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Fibrin deposition is an important histopathological feature of inflammatory skin lesions and is mediated in part, by procoagulants generated by mononuclear leucocytes (MNL). We examined whether MNL from patients with atopic dermatitis or psoriasis generate enhanced procoagulant activity (PCA). MNL isolated from the peripheral blood of 15 healthy control individuals, 15 patients with atopic dermatitis and 15 patients with psoriasis were incubated for 24 h in the presence or absence of bacterial lipopolysaccharide (LPS). MNL or the cell culture supernatants were then added to recalcified human plasma to determine the clotting time. We found that in both atopic dermatitis and psoriasis MNL cultured in the presence or absence of LPS expressed greatly enhanced PCA (p

Chloroquine is known to exacerbate psoriasis. Since immunological stimuli are considered to be important for the pathogenesis of psoriasis, we compared the effects of chloroquine on cell-mediated immunity in 15 healthy control individuals and 15 patients with psoriasis. We employed the spontaneous and phytohemagglutin (PHA)-induced uptake of 3H-thymidine to measure lymphocyte proliferation. Chloroquine was added to the cultures at concentrations ranging from 0.022 to 220 microM. We found that both spontaneous and PHA-driven lymphocyte proliferations were significantly lower in patients with psoriasis (p0.002). The spontaneous blastogenesis in both controls and patients remained stable under chloroquine. In PHA-driven cultures in controls, 0.022-2.2 microM chloroquine had no effect, higher concentrations of the drug suppressed proliferation. In patients, 22 microM chloroquine surmounted the suppression of the PHA-induced proliferative response found in controls; moreover, 2.2-0.022 microM chloroquine increased lymphocyte proliferation by300% (p0.002). Our data indicate that in psoriasis the lower lymphocyte transformation is abnormally stimulated by the addition of pharmacological doses of chloroquine.

During a therapeutic trial to treat psoriasis with either etretinate or cyclosporin A (CyA) we measured the respiratory burst activity of polymorphonuclear leukocytes (PMN). Six patients received 0.5-0.75 mg/kg etretinate and 14 patients 2.5-5.0 mg/kg CyA over a period of 10 weeks. The extent of psoriasis was graded by the psoriasis area-and-severity index (PASI score). The respiratory burst of PMN isolated from the peripheral blood was measured employing luminol-enhanced chemiluminescence at weeks 0, 3 and 10 and compared with that of 26 healthy control individuals. PMN were stimulated with zymosan particles, aggregated immunoglobulin (aggIg) and concanavalin A (ConA). Both treatment regimens improved psoriasis; at 10 weeks there was an approximate 40% PASI score reduction under etretinate and an 80% improvement under CyA. Before treatment the respiratory burst was abnormally high under stimulation with the three stimuli in patients (p = 0.021 to less than 0.0001). After 3 to 10 weeks PMN activity normalized in all patients and even tended to drop below values correlating with an improvement in skin lesions. We conclude that the elevated respiratory burst of PMN in psoriasis normalizes under treatment with both etretinate and CyA.

Ethanol has been reported to exacerbate psoriasis. Since immunological mechanisms are considered to be important for the pathogenesis of psoriasis, we compared the effects of ethanol on lymphocyte proliferation in 15 healthy control individuals and 15 patients with psoriasis. We employed the spontaneous and phytohemagglutin in (PHA)-induced uptake of 3H-TdR to measure lymphocyte proliferation. Ethanol was added to cultures at concentrations ranging from 0.5 to 0.0005% (vol./vol.). We found that both spontaneous and PHA-driven lymphocyte proliferations were significantly lower in patients with psoriasis (P0.002). Spontaneous blastogenesis in both controls and patients remained stable under ethanol. In controls, ethanol suppressed the PHA-driven lymphocyte proliferation in a dose-dependent fashion. By contrast, in patients with psoriasis ethanol significantly increased lymphocyte proliferation by 2-3 times (p0.002). Our data indicate that in psoriasis the lower lymphocyte transformation is abnormally enhanced by minimal doses of ethanol.

The purpose of this study was to measure soluble CD14 (sCD14) molecules in the skin and in serum of patients with psoriasis. CD14 is a newly discovered cell surface marker on monocytes that is shed after cell activation. The following procedures were used: suction blisters were raised over the abdominal skin of 9 healthy control individuals and 8 patients with psoriasis. Serum of 17 healthy controls and 17 patients with psoriasis was collected. sCD14 was determined in suction blister fluid and serum by the ELISA technique. The clinical status of psoriasis was rated by the psoriasis area and severity index (PASI score). We found that sCD14 levels in suction blisters of healthy skin (1,050 +/- 236 ng/ml, mean +/- SE) were similar to those of nonlesional psoriatic skin (841 +/- 113 ng/ml). By contrast, control serum contained 2,687 +/- 167 ng/ml, but psoriatic serum 4,059 +/- 388 ng/ml sCD14 (p = 0.001, Wilcoxon test). Linear-regression analysis revealed that serum sCD14 levels and the PASI score of patients did not correlate. We conclude that there is an abnormal monocyte stimulation in blood but not in nonlesional skin in psoriasis that is independent from the clinical status expressed by the PASI score.

