British Journal of Dermatology

EEDY, D.J.

doi: 10.1111/j.1365-2133.1993.tb00252.xpmid: 8338743

MCGREGOR, J.M.; YU, C.C‐W.; DUBLIN, E.A.; BARNES, D.M.; LEVISON, D.A.; MACDONALD, D.M.

doi: 10.1111/j.1365-2133.1993.tb00253.xpmid: 8338744

SummaryExpression of the tumour suppressor protein, p53, was determined in 77 cutaneous melanocytic lesions, and in five lymph node metastases from malignant melanoma, in an immunohistochemical study employing CM‐1, an antiserum raised against recombinant human p53 protein. Because wildtype p53 protein is rapidly degraded in normal cells, p53 immunoreactivity suggests the presence of an abnormally stable p53 protein. This may occur through either post‐translational mechanisms or gene mutation.A highly significant correlation was found between p53 immunoreactivity and malignancy in melanocytic lesions (P<0.0001). Overall, p53 immunoreactivity was observed in 63% of tumour specimens examined, but not in benign melanocytic naevi, although occasional foci of weak nuclear p53 immunoreactivity were observed in a minority of dysplastic naevi and a solitary Spitz naevus. A significant correlation was also found between strong p53 immunoreactivity and malignant melanomas associated with a poor prognosis (P=0.008).These data suggest an important role for p53 tumour suppressor protein in the biology of human cutaneous malignant melanoma.

GISSLER, H.M.; FRANK, R.; KRAMER, M.D.

doi: 10.1111/j.1365-2133.1993.tb00254.xpmid: 7687853

SummaryThe relative topographical distribution of urokinase‐type plasminogen activator (uPA), tissue‐type PA (tPA). PA‐inhibitor‐1 (PAI‐1). PA‐inhibitor‐2 (PAI‐2), plasmin(ogen), α2‐antiplasmin, and α2‐macroglobulin was studied in lesional epidermis of psoriasis vulgaris, and in normal epidermis, by immunohistochemistry. In psoriatic epidermis, tPA predominated, although uPA was found in some biopsies. PAs were not detected in normal epidermis. PAI‐1 was not detected in normal epidermis and was only present in a proportion of biopsies of psoriatic lesions. PAI‐2 was found in normal and psoriatic epidermis. Plasmin(ogen) was confined to the basal cell layer of normal epidermis, whereas in lesional psoriatic skin it was scattered throughout the epidermis, α2‐antiplasmin and α2‐macroglobulin were not found in the epidermis of normal skin. In psoriatic epidermis α2‐antiplasmin was confined to the subcorneal layer, whereas staining for α2‐macroglobulin was found only in a proportion of biopsies, in the upper epidermis. Our immunohistological findings indicate that colocalization of tPA and its substrate plasminogen may allow efficient generation of plasmin, and that the focal absence of plasmin inhibitors may then favour the persistence of plasmin activity.

HERTL, M.; GEISEL, J.; BOECKER, C.; MERK, H.F.

doi: 10.1111/j.1365-2133.1993.tb00255.xpmid: 8338745

SummaryThe presence, phenotype, and functional characteristics of peripheral blood penicillin‐specific T lymphocytes in individuals with cutaneous allergic reactions to penicillin were investigated using in vitro long‐term culture techniques. Peripheral blood mononuclear cells from two penicillin‐allergic patients were stimulated in vitro with penicillin, and T‐cell blasts were clonally expanded by limiting dilution. Seven T‐cell clones were derived, all of which were CD3+ CD4− CD8+ HLA‐DR+, and produced IL‐2 and IFN‐γ upon stimulation. T‐cell proliferation required the presence of antigen and autologous, but not allogeneic, antigen‐presenting cells. In addition to the parent compound, the T‐cell clones also developed a proliferative response to penicilloyl, the major metabolite of penicillin. The cloned T‐cell lines were found to exhibit marked suppressor activity for Con A mitogenesis. The observed suppressor activity required cell‐to‐cell contact, as supernatants from these T‐cell clones had no comparable inhibitory effect. These findings indicate that there is a predominance of penicillin‐specific CD8+ T cells in the peripheral blood of individuals sensitized to beta‐lactam antibiotics.

