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Vascular cell adhesion molecule-1: expression in normal and diseased skin and regulation in vivo by interferon gamma.

BACKGROUND: Vascular cell adhesion molecule-1 (VCAM-1) is an endothelial protein with adhesive properties for inflammatory cells including lymphocytes. Its role in skin disease and regulation in vivo are uncertain. OBJECTIVE: Our purpose was to determine expression of VCAM-1 in normal and inflamed skin and the effect on this of the T-cell-derived cytokine interferon gamma (IFN-gamma). METHODS: VCAM-1 was detected immunohistochemically in frozen-section biopsy specimens of inflammatory dermatoses and skin tumors. Volunteers received intradermal IFN-gamma and underwent biopsy 2 hours to 6 days later. RESULTS: In normal skin, VCAM-1 was present on perivascular dendritic cells and some follicular keratinocytes. In allergic contact dermatitis, atopic dermatitis, and psoriasis, VCAM-1 was variably upregulated on dermal endothelium and dendritic cells, but was most pronounced in lichen planus. IFN-gamma led to marked upregulation of endothelial and dermal dendritic cell VCAM-1. CONCLUSION: VCAM-1 may be involved in the pathogenesis of various skin diseases and in vivo, IFN-gamma is a potent modulator of its expression.

Cell Adhesion Molecules↗

Distribution of anti-p80-coilin autoantibody in collagen diseases and various skin diseases.

Anti-p80-coilin antibody produces a unique pattern of immunofluorescence staining called nuclear dots characterized by the presence of up to six discrete nuclear bodies in interphase cell nuclei. The distribution of this antibody and its clinical relevance have not been established. We studied the prevalence of anti-p80-coilin antibody in the sera from 810 patients with collagen diseases and various skin diseases. Five sera showed the nuclear dot pattern by indirect immunofluorescence on an HEp-2 cell substrate, and reacted by immunoblotting with 80-kDa protein in a nuclear extract from HeLa cells. Four of these sera were from patients with localized scleroderma, and the other was from a patient with primary Raynaud's phenomenon. The patients with localized scleroderma who were positive for anti-p80-coilin antibody had all been classified as having linear scleroderma. They had only one or two lesions, and were negative for antihistone and anti-single-stranded DNA antibodies. Our data indicate that anti-p80-coilin antibody is uncommon in skin diseases: however, this antibody is present in patients with a milder form of linear scleroderma, although the incidence of positivity may not be high.

Autoantibodies↗

Calculation of nail plate and nail matrix parameters by 20 MHz ultrasound in healthy volunteers and patients with skin disease.

BACKGROUND/AIMS: The objective, but noninvasive, assessment of the nail plate and nail matrix is of interest in dermatology, and cosmetics as well. These cutaneous structures were investigated with 20 MHz ultrasound. This study was performed to obtain data on normal nails in adults of different age groups, with a left-right comparison, and to investigate nail changes in selected dermatologic diseases. METHODS: Healthy controls (n = 34) and patients with dermatologic complaints and nail disease (n = 37) were included after informed consent. In the control group, 18 woman and 16 men with a mean age of 37.2 years (range 15 to 82 years) were investigated for age- and gender-related differences. Patients with one of the following disorders were investigated: systemic lupus erythematosus (SLE; n = 11), systemic sclerosis (PSS; n = 8), psoriasis (n = 9), chronic hand eczema (n = 5), and others (n = 4). Measurements of length and width of the nail plate and the lunulae were performed with a micrometer device. Sonography was performed with a 20 MHz probe in B-scan mode. RESULTS: The mean nail thickness of healthy controls varied between 0.481 mm (right thumb) and 0.397 mm (left fifth finger). The nail volume and the matrix volume disclosed a positive, but mostly nonsignificant, correlation for all controls. Age-specific differences were investigated for both genders. In men and women, the matrix volume increased significantly with age. The nail and matrix volume was higher in men than in women, independent of age. The left-right comparison disclosed a trend to higher nail and matrix volumes on the right hand. In patients with SLE there was an increase in nail thickness and in matrix volume. Patients with PSS showed a significant decrease in nail thickness and matrix volume. In other diseases the measurements disclosed no confident differences to healthy controls. CONCLUSION: The 20 MHz ultrasound offers a noninvasive method to calculate nail thickness, nail volume and matrix volume in healthy volunteers and in nail disease. Skin diseases show characteristic quantitative changes in these parameters.

