Psoriasis epidermis

For the topical treatment of some chronic inflammatory skin diseases (like atopic dermatitis) immunosuppressive macrolides (like TRL and pimecrolimus) that permeate the inflamed epidermis are of benefit for patients. Severe side effects comparable to those after systemic application of TRL in transplanted patients (see above) have not been observed so far. For the treatment of psoriasis vulgaris these drugs are less effective. The CD2 antagonist alefacept may be a suitable alternative to allergic reactions. 

We have already stressed the potential importance of lipid-rich membranes in the skin as potential targets for ROS-induced damage and ageing of human skin is morphologically identical to changes found by peroxidative processes (Serri et al., 1977). The involvement of AA metabolites in skin disease, and in particular psoriasis, has been the subject of much recent interest. Studies have included topical and intradermal administrations of AA metabolites, and assay of such products in clinical specimens. Results show that concentration of AA, 12-hydroxy-eicosatetraenoic acid (12-HETE), PG and leu-kotrienes are increased in psoriatic lesions (Hammarstrom etal., 1975 Camp etal., 1983 Brain etal., 1984 Duell et al., 1988) and also that full-thickness epidermis from normal and diseased skin has the enzymatic capacity to convert AA to some of the same metabolites (Hammarstrom etal., 1975, 1979 Camp etal., 1983 Brain etal., 1984 Ziboh et al., 1984 DueU et al., 1988). The biological effect of both 12-HETE and leukotrienes was confirmed by both topical application and intradermal injection, which caused epidermal inflammation and... 

In mouse models of skin inflammation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), there is a close association between elevated XO activity in the epidermis and hyperplasia (Pence and Reiners, 1987). This association is also seen in psoriasis patients (Eisen and Seegmiller, 1961 Zimmer and Demis, 1966 Kizaki et al., 1977). In the study by Kizaki etal. (1977), the epidermis was increased about five-fold in comparison to normal. It is not known whether XO-derived ROS have any role in psoriatic epidermal hyperproliferation but low levels of hydrogen peroxide added to the culture medium are well known to induce skin fibroblast proliferation in vitro, an eflfect that is greatest at low passage numbers (Murrell et al., 1990). The generation of... 

Hammarstrom, S., Hamberg, M., Samuelsson, B., Duell, E.A., Stawiski, M. and Voorhees, J.J. (1975). Increased concentrations of non-esterified arachidonic acid, 12L-hydroxy-5,8,10,14-eicosatetraenoic acid, prostaglandin E2 and prostaglandin F2 in epidermis of psoriasis. Proc. Natl Acad. Sci. USA 72, 5130-5134. 

The remarkable efficacy of topical corticosteroids in the treatment of inflammatory dermatoses was noted soon after the introduction of hydrocortisone in 1952. Numerous analogs are now available that offer extensive choices of potencies, concentrations, and vehicles. The therapeutic effectiveness of topical corticosteroids is based primarily on their antiinflammatory activity. Definitive explanations of the effects of corticosteroids on endogenous mediators of inflammation await further experimental clarification. The antimitotic effects of corticosteroids on human epidermis may account for an additional mechanism of action in psoriasis and other dermatologic diseases associated with increased cell turnover. The general pharmacology of these endocrine agents is discussed in Chapter 39. 

Potassium, sodium and calcium sulphides are applied externally to soften the skin by dissolving the epidermis in diseases such as psoriasis, acne and seborrhea. Mixtures of calcium or potassium polysulphides and thiosulphate behave similarly and are also depilatories. Another common hair remover is barium sulphide, mixed with starch or zinc oxide, whereas selenium suphide and cadmium sulphide are applied topically, in shampoos, to control dandruff. 

Although the physiological function of IL-20 has not been identified, three lines of evidence support a role for IL-20 and its receptor in inflammatory skin diseases such as psoriasis. For example, overexpression of IL-20 in transgenic mice results in neonatal lethality with skin abnormalities similar to those observed in human psoriatic skin (Bll). These include several hallmark characteristics of this multigenic diseases such as increased proliferation of keratinocytes in the basal and the suprabasal layers of the epidermis, aberrant epidermal differentiation, and infiltration of immune cells into the skin (R3). Recombinant IL-20 protein... 

