Different pattern of collagen cross-links in two sclerotic skin diseases: Lipodermatosclerosis and circumscribed scleroderma

Changes in the process of cross-linking of collagen molecules are associate d with defects in the biomechanical stability of the extracellular matrix. Fibrosis of skin is characterized by an increase in pyridinolines, which ar e hydroxylysine aldehyde derived cross-links usually absent in healthy skin . In this study, we analyzed cross-links in lipodermatosclerosis and locali zed scleroderma to address the question whether all the mature cross-links currently characterized are increased in fibrosis in addition to the increa se in pyridinolines. As psoralen plus ultraviolet A treatment leads to clin ical improvement of fibrotic plaques in localized scleroderma we analyzed t he cross-link content in lesional skin after bath psoralen plus ultraviolet A therapy. In skin from patients with localized scleroderma an increase in the total number of mature cross-links was found to be due to an increase in both pyridinolines and dehydro-histidinohydroxymerodesmosine. The concen tration of histidinohydroxylysinonorleucine was unchanged. By contrast, the total number of mature cross-links was decreased in lipodermatosclerosis. This decrease was caused by a decrease of lysine aldehyde derived cross-lin ks (dehydro-histidinohydroxymerodesmosine and histidinohydroxylysinonorleuc ine), whereas the concentration of pyridinolines increased. A decrease in t he content of pyridinolines after bath psoralen plus ultraviolet A treatmen t was found in six out of nine patients with localized scleroderma, which m ight reflect a remodeling of the extracellular matrix. Our data provide evi dence that sclerosis of skin is associated with either an increase in the n umber of cross-links per molecule of collagen or a change in the molecular nature of the cross-links formed.