTP. Thus, the DKG decided to continue patch testing with CTP 0.5% pet. in the rubber series. Manufacturers' information about the use of CTP seem to partly contradict the patients' characteristics seen in this study. So the relevance of positive CTP patch test reactions, and the causative exposures in patients with CTP allergy, still remain to be clarified.

Adult↗

[Allergic contact eczema from shellac and 1,3-butylene glycol in an eyeliner].

BACKGROUND: The diagnostic approach to eyelid eczema is often a great problem in daily practice. PATIENT AND METHOD: A 16-year old girl developed recurrent severe pruritic edema of the eyelids, followed by redness and scaling. Various cosmetics particularly an eyeliner were considered as possible causes. Patch testing was performed with the standard series, some supplemental series and all ingredients of the eyeliner. RESULTS: The eyeliner produced a papular reaction after 2 days of open application, confirming a high degree of contact sensitization. The patient reacted with a 3+ reaction to the ingredients shellac (20% in ethanol) and 1,3-butylene glycol (2% in water). All remaining materials failed to produce a reaction. CONCLUSIONS: Careful allergologic investigations are necessary in cases of edema and/or eczema of the eyelids; the cosmetics used by the patients are of utmost importance. The causative allergen may not be present in the usual patch test series and can only be identified by testing all ingredients. Shellac is now widely used in cosmetics and is increasingly identified as a contact allergen in eye make up.

Adolescent↗

Patch tests with thiurams at 0.25% pet. and 1% pet. are of equal diagnostic value.

Thiuram mix is tested in the standard series at a test concentration of 1% pet. The single thiurams (DPTD, TMTD, TMTM, TETD), however, are usually tested at 0.25% pet. in Germany. In other countries, the individual components of thiuram mix are tested at 1% pet. The German Contact Dermatitis Research Group (DKG) compared both patch test concentrations in 530 patients in order to find out if (i) a significant number of positive patch tests are missed by testing at the lower concentration, (ii) problems with irritant test reactions occur by increasing the test concentration to 1%, and (iii) the sensitivity of the thiuram mix rises when the breakdown test is done with the higher concentration. Slightly more positive reactions were seen with the higher concentration, but this increase did not reach statistical significance. The reaction index, as a measure for the relation of positive to irritant and/or questionable reactions, remained unchanged for the individual thiurams. The sensitivity of the mix also did not change when the breakdown test was performed with 1% pet. instead of 0.25% pet. Thus, we conclude that both concentrations are of equal diagnostic value in patch testing.

Dermatitis, Allergic Contact↗

Lyral has been included in the patch test standard series in Germany.

Lyral 5% pet. was tested in 3245 consecutive patch test patients in 20 departments of dermatology in order (i) to check the diagnostic quality of this patch test preparation, (ii) to examine concomitant reactions to Lyral and fragrance mix (FM), and (iii) to assess the frequency of contact allergy to Lyral in an unselected patch test population of German dermatological clinics. 62 patients reacted to Lyral, i.e. 1.9%. One third of the positive reactions were + + and + + +. The reaction index was 0.27. Thus, the test preparation can be regarded a good diagnostic tool. Lyral and fragrance mix (FM) were tested in parallel in 3185 patients. Of these, 300 (9.4%) reacted to FM, and 59 (1.9%) to Lyral. In 40 patients, positive reactions to both occurred, which is 13.3% of those reacting to FM, and 67.8% of those reacting to Lyral. So the concordance of positive test reactions to Lyral and FM was only slight. Based on these results, the German Contact Dermatitis Research Group (DKG) decided to add Lyral 5% pet. to the standard series.

Aldehydes↗

Patch test reactions to Biobans in metalworkers are often weak and not reproducible.

Contact allergy to the industrial preservative group of Biobans has been reported in individual cases. We have performed a prospective study on 408 metalworkers who were tested with 6 different Biobans, formaldehyde and 5 other preservatives. Furthermore, retesting was performed after a time interval of 6 months to 4 years. The test results were also compared with those of the multicentric data provided by the Information Network of Departments of Dermatology in Germany and Austria (IVDK), particularly with regard to cross-reactivity between the various Biobans and formaldehyde. In 408 metalworkers 14 (3.4%) showed positive reactions to Biobans (2.2% P 1487, 2.0% CS 1246, 1.5% CS 1135), the majority being + reactions. On retesting 10 patients, the reactions were confirmed in only 2 cases (P 1487 and CS 1135). 4 patients showed positive reactions to 3 Biobans (P 1487, CS 1135, CS 1246), while 9 patients had only solitary sensitizations. Concomitant sensitization to formaldehyde was present in 5 out of 10 patients, being reproducible in 3 of them. In the IVDK data, sensitization prevalence in 3400 patients ranged from 1.8% (P 1487) to 0.8% (CS 1246). A high proportion of doubtful or irritant reactions as well as weak + reactions was observed. Cross-reactivity between the various Biobans was low, moderate agreement being calculated for CS 1135 and CS 1246 (kappa coefficient 0.43). The consensus pattern between formaldehyde and the tested Biobans was even lower. In conclusion, patch test reactions to Biobans are not rare among metalworkers but are often weak and not reproducible. Simultaneous reactivity to various Biobans and formaldehyde may be due to cross-reactivity or cosensitization from common exposure.

