SCLEREDEMA ADULTORUM - CASE-REPORT AND DEMONSTRATION OF ABNORMAL EXPRESSION OF EXTRACELLULAR-MATRIX GENES IN SKIN FIBROBLASTS IN-VIVO AND IN-VITRO

To elucidate the mechanisms involved in the development of cutaneous f ibrosis in scleredema adultorum, we studied a patient with long-standi ng scleredema who had no history of diabetes mellitus or preceding feb rile illness. Histological examination of a biopsy specimen from invol ved forearm skin demonstrated marked thickening of the dermis and accu mulation of mucin between collagen bundles. Increased levels of type I collagen mRNA, as evidenced by positive in situ hybridization signals with an alpha 1(I) procollagen cDNA were found in numerous fibroblast s throughout the dermis. The expression of several genes coding for pr oteins involved in the maintenance of connective tissue was examined b y determining in vitro protein production and mRNA levels in fibroblas ts from the affected skin, Total protein production, glucosamine incor poration and collagen synthesis, were elevated by 44-97% in scleredema fibroblasts, compared with fibroblasts from two healthy individuals. Levels of mRNAs for alpha 1(I) and alpha 1(III) procollagens and fibro nectin were elevated in scleredema fibroblasts, whereas mRNA levels fo r the tissue inhibitor of metalloproteinase were unaltered compared wi th control cultures. The results suggest that fibroblasts from the inv olved skin in non-diabetic patients with scleredema may exhibit a bios ynthetically activated phenotype, which persists for several years. Th ese alterations are likely to be involved in the development of the cu taneous induration and thickening which is characteristic of this dise ase.