FAULER, J.; NEUMANN, CH.; TSIKAS, D.; FRÖLICH, J.C.

doi: 10.1111/j.1365-2133.1993.tb00256.xpmid: 8393333

Synthesis of cysteinyl leukotrienes was assessed in patients with atopic dermatitis (AD; n=8) and healthy volunteers (n=8) by measuring urinary excretion of leukotriene E4 (LTE4), the main index metabolite of cysteinyl leukotrienes in man.Using this non‐invasive method we demonstrated a significant (P<0.05) 4.5‐fold increase in excretion of LTE4 compared with healthy volunteers. The identity of LTE4 was unequivocally demonstrated by gas chromatography‐mass spectrometry/mass spectrometry (GC‐MS/MS). LTE4 was routinely measured by radioimmunoassay (RIA), and quantitative measurement of LTE4 by RIA was validated by GC‐MS/MS. There was a linear correlation between LTE4 measured by RIA and by GC‐MS/MS (r=0.994). Tn representative samples, LTE4 was also quantitatively assessed by GC‐MS/MS. In these samples, LTE4 values obtained by GC‐MS/MS differed <10% from those obtained by RIA. The present findings suggest that cysteinyl leukotrienes play a role in AD.

MCFADDEN, J.P.; NOBLE, W.C.; CAMP, R.D.R.

doi: 10.1111/j.1365-2133.1993.tb00257.xpmid: 8338746

SummaryAlthough the deieterious effect of Staphylococcus aureus on atopic eczema is well recognized, the mechanism of this effect may be more complex than pyogenic infection aione. We have shown that the majority of S. aureus cuitures isoiated from atopic eczema produced exotoxins with superantigenic properties, although this was no more frequent than in a controi group, and was not restricted to one particular superantigen. However, the widespread nature of staphyiococcai infections in atopic eczema indicates that sufficient superantigen may be released to cause T‐lymphocyte activation, cytokine release, and mast cell degranulation. These mechanisms could, in part, expiain the exacerbations of atopic eczema associated with S. aureus infection.

AALTO‐KORTE, K.; TURPEINEN, M.

doi: 10.1111/j.1365-2133.1993.tb00258.xpmid: 8338747

SummaryPercutaneous absorption of hydrocortisone was measured in tbree children and six adults with widespread dermatitis, after the application of 1% bydrocortisone cream. Before appiication of the cream, the transepidermal water loss (TEWL) was measured on six skin areas. A highly significant correlation was found between the post‐application rise in plasma cortisol level and the mean transepidermal water loss. Thus, measurement of TEWL affords a simple, non‐invasive method for assessing the systemic effect of hydrocortisone applied to widespread dermatitis.

ZILLIKENS, D.; AMBACH, A.; ZENTNER, A.; DUMMER, R.; SCHÜSSLER, M.; BURG, G.; BRÖCKER, E.B.