Allergens↗

Assessment of contact allergen cross-reactivity by retesting.

At former allergic contact dermatitis reaction sites retesting causes augmented hyper-reactivity, characterized by an accelerated onset within a few hours. This expression of 'local skin memory' has been ascribed to locally persisting allergen-specific effector/memory T cells. To verify this hypothesis, we investigated whether accelerated retest reactivity also occurs with cross-reactive allergens. Guinea pigs were immunized with either or both 2,4-dinitrochlorobenzene (DNCB) and 2-hydroxyethyl methacrylate (HEMA), and primary skin tests to these and cross-reactive methacrylic compounds were performed 12-21 days later. Subsequently, new skin tests were conducted 3 weeks later both at the former test ('retest') and contralateral, non-pretreated test ('control') sites, and skin test readings started 2 h later. Retest reactivity was evaluated by comparing retest and contralateral control reactions. Both contact sensitizers, HEMA and DNCB, induced strong retest reactivity, peaking at 4-6 h. Fully allergen-specific retest reactivity was observed when primary skin tests had been postponed until 21 days after immunization, most probably reflecting loss of accumulation of irrelevant allergen-primed T cells at that time. As hypothesized, retesting with various methacrylate congeners at primary HEMA, but not DNCB, skin test sites showed early hyperreactivity strengths in line with those observed earlier in conventional cross-reactivity studies. These results, therefore, support the view that local skin memory exhibits allergen specificity through residual allergen-primed T cells. Because the retesting procedure is readily applicable in clinical practice, it provides a tool not only for confirmation of doubtful contact allergic skin reactions, but also for distinguishing between true cross-reactivity and coincident multiple sensitization in man.

Allergens↗

An attempt to improve diagnostics of contact allergy due to epoxy resin systems. First results of the multicentre study EPOX 2002.

Epoxy resin systems (ERSs) are a frequent cause of occupational allergic contact dermatitis. Sensitization occurs not only to the resins, but also to hardeners and reactive diluents. However, only a fraction of the ERS components currently in use are available for patch testing. With the multicentre study EPOX 2002, we attempted to improve diagnostics in this field by patch testing with components currently used in ERSs. During the first study period (October 2002 to July 2003), in addition to commercially available ERS patch test substances, 16 study substances (1 resin, 9 hardeners and 6 reactive diluents) were patch tested in 70 patients with suspected contact allergy due to ERSs and 22 patients with a prior positive patch test reaction to epoxy resin (ER) in the standard series. Most frequently, allergic reactions to ER based on diglycidyl ether of bisphenol A and F were observed (55.2% and 43.7%, respectively). Agreement between positive reactions to both resins, which can be explained by immunological cross-sensitization and/or coexposure, was substantial [Cohen's kappa 0.65 (95% CI: 0.49-0.80)]. Among the reactive diluents, 1,6-hexanediol diglycidyl ether (1,6-HDDGE) and 1,4-butanediol diglycidyl ether (1,4-BDDGE) were the most frequent allergens, with 19.5% and 18.4% positive reactions, respectively. Although agreement between positive reactions to 1,6-HDDGE and 1,4-BDDGE was even better than with the 2 resins, the sample size is considered too small to decide reliably whether 1,6-HDDGE alone could serve as a marker allergen for both. Allergic reactions to p-tert-butylphenyl glycidyl ether and to phenyl glycidyl ether (PGE) occurred in 11.5% of the patients tested, with only moderate agreement. All patients positive to cresyl glycidyl ether (6.8%) also reacted to PGE. Of the hardeners tested, m-xylylene diamine was the most frequent allergen (13.8%), followed by isophorone diamine (5.7%). No reactions were observed to several substances, the test concentration of which may have been too low and will be increased in the future.

Adolescent↗

Disseminated hyperkeratotic and granulomatous nodules in a child with fatal Epstein-Barr-virus-associated hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis is a rare and potentially fatal syndrome associated with a variety of genetic, malignant, autoimmune, or infectious conditions. The importance of cutaneous presentations of this syndrome has only recently been brought forward. We report the first case of Epstein-Barr-virus-associated hemophagocytic lymphohistiocytosis presenting with papulonodular and granulomatous skin lesions. A girl of African origin developed several umbilicated papules on her extremities and face at the age of 18 months. She was born in Germany, had never visited Africa, and was otherwise healthy. Over the next 5 months the lesions progressed in size and number and became hyperkeratotic. Histopathologic analysis of early lesions revealed a superficial lympho- and plasmacellular dermatitis with some features of panniculitis. Later biopsy specimens from nodular lesions showed the formation of tuberculoid granulomas in the deep dermis. At the age of 23 months she became severely ill, rapidly developing high fever, hepatosplenomegaly, icterus, pancytopenia, and ascites. On the basis of bone marrow and lymph node biopsies, the diagnosis of hemophagocytic lymphohistiocytosis was established. However, this phenomenon could not be detected in any of the skin specimens. An active Epstein-Barr virus infection was diagnosed by polymerase chain reaction in blood, lymphoid tissue, and skin. Despite chemotherapy with etoposide and cortisone, the girl expired 14 days after clinical onset of her systemic disease.

Biopsy, Needle↗