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Notes: Contact allergy to methyldibromo glutaronitrile (MDBGN), often combined with phenoxyethanol (PE) (e.g., Euxyl K 400®), increased throughout the 1990s in Europe. Consequently, in 2003, the European Commission banned its use in leave-on products, where its use concentration was considered too high and the non-sensitizing use concentration as yet unknown. The 2 objectives of the study are (a) to find a maximum non-eliciting concentration in a leave-on product in MDBGN/PE-sensitized patients, which could possibly also be considered safe regarding induction and (b) to find the best patch test concentration for MDBGN. We, therefore, performed a use-related test (ROAT) in patients sensitized to MDBGN/PE (n = 39) with 3 concentrations of MDBGN/PE (50, 100 and 250 p.p.m. MDBGN, respectively). A subset of these patients (n = 24) was later patch-tested with various concentrations (0.1, 0.2, 0.3 and 0.5% MDBGN, respectively). 15 patients (38%, 95% confidence interval (CI) = 23–55%) had a negative and 24 (62%; 95% CI = 45–77%) a positive overall repeated open application test (ROAT) result. 13 reacted to the lowest (50 p.p.m.), 8 to the middle (100 p.p.m.) and 3 to the highest concentration (250 p.p.m.) only. In those 13 reacting to the lowest ROAT concentration, dermatitis developed within a few days (1–7). The strength of the initial and the confirmatory patch test result, respectively, and the outcome of the ROAT were positively associated. Of the 24 patients with a use and confirmatory patch test, 15 reacted to 0.1% MDBGN, 16 to 0.2%, 17 to 0.3% and 22 to 0.5%. With the patch test concentration of 0.5%, the number of ROAT-negative patients but patch-test-positive patients increases considerably, particularly due to + reactions. A maximum sensitivity of 94% (95% CI = 70–100%) is reached with a patch test concentration of 0.2%, and is not further improved by increasing the concentration. However, the specificity decreases dramatically from 88 (95% CI = 47–100%) with 0.2% to a mere 12.5% (95% CI = 0–53%) with 0.5%. It can be concluded (a) that for MDBGN 0.2% is very likely the best patch test concentration and (b) that 50 p.p.m. in a leave-on product can elicit contact dermatitis in sensitized persons. We were, therefore, unable to find a safe, still microbicidal, concentration for leave-on products. By contrast, with other contact allergens, dose–response use tests may be able to identify a non-eliciting concentration, which could give valuable clues to a non-inducing (i.e., safe) concentration in products.

Notes: Sensitization rates to contact allergens vary between centers and are influenced by sex and age. Eliminating the latter 2 factors by standardization of data by age and sex, the present analysis address possible differences between centers remaining after elimination of these confounders, and analyzes other factors which might influence rates, e.g. the MOAHL index. Overall standardized rates were well within the range reported in previous studies and may be regarded as representing the rates of the “patch test population” in Central Europe (e.g. nickel sulfate 12.9%, fragrance mix 10.5″. balsam of Peru 7.3%. thimerosal 5.6%). For this analysis, data of those departments which contributed more than 2000 patients or of those with extreme proportion concerning sex, age and occupational cases were selected. Patients from these 10 departments differed considerably will regard to the items of the MOAHL index and with regard to standardized rates. The items of the MOAHL index proved to be suitable for describing different patch test populations and for explaining some differences between centers. Only ‘atopic dermatitis’ seems to have little influence on (standardized) rates. Face dermatitis is not yet represented in the MOAHL index, but should be included, together with age 〉 40 years, in an extended index (acronym: MOAHLFA). Regional allergen exposure (with striking differences between East Germany, West Germany and to a lesser extent Austria) seems to have a great influence on the sensitization pattern observed in a department. In addition, sociological factors may influence sensitization rates, which is exemplified by high rates of nickel allergy in a socially delined subgroup. Future studies should focus on these factors, as well as on factors concerning patch test practices and quality control.

