ABSTRACT
Changes in the process of cross-linking of collagen molecules are associated with defects in the biomechanical stability of the extracellular matrix. Fibrosis of skin is characterized by an increase in pyridinolines, which are hydroxylysine aldehyde derived cross-links usually absent in healthy skin. In this study, we analyzed cross-links in lipodermatosclerosis and localized scleroderma to address the question whether all the mature cross-links currently characterized are increased in fibrosis in addition to the increase in pyridinolines. As psoralen plus ultraviolet A treatment leads to clinical improvement of fibrotic plaques in localized scleroderma we analyzed the 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 concentration 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-links (dehydro-histidinohydroxymerodesmosine and histidinohydroxylysinonorleucine), whereas the concentration of pyridinolines increased. A decrease in the content of pyridinolines after bath psoralen plus ultraviolet A treatment was found in six out of nine patients with localized scleroderma, which might reflect a remodeling of the extracellular matrix. Our data provide evidence that sclerosis of skin is associated with either an increase in the number of cross-links per molecule of collagen or a change in the molecular nature of the cross-links formed.
Subject(s)
Collagen/metabolism , Cross-Linking Reagents/metabolism , Desmosine/analogs & derivatives , PUVA Therapy , Scleroderma, Localized/drug therapy , Scleroderma, Localized/metabolism , Amino Acids/metabolism , Desmosine/metabolism , Fibrosis , Humans , Hydroxylation , Hydroxylysine/metabolism , Pyridones/metabolism , Scleroderma, Localized/pathology , Ultraviolet RaysABSTRACT
BACKGROUND: Scleredema adultorum (SA) is a rare connective tissue disorder for which no treatment has proven to be effective. OBJECTIVE: Our purpose was to determine the effect of bath-PUVA therapy on SA. METHODS: Three patients were treated. Clinical evaluation of skin induration and thickness as well as ultrasonography were performed at baseline and after treatment. RESULTS: All three patients showed substantial clinical improvement with bath-PUVA therapy (median of 59 treatments and a cumulative UVA dose of 245.7 J/cm2). Ultrasonography showed significant reduction in both skin thickness and density. CONCLUSION: Bath-PUVA therapy appears to be effective in the treatment of SA.
