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Notes: Apparently normal, and lesional skin from patients with atopic eczema were investigated immunohistochemically with anti-HLA-DR, -CD1a and -IgE antisera. A CD1a + intercellular pattern was observed in uninvolved skin in the majority of the patients whereas an HLA-DR +/CD1a+ network, mostly localized in basal and supra-basal areas, was shown in lesional skin of virtually all of them. Moreover, an HLA-DR +/CD1a + IgE + intercellular pattern was observed in some of the patients only and was predominantly localized in those areas characterized by lymphocyte exocytosis, spongiosis or vesicle formation. Whether keratinocytes are able to synthesize CD1a antigen and FcɛR or if these molecules are only produced and shed by CD1a +/IgE + epidermal dendritic cells remains unclear.

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: Background  Combinations of topical treatments and ultraviolet (UV) B phototherapy for plaque psoriasis may be more beneficial than either type of treatment used alone. Objectives  To determine the efficacy of calcitriol 3 µg g−1 ointment in combination with UVB phototherapy in treating plaque psoriasis. Methods  Calcitriol ointment with UVB was compared with vehicle plus UVB in a randomized, double-blind study in 104 patients. Results  Mean global improvement scores for both groups increased over the 8-week study period; there was a statistically significant difference (P 〈 0·05) in favour of the calcitriol/UVB combination from week 1. At end-point, 45% of the calcitriol/UVB group showed considerable improvement or clearing of psoriasis, compared with 21% of the control group. The superiority of calcitriol plus UVB was also reflected in the global severity and Psoriasis Area and Severity Index (PASI) scores; at end-point the mean percentage decrease in PASI score was 65% for the calcitriol/UVB group and 43% for vehicle/UVB (P = 0·0014). The incidence of skin-related adverse events was low (〈 12%) and similar in the two treatment groups. No clinically significant changes in blood chemistry, in particular calcium levels, occurred. The greater efficacy of combined calcitriol and phototherapy allowed a 34% decrease in total UVB exposure. Conclusions  Calcitriol 3 µg g−1 ointment and UVB phototherapy in combination provides a promising therapy for managing chronic plaque psoriasis.

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: 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.

Notes: Summary The clinical and histopathological classification of erythema exudativum multiforme major (EEMM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are difficult, due to the lack of clear-cut criteria. Based on a new clinical classification, 149 of 219 (68%) histopathological specimens, from a total of 534 patients with EEMM. SJS and TEN, have been reviewed. A comparison was made with the clinical picture, and any past history of infection or drug intake. All patients had been included in the German Registry of Severe Skin Reactions between April 1990 and December 1993. No differences could be found between the biopsies examined and the total number of histopathological specimens, concerning clinical diagnosis, gender and age. Sections from 28 of 149 specimens were not diagnostic or were too old to be properly evaluated. In nine cases, other diagnoses were proposed. One hundred and eleven of the histological slides with the diagnosis of EEMM (n= 16), SJS (n=34) and TEN (n=61), were classified as epidermal type of erythema multiforme. In these 111 slides, necrotic keratinocytes could be found, ranging from individual cells to confluent epidermal necrosis. The epidermo-dermal junction showed changes ranging from vacuolar alteration up to subepidermal blisters. The dermal infiltrate was superficial and mostly perivascular. It was sparse in SJS and TEN, and more pronounced in EEMM. Oedema in the papillary dermis was evident occasionally in all clinical groups. In 59 of 111 cases (53%), at least one eosinophil was present in the dermis. In 11 of 111 (10%), more than 10 eosinophils per field could be seen. Eosinophils were less common in the patients with the most severe forms of TEN, in whom there was detachment of more than 30% of the skin surface area. No differences in the history for drug intake, or for infection with Mycoplasma pneumoniae, herpes simplex and other organisms, could be detected between patients with or without eosinophils in their skin sections. This dermatopathological study of patients with EEMM. SJS and TEN indicates that the epidermal type of erythema multiforme is the pathological correlate for these diseases.

Notes: Summary Background Colonization of human skin by Staphylococcus aureus is a characteristic feature of several inflammatory skin diseases, which is often followed by tissue invasion and severe cell damage. A crucial role has been attributed to staphylococcal haemolysins in the cytotoxicity to epidermal structures. Objectives To investigate haemolysin-independent virulence to human keratinocytes. Methods The stable α-haemolysin, β-haemolysin double-negative S. aureus mutant DU 5720 was compared with the fully virulent parent strain 8325-4 and with its isogenic fibronectin-binding protein A/B-negative variant DU 5883 in an invasion model. Results This assay showed dose-dependent internalization of all the strains investigated by human HaCaT keratinocytes, with reduced internalization of DU 5883. Transmission electron microscopy revealed adhesion of staphylococci to cellular pilus-like extrusions, followed by the embedding of the bacteria in cellular grooves. Following attachment to the keratinocytes the staphylococci were engulfed into vesicles within the cytoplasm where some bacteria persisted for 24–48 h. Addition of cytochalasin D strongly reduced the bacterial uptake, suggesting an active keratinocyte process. Bacterial invasion was followed by severe keratinocyte cell damage showing the morphological changes of cytotoxic and, to a lesser extent, apoptotic cell death as determined by the trypan blue exclusion test and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling assay. The highest levels of lethal cytotoxicity were observed in haemolysin-producing strains, whereas the induction of apoptosis seemed to depend on internalization. Conclusions Staphylococcal invasion of human keratinocytes represents a potent staphylococcal virulence factor, which, independently of α- and β-haemolysins, leads to necrotic and apoptotic cell damage.