Adolescent↗

Inflammatory mediators in normal, sensitive and diseased skin types.

The role of inflammatory mediators in the pathogenesis and pathophysiology of skin diseases is now widely accepted. We analysed the profiles of inflammatory mediators in normal, sensitive (past history of eczema, but currently patch test negative) and diseased (psoriasis and eczema) skin types to identify the patterns associated with various degrees of inflammatory dermatoses. Compared with normal skin, prostaglandin E2 was increased approximately 3.8-fold (p<0.0002) and 4.7-fold (p<0.0001) in suction blister fluids from sensitive and diseased skin types, respectively. Leukotriene B4 and interleukin-1alpha showed no differences between normal and sensitive skin types. However, in lesional skin from psoriasis and eczema patients, leukotriene B4 was increased approximately 6.6-fold (p<0.0001), whereas interleukin-1alpha was decreased approximately 3.1-fold (p<0.001). Interleukin 6 and tumour necrosis factor-alpha could not discriminate between skin types. We conclude that only prostaglandin E2 showed a significant stepwise increase on progression from normal through sensitive and inflammatory skin diseases. Levels of leukotriene B4 and interleukin-1alpha were also indicative of disease state and may be important in the pathophysiology of these conditions.

Adult↗

Prenatal diagnosis of genetic skin disease using fetal skin biopsy samples.

BACKGROUND: Understanding normal skin development and identifying markers of genetic skin disease expressed in postnatal skin have permitted the prenatal diagnosis of many severe genodermatoses: bullous diseases, keratinization diseases, pigment cell disorders, and disorders of the epidermal appendages (ectodermal dysplasias). Samples of 16 to 22 weeks' gestation fetal skin obtained by ultrasound-guided biopsy are evaluated using morphologic, immunohistochemical, and biochemical methods. OBSERVATIONS: The 12-year experience in evaluating samples from fetuses at risk of these disorders has allowed us to establish conditions that must be met before the samples are taken and the criteria for recognizing the disorder, to recommend the site(s) for sampling, and to be mindful of pitfalls that may be encountered in interpreting the tissue structure. CONCLUSIONS: Fetal skin biopsy is an important diagnostic tool that has permitted families in which members carry the abnormal gene for one of these severe skin diseases to undertake a pregnancy knowing that the condition of the fetus can be determined. Nonetheless, the ultimate goal is phase out this procedure when linkage of more of these disorders to specific genes is understood, specific mutations are characterized, and probes are available for molecular diagnoses using tissue obtained at earlier fetal ages. Until this is possible, fetal skin biopsy remains an important tool that can be used with reasonably high levels of safety and confidence.

Amniotic Fluid↗

[Cytokeratins--survey of incidence in normal and diseased skin. II. Cytokeratin expression in diseased skin].

The distribution patterns of cytokeratins demonstrated by different authors in benign and malignant tumours of the skin are presented and the resulting possibilities for histological differentiation are discussed. The monoclonal antibody A53-B/A2 made in GDR may be useful in the diagnosis of Merkel cell tumours or of the extramammary Morbus Paget. -For different dermatoses, especially some disease with abnormal types of keratinization, the expressed polypeptides are described.

Biomarkers, Tumor↗

[Incidence of occupation-related skin diseases in skin-exposure occupational groups].

