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Notes: Severity scoring of atopic dermatitis (SCORAD) was introduced as a standard tool but has not been used in a population-based epidemiological study; the objective of the present study was to determine the practicability of this instrument in this setting. We assessed the distribution of the severity of atopic eczema in the community and investigated differences between east and west Germany. A factor analysis was then carried out to characterize the variables of this scoring system and to analyse possible relationships within them. A multicentre cross-sectional study was carried out in five east German and two west German locations in 1994; pre-school children (5–6 years old) were investigated and cases of atopic eczema identified by a dermatological examination. The SCORAD was used to determine the severity of atopic eczema and the results assessed using analysis of variance and principal component analysis (varimax rotation). In all, 1511 (76·2%) of the children originally contacted participated and 11·3% were diagnosed with atopic eczema at the time of examination. The median severity score was 21·4 (interquartile range 13·5) and there was a tendency to higher scores in west Germany for the mean overall score, the intensity score and the extent. ‘Erythema’ (1·30 vs. 1·06; P= 0·006) and ‘excoriation’ (0·77 vs. 0·36; P= 0·002) were significantly more prominent in children with eczema from west Germany (adjusted for observer). Interobserver variabilities of the SCORAD parameters were calculated, adjusted for location and were in accordance with earlier findings. Principal component analysis identified three independent factors accounting for 54·1% of the total variance. A severity factor, characterized by ‘extent’, ‘lichenification’, ‘excoriation’ and ‘pruritus’, was separated from a factor with an acute eczema-type profile (‘erythema’, ‘oedema’, ‘oozing’) and a factor whose major characteristics were ‘extent’, ‘dryness’, and ‘sleep loss’. We conclude that atopic eczema is frequent in pre-school children. The SCORAD proved to be readily applicable and useful in epidemiological studies, but further validation is needed.

Notes: A 51-year-old white male suffering from metastatic malignant melanoma of the skin presented with lymph node metastases and paraneoplastic retinopathy 4 years after resection of the primary tumour. There were no cerebral metastases. Ocular symptoms consisting of night blindness and sensations of ‘shimmering lights’ persisted after total resection of the inguinal lymph node metastases and administration of dacarbazine and prednisone. Perimetry of both eyes was abnormal with concentric restriction. Electroretinography showed significantly reduced amplitudes in both eyes. Only 11 patients with melanoma-associated retinopathy (MAR) have been described. High titres of autoantibodies against whole retina extract were detected by enzyme-linked immunosorbent assay (ELISA) reactions. Indirect immunohistochemistry showed strong autoantibody activity against retinal bipolar cells.

Notes: After contact with grass pollen, seasonal exacerbations of eczematous skin lesions have been described in a subgroup of patients with atopic eczema (AE). Epicutaneous patch testing with aeroallergens (atopy patch test, APT) has been used to investigate these patients. We performed comparative APT in 79 patients with AE and 20 control subjects (14 non-atopic volunteers and six patients with grass pollen allergic rhinoconjunctivitis). Subjects were tested with grass pollen allergen extract in petrolatum and with unprocessed native dry pollen of Dactylis glomerata. Results after 48 h were compared with the patient's history, corresponding skin prick test and specific IgE. Fifteen of the 79 AE patients showed clear-cut eczematous reactions to unprocessed D. glomerata pollen; 14 of these had an elevated serum IgE to D. glomerata and 13 had a positive skin prick test. Twenty patients had a positive APT reaction to grass pollen allergen extract, including 12 of the D. glomerata reactive subjects (P 〈 0.001). Positive patch test reactions to D. glomerata were seen in 66.7% of cases with and 10.5% of patients without a predictive history of exacerbations during the pollen season. For the standardized extract, these percentages were 75% vs. 16.4% (P 〈 0.001). No side-effects were observed. Control subjects showed no positive reactions. We conclude that grass pollen preparations may be used to investigate trigger factors for eczematous skin lesions in a subgroup of patients with AE.

Notes: Cytokines have been proposed as histamine-independent itch mediators. To investigate this hypothesis, single doses of interleukin-2 (IL-2, 10MU/mL) and tumour necrosis factor α (TNF-α, 10 μg/mL) were delivered to the epidermis of 10 healthy volunteers with a controlled skin-prick model; 1% histamine and solvent controls were included in a double-blind, randomized crossover design. Itch ratings (computerized visual analogue scale) were obtained every 20s for 15 min and cutaneous reactions (weal, flare and temperature) were measured. Reactions were also recorded after 2, 24 and 48 h. The mean itch ratings were: histamine 35·5, IL-2 3·3 (both P〈0·01 compared with control), TNF-α 1.6 and solvent control 1.75 (not significant). Weal and flare occurred only with histamine. In two volunteers, an inflammatory papule with transient pruritus developed 12–18 h after applying IL-2. In conclusion, IL-2 showed a rapid, low pruritogenic effect, which may be followed by an inflammatory response. TNF-α induced no itching in this setting. Skin-prick testing with appropriate doses of potential pruritogens provides a safe and sensitive model for further chemoreceptor studies.

