Penetration of chromium in intact human skin in vivo.

Graphite furnace atomic absorption spectroscopy was modified to permit analysis of solid material, thereby fully utilizing the high sensitivity of the method. Tangential sections of biopsies from skin tested epicutaneously with K2Cr2O7 were analyzed for the content of chromium 5, 24, and 72 hr after application of the test substance in various concentrations, either in petrolatum or in water. The concentration of chromium as a rule showed 2 maxima, one at the dermal-epidermal junction and the other in upper mid-dermis. The content of chromium was of the same order of magnitude at all 3 times after application. This indicates that a steady state is reached already after 5 hr and that penetration is continuing at 72 hr. The chromium content in normal skin was 0.4-2 ppm. K2Cr2O7 in petrolatum penetrated to a greater extent than in water. The relative penetration of chromium was lower for 0.5% concentration than for 0.05%. A complex of chromium and glycine was found to penetrate into the skin but to a lower extent than K2Cr2O7. It also elicited a positive epicutaneous test reaction in 1 out of 2 individuals hypersensitive to chromium.

Increased expression of keratinocyte interleukin-8 in human contact eczematous reactions to heavy metals.

Heavy metal-induced contact eczematous human skin reactions to cobalt chloride and mercuric chloride were investigated for immunoreactivity to interleukin-8 (IL-8), by using an indirect immunoperoxidase staining technique. There was suprabasal epidermal staining for IL-8, with a decrease in the vicinity of areas with parakeratotic epithelium. However, in the immediate vicinity of a vesicular formation, intense staining of some apically situated keratinocytes was found. In addition, increased immunoreactivity over the acrosyringial area compared with the surrounding epidermis was obtained. These findings indicate an increased synthesis of keratinocyte IL-8 in contact eczematous skin.

Vasoactive intestinal polypeptide inhibits the established allergic contact dermatitis in humans.

There is increasing evidence indicating that the nervous system influences the immune response. In the present study the potential immunomodulatory role of vasoactive intestinal polypeptide (VIP) in established allergic contact dermatitis in humans was investigated. Positive patch-test reactions were elicited by application of nickel sulphate for 48 h. VIP was applied under patch-test conditions after another 24-h period. The test areas were measured before and 24 h after application of VIP and biopsy specimens were taken for immunohistochemistry. After application of VIP at 10(-5) mol/L, there was a significant reduction in the diameter of the test reaction. In addition, there was a reduction in the number of Leu 3a+ cells. The influence of VIP on the proliferative response of peripheral blood mononuclear cells from nickel-allergic subjects to nickel sulphate was also tested. The cells were cultured for 6 days and VIP was added after 3 days. There was no effect on the proliferative response. However, when VIP was added at 10(-6) and 10(-5) mol/L, a higher level of interferon gamma was found in the nickel-treated cell cultures compared to the controls. In conclusion, VIP may have an inhibitory effect on established allergic contact dermatitis. This inhibitory effect is possibly mediated through an increased production of interferon gamma by peripheral blood mononuclear cells.

Gamma/delta T cells and human skin reactivity to heavy metals.

Gamma/delta T cells may act as a first line of defence and respond to stress signals from the surrounding tissue. In the present investigation the occurrence of gamma/delta T cells was studied in the human skin after application of heavy metal salts by a routine epicutaneous patch-testing procedure. Gamma/delta cells were not found in normal skin. They were observed in all 14 allergic or irritant patch-test reactions to gold chloride and in 6/8 such reactions to mercuric chloride, where they comprised 16 +/- 6% and 15 +/- 6%, respectively, of the CD3+ cells in the dermis. They were also epidermotropic. Very few of these cells were found in reactions to salts of nickel and silver, except that they were increased in hair follicle epithelium in a reaction to silver nitrate. The gamma/delta cells expressed the V delta 2 and the V gamma 2 gene segments and were CD4-8-, indicating that they had the same phenotype as gamma/delta lymphocytes in the peripheral blood. Moreover, they were 'memory' T cells. These results indicate that gamma/delta lymphocytes play a role in the skin defence against highly reactive heavy metals.

Migration-stimulating effect of psoriatic scales on polymorphonuclear leukocytes.

Several previous studies have demonstrated a chemotactic factor for white blood cells in extracts from psoriatic scales. In the present work, the question was studied whether chemotaxis is a primary or a secondary event in the development of a psoriatic lesion. The migration-stimulating properties of polymorphonuclear leukocytes of different extracts were determined by means of a modified Boyden technique. Aqueous extracts of psoriatic scales were good stimulators of migration of both autologous and homologous leukocytes. Uninvolved skin adjacent to psoriatic plaques (perilesional skin) has previously been shown to differ from control skin in various respects. Extracts of such perilesional skin of psoriatic patients did not have migration-stimulating properties. This result indicates that chemotaxis is a secondary event in the pathogenesis of psoriasis.

Immunohistochemical localization of interleukin-6-like immunoreactivity to peripheral nerve-like structures in normal and inflamed human skin.

Interleukin-6-like (IL-6-like) immunoreactivity was sought in inflamed and normal human skin using the same immunohistochemical technique as for detection of neuropeptides. Such immunoreactivity was found in dermal and in a few intraepidermal nerve-like fibres in biopsy specimens from inflamed skin from patients with positive epicutaneous patch-test reactions to nickel sulphate, and in skin specimens from patients with atopic dermatitis and prurigo nodularis. However, IL-6-like immunoreactivity was also found in nerve-like fibres in specimens from nonlesional skin. In skin from patients with positive epicutaneous patch-test reactions there was a statistically significantly (P < 0.01) higher number of IL-6-positive nerve fibres in the epidermis than in normal skin, in contrast to the papillary dermis, in which no difference was found. Moreover, there were clusters of nerve-like fibres with IL-6-like immunoreactivity in the dermis of prurigo nodularis lesions. In these nerve-like fibres, the colocalization of the immunoreactivities for IL-6 and calcitonin gene-related peptide was indicated. Localization of immunoreactivity to nerve-like structures surrounding the eccrine sweat glands indicates that IL-6 is present in autonomic as well as in sensory nerve fibres.