Notes: Background Although most of the common allergen extracts that are used for diagnosis of type 1 hypersensitivity are now well standardized, this gives no assurance that they are within the concentration range that gives the best chance of a true diagnosis.Objective The objective of this study was to identify the most appropriate concentration range of timothy grass pollen Phleum pratense extract to diagnose sensitivity to this pollen correctly through skin-testing.Methods Dilutions of a well-standardized extract were made and used to skin test ‘true’ positive and ‘true’ negative populations of subjects as identified by case history, challenge tests and radioallergosorbent test (RAST). Weal diameters were measured and the data were submitted to receiver operating characteristics (ROC) analysis. For any particular weal size cut–off, the optimal diagnostic concentration (ODC) range was thus calculated.Results A 3 mm weal diameter cut-off was chosen as an appropriate size for routine diagnosis. Therefore the ODC range at this diameter was used to establish a product target concentration and specification for formulation of the diagnostic reagent. This method of allergen extract standardization can lead to a true-biological unitage that can be used for labelling purposes.Conclusion The optimun concentration range at which to formulate an allergen extract, in terms of an in vitro immunologically based assay, can be determined by carrying out ROC analysis of the results of clinical studies as described in this communication. Diagnostic units (DU), are now used by us for labelling of such final formulations which conveys the information that the product is at the most appropriate concentration for diagnosis.

Notes: Reduction in the size of the allergen-induced late-phase reaction (LPR) is seen as a consequence of successful allergen specific immunotherapy.〈section xml:id="abs1-2"〉〈title type="main"〉ObjectiveIt was the aim of this study to characterize the cellular infiltrate at the sites of cutaneous LPR that may occur following injection of a depot pollen allergoid (Allergovit®) during immunotherapy and thereby determine the immunological nature of the response.〈section xml:id="abs1-3"〉〈title type="main"〉MethodsPunch biopsies were taken 24 h after subcutaneous injection of a depot pollen allergoid from eight patients that showed LPR and a further five patients that did not. Additional biopsies taken 24 h after injection of allergoid-free depot in the same patients served as controls. Immunoenzymatic labelling of the cryostat sections with different antibodies was performed with the APAAP technique. Results were expressed as cells/field (400 × magnification).〈section xml:id="abs1-4"〉〈title type="main"〉ResultsSimilar dermal cellular infiltrations were seen following depot allergoid injections in patients both with and without LPR. Patients with LPR showed statistically significant increases in total cells, CD4+ cells, CD11c+ cells, CD45RO+ cells, CD45RB+ cells and activated eosinophils at the reactions sites as compared with control sites. In patients without LPR CD11c+ cells, HLA-DR+ cells and CD45RA+ T cells increased significantly. CD8+, CD1a+, NP57+, CD23+ and CD25+ cells did not differ significantly in either group.〈section xml:id="abs1-5"〉〈title type="main"〉ConclusionThese results indicate that activation of T cells, monocytes/macrophages and eosinophils at the sites of LPR following injection of depot allergoid are comparable with those following injection of allergen. Even in the absence of a cutaneous LPR, subsets of T cells and monocytes/macrophages increased. These cell activations may reflect events associated with the mechanisms of allergoid-based specific immunotherapy, and suggest that at least part of the late-phase reaction may be independent of IgE.

