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Objective: A meta-analysis of 3 major German studies conducted between 1989 and 1994 with cyclosporine in severe psoriasis was performed to allow an integrated evaluation of the efficacy and tolerability of cyclosporine in this indication., Design and Setting: All 3 studies were prospective, randomized, parallel group studies. The studies were conducted in 61 dermatologic centers in Germany., Patients and Interventions: The studies involved 597 patients with severe plaque type psoriasis. Treatment consisted of cyclosporine (at a dosage of 1.25, 2.5 or 5 mg/kg/day), etretinate (at a mean daily dose of 0.53 mg/kg/day) or placebo in a total of 756 treatment cycles with a maximum duration of 12 weeks., Main Outcome Measures: The main outcome measures were the psoriasis area and severity index (PASI) and serum creatinine level., Results: The meta-analysis revealed that cyclosporine given in a dosage of 2.5 and 5 mg/kg/day was significantly superior to etretinate. In addition cyclosporine 1.25 mg/kg/day proved to be significantly more effective than placebo. An increase in serum creatinine level that required intervention occurred in 3.4% of cyclosporine treatment cycles., Conclusion: Cyclosporine is highly effective and well tolerated in the short term treatment of severe psoriasis.

The chemoattraction of polymorphonuclear leukocytes (PMNs) from psoriatic patients, atopic patients and healthy control persons by Pityrosporum orbicularelovale was investigated using the Boyden chamber method. The chemotactical attraction of PMNs from psoriatic patients by Pityrosporum (stimulation index SI = 58 +/- 50) was significantly increased (p < 0.05) compared to PMNs from atopic patients (SI = 20 +/- 17) and control persons (SI = 26 +/- 24). This effect seems to be specific for Pityrosporum, since the chemotactical response to Staphylococcus epidermidis was not increased in psoriasis. The chemotactical factor produced by Pityrosporum is hydrophilic and is destroyed by acid hydrolysis, indicating its protein nature. The yeast Pityrosporum may thus play a role in the koebnerization of psoriasis.

Although cyclosporin is effective in immunosuppression following organ transplantation and in the treatment of psoriasis, its use is limited by its side-effects, notably impaired renal function and hypertension. As SDZ IMM 125, a new derivative of the cyclosporin family, showed considerable immunosuppressive activity in experimental studies, with less effect on renal function, it was considered a potential successor to cyclosporin for both indications. In this multicentre, double-blind, placebo-controlled study, the efficacy and tolerability of 40, 100, 200 and 400 mg SDZ IMM 125 daily were studied in 59 patients with psoriasis. Patients were followed for a period of 5 weeks (4 weeks treatment, and 1 week post-treatment observation). A dose-dependent effect of SDZ IMM 125 was observed. A significant correlation was found between the dose of SDZ IMM 125 and changes in the sum of severity scores of three indicator plaques. There was a significant decrease in the body surface area affected by psoriasis in the 400-mg group (P < or = 0.01), whereas a decrease of the global psoriasis severity was observed in the 200-mg (P < or = 0.01) and the 400-mg groups (P < or = 0.001). No serious adverse events occurred during the 4 weeks of treatment. Three patients discontinued treatment because of adverse events (one sore throat, two influenza). Clinical adverse events were similar to those reported with cyclosporin, the most frequent being gastrointestinal disturbances. Estimation of renal function indices showed that increases from baseline values were dose-dependent, and appeared to be similar to those seen with cyclosporin.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: High-dose cyclosporine therapy significantly alleviates psoriasis within 2 to 4 weeks but is associated with a high rate of side effects. Reports are conflicting on the frequency and promptness of relapse after discontinuation of cyclosporine therapy., Objective: Our purpose was to compare the efficacy and safety of low-dose cyclosporine with that of etretinate and the stability of remission after replacing cyclosporine therapy with topical anthralin during tapering of cyclosporine., Methods: In a multicenter study 210 patients with moderate to severe chronic plaque-type psoriasis were randomly assigned to treatment with cyclosporine or etretinate. The initial dosages were 2.5 mg/kg/day for cyclosporine and 0.5 mg/kg/day for etretinate, which could be individually adjusted to 5.0 and 0.75 mg/kg/day, respectively. After a treatment phase of 10 weeks (phase 1) patients receiving cyclosporine were again randomly assigned to a group in which cyclosporine was replaced by topical dithranol (anthralin), or to another group in which the drug was tapered during the next 12 weeks (phase 2). All patients treated with etretinate discontinued therapy after 10 weeks and used topical dithranol., Results: Mean Psoriasis Area and Severity Index decreased by 71% in the cyclosporine group and by 47% in the etretinate group during phase 1. After 10 weeks of treatment 47% of the patients treated with cyclosporine and 10% of those treated with etretinate showed a reduction of more than 80% in skin involvement. Sixty-four percent of the cyclosporine group and 48% of the etretinate group did not require an increase in the initial dosage, resulting in a mean daily dose of 3.0 and 0.53 mg/kg, respectively. There was significant alleviation of nail involvement and joint complaints in both groups. In phase 2 the increase in mean Psoriasis Area and Severity Index and the incidence of relapse were significantly higher in patients in whom cyclosporine was discontinued and replaced by dithranol than in patients in whom cyclosporine was tapered or who were pretreated with etretinate. During treatment four patients from the cyclosporine group and three patients of the etretinate group discontinued the study because of side effects., Conclusion: Low-dose short-term cyclosporine therapy for psoriasis is, in comparison with etretinate, highly effective and well tolerated. Individually adjusted cyclosporine therapy allows the majority of patients to continue the low dosage of 2.5 mg/kg/day and still achieve a good clinical response. Remission can be better preserved by tapering the drug than by discontinuing treatment abruptly.