doi: 10.1111/j.1365-2133.1993.tb00259.xpmid: 8338748

SummaryPemphigus is an autoimmune blistering disease in which autoantibodies have clearly been shown to be pathogenic. Because autoantibodies are also found in uninvofved skin, further mechanisms may be important in the development of pemphigus lesions. In addition to granulocytes, mononuclear cells are commonly found in pemphigus lesions. To elucidate the role of mononuclear cells in the pathology of this disease, we determined the levels of soluble interleukin‐2 receptor in blister fluid and serum samples from pemphigus patients prior to treatment. The interleukin‐2 receptor (IL‐2R) is expressed on activated mononuclear cells. Depending on its rate of synthesis, a portion is released from the cell surface in a soluble form (sIL‐2R), In blister fluid, sIL‐2R levels were 2186±288 U/ml (±SD), which was significantly higher than levels in concurrently obtained serum samples (1299±165 U/ml: P<0.001). In suction blisters in volunteers, and in patients with second‐degree burns or friction‐induced bullae, sIL‐2R levels were normal in both blister fluid and serum. In pemphigus patients, sIL,‐2R serum levels continuously declined during systemic therapy, correlating with disease activity, Immunohistological studies demonstrated a marked increase in IL‐2R+ cells in both the epidermis and dermis of lesional skin compared with perilesional skin. In the dermis, CD3+ T cells predominated, whereas monocytes/macrophages were most frequent in the epidermis. In pemphigus vulgaris, monocytes/macrophages were restricted to the basal keratinocytes. whereas in pemphigus foliaceus, they were found throughout the lesional epidermis. Our data indicate that activated mononuclear cells are present in lesional skin of pemphigus patients, and may contribute to the pathology of this disease.

KIKUCHI, A.; SAKURAOKA, K.; SHIMIZU, H.; NISHIKAWA, T.

doi: 10.1111/j.1365-2133.1993.tb00260.xpmid: 7687854

SummaryWe have examined the character and carcinogenic properties of the normal‐appearing epidermis overlying basal cell carcinomas by immunohistochemical methods, employing a series of monoclonal antibodies. The labelling index was significantly increased in the atrophic epidermis overlying basal cell carcinomas (solid type, n=20). compared with the epidermis overlying or adjacent to squamous cell carcinoma (n=20). keratoacanthoma (n= 10). dermatofibroma (n=10), neurofibroma (n= 10). soft fibroma (n=10). pyogenic granuloma (n=10) and cutaneous leiomyoma (n=5). Cells which expressed epidermal growth factor (EGF) receptor were detected in all layers of the epidermis over the basal cell carcinomas, hut not the other tumours. Basement membrane‐related antigens, including bullous pemphigoid antigen and GB3 antigen, were decreased in the epidermis. AEl. the monoclonal antibody against basal cell keratin, reacted with the uppermost layers of the normal‐appearing epidermis overlying the basal cell carcinomas. ICAM‐1 expression was very weak in the overlying epidermis. The dermis subjacent to the proliferating epidermis showed staining for transforming growth factor‐α (TGF‐α). strong positive PECAM‐1 staining of endothelium. and numerous HLA‐DR‐positive cells.From these results, we suggest that the proliferative activity in the epidermis overlying basal cell carcinomas is not a state induced by the dermal infiltrate, but represents carcinogenic activity of the epidermis.

FORTON, F.; SEYS, B.

doi: 10.1111/j.1365-2133.1993.tb00261.xpmid: 8338749

SummaryA standardized skin‐surface biopsy (1 cm2) of the cheek was performed in 49 patients with rosacea [13 with erythematotelangiectatic rosacea (ETR). three with squamous rosacea (SR), 33 with papulopustular rosacea (PPR)], and 45 controls.A mean density of 0.7 Demodex folliculorum/cm2 was found in controls, 98% of whom had less than five Demodex/cm2. When all clinical types of rosacea were considered collectively, the density of Demodex was significantly higher in patients with rosacea than in controls (mean=10.8/cm2: P<0.001). When the various clinical types of rosacea were considered separately. Demodex density was statistically significantly higher than in controls only in the PPR patients (mean=12.8/cm2; P<0.001).The same type of comparison was also made for three other groups of subjects—patients with isolated inflammatory papules (n=4). rhinophyma (n=3), and HIV infection (n=21), respectively: in these groups, the Demodex density did not differ significantly from controls.The present study demonstrates a high density of D. folliculorum in PPR, and supports its pathogenic role in the papulopustular phase of rosacea. The study suggests that standardized surface biopsy could be a useful diagnostic tool for PPR, with a 98% specificity when Demodex density is higher than 5/cm2.