In a recent study of clinically normal skin from patients with psoriasis, a high Fe content of the horny layer was demonstrated, whereas there was no detectable Fe in the horny layer of normal healthy control individuals.38 Obviously, this finding in psoriasis demonstrates that the entire differentiating epidermis of these patients is involved in the disorder, whether clinically expressed or not. 

Psoriasis is universal in occurrence. It is a disease of the skin characterized by variable clinical features. The cutaneous lesions are usually so distinct that a clinical diagnosis is easy to make. Psoriatic lesions are classified as erythrosquamous, which indicates that both the vasculature and the epidermis are involved.1... 

Psoriasis is a chronic disease with hyperproliferation of the epidermis and inflammatory reactions of the dermis and epidermis. Psoriasis is characterized by an elevated turnover rate of keratinocytes. The duration of the cell cycle is shortened. Inflammation is characterized by the release of cytokines and an expression of CD4+ cells in psoriatic lesions of affected patients. Scaling marks the clinical feature associated with hyperkeratosis, pruritus, inflammation, and stratum corneum dryness. 

Disturbances in lipid metabolism occur in the skin in psoriasis. Increased phospholipase A2 activity is seen in lesional and nonlesional skin, while phospholipase C activity is elevated in lesional skin.183-184 Increased elongase activity is also observed in psoriatic epidermis. A local increase in AA occurs, and this appears to be preferentially metabolized by the lipoxygenases, resulting in a marked increase in 12-HETE and LTB4, while there appears to be a relative or absolute reduction in metabolism by the COX pathway.185 Leukotriene B4 is a very potent chemoattractant, and topical application causes epidermal hyperproliferation in addition to neutrophil microabscesses.186 A defective transmembranous cell-signaling system is also suggested by elevation of both IP3 and DAG in the psoriatic plaque.187... 

Forster, S., Ilderton, E., and Norris J.F.B., Characterisation and activity of phospholipase A2 in normal human epidermis and in lesion free epidermis of patients with psoriasis or eczema, Br. J. Dermatol., 112, 135, 1985. 

In reconstructed human epidermis the presence of vitamin C was required to normalize stratum corneum lipids, which was accompanied by an improvement of skin barrier formation.36 Interestingly the ascorbic acid concentration in the skin of atopic dermatitis37 and psoriatic patients38 measured in vivo by microdialysis was significantly lower than in healthy subjects. In psoriasis there was no significant difference in lesional versus nonlesional skin. There has also been demonstrated a decrease of ascorbic acid concentration in skin with increasing age.39... 

This appears as areas of reddened and flaky skin and can be a lifelong condition although it tends to flare up in the teens and twenties and then again in old age. About 1 person in 50 suffers from psoriasis at some time in their life. Why it occurs is still not understood. Psoriasis is caused by over-reactive skin cells in the lower layer of the epidermis dividing 20 times faster than normal. A normal skin cell takes around 4 weeks to mature and reach the surface of the skin, there to be shed. Psoriatic cells go through this process in only two days and they accumulate at the surface as a layer of dead skin. Skin affected by psoriasis has a thickened epidermis with an excessive growth of blood vessels, and there are clusters of immune cells. Plaque psoriasis is the most common and occurs on the knees, elbows, lower back, and scalp. 

Amino acid Epidermis " Epidermis Normal callus Keratin B from normal callus- Psoriasis scales" Exfoliate dermatitis scales ... 

In psoriasis there is increased (x 10) epidermal undifferentiated cell proliferation and inflammation of the epidermis and dermis. The consequence of increased numbers of horn cells containing abnormal keratin is that no normal stratum comeum is formed. Drugs are used to... 

Cyclic Nucleotides in Psoriasis - In 1971 Voorhees and Duell proposed the first working model of a potentially deranged cyclic AMP system in psoriasis. 13 The model was based on the fact that three characteristic features of the lesional epidermis of psoriasis are glycogen accumulation,8 decreased terminal differentiations and increased proliferation.14 In other tissues and experimental systems, cyclic AMP was capable of reversing... 

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