hydroxylysine and Scleroderma--Localized

Topics: Amino Acids; Blood Vessels; Cell Nucleus; Collagen; Connective Tissue; Cornea; Cytoplasm; Elasticity; Endothelium; Glycosaminoglycans; Humans; Hydroxylysine; Hydroxyproline; Proline; Regional Blood Flow; Rheology; Scleroderma, Localized; Scleroderma, Systemic; Skin; Skin Pigmentation; Sweat Glands; Ultrasonography

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.

Topics: Amino Acids; Collagen; Cross-Linking Reagents; Desmosine; Fibrosis; Humans; Hydroxylation; Hydroxylysine; PUVA Therapy; Pyridones; Scleroderma, Localized; Ultraviolet Rays

We studied the molecular packing of collagen fibrils by x-ray diffraction in skin specimens of patients with lipodermatosclerosis and in controls. A difference in the tilt angles of the collagen molecules relative to the fiber axis is suggested by a D-stagger that is 1 nm larger in sclerotic skin than in normal skin. In parallel, the collagen cross-links in the skin specimens were analyzed, and a marked increase of both hydroxylysylpyridinoline and lysylpyridinoline, the trivalent mature cross-links characteristic of skeletal tissues, was found. The content of hydroxylysylpyridinoline and lysylpyridinoline was higher in the deep layer of the affected dermis than in the superficial dermis. This increase was always accompanied by an increase in the hydroxylysylpyridinoline/lysylpyridinoline ratio, suggesting that hydroxylysylpyridinoline is a sclerosis-associated cross-link. In addition, lysyl hydroxylation was increased in affected skin, and this increase was apparently restricted to the collagen telopeptides, which are crucial anchoring structures for lysyl dependent cross-links.

Topics: Amino Acids; Biopsy; Collagen; Drug Residues; Humans; Hydroxylysine; Hydroxyproline; Leg; Reference Values; Scleroderma, Localized; Skin; X-Ray Diffraction

Hydroxyproline (Hyp), hydroxylysine (Hyl), and proline (Pro) were assayed in the urine from 28 patients with localized scleroderma (13 with localized morphoea plaques, 13 with generalized morphoea, and two with scleroderma en coup de sabre), as well as 17 control persons. The levels of Hyp, Hyl and Pro were elevated in patients with localized morphoea plaques as compared to the controls indicating major changes of the collagen metabolism in this type of localized scleroderma.

Topics: Adolescent; Adult; Aged; Collagen; Cornea; Female; Humans; Hydroxylysine; Hydroxyproline; Male; Middle Aged; Proline; Scleroderma, Localized

Hydroxyproline, hydroxylysine and proline were determined on skin from 18 patients with localized scleroderma (10 with localized morphoea plaque and 8 with generalized morphoea). Three skin biopsies (4mm punch) were obtained from each patient: One from the center of a sclerotic plaque, one from the perilesional area, and one (control) from unaffected skin of the same region. Clinically, the sclerosis was more pronounced (p less than 0.01) in localized morphoea plaque as compared to generalized morphoea. Patients with localized morphoea plaque had an increased concentration of hydroxylysine (p less than 0.01) and an increased ratio of hydroxylysine to hydroxyproline (p less than 0.01) in the plaques. Hydroxylysine concentration was not changed in patients with generalized morphoea. In the entire material, increased hydroxylysine concentration were related to shorter age of the plaques (p less than 0.05) and to advanced degree of sclerosis (p less than 0.05). The hydroxylysine and hydroxyproline content per mm2 skin surface, and the weight of the dried defatted biopsy cores were increased in sclerotic plaques (p less than 0.01) in localized as well as generalized morphoea. There were no changes in the hydroxyproline and proline concentrations in any of the groups. Specimens from perilesional area showed intermediate changes. The results were compared with selected cases of lichen sclerosis et atrophicus and atrophic skin diseases. The increase in hydroxylysine concentration and ratio to hydroxyproline indicate that patients with localized morphoea plaque contain an increased proportion of newly synthesized collagen in the fibrotic plaque.

Topics: Adolescent; Adult; Aged; Amino Acids; Collagen; Female; Humans; Hydroxylysine; Hydroxyproline; Male; Middle Aged; Proline; Scleroderma, Localized; Skin; Skin Diseases

A significant decrease in the content of hydroxyproline and hydroxylysine was found in the skin of patients with generalized scleroderma (acrosclerosis), the lowering of Hyp being more marked than that of Hyl. The production of an abnormal collagen or a change from one collagen type to another is suggested to take place.

Topics: Collagen; Humans; Hydroxylysine; Hydroxyproline; Scleroderma, Localized; Skin

Topics: Adolescent; Adult; Age Factors; Aged; Amino Acids; Animals; Biopsy; Collagen; Culture Techniques; Female; Humans; Hydroxylysine; Hydroxyproline; Male; Middle Aged; Norleucine; Penicillamine; Rats; Scleroderma, Localized; Scleroderma, Systemic; Skin