We examined granulocytes or polymorphonuclear leukocytes (PMN) in an HLA B8+ patient with palmoplantar pustulosis (PPP). Controls included another patient with PPP, however, lacking this antigen and a healthy, HLA B8+ person. Chemiluminescence (CL) served to monitor the respiratory burst in PMN comparing as stimuli zymosan, opsonized zymosan, phorbol myristate acetate, as well as aggregated immunoglobulin (aggIg), the latter as Fc-receptor (FcR) stimulus. FcR density on PMN was determined using 125I-IgG and expressed in the form of Scatchard plots. The effects of serum on the aggIg-induced CL were also measured. We found both control individuals to respond to stimulation by aggIg as a function of a dose-dependent increase of CL. By contrast, the HLA B8+ patient with PPP failed to respond to aggIg; only the highest concentration of aggIg induced marginal CL. Conversely, stimulation by the other agents was similar in all three individuals. The patient with the functional FcR defect expressed 2.5 times more FcR/PMN than the controls. No difference emerged in comparing autologous serum with a reference normal serum on the aggIg-induced CL, ruling out saturation by serum factors alone to be a cause for the defect. In remission, the functional FcR was absent. Our results suggest a defect of signal transduction in PMN from numerically enhanced FcR to the cytosol in the patient with PPP.

In 30 female patients suffering from acne vulgaris and 32 female controls, we determined the plasma levels of androstenedione, testosterone and dihydrotestosterone. The average rates of all three androgens were significantly increased in acne. But only the dihydrotestosterone rate showed a clear separation from the individual values of the two collectives. These findings suggest increased synthesis of dihydrotestosterone within the skin of patients with acne vulgaris.

Until now is not clear, whether bile acids play a role in hepatogenic pruritus in patients with cholestasis. A correlation between serum levels and itching does not exist, and therefore an accumulation of bile acids in the skin was made responsible for the etiology of pruritus. However, this could not be proved in skin homogenisates whereas bile acids were found accumulated in the surface lipids of the skin. For this reason, the investigations presented here deal with the determination of glycocholate and sulfalithoglycocholate in suction blister fluid and in serum. The levels of these bile acids were remarkably lower in the fluid of the subepidermally located blisters than in the serum. No significant difference was found between the group of patients with pruritus and cholestasis and the group without cholestasis. These results show that an accumulation of bile acids in the skin does not exist. A correlation between bile acids in the skin and pruritus cannot be proved.

Based on reports suggesting aberrant cell-mediated immunity and altered infiltration of immunocompetent cells into the skin in psoriasis, we studied the stimulation of T cells by autologous non-T mononuclear leukocytes (autologous mixed lymphocyte reaction, AMLR) and by epidermal cells isolated from lesional and clinically uninvolved skin in psoriasis (autologous mixed epidermal cell lymphocyte reaction, AMECLR). Age- and sex-matched individuals served as controls. We found that the AMLR in psoriasis (n = 11) was similar to that in healthy controls (n = 16); furthermore, cell proliferation was alike in the presence of either 5% AB-serum or autologous serum. By contrast, while the AMECLR in healthy controls (n = 9) resembled that in psoriatics employing epidermal cells from univolved skin, epidermal cells from lesional sites (n = 10) induced a significantly higher proliferation of autologous T cells in the AMECLR (P less than 0.01). We conclude that the in vitro stimulation of T cells by non-T mononuclear leukocytes is normal in psoriasis and is not regulated by autologous serum. Lesional psoriatic epidermal cells, however, are more active in stimulating autologous T cell proliferation than cells from univolved psoriatic or normal epidermis.

Absorption and clinical efficacy of a preparation containing 20% benzoyl peroxide were studied in 20 patients with leg ulcers of varying etiology. Benzoic acid formed from benzoyl peroxide on penetration through the skin cannot be demonstrated in the plasma until three days after commencing application at the earliest. This indicates a building up of deposits of benzoyl peroxide in the skin. The plasma benzoic acid levels in all patients amounted to less than 5 mumol/l and is therefore toxicologically inoffensive. Clinically, the known therapeutic effects of benzoyl peroxide were confirmed. Neither sensitization nor allergic reactions were found in the 20 patients taking part in this study.

Clinical, X-ray, and scintigraphic (6mCi 99mtechnetium pertechnetate, 4mCi 99mtechnetium pyrophosphate) tests for joint involvement were conducted on 11 inpatients with psoriasis (4 female, 7 male), 6 of them cases of what is conventionally termed psoriatic arthropathy. These tests were performed both before and after a 12-day period of therapy with daily 4 x 1 coated tablets of Demoplas containing 150 mg phenylbutazone Scintigraphic tests showed that pathological radionuclide concentrations were present in at least one joint or group of joints in 10 out of 11 patients. Following therapy the previously pathological scintigraphic findings had stabilized completely in 4 patients and partially in 3 patients, but had not stabilized in 3 patients. The results of therapy with Demoplas as demonstrated by joint scintigraphy were thus good to satisfactory in 7 patients and unsatisfactory in 3 patients- possibly owing to the short duration of therapy. The improvement in scintigraphic results testifies to the therapeutic action of phenylbutazone on arthritic psoriasis. This can also be regarded as additional proof that psoriatic joint involvement is of an inflammatory and proliferative nature.