Background: In the psoriatic plaque both IL-1 dysregulation and ICAM-1 expression on keratinocytes have been previously described. Furthermore systemic administration of fumarates has been reported to be effective in psoriasis. We, therefore, studied the effect of dimethyl-fumarate ester (DMF) on the putative IL-1-induced ICAM-1 expression., Methods: Hyperproliferative human keratinocytes (HaCaT cell line) were incubated in 10 to 100 U/mL IL-1 alpha for 24 h with and without preincubation with 0.4-12.0 microM DMF: Expression of ICAM-1 was measured by a special ELISA-APAAP technique., Results: The exposure to IL-1 led to a significant dose-dependent induction of ICAM-1 expression of from 124 +/- 17 to 194 +/- 22% (control 100 +/- 12%), while proliferation remained unaltered. Pretreatment with > or = 4 microM DMF resulted in a distinct suppression of ICAM-1 expression and a slight decrease in proliferation., Conclusions: The present results show that ICAM-1 expression on hyperproliferative keratinocytes may be triggered by IL-1 alpha and serve as a molecular target for antipsoriatic DMF.

Anthralin is still the most effective and safest therapeutic agent for treatment of psoriasis. Our data may assist toward an understanding of its mode of action and introduce new derivatives, more antiproliferative and less toxic than anthralin in vitro. Anthralin exerts a direct effect on keratinocytes and leukocytes. In time-lapse studies it significantly prolonged the prophase of mitotic keratinocytes in subtoxic doses and suppressed the expression of keratin 6 mRNA in the immediately suprabasal layer of psoriatic epidermis in vivo. Anthralin inhibits the transformation of lymphocytes and the release of reactive oxygen species from activated leukocytes, in vitro. We provide evidence that these effects of anthralin are mediated by protein kinase C. Twelve new hydrophilic derivatives of anthralin, including a 1,8-dimethoxy compound, as well as C-2 and C-10 substituted anthrones were tested on human keratinocytes. The antiproliferative effect of those derivatives bearing lacton rings at a C-10, consisting of 4, 5, or 6 C atoms, exceeded that of anthralin and were equally or less cytotoxic than the parent drug. These compounds had no pro-drug character in vitro, since they did not metabolize via anthralin, as shown by HPLC. These data indicate that there may be anthralin derivatives with more favourable properties for topical therapy than anthralin itself.

Biopsy specimens from lesional psoriatic skin and from normal controls were investigated by immunohistochemistry for the presence of epidermal Merkel cells (MC). MC were defined as epidermal cells expressing simple-type keratins, i.e. nos. 8, 18, and 19. A significant number of MC could be found at the bottom of the rete ridges of psoriatic lesions (about 19.6 MC per square mm skin surface area) and of normal skin (about 14.0 MC per square mm surface area). In contrast to normal skin, MC of psoriatic lesions were positive for synaptophysin (21.7% of simple-type keratin positive epidermal cells, i.e. MC), pancreatic polypeptide (14.8%), somatostatin (7.0%), and chromogranin A (less than 3%). The immunostaining was rather faint though significantly different from normal skin. The findings suggest that in psoriasis, epidermal MC show variations of the expression of neuropeptides compared to normal skin. Since some of the neuropeptides are thought to be involved in hyperproliferation and/or skin immunology, our findings might suggest a functional activity of epidermal MC in psoriatic lesions different from normal controls.