BACKGROUND AND OBJECTIVE: Occupational skin diseases (OSD) rank at the top of occupational diseases in Germany. We studied the cases with initial medical report of an OSD reported to our Register of OSD in North Bavaria (BKH-N). PATIENTS/METHODS: From 1990-99 5.285 cases were closed and recorded. Since the number of employees in the different occupations was known, a population-based study was performed to investigate incidences and demographic characteristics in occupations classified into 24 groups. RESULTS: In the occupational groups in 3.097 cases a work-related skin disease was stated. The estimated overall incidence was 6.7 cases per 10,000 workers per year. The highest incidence was in hairdressers (97.4), bakers (33.2), and florists (23.9), while the largest number of cases was in hairdressers (856), health services (481), and metal-surface workers (260). The median age of all cases was 25 years. In 1.611 cases (52%) a delayed-type sensitisation with occupational relevance was perceived. CONCLUSIONS: The descriptive data of the BKH-N highlight occupational groups being at risk for OSD. The results assist in working out prevention measures aiming on lowering the incidence of OSD.

Adult↗

[Telemedicine in diagnosis and treatment of occupational skin diseases].

Advances of new data transfer technologies in medicine enable distant consultations for far places residents. Scandinavian countries, especially Sweden, have accumulated significant experience with using television medicine in dermatology. Applying television medicine technologies in occupational dermatology is the most topical item for Nizhny Novgorod region. In these cases transfer could cover not only images of diseased skin sites, but also text (history description and other medical information). International cooperation with foreign colleagues including Swedish doctors is considered prospective.

Humans↗

Expression of complement receptor CR2 (CD21) on human subcorneal keratinocytes in normal and diseased skin.

Human keratinocytes are able to synthesize and express cell surface moieties characteristic of effector and/or accessory cells of the immune system (CD16, CD36, HLA-DR, intercellular adhesion molecule-1). In the present study, skin biopsies from healthy volunteers, from patients with psoriasis vulgaris (PV), mycosis fungoides (MF), purpura pigmentosa chronica (PPC), acute urticaria (AU) and from positive tuberculin skin tests were investigated with regard to the reactivity with the monoclonal antibodies to complement receptors CR1 CR2 and CR3 by means of a multistep immunoperoxidase method. In the clinically involved skin of all patients with PV, MF or PPC, and in biopsies obtained from positive tuberculin tests, specific epidermal intercellular staining with OKB7 and Leu anti-CR2 was seen on subcorneal keratinocytes. This finding suggests a differentiation-linked expression of CR2 on human keratinocytes in cytokine-mediated skin diseases whereas CR1 and CR3 are apparently not expressed.

Antigens, CD↗

The 43 kDa papain inhibitor in normal and diseased skin.

The presence of 43 kDa papain inhibitor in 43 different skin diseases was immunohistochemically studied by using both poly- and monoclonal antibodies. Psoriasis and various eczematoid reactions as well as viral infections showed the most pronounced staining in the squamous cells of the epidermis. The antigen was also present in benign tumours or precancerous lesions which showed keratinization. Cells of poorly differentiated squamous cell carcinomas, basal cell carcinomas and melanocytic tumours were negative. The antigen seems to be related to disturbed keratinization and benign proliferation in non-neoplastic dermatoses and it is also present in differentiating squamous neoplasms.

Antibodies↗

Redox-modulated pathways in inflammatory skin diseases.

Inflammatory skin diseases account for a large proportion of all skin disorders and constitute a major health problem worldwide. Contact dermatitis, atopic dermatitis, and psoriasis represent the most prevalent inflammatory skin disorders and share a common efferent T-lymphocyte mediated response. Oxidative stress and inflammation have recently been linked to cutaneous damage in T-lymphocyte mediated skin diseases, particularly in contact dermatitis. Insights into the pathophysiology responsible for contact dermatitis can be used to better understand the mechanism of other T-lymphocyte mediated inflammatory skin diseases, and may help to develop novel therapeutic approaches. This review focuses on redox sensitive events in the inflammatory scenario of contact dermatitis, which comprise for example, several kinases, transcription factors, cytokines, adhesion molecules, dendritic cell surface markers, the T-lymphocyte receptor, and the cutaneous lymphocyte-associated antigen (CLA). In vitro and animal studies clearly point to a central role of several distinct but interconnected redox-sensitive pathways in the pathogenesis of contact dermatitis. However, clinical evidence that modulation of the skin's redox state can be used therapeutically to modulate the inflammatory response in contact dermatitis is presently not convincing. The rational for this discrepancy seems to be multi-faceted and complex and will be discussed.

