Browsing by Author "Brasch, Jochen"

Although genetic factors probably account for differences in susceptibility to contact allergy, they have not yet been identified, partly due to an insufficient understanding of 'susceptibility'. Regarding polysensitization (PS) as a sign of increased susceptibility, we studied the relationship between PS and sensitization to weak versus strong allergens. Patch test data from 66 835 patients registered by the multicentre project, Information Network of Departments of Dermatology (IVDK) between 1 January 1997 and 31 December 2004, were analysed. The association between the number of sensitization to standard series allergens, and contact allergy to a strong allergen methyldibromoglutaronitrile (MDBGN) and to a weak allergen (paraben mix), was analysed with adjusted logistic regression analysis. In paraben-positive (++/+++) patients, the risk of >= 2, >= 3 or >= 4 additional reactions were significantly increased by a factor of 2.1-4.6 compared to MDBGN-sensitized (++/+++) patients. Varying the basic model, a higher risk of additional positive reactions associated with paraben sensitization was consistently identified. The association between PS and sensitization to weak allergens adds a further characteristic of susceptibility to former findings of the IVDK, where PS was related to an increased risk of induction, elicitation, and cytokine polymorphisms. PS can be regarded as a phenotype to be considered in genetic studies.

Background: Patch testing is the standard clinical procedure to prove contact sensitization. It is a common practice to attach multiple patch tests at the same time. However, synchronous reactions to unrelated allergens may not be completely unassociated. If so, the reaction in a given test field might be influenced by other positive test reactions in a distance-related degree. This article analyses whether there is a distance-related effect of synchronous positive patch test reactions on the outcome of a target patch test. Methods: Data collected from patients patch tested for diagnostic purposes with 15 standard allergens attached in a specific pattern between 1992 and 2004 in 20 centres in a Central European network were retrospectively evaluated. The association between the target patch test result (allergic vs negative reaction to the thiuram mix) and the number and cumulated strength of synchronous positive reactions (positive patch test load) to allergens placed in nearby or distant positions to the target patch was analysed by using logistic regression analysis. Results: The likelihood of a positive reaction to thiuram mix significantly increased with an increasing synchronous positive patch test load generated by positive reactions to allergens unrelated to thiuram mix. The effect of allergens neighbouring the target allergen was not significantly stronger than that of allergens placed in distant positions. Conclusion: For the interpretation of patch test results, the potentially enhancing effects of a synchronous positive patch test load should be considered. The local distribution of the patches on the back is, however, not critical.

Objective: Thimerosal is an important preservative in vaccines and ophthalmologic preparations. The substance is known to be a type IV sensitizing agent. High sensitization rates were observed in contact-allergic patients and in health care workers who had been exposed to thimerosal-preserved vaccines. There is evidence for the involvement of the glutathione system in the metabolism of thimerosal or its decomposition products (organomercury alkyl compounds). Thus detoxification by polymorphically expressed glutathione S-transferases such as GSTT1 and GSTM1 might have a protective effect against sensitization by these substances. Methods: To address this question, a case control study was conducted, including 91 Central European individuals with a positive patch-test reaction to thimerosal. This population was compared with 169 healthy controls and additionally with 114 individuals affected by an allergy against para-substituted aryl compounds. The latter population was included in order to test whether possible associations were due to substance-specific effects, or were a general feature connected with type IV immunological diseases. Homozygous deletions of GSTT1 and GSTM1 were determined by polymerase chain reaction. Results: Glutathione S-transferase M1 deficiency was significantly more frequent among patients sensitized to thimerosal (65.9%, P = 0.013) compared with the healthy control group (49.1%) and the "para-compound" group (48%, P = 0.034). Glutathione S-transferase T1 deficiency in the thimerosal/mercury group (19.8%) was barely elevated versus healthy controls (16.0%) and the "para-compound" group (14.0%). The combined deletion (GSTT1-/GSTM1-) was markedly more frequent among thimerosal-sensitized patients than in healthy controls (17.6% vs. 6.5%, P = 0.0093) and in the "para-compound" group (17.6% vs. 6.1%; P = 0.014), revealing a synergistic effect of these enzyme deficiencies (healthy controls vs. thimerosal GSTM1 negative individuals, OR = 2.0 [CI = 1.2-3.4], GSTT1-, OR = 1.2 [CI = 0.70-2.1], GSTM1/T1-, OR = 3.1 [CI = 1.4-6.5]). Conclusions: Since the glutathione-dependent system was repeatedly shown to be involved in the metabolism of thimerosal decomposition products, the observed association may be of functional relevance.