In psoriatic patients, anthralin is known to attenuate lesional inflammation, but often generates perilesional dermatitis. This phenomenon is well reflected by the contrasting action of anthralin on human leukocytes. The release of reactive oxygen species (ROS) is inhibited by anthralin in phorbol ester-activated leukocytes, whereas anthralin directly induces this cellular response in unstimulated cells. In order to elaborate further the underlying mechanisms, we compared the kinetics of anthralin and different well-characterized stimuli, including the phorbol ester, phorbol-12-myristate-13-acetate, in this test system. Compared with standard stimuli, anthralin only marginally induced the release of ROS from human leukocytes and displayed different kinetics. Protein kinase C (PKC), the major cellular phorbol ester receptor, is considered to be involved in the regulation of this cellular response. Furthermore, its involvement in the pathophysiology of psoriasis has been suggested. Therefore, we also investigated the effects of anthralin on purified PKC. Anthralin was found to inhibit the enzyme activity in a dose-dependent manner but not to display any stimulatory effects. The present results provide first evidence that the therapeutic activity of anthralin, at least in part, might be mediated by inhibition of PKC.

Two groups of patients with chronic plaque psoriasis were topically treated either with 10% cyclosporin in a jelly base or with 5% cyclosporin in an ointment base under occlusion. We found that cyclosporin penetrates into the lower epidermis and the dermis, when it is applied under occlusion. Obviously, the target cells are neutrophil granulocytes, since they decrease in number under cyclosporin, whereas the other inflammatory cells as well as the epidermal proliferation remain unchanged. In contrast to systemic application of cyclosporin, we did not observe any clinical differences between plaques treated with cyclosporin and those treated with placebo.

The in vivo expression of the proliferation keratins K 6 and K 16 is characteristic for hyperproliferative diseases and positive in psoriatic lesions. Our study was performed in order to investigate the in vitro expression of proliferation keratins and to settle the question whether they are also inducible in organ cultures of uninvolved psoriatic skin, possibly differing from normal skin.

In a randomized open study we compared the effect of conventional dithranol therapy (CSV-therapy, 7 patients) with a combination regimen, in which patients were pretreated with a 0.064% betametason dipropionate ointment (Diprosis) for 1 week before the onset of dithranol therapy (B + CSV-therapy). Clinical evaluation was performed by grading 4 representative lesions per patient for erythema, plaque thickness and scaling every week (EPS-score). After one week of therapy glucocorticoid was superior to dithranol (reduction of EPS-scores 68% vs. 35%). Thereafter the benefit of CSV-therapy surpassed that of B + CSV-therapy. 33 days after onset of therapy there was a 95% reduction of skin lesions in the CSV-group compared to a 75% reduction in the B + CSV-group. In terms of a 95% reduction the CSV-group required 32.9 +/- 5.5 days versus 45.1 +/- 19.7 days of the B + CSV-group. During the 6 months follow-up relapses occurred in 3 of 7 patients of the CSV-group 15.32 and 34 days after discontinuation of therapy and in 2 of 7 patients of the B + CSV-group 64 and 82 days after discontinuation of therapy. The present findings reveal that a pretreatment of psoriasis with topical glucocorticoids reduces the response to dithranol and the duration of remission.

The pharmacology, the biological action, as well as the clinical indications for systemic or topical application of cyclosporin A (CSA) is reviewed. Our studies yielded the following results: In chronic stationary psoriasis, systemic treatment with CSA in very low doses (2.5 mg/kg/d, 13 patients, 10 weeks) led to a 75% reduction of the PASI score without any side reactions. After topical application of CSA (40 patients, 1/5/10% gel and ointment), we observed a subclinical effect. CSA permeated into the deeper layers of the skin and accumulated up to a concentration of 3.880 ng/g (80-39.000 ng/g, polyclonal RIA); these quantities correspond with those found after systemic administration. In spite of this, CSA was not measurable in the blood. Topical CSA reduced the neutrophils in psoriatic skin both selectively and significantly, but did not affect the epidermal synthesis of DNA.

