Psoriatic skin lesions

Psoriasis is a T-lymphocyte-mediated inflammatory disease that results from a complex interplay between multiple genetic factors and environmental influences. Genetic predisposition coupled with some precipitating factor triggers an abnormal immune response, resulting in the initial psoriatic skin lesions. Keratinocyte proliferation is central to the clinical presentation of psoriasis. 

Activated T cells begin releasing cytokines including interleukin-2 (IL-2), interferon-y, (IFN-y), tumor necrosis factor (TNF-a), and others.4,13 Cytokine activity leads to a rapid proliferation and turnover of skin cells, triggering the inflammatory process and the development of psoriatic skin lesions.4,13,14 TNF-a may have a role in disease severity it upregulates endothelial and keratinocyte expression of ICAM-1,... 

Fetal pig epidermis contains hyaluronic acid and chondroitin 4-sulfate containing mucopolysaccharide (S15) as does human epidermis (M13), and some of the enzymes of uronic acid metabolism are present in human epidermis (F24). Also Barker et al. (B6) have shown uptake of radioactive sulfate into epidermis, and Braun-Falco et al. (B33) have shown that psoriatic epidermis is more active than normal epidermis in accumulating radioactive sulfate in vitro. There is also a suggestion that methionine sulfur may be preferentially accumulated in psoriatic lesions (B26, L6). There seems to be little doubt, therefore, that mucopolysaccharides are formed, and there is some suggestion that they may be formed in greater amounts in psoriatic skin lesions. The next section will consider the possibility that they are of importance in the cell membrane and intercellular contact. 

Takayama K, Satoh T, Hayashi M, Yokozeki H. Psoriatic skin lesions induced by BCG vaccination. Acta Derm Venereol 2008 88 621-2. 

Piskin G, Sylva-Steenland RM, Bos JD, Teunissen MB In vitro and in situ expression of IL-23 by keratinocytes in healthy skin and psoriasis lesions enhanced expression in psoriatic skin. 

Etanercept is approved in the United States for the treatment of psoriatic arthritis and rheumatoid arthritis. Although etanercept has not been specifically approved for the treatment of the cutaneous manifestations of psoriasis, it significantly improves the skin lesions of patients with moderate to severe cutaneous psoriasis who have used it for psoriatic joint disease. 

Psoriasis is a disease of the immune system that involves T lymphocytes. The etiology and pathogenesis of psoriasis results from complex communications that cause activation of T lymphocytes and trafficking to the skin. Further reactivation causes inflammation and overproduction of skin, resulting in lesions and plaques. In psoriatic skin, there is an upregulation of intracellular adhesion molecule-1 (ICAM-1) on endothelium and keratinocytes. 

The trace element distributions of uninvolved psoriatic skin merit special comments. The main Fe peak appears closer to the mass distribution peak than in normal skin. Also, there are obvious variations in the Fe content in different strata (cell layers), and the lowermost values are consistently at least twice as high as those in normal skin. Our PIXE investigation substantiates the previously reported finding that psoriatic patients lose Fe through the shedding of stratum corneum cells in lesional areas by demonstrating that clinically normal skin of psoriatic patients contains higher than normal amounts of Fe.36,37... 

Methotrexate is used widely as a DMARD for rheumatoid arthritis, psoriatic arthritis, and for its steroid-sparing effects in many other conditions, especially if azathioprine is not tolerated. In high dose, with folinic acid rescue, methotrexate is used to treat solid and haematological malignancies (see p. 612). Low dose methotrexate slows the progression of rheumatoid arthritis. The evidence for a true disease-modifying effect on psoriatic arthritis is less definite, but methotrexate is often preferred to other DMARDs for its beneficial effect on the skin lesions. 

A 54-year-old woman with psoriatic polyarthritis was treated with aurothiomalate 50 mg/week. When the cumulative dose reached 250 mg she developed weakness, dyspnea, fever, nausea, vomiting and erythematous skin lesions. Chest X-ray and CT scan showed diffuse interstitial pneumonitis. Gold was withdrawn and she was given prednisone 60 mg/day. She recovered in 6 months. 

The most striking aspect of psoriatic skin under the microscope is the tremendous epidermal hypertrophy accompanied by its equally well developed papillary blood supply. As discussed previously, in psoriasis the. lower 3 cell layers are the germinative or dividing cell population. Most likely the number of cell layers that can divide is determined by their distance from a blood vessel, since in elegant studies of the hair follicle (whose papilla resembles in many ways those of the psoriatic lesion) Van Scott et al. (V5) have shown that this critical distance is approximately 180 fi. Does this increase in germinative population necessarily imply a thickened epidermis ... 

Is the increased epidermal thickness accompanied by an increase in size of the epidermal cell (hypertrophy) Or are there just more cells (hyperplasia) Despite histologic (H2) and electron microscopic (B36) impressions to the contrary, biochemical evidence indicates that the cell size in the psoriatic lesion is no different than normal. This conclusion is based on measurements indicating that both normal and psoriatic epidermis contain approximately two-thirds water by weight (H2, M15, S17) and, therefore, have the same wet dry weight ratio in conjunction with DNA measurements which have been made in normal and psoriatic skin. 