Dermatitis, Allergic Contact↗

Expression of monoclonal antibody HECA-452-defined E-selectin ligands on Langerhans cells in normal and diseased skin.

The cutaneous lymphocyte-associated antigen recognized by the monoclonal antibody HECA-452 has been thought to play a major role in the homing of memory T-cell subsets to the skin by virtue of its ability to bind to E-selectin of dermal microvascular endothelial cells. Considering that the homing of different leukocyte populations to the skin may involve similar mechanisms, we studied the expression of HECA-452-reactive molecules on CD1a+ epidermal Langerhans cells. Immunofluorescence double-labeling of cryostat sections and epidermal sheets of normal skin revealed HECA-452 immunoreactivity on a subpopulation of dermal and epidermal CD1a+ cells, whereas upon flow-cytometric analysis of epidermal single cell suspensions virtually all CD1a+ cells bound HECA-452 antibodies. We observed a marked upregulation of HECA-452-antigen expression on CD1a+ epidermal cells and a pronounced increase in the number of HECA-452+/CD1a+ dermal cells in lesional skin from inflammatory and neoplastic lymphocytic skin diseases, compared to normal skin. The molecule detected by the HECA-452 antibody on Langerhans cells is neuraminidase sensitive and contains a CD15 (LewisX) carbohydrate backbone. Because Langerhans cells react with the sialyl-LewisX-specific antibody CSLEX1, it is very likely that the HECA-452-reactive structure is or contains sialyl-LewisX. Our data are compatible with the view that i) resident epidermal Langerhans cells upregulate HECA-452-antigen expression due to the cytokine profile generated in the disease process or ii) that Langerhans cell precursors express HECA-452-antigens and show an enhanced immigration into lesional skin. The characterization of HECA-452+ cells in peripheral blood may not only clarify this issue but may also help to identify the still elusive Langerhans cell-precursor.

Antibodies, Monoclonal↗

Psoriatic arthritis: outcome of disease subsets and relationship of joint disease to nail and skin disease.

Subgroups of PsA have been described but their relationship to the mode of onset of arthritis, to DIP joint disease and to nail and skin disease remains controversial. Therefore, the pattern of disease was documented in 100 patients with PsA in whom the mode of onset was known. The patients were divided into six subgroups: monoarthritis; DIP joint disease only; oligoarthritis; polyarthritis; spondyloarthropathy and arthritis mutilans. Sixty-four patients changed pattern. Nail disease (67% of total) was more common in patients with DIP joint disease (27% of total) and was significantly associated with adjacent DIP joint disease. Skin and nail disease severity did not correlate with joint severity, joint activity or functional status, nor differ between subgroups. Therefore, the mode of onset does not predict outcome in the majority. The topographic association of nail disease and involvement of the adjacent DIP joints suggests a common local inflammatory mechanism.

Adolescent↗

Occupational skin disease.

Occupational skin diseases are the most frequent occupational diseases. Certain industries are at a particularly high risk. Important factors to consider include percutaneous absorption and alterations in resistance to microbial agents. The most common condition is contact dermatitis, usually irritant but frequently causing allergy. Other selected conditions include photosensitization, acne and chloracne, fiberglass dermatitis, pigmentary changes, and skin tumor. The approach to the patient and diagnostic criteria for occupational skin disease are described.

Adult↗

[Cytokines and skin diseases].

Many skin diseases such as eczema and psoriasis are characterised by a chronic inflammatory skin condition. In this respect they resemble other chronic diseases such as rheumatoid arthritis, bronchial asthma, ulcerous colitis and Crohn's disease. A persistent accumulation, predominantly of T-lymphocytes constitutes the central pathophysiological feature of such diseases. The past 15-20 years have witnessed the characterisation of an extensive series of peptides known as cytokines. These are soluble, relatively low molecular weight peptides which at low concentrations mediate regulation of cellular receptors, new phenotype expression, secretion and migration. Many cytokines have been found to be present in conjunction with skin diseases, and it is suggested that they are involved in the development of inflammation.

CD4-Positive T-Lymphocytes↗