Notes: Summary Atopic eczema (AE) is a common skin disorder. Eczematous lesions showing macroscopic, microscopic and immunopathological resemblance to lesional AE can be induced by aeroallergens by epicutaneous testing (atopy patch test, APT). Altered epidermal barrier function, as determined by transepidermal water loss (TEWL), is a typical feature of patients with AE. The present investigation was performed to define the differences in the epidermal barrier function between positive APT reactions to aeroallergens and positive patch test reactions to contact allergens in AE patients. Allergen extracts from grass pollen, birch pollen, cat dander and house dust mite (Dermatophagoides pteronyssinus) were applied in large Finn chambers on Scanpor for 48h on the clinically unaffected and untreated skin of the back, in 11 patients with AE. The same procedure was done with 27 contact allergens of a standard test battery. Test reactions were read and TEWL was measured after 48 and 72h. Eight of the 11 patients developed positive APT reactions toD. pteronyssinus, two to cat dander and one to birch pollen. Seven of the 11 patients showed positive patch test reactions to nickel sulphate, two to potassium dichromate, one to thiuram-mix and one to paraphenylenediamine. Vehicle controls were negative. The TEWL of the positive APT reactions was significantly higher, both after 48 h (mean ± standard deviation 10·0±6·5 g/m2h) and after 72 h (9·7±5·4g/m2h) as compared with the control site (48/72h: 4·4±1.5/4·1±1·4 g/m2h) (P〈0·01). In contrast, TEWL of the positive patch test reactions to contact allergens (48/72h; 5·4±2·2/5·4±1·9g/m2h) was similar to that of the control site (48/72 h: 5·2±2·1/5·0± 1·8g/m2h) (not significant). The relative TEWL at 48 h and 72 h, expressed as the ratio between the positive patch test and the control site, was significantly higher in the positive APT reactions (48/72 h: 218·8±80·4%/232·0±85·9%) compared with positive patch test reactions to contact allergens (48/72 h: 102·1±12·0%/107·1±9·5%) (P〈0·01). It is concluded that the epidermal barrier function in AE patients is altered only in positive APT reactions, in contrast to positive patch test reactions to contact allergens. As a consequence of this aeroallergen-induced altered epidermal barrier function, further allergens can more easily penetrate the skin, inducing a vicious circle and perpetuating the eczematous lesions.

Notes: We report the occurrence of a malignant melanoma in a patient with neurofibromatosis (von Recklinghausen's disease; NF 1). Neurofibromatosis, like malignant melanoma, is believed to be a disorder of neural crest origin, and is associated with a number of different malignancies, but a definite association between cutaneous malignant melanoma and neurofibromatosis has not been established. We describe a patient with a malignant melanoma and with neurofibromatosis, and review the literature pertinent to this topic. The malignant melanoma was not related to a café-aulait patch or congenital naevus. The paucity of reports of patients with neurofibromatosis associated with cutaneous malignant melanoma suggests that these diseases probably do not occur together with any greater frequency than that determined by chance alone.

Notes: During rush venom immunotherapy (VIT), about 65% of patients develop large local reactions (LLR) at the application site that last for at least 24 h. However, LLR subside during long-term treatment. To learn more about the provenance of infiltrating cells in late, local skin reactions during VIT, we analyzed the skin infiltrates of 23 Hymenoptera venom (HV)-allergic patients. Punch biopsies were obtained 24 h after s.c. injection of HV allergens from 23 HV-allergic patients and five nonallergic controls. Seven patients did not show LLR at the beginning of VIT. Ten patients had LLR when the dose of HV allergens was increased. Six patients showed reduced LLR after long-term treatment. Immunoenzymatic labeling of the cryostat sections with a panel of monoclonal antibodies was performed by the APAAP method. S.c. application of HV allergens induced a perivascular and periadnexial cutaneous mononuclear cell infiltrate consisting mainly of CD4+, CD45RO+, and HLA-DR+ cells in patients without clinically apparent LLR. In contrast, LLR were associated with a significant increase in total cells, CD4+ cells, CD8+ cells, CD11c+ cells, EG2+ cells, NP57+cells, HLA-DR+ cells, CD45RO+ cells, CD45RA+ cells, CD23+ cells, and CD25+ cells (P 〈 0.001). Decreased LLR after long-term VIT was correlated with a significantly reduced recruitment of CD4+ cells, EG2+ cells, and CD23+ cells as compared to LLR in the course of dose increases (P〈0.05), whereas the number of CD8+ cells, CD11c+ cells, NP57+ cells, and CD25+ cells remained high. Our data suggest that s.c. injections of HV allergens attract CD4+ helper T cells, of both the naive (CD45RA+) and memory (CD45RO+) phenotypes, to the allergen application site. LLR represent delayed allergic rather than toxic reactions to HV components and might be relevant to the development of clinical protection during VIT.