Isoenzymes. Weber (W3), Grosfield et al. (G15, G16), and Marghescu (M5) have all examined the LDH isoenzyme patterns in normal and psoriatic skin. The pattern in both is that of an anaerobic tissue, i.e., a predominance of the cathodal bands 4 and 5. Psoriatic lesions tend to have increased activity and a slight shift to a more aerobic pattern. 

NADPH-specific isocitric dehydrogenase shows at least 3, and probably 4, bands separable by starch gel electrophoresis in normal epidermis (F25, 03) whereas in psoriatic skin the most anodal bands disappear (F26) (Fig. 11). They reappear with treatment of the lesion. Basal cell carcinoma also shows no activity of this anodal band. We think the most anodal band is somehow linked to normal keratinization since the basal cell carcinoma has a rate of proliferation which is not much faster... 

Grignani et al. (G14) studied several of the enzymes of folate metabolism in human epidermis—both normal and psoriatic. Increased levels of folate reductase were found in the psoriatic lesion, and further enzyme could be induced by treatment of the patients with amethopterin. By contrast, formate-activating enzyme, 5,10-methylenetetrahydrofolate dehydrogenase, serine hydroxylase, and cyclohydrolase were normal in the psoriatic lesion. Formiminotetrahydrofolate transferase could not be measured either in normal or psoriatic skin. The activities of the above enzymes as well as the absence of the transferase are similar to the findings for small bowel but not to other tissues studied. How these findings... 

As a result of pathogeiuc T-ceU production and activation, psoriatic epidermal cells proliferate at a rate sevenfold faster than normal epidermal cells. The germinative cell population increases in psoriatic skin, and duration of the epidermal cell cycle is calculated at 37.5 hours (versus 300 hours in normal skin). Lesion-free skin in psoriatic patients generally is considered to be involved because epidermal proliferation is elevated in apparently normal skin of psoriatic... 

Psoriatic arthritis occurs in approximately 15% of patients with psoriasis. The cause is unknown. Skin lesions are minimal with a polyarthritis affecting particularly the small joints of the hand in an asymmetrical pattern. Usually the disease is mild but chronic. Sometimes the joint involvement is similar to that seen in rheumatoid arthritis, that is, symmetrical polyarthritis. Rarely, the disease is rapidly progressing with joint destruction. The serum is rheumatoid factor negative. 

Psoriasis appears to be a uniquely human disease, as in several animal models single-gene mutations or deletions failed to generate skin lesions with relevant psoriatic characteristics [240-243]. Nevertherless, immunodeficient mice transplanted with human psoriatic plaques (SCID mice) show the implication of T cells [266]. Furthermore, human symptomless skin engrafted onto AGR129 mice spontaneously develop plaques, which are used to test drug-like compounds to prevent the development of psoriasis [242, 243). 

Clinically, psoriasis of the hands presents as kerato-tic patches on the palms and often the bony prominences of the hands. The skin lesions on the palms do not display the classical features of psoriatic lesions elsewhere on the body. A high degree of suspicion is necessary to recognise the condition. The presence of psoriatic lesions elsewhere, e.g., on the elbows, knees, trunk and scalp, and the associated nail changes of psoriasis often help the physician to establish the diagnosis. 

Psoriatic patients frequently present with altered ser am urate levels, a disturbance which is commonly attributed to some changes in nucleoprotein metabolism directly linked to the pathological process of the skin lesions in fact, it is well known that an increased turnover rate of the epidermal cells (from the normal value of 27 days to 3-4 days only) is responsible for the psoriatic skin changes (Fitzpatrick and Haynes, 1980). To date, no tracer turnover studies with labelled uric acid have been reported in patients affected by psoriasis. We present here the metabolic results obtained with the aid of C-uric acid in a group of psoriatic patients with various degrees of severity of the disease. The aim of the study was to elucidate some pathophysiologic aspects of uric acid turnover in such clinical conditions. 

TOPICAL ANTIPSORIATICS. The nurse may be responsible for applying the product and inspecting the areas of application. Care is exercised so that the product is applied only to the psoriatic lesions and not to surrounding skin. The nurse brings signs of excessive irritation to tlie attention of the primary health care provider. 

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... 

Koebner phenomenon The occurrence of psoriatic lesions due to skin trauma. 

Although ciclosporin and tacrolimus applied systemically improve psoriatic lesions, they are clearly less active when applied topically. Therefore, liposomal preparations have been developed. Indeed, ciclosporin penetrates deeper strata of rodent and human cadaver skin more efficiently when incorporated into liposomes [51], Moreover, tacrolimus concentrations in murine skin have increased ninefold, and skin graft survival prolonged, if the drug is liposome encapsulated [52]. This indicates that topical psoriasis therapy with tacrolimus may become possible. At present, topical tacrolimus is confined to the less recalcitrant forms of mild eczema. 

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