Objectives: To compare the diagnostic accuracy of strip patch tests and patch tests in detecting sensitizations in patients with suspected allergic contact dermatitis by using patient history as the reference standard. Patients/methods: In a multicentre, prospective, investigator-blinded study 790 patients were enrolled. The defined reference standard was established prior to patch testing. Patch tests were performed with nickel sulfate, potassium dichromate, and lanolin alcohol. Duplicate tests were simultaneously performed on both sides of the back, of which one randomly chosen side was tape stripped beforehand, according to a standardized procedure. Primary outcome was the difference in sensitivity between strip patch test and patch test. Results: Seven hundred and eighty-seven patients were included in the analysis. Strip patch tests detected considerably more sensitization to nickel sulfate and potassium dichromate than patch tests: differences of sensitivities were 16.4% (95% CI, 8.7-24.1%) for nickel sulfate and 25.0% (95% CI, 8.9-41.0%) for potassium dichromate, both favouring the strip patch test. Conclusions: The standardized strip patch test proved to be accurate and clinically safe and is promising to improve diagnosis of allergic contact dermatitis beyond the patch test.

Background Iodopropynyl butylcarbamate (IPBC) is a new preservative in medical and cosmetic leave-on products. Although cases of allergic contact dermatitis to IPBC have been reported, it is not known whether the usual test concentration of 0.1% is appropriate for screening tests with IPBC. Objectives To determine the concentration of IPBC that should be used in screening patch tests. Methods An analysis was made of data filed by 26 centres of dermatology on patch tests performed with one or two concentrations of IPBC (0.1%, 0.2%, 0.3% or 0.5%) in 8106 unselected patients. Criteria used to determine the best test concentration of IPBC were the reaction index, the positivity ratio, the rate of crescendo reactions, and the relations between IPBC reactions and the MOAHLFA index irritant reactions to sodium lauryl sulphate (SLS), and allergic reactions to other contact allergens including preservatives. Results IPBC 0.1%, 0.2%, 0.3% and 0.5% yielded 0.5%, 0.8%, 1.3% and 1.7% positive reactions, but this increase was accompanied by an even greater increase in doubtful and irritant reactions. These figures and the other criteria examined suggested the range of suitable test concentrations of IPBC to lie between 0.2% and 0.3%. A detailed analysis of MOAHLFA indices and of associations between reactions to IPBC and reactions to other allergens and to SLS showed that most of the positive reactions to IPBC 0.2% can be assumed to be allergic ones and that with IPBC 0.2% fewer false-positive reactions can be expected than with IPBC 0.3%. Conclusions Patch testing with IPBC 0.2% is suggested for patients with eczema possibly related to preservatives.

p-Phenylenediamine (PPD) 1% in petrolatum has been shown in a prospective study to elicit late reactions in 1.5% of routine patch tests, which may be indicative of patch test sensitization. Objectives. To assess the frequency of late reactions to reduced PPD patch test concentrations. Methods. In 1838 patients, PPD was tested at three concentrations (0.5% pet., group I; 0.4% pet., group II; and 0.35% pet., group III). Patch tests were read on D1 (D2) to D3 (D4); additional late readings were performed on D7, D14, and D21. Patients who were not able to return for all scheduled late readings were telephoned on D7, D14, and D21, and questioned about a reaction at the patch test sites. Results. Data of 1666 patients (1069 women and 597 men) were eligible. Late reactions were observed in 9 patients, 3 in group I (0.49%) and 5 in group II (0.63%). In 7 of 8 of the patients with late reactions, patch tests were applied for 48 hr. On retesting, 4 of 5 patients became positive at D2 or D3. Conclusions. The occurrence of late reactions to PPD may be influenced by patch test concentration and duration. PPD 0.4-0.5% pet. may cause late reactions indicative of active sensitization.

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.

Lyral(R) 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.

There is still some doubt about the reproducibility of patch tests, A sound assessment needs optimized and unbiased studies. This study analysed the results of a double-blind multicentre study with nickel sulfate and potassium dichromate patch tests attached synchronously to both sides of the back of patients with a history of nickel allergy, conducted with a highly standardized randomized test system (TRUE-test((R))), Out of 589 patients tested, a total of 388 had responded with allergic reactions to nickel sulfate and 130 to potassium dichromate, The reproducibility of positive nickel (dichromate) patch tests mas 99.2% (90.8%), The reaction index nas also calculated, which relates the number of allergic reactions obtained with a test preparation to the number of questionable and irritant reactions; the reaction index can range from -1 (questionable and irritant reactions only occur) to 1 (allergic reactions only occur). For nickel sulfate the reaction index mas 0.91, but it was only 0.23 for potassium dichromate, as a result of considerably more questionable reactions. In conclusion, a highly synchronous reproducibility of results can be achieved by using a well-standardized patch-test system, especially with nickel sulfate, However, distinct allergens and test systems need to be evaluated separately.

Patch testing is the standard procedure to detect contact sensitivity. The most frequent contact allergens are included in the standard series. We report on current trends regarding results obtained with the standard series from 2001-2004 in Germany, Austria (Graz, Vienna) and Switzerland (Basel). This analysis includes the frequency of the most common contact allergens and other aspects such as age and gender distribution and parameters of diagnostic quality such as reaction index and positivity ratio. Information on the most common contact allergens is updated.