The aim of the study was to determine a biochemical basis for the augmented oxidative metabolism found in mononuclear leukocytes (MNL) of patients with active psoriasis. Dehydroepiandrosterone (DHEA) is known to inhibit glucose-6-phosphate dehydrogenase (G-6-PDH). We determined the activity of G-6-PDH as well as the penetration and metabolism of DHEA - diminished plasma concentrations of which have been found in psoriatics previously - in 16 patients with active psoriasis and 16 controls. MNL in patients with psoriasis possessed 52% more (p less than 0.05) G-6-PDH activity, based on cell number, and 34% more (p less than 0.05) activity, based on soluble protein. No difference in DHEA penetration and metabolism in MNL was found between psoriatics and controls, in contrast with previous findings of reduced penetration and increased reduction in erythrocytes of psoriatics. We conclude that the enhanced G-6-PDH activity in MNL of patients with active psoriasis is not due to altered DHEA penetration or metabolism.

Based on previous in vitro examinations, we compared different stimuli eliciting a "respiratory burst" in phagocytes of patients with psoriasis and controls. - Measurements were performed be chemiluminescence (CL). - The results show similar CL in resting phagocytes. Upon stimulation, psoriatic macrophages display augmented CL with aggregated immunoglobulin (aggIg), zymosan (Z), and opsonized zymosan (C3b), macrophages with aggIg, Z, phorbol myristate acetate, and concanavalin A. - The capability for increased phagocytic CL in psoriasis may be modulated by different cell membrane receptors. Changes in the metabolism of arachidonic acid analogous to those encountered in psoriatic epidermis may be responsible for the augmented CL in psoriasis.

In the plasma of psoriatics and controls the steroids dehydroepiandrosterone and 5-androstene-3 beta, 17 beta-diol were determined by radioimmunoassay. Corresponding earlier findings obtained by photometric methods in psoriatics the plasma level of dehydroepiandrosterone is increased and that of androstenediol is decreased.

Free dehydroepiandrosterone (DHEA), DHEA sulphate, testosterone, LH and FSH were measured in plasma from 67 patients with renal disease before and after haemodialysis or haemofiltration. Plasma concentration of the steroid hormones was lower in patients with renal failure than in normal controls, while that of the gonadotrophic hormones was elevated. After haemodialysis or haemofiltration DHEA sulphate level in plasma decreased, free DHEA increased significantly reaching almost the initial value of the control group. There was no change in concentration of the other steroid and gonadotrophic hormones. The likely mechanism is that haemodialysis removes DHEA deficiency in patients with psoriasis which is assumed to be an aetiopathogenetic factor in the disease.

Human melanomas were investigated for the presence of high-affinity estrogen-, gestagen-, and glucocorticoid-binding proteins. A statistically significant difference was found for mean estrogen receptor (ER) concentrations in melanomas of male versus female origin: female origin 37.6 (0-107) fmol/mg protein, male origin 3.9 (0-8.3) fmol/mg protein. No significant difference between sexes was found for gestragen receptors: 41.5 (0-194) fmol/mg protein for melanomas of female origin versus 99 (0-362) fmol/mg protein for male. Sucrose density gradient analyses revealed specific binding for both receptor types in the 4-5 S region as well as in the 8 S region. The binding affinities were in the same order of magnitude as reported for receptors found in typical steroid target organs. No significant difference in receptor values depending on sex was found for the glucocorticoid receptor: 19.2 (0-43) fmol/mg protein.

Urinary excretion of steroid hormone metabolites pregnandiol, pregnantriol, aetiocholanolone, dehydroepiandrosterone and androsterone of 20 patients with Turner's syndrome was measured by gas chromatography. In some of the patients urinary excretion did not reach the minimal value obtained in a control group. Sixteen of these patients were given an average daily dose of 0.1 mg oxandrolone/kg body-weight. Mean value for bone age, after an average treatment duration of 17.3 months (s = 9.7), increased by 12.6 months (s = 12.7). Growth rate was 5.9 cm (s = 1.9) per year. Androsterone and dehydroepiandrosterone excretion in patients in whom the chronological age/bone age ratio had worsened, was more than double that in patients in whom it had improved. Measurement of the urinary excretion of dehydroepiandrosterone and androsterone thus seems to be of prognostic value in the treatment of Turner's syndrome with androgens.

Previous literature reports as well as own investigations concerning exogenously and endogenously induced Koebner-reactions in psoriatics are presented. The time interval between irritation and the Koebner-reaction is emphasized. It is proposed, that the intensity of the psoriatic reaction is mediated by circulating DHEA-deficiency. Hypothetical models are presented which allow to explain the different developmental rates of psoriatic lesions in relation to the type of irritation, the area affected and the subsequent proliferative responses.