The effect of tar on anthralin-induced erythema was epicutaneously tested in ten patients. 3%, 5%, or 10% crude coal tar or coal tar solution was added to vaseline containing anthralin. A 5% or 10% tar preparation significantly suppressed the anthralin erythema induced by 0.5 to 1.0% anthralin having been applied for 24 hrs. In these concentrations, coal tar solution was at least as effective as coal tar itself.

The phospholipid pattern of the involved and the uninvolved epidermis from 48 psoriatic patients and of the normal epidermis from 23 healthy controls was determined by thin-layer chromatography. A higher amount of total phospholipids was found only in the involved psoriatic epidermis, whereas significant alterations in the phospholipid pattern were observed in the psoriatic lesion and in the lesion-free epidermis. Namely, the decrease of phosphatidylserine and the increase of phosphatidylinositol were identically present in both the involved and the uninvolved psoriatic epidermis. It seems likely that these alterations in the phospholipid pattern in psoriasis may be related to subclinical alterations of the epidermis in this disease.

Coal tar applied simultaneously showed a suppressive effect on anthralin erythema. This effect was demonstrated by an epicutaneous test 24 hours (27 patients) and 1 hour (46 patients) after application of various concentrations of anthralin combined with tar 3%. In a clinical study on 9 patients, anthralin 3% alone or combined with tar 10% were administered in a right and left comparison on symmetrical chronic psoriatic lesions for 1 hour daily. Anthralin plus tar exhibited a stronger anti-psoriatic effect than anthralin alone did. Tar reduced the anthralin erythema in the perilesional skin. These findings favor the combination of coal tar and anthralin in the 1-hour treatment schedule of psoriasis.

Using murine monoclonal antibodies against human HLA-DR antigen and against human T cells, we investigated the indirect immunofluorescence staining pattern of involved and uninvolved skin from patients with psoriasis. The staining pattern of involved psoriatic epidermis is different from the pattern seen in uninvolved skin from the same patient and consists of scattered, single HLA-DR positive cells alternating with groups of HLA-DR positive cells. These HLA-DR positive cell clusters can be seen at any level of the epidermis. In some patients, the dermis of involved skin shows prominent accumulations of T cells which are HLA-DR positive and thus represent activated T cells.

In 44 patients with chronic plaque psoriasis anthralin therapy was used as high-strength short-contact therapy in a bilateral comparison of anthralin versus 5% crude coal tar-anthralin combination. These two trials were undertaken with and without ultraviolet (UV) irradiation immediately after anthralin therapy. The combined tar-anthralin therapy was significantly less of an irritant during the first 3 weeks of treatment than anthralin alone, and it did not decrease the antipsoriatic efficacy. The use of UV irradiation, either with anthralin or tar-anthralin combination, did not produce an additional therapeutic effect. These findings lead us to prefer combined tar-anthralin therapy because of its lower irritancy in comparison with anthralin alone and they show the ineffectiveness of additional UV irradiation under the conditions of this study.

A total of 66 patients with psoriasis was treated with one percent anthralin for one hour (one-hour-treatment) and UV-light. 17 out of 26 out-patients treated with anthralin and UVB showed a good response. In 40 in-patients the one hour regimen was administered in combination with UVA or UVB, in part in right-left side comparison in order to evaluate whether anthralin with UV-light is more effective than anthralin alone. Within six weeks remission was obtained with anthralin alone as well as with combined treatment with anthralin and UVA or UVB. In right-left side comparison UV-light had no significant additional effect in this regimen. The one-hour-treatment was effective but did not seem to be superior to the conventional therapy with anthralin in in-patients. However, the one-hour-treatment is advantageous and convenient for out-patients.

The total membrane-bound ATP hydrolytic activity in human epidermis is due to the activities of at least three differently located enzymes, namely Mg++-activated ATPase, phosphomonoesterase and adenyl cyclase. Cytochemical studies on psoriatic epidermis with various inhibitory and stimulatory substances showed reduced activities of ATPase and phosphomonoesterase, and a lack of sensitivity of adenyl cyclase to specific stimulators such as isoproterenol and glucagon. Since no differences of basal adenyl cyclase activity were observed between normal and psoriatic human skin without stimulation, it seems likely that in psoriasis a latent defect of adenyl cyclase may exist, resulting in a deficient response of this enzyme to regulatory agents. In conclusion, the present study reveals that not a single enzyme but the entire membrane-bound nucleotide metabolism is altered in psoriatic keratinocytes, causing a disturbance of the membrane-bound energy utilization, similar to findings in proliferating tumour cells.

