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Earlier findings indicate the acrosyringium as the target for the inflammation in the chronic and intensely inflammatory skin disease palmoplantar pustulosis (PPP). The sweat gland apparatus seems to be an immune-competent structure that probably contributes to the defence of the skin. Furthermore, the sweat gland and duct may be a hitherto unrecognized neuroendocrine organ because it expresses cholineacetyl-transferase and acetylcholinesterase, nicotinic receptors, beta-adrenergic and angiotensin receptors. The aim of this study was to obtain further information about neuroendocrine properties of the sweat gland apparatus by examining the expression of common neuroendocrine markers synaptophysin and chromogranins A and B in healthy palmar skin and in PPP skin. Synaptophysin and chromogranins were expressed in the sweat glands and ducts with some variation in the pattern and intensity of the expression. In PPP skin the expression differed, being higher and lower, depending on the part of the sweat duct. Chromogranins were further expressed in the epidermis, endothelium and inflammatory cells, but its intensity was weaker in epidermis than in the sweat gland apparatus. In most cases, chromogranins in epidermis in involved PPP were weakly expressed compared to healthy controls. The presence of synaptophysin and chromogranins in palmoplantar skin may have marked neuroendocrine effects, and the palmoplantar skin is likely to have important neuroimmuno-endocrine properties. Moreover, the altered chromogranin expression in PPP skin might influence both the neuroendocrine and neuroimmunologic properties of palmoplantar skin in these patients. These results indicate important neuroendocrine properties of the palmoplantar skin.

Patients with palmoplantar pustulosis (PPP) frequently report that stress worsens their condition. A study was therefore made of the distribution and number of nerve fibres positive for protein gene product (PGP) 9.5 (a general nerve marker) and nerve fibres with substance P- and calcitonin gene-related peptide-like immunoreactivity in involved skin from patients with PPP and in skin from healthy controls. The number of mast cells in the papillary dermis was larger (P = 0.0003) in lesional palmar PPP skin than in control skin, and the number of contacts between mast cells and nerve fibres was significantly larger (P = 0.02) in PPP skin than in control skin. Image analysis of the nerve fibres around the sweat glands showed that the positively stained area as a percentage of the total area of the sweat gland (coil + surrounding nerves) was significantly lower in PPP skin (P = 0.0006). Furthermore, the nerves seemed to be fragmented. Neutrophils within and below the pustules and in the papillary dermis showed positive substance P staining. The increased number of contacts between nerves and mast cells in PPP skin and the intense substance P-like immunoreactivity of the neutrophils indicate that neuromediation may influence the inflammation in PPP, whereas the destruction of the nerve fibres around the sweat glands might be a result of the inflammation.

The function of the fixed macrophage system in 18 psoriasis patients was evaluated by measuring the elimination rate of injected autologous erythrocytes coated with iC3b or IgG. The mean half-life of iC3b-coated erythrocytes was significantly prolonged in patients with psoriasis compared with healthy controls (4.7 +/- 0.8 vs 2.7 +/- 0.2 min, P = 0.01). There was also a decrease in the total number of cells eliminated from the circulation (2.5 +/- 0.2 x 10(8) vs 3.3 +/- 0.2 x 10(8), P = 0.01). There was an even more pronounced increase in the half-life of IgG-coated erythrocytes (85 +/- 18 vs 20 +/- 5 min, P < 0.001), with normal values in only 5 of 15 patients, and 4 of these 5 patients were receiving systemic treatment. The slow elimination was interpreted as being caused by primary or secondary defects in receptor function rather than by blocking of the receptors by immune complexes, since patients with psoriasis show normal levels of circulating immune complexes. Further studies are needed to elucidate the nature of these defects.

Twenty patients with palmoplantar pustulosis (PPP) and 21 patients with psoriasis were compared with respect to the chemotactic response and random migration of their neutrophils (PMNs) and to the chemotactic and chemokinetic activities of their serum. The Boyden chamber technique was used. Compared with the reference group, the PPP neutrophils showed a significant decrease in random migration (p = 0.036) and chemotactic response to casein (p = 0.031), but not to zymosan-activated serum. The psoriasis PMNs had normal chemotactic response, but decreased random migration (p = 0.001). The chemokinetic effects of serum from PPP and psoriatic patients on normal neutrophils were increased (for PPP, p = 0.019 and for psoriasis p = 0.024). The chemokinetic activity of the heated sera was decreased and inversely correlated to the serum level of IgA in both disorders (PPP, p = 0.021; psoriasis, p = 0.013). The chemotactic activity of serum on normal PMNs was decreased in both conditions (PPP, p = 0.001; psoriasis, p = 0.047); this was due to the presence of chemotactic factor inhibitors in 34% of the sera. It seems likely that the high chemokinetic effect of serum both from the PPP and from the psoriasis patients compensates for the slightly low or normal migratory activity of neutrophils from these patients.

The long-chained fatty acids, which are precursors of prostaglandins and leukotrienes, were examined in plasma lipid esters and adipose tissue obtained from 20 male psoriatic patients and 36 matched controls. The fatty-acid composition of the plasma lipid esters (cholesterol esters, triglycerides and phospholipids) and adipose tissue was assayed using thin-layer and gas chromatography. In comparison with healthy controls, the patients' plasma lipid esters contained significantly lower levels of linoleic acid (18:2 omega 6) and alpha-linolenic acid (18:3 omega 3), and higher levels of dihomo-gamma-linolenic acid (20:3 omega 6). In the adipose tissue of the patients, the amount of alpha-linolenic acid was significantly decreased, while that of arachidonic acid (20:4 omega 6) was increased. The observed changes were more pronounced in patients with severe psoriasis than in those with a milder form of the disease. Our results suggest that psoriatic patients differ from healthy controls with regard to the distribution of several of the essential long-chained fatty acids involved in the biosynthesis of prostaglandins and leukotrienes. The relevance of these findings to the development of psoriasis remains to be established.

The relationship between psoriasis and palmoplantar pustulosis (PPP) is uncertain, as is the role of the neutrophil granulocyte in these conditions. In a previous comparative study of the rate of polymorphonuclear leucocyte (PMN) phagocytosis of IgG- and IgG-C3b-coated particles, an increased uptake rate was found in both diseases. Further information on the in vivo activity of PMNs in these conditions may be obtainable by determining the level of lactoferrin (LF) in serum from such patients, since LF serves as a specific marker of the turnover and activity of the circulating pool of neutrophils. In this study on 19 patients with psoriasis and 20 patients with PPP, elevated levels of LF were found in both conditions. In contrast, the levels of lysozyme and beta 2-microglobulin, which are markers of monocyte-macrophage and lymphocyte activity, respectively, were normal. This suggests the selective activation of neutrophils in these disorders. LF was significantly correlated (P less than 0.05 and 0.001, respectively) to the rates of phagocytosis of IgG- and IgG-C3b-coated particles, but not to the chemotaxis of isolated PMNs. There was no correlation between the severity of the disease and the levels of serum LF. The data suggest the increased in vivo activity of neutrophils in psoriasis and PPP.