Serotonin in human allergic contact dermatitis. An immunohistochemical and high-performance liquid chromatographic study.

Allergic contact dermatitis (ACD) is a common clinical condition leading to considerable morbidity. We have recently demonstrated that ketanserin, a serotonin antagonist, significantly inhibits nickel sulphate-induced ACD. Furthermore, serotonin-immunoreactive (IR) cells have previously been demonstrated in normal human cutaneous melanocytes. To further elucidate the role of serotonin in cutaneous contact hypersensitivity, we compared ACD involved skin and uninvolved skin from nickel-allergic patients, and normal skin from healthy volunteers, for the presence of serotonin-like immunoreactive cells using immunohistochemistry. In addition, serotonin concentrations in ACD involved and uninvolved skin were compared by high-performance liquid chromatography (HPLC). In the skin of normal healthy volunteers, the serotonin-IR cells were situated in the basal layer of the epidermis. In uninvolved skin the cells were also situated in the basal layer, but they were more numerous and the immunofluorescence intensity was greater. In involved skin, the IR cells were fewer and they were found higher up in the epidermis. Also, the configuration of these cells was different: they showed enlarged and elongated dendrites as well as dendritic spines. The serotonin antiserum-labelled cells in ACD involved skin were also NKI-beteb positive (the latter is known as a reliable marker of melanocytes). The concentration of serotonin in involved skin was significantly higher than that in uninvolved skin in ACD patients (P < 0.05). Taken together, our previous and present results indicate that serotonin plays an important role in ACD. The basal epidermal serotonin-IR cells are more dendritic in ACD, and are found more superficial in the epidermis, where they might release their content of serotonin, thereby influencing the inflammatory process.

A cognitive-behavioral treatment of patients suffering from "electric hypersensitivity". Subjective effects and reactions in a double-blind provocation study.

This study tested psychological treatment of patients with "electric hypersensitivity." Seventeen patients were randomly assigned to a treatment group or a waiting-list control group in a pretest-posttest control group design. The patients were also taking part in double-blind provocation tests before and after the treatment. Subjective ratings of symptoms were registered and blood samples were taken and analyzed for "stress-related" variables, such as prolactin, cortisol, dehydroepiandrosterone, and cholesterol levels. The patients in the experimental group reduced their evaluations of the disability more than the control group did. This indicates that psychological treatment may be of value in this disease. However, none of the psychophysiological measures or the subjective reactions to the provocation test showed any significant between-group difference. The conclusion from the provocation test is that this group of alleged hypersensitive patients did not react to the electromagnetic fields.

Skin problems in users of video display terminals. Discrepancy between subjective symptoms and objective signs.

The skin has become a target organ for concerns related to work with video display units (VDU). The aim of this investigation was to describe the clinical picture, to investigate whether skin problems are more common in VDU-exposed persons than in non-exposed controls, whether there are differences in objective and/or subjective symptoms and signs, and whether there is a "specific" dermatosis associated with VDU work. A self-reported questionnaire was mailed to 3,877 individuals. One out of five questions concerned the presence of skin problems. Of this group, 809 underwent a clinical dermatological evaluation in addition to filling out a structured questionnaire. Self-reported skin symptoms increased with increasing exposure to the VDU. The clinical diagnosis, based on objective signs and anamnestic data showed a somewhat attenuated association with exposure. The status diagnosis, based solely on objective signs, failed to show any association to VDU exposure. Unilateral skin rashes occurred at the same frequency in the exposed and the non-exposed groups. It is concluded that there is nothing in this investigation, or in any other investigation, that would speak against the notion that VDU-related skin problems and the allergy to electricity is just another facet of the "20th century syndrome". It is possible that individuals suffering from this condition, are conditioned to respond to certain stimuli by neurogenic release of mediators.

Clinical evaluation in acne.

Various methods for clinical evaluation of the effect of treatment of acne vulgaris have been studied. Counting of acne lesions was found to be more sensitive than the opinion of the patients and the assessment of colour photographs. The correlation between the results obtained by lesion counts and evaluation by photographs was low, as was also the reproducibility of photographic assessment. This methodological study was performed during a 6 week period, using a double-blind technique for comparing the effect of 0.6 g of oral zinc sulphate daily versus placebo in 54 patients. With zinc treatment acne improved with about one third as rated with a score system. Compared to placebo this result is slightly better (p less than 0.05). Inflammatory acne of grades 2-3 responded more favourably than comedonal acne to zinc treatment.

HLA antigens in allergic contact dermatitis.

The relationship between HLA factors and allergic contact dermatitis was examined in a series of 149 patients with unequivocal positive reactions to one or several allergens on epicutaneous testing. Nine statistically significant associations involving 6 different HLA antigens and 6 different allergens were found. Four allergens (chromium, formalin, balsam of Peru and wool alcohol) were positively associated with the B7 antigen. Furthermore chromium allergy was associated with A3, formalin allergy with A2 (negative association) and A9, nickel allergy with B8 and colophony allergy with B27. The B7 antigen and the combination A3+B7 showed significant regressions on number of allergies. The results fit the hypothesis that some HLA factors (like B7) may predispose for multiple contact allergy and others for allergen specific reactions.