The system glycocalyz - membrane bound enzymes - cAMP may be regarded as a regulatory mechanism for the control of epidermal growth. The glycocalyz of the epithelial cell membrane is obviously a receptor and accumulator for agents stimulating adenyl cyclase and other membrane-bound enzymes of energy utilisation; cAMP, on the other hand, serves as an intracellular 'mediator' between proliferative stimuli and the DNA of the keratinocytes. Numerous cytological, cytochemical, and enzymatic biochemical studies indicate that this mechanism is profoundly disturbed in psoriasis, particularly at the membrane-bound stage.

In a multicentre, cooperative study into the treatment of extensive psoriasis with a new aromatic retinoid (Ro 10--9359) trichogram, liver function tests and the light erythema threshold were investigated. In some of the patients hair loss occurred, usually in the fifth to eighth week after a total dose of 1.9 g retinoid. In all cases this improved an average of six weeks after dose reduction or cessation of treatment. The trichogram in 27 patients showed a diffuse toxic hair loss. In 70% the effluvium was telogenic, in 22% telogen-dystrophic. GPT, GOT, alkaline phosphatase and prothrombin index showed no significant alterations during retinoid treatment. However, in individual cases there was a rise in GOT and GPT up to 80 U/l. Furthermore there was a statistical tendency in rising bilirubin levels. Finally there was no evidence for an increase in light sensitivity after three weeks of retinoid treatment. Measurement of the erythema threshold showed rather more a reduction in light sensitivity under treatment.

Glucagon and beta-adrenergic compounds such as 1-isoproterenol stimulated the low activity of an ATP-utilizing enzyme located on the cell membranes of normal keratinocytes. Addition of beta-antagonist propranolol to the incubation medium prevented the stimulatory effect of 1-isoproterenol. We considered, therefore, the reaction product being due to epidermal membrane-bound adenyl cyclase activity. In psoriatic epidermis the basal adenyl cyclase activity was low, similar to normal epidermis, however, glucagon and 1-isoproterenol failed to stimulate the enzyme activity in psoriasis under the same conditions. It seems, therefore, that the beta-adrenergic-cAMP cascade as a regulatory epidermal control mechanism of induced proliferation is ineffective in this disease.

The combination of different antipsoriatics or treatment regimens should increase the therapeutic effect and reduce the adverse reactions. The combination of dithranol and tar (cignolin-salicyl-vaseline + tar, CSVT) reduces dithranol erythema and increases the antipsoriatic effect. CSVT treatment is highly effective, but patients tend to accept it less than other treatment regimens. On the other hand, Goeckerman therapy (tar + UV irradiation) is more accepted but less effective. Combinations of dithranol with UV irradiation or with tar and UV irradiation (Ingram regimen) are not advantageous. Dithranol and Goeckerman therapy are relatively secure treatment regimens, as they have been applied for more than 50 years without knowledge of significant late defects. PUVA therapy, although highly effective, is not superior to dithranol therapy. Even though PUVA therapy is more easily accepted than dithranol treatment, PUVA therapy should be applied only in severe cases. The combinations of aromatic retinoid with (selective) UVB irradiation (ReSUP) or with PUVA therapy (RePUVA) are highly effective. Retinoids can reduce the UV doses and most likely limit the risk of late damage. For routine treatment, ReSUP is preferable to RePUVA therapy.

This study has been undertaken to elucidate the localization and the activity of cyclic nucleotide phosphodiesterase (PDE) in psoriatic epidermis compared to normal. The results showed that the evaluation of cytochemical methods may be difficult because of the various factors which interfere with the reaction and the considerable amount of background staining. Additionally, only the tissue bound particulate enzyme fraction may be demonstrated by cytochemical means. Nevertheless, the method did reveal that the activity of PDE, if any, is localized on the cytoplasmic membranes of the cells, independent of their origin, and not on the cell surface. Moreover, no differences were found between normal and psoriatic skin. It seems, therefore, that the intracellular degradation of cAMP remains unaltered in psoriasis.