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.

Notes: Summary Interactions between keratinocytes and mononuclear cells via cytokines and adhesion molecules are thought to play a crucial part in inflammatory skin diseases. The cytokine-mediated effects of peripheral blood mononuclear cells (PBMC) from patients with atopic eczema (AE) and healthy individuals on keratinocytes (HaCaT) were investigated in vitro. A new coculture model (Transwell system) which consists of a lower and an upper compartment, which are separated by a polycarbonate-treated membrane, was established. 3[H]thymidine incorporation of keratinocytes and lymphocytes, as well as IL-6. IL-8 and IFN-γ synthesis, were measured. Keratinocyte proliferation was significantly enhanced in the presence of PBMC from patients with AE. In contrast, PBMC from normal donors did not enhance HaCaT cell proliferation when they were cocultttred. Lymphocytes from patients with AH showed a significantly enhanced proliferation after coculture with keratinocytes. However, PBMC from normal donors did not proliferate in the presence of HaCaT cells. Keratinocyte supernalants incubated with PBMC from either atopic or normal volunteers induced a suppression of lymphocyte 3[H]thymidine incorporation. In supernatants from cocultures of PBMC from patients with AE and keratinocytes. significantly enhanced amounts of IL-6 and IL-8. compared with normal donor's lymphocytes and HaCaT cells, were measured. No differences in TFN-γ production were observed. When PBMC were cultured without HaCaT cells, supernatants contained equal levels of IL-6, IL-8 and IFN-γ in normal donors and in patients with AE. Interestingly. HaCaT cells spontaneously secrete measurable amounts of IL-6, IL-8 and IFN-γ. Blocking experiments with neutralizing antibodies against these interleukins showed a complete inhibition of keratinocyte proliferation when PBMC from normal donors were used whereas the proliferative potency of PBMC supernalants from patients with AE on keratinocytes remained. Our data indicate that (i) PBMC from patients with AE stimulate keratinocyte proliferation via soluble factor(s) that are different from IL-6. IL-8 and IEN-γ (ii) probably, HaCaT cells spontaneously produce lymphocyte/monocyle inhibitory soluble factors and IL-6, IL-8 as well as IFN-γ and (iii) secretion and/or activity of keratinocytederived inhibitory mediators is regulated via cytokines of PBMC infiltrating inflammatory skin.

Notes: Glycoprotein Ilb-IIIa (integrin alpha lib beta3) is an adhesive receptor involved in platelet aggregation and adhesion to the extracellular matrix. Previous.studies showed the presence of IIb-IIIa-like glycoproteins on cells of melanoma cell lines and on cells of lymph node metastases. This study evaluates the presence of glycoprotein IIb-IIIa subunits on cells of primary cutaneous malignant melanomas wilh (n= 4) and without (n= 9) metastases over a period of 6 years and on naevus cells (n= 4). Monoclonal antibodies directed against the subunits of the glycoprotein IIb-IIIa receptor were used on paraffin-embedded sections and evaluated by means of immuno-histochemistry. The giycoprotein lib subunit was exclusively present on cells of metastatic melanomas. It was not found on non-metastatic melanomas or benign melanocytes. These data favour the role of the integrin receptor glycoprotein IIb-IIIa in the metastatic behaviour of malignant melanomas.

Notes: Summary In a subgroup of patients with atopic eczema (AE), eczematous skin lesions can he induced by epicutaneous testing with aeroallergens (the atopy patch test: APT). An increased frequency of positive APT has been found in AK patients showing a predictive lesional pattern affecting air-exposed skin areas. This study investigates the dose-response ofthe APT in two dilTerent patient groups with AE. Petrolatum preparations of house dust mite, cat dander and grass pollen allergens in four concentrations (500–10,000) protein nitrogen imits) were tested epicutaneously in 57 patients with AE. who were prospectively divided in two groups according to whether their AE pattern was with (group I) or without (group II) a predictive distribution. Sixty-nine per cent of patients in group I. and 39% in group II. had positive APT reactions (P = 0.02). The reactions in group I were elicitable with lower allergen concentrations (P = 0.03). A clinically recognizable subgroup of patients with AE showed increased cutaneous sensitivity to aeroallergens.