In the psoriatic skin, nexus were most prominent in the upper layers of the viable epidermis, using the Alcian blue-Lanthanum technique. There, they reached double and manifold the length (giant nexus) of those in normal epidermis. According to the villous transformation of the epidermal cell surface in psoriasis, the nexus showed a great variation in their shape. Undulating nexus were seen beside invagination--and anular nexus. On ther other hand, nexus were lacking in the deepest layers of the psoriatic epidermis in contrast to normal epidermis. From these findings it seems that the intercellular communication by specialized low resistant junctions is reduced in the deepest layers of the psoriatic epidermis. In the upper epidermal layers, however, the extensive formation and the variable configuration of the nexus express a high synthetic activity and a well developed intercellular information in these areas of the psoriatic epidermis.

Microtubules (MT) occur in the keratinocytes as 20 nm broad tubular structures with an electron-lucent core surrounded by an electron-dense wall. The number and the length of the MT increased to the upper epidermal layers. In the normal keratinocytes the MT were relatively short (maximal length 2.2 microns) and slightly tortuous. Their outline was tenuous and irregular. Sometimes the MT were interrupted indicating a high fragility. In the upper layers of the psoriatic epidermis the MT reached a maximal length of 3.1 microns, showing a greater elongation than in the normal epidermis. The MT were stright and distinctly limited, most likely resulting from a higher grade of stabilization or polymerisation. By their interaction with the tonofilaments the MT may contribute to the stability of the cell shape, delaying the flattening of the psoriatic keratinocytes in the upper epidermal layers. Nowhere did the MT make direct contact with the cell membrane. At some places they did gain access to the cell membrane by short microfilaments.

Anthralin has been applied in low and high concentrations with and without UV-irradiation in the treatment of psoriasis (Schauder & Mahrle, 1982a,b). We have studied the relationship between the sensitivity to anthralin and UV-irradiation which might possibly help us to give a more individually adapted therapy.

Fifty-one patients with psoriasis were treated with 1% anthralin for 1 h (1-h treatment) and UV-light. Seven of 11 out-patients treated with anthralin and UV-B showed a good response. In 40 in-patients the 1-h regimen was administered in right-left side comparison to evaluate (1) whether UV-A or UV-B combined with anthralin was more effective than anthralin alone and (2) whether anthralin was photoactivated by UV-A or UV-B. As to the latter, one body side of the patients was exposed to UV radiation before and the other body side after application of anthralin. In in-patients the response to therapy was monitored by a defined score system. We did not find any significant differences in the paired comparisons. We therefore summarized the different treatment regimens and rated 42% with very good or good, 26% with fair, and 32% with poor. The results show that the 1-h treatment with 1% anthralin seems to be advantageous especially for the treatment of out-patients with circumscribed chronic psoriatic lesions. UV-light did not improve considerably the therapeutic effect of anthralin in the regimen of this study.

Numerous laboratory parameters were examined 235 patients with generalized psoriasis treated orally with retinoid and in 35 patients treated topically with anthralin as control. Computer evaluation of the obtained data revealed statistical trends to elevation of the total serum bilirubin level and increasing number of blood monocytes after long-term oral treatment. No other statistically significant changes of the laboratory data were found. Particularly, the liver function tests (transaminases, prothrombin and alkaline phosphatase) showed no significant alterations. Only in a few cases did the retinoid compound have an influence on the GPT and GOT levels. The reasons for this individual sensitivity to the drug remain unknown. No significant alterations were found in the control group treated topically with anthralin.

Lanthanum has been used as a tracer for the intercellular space and the surface coats in different epithelia including human epidermis, however, lanthanum compounds may or may not penetrate into skin specimes and reaction product may or may not be present in the intercellular space. After treatment with alcian blue prior exposure to lanthanum the trilaminar plasma membrane was more regularly stained and a thin coat of reaction product corresponding to superficial glycoconjugates outlined the cell surface and filled the narrow intercellular space in normal epidermis. In psoriatic epidermis the quantity of superficial membrane-bound glycoconjugates was rather reduced, their distribution and compartmentalization was profoundly changed and the outer leaflet of the trilaminar plasma membrane was not always clearly seen, having a "moth-eaten appearance" in some places. These findings show once more that alterations of the cell membranes and their surface architecture are present in psoriasis. They may play a major role in the pathogenesis of the disease, influencing the activities of membrane-bound enzymes and the flow of the epidermal growth control mechanism. The glycocalyx may serve in this mechanism as an accumulator of energy rich compounds or as a receptor site of membrane-bound ezymes. According to our views it represents a "ground substance" of epidermal origin, which controls the social behaviour of the keratinocytes in tissue.