Endothelial and fibroblastic activation in scleroderma. The myth of the "uninvolved skin"

Arthritis Rheum. 1991 Dec;34(12):1495-501. doi: 10.1002/art.1780341204.


We studied the immunohistochemistry of the skin of scleroderma patients to determine the differences (if any) between clinically "affected" and "nonaffected" areas. We examined paired skin biopsy samples from clinically involved forearm skin ("affected") and clinically uninvolved proximal skin ("nonaffected") taken from 19 patients with diffuse scleroderma and from 15 normal control subjects. We stained the sections with antibodies to endothelial leukocyte-adherence molecule type 1 (ELAM-1; to detect endothelial activation) and to procollagen-1 (PC-1; to detect newly formed, unprocessed collagen). There was increased expression of ELAM-1 and PC-1 in sclerodermatous skin as compared with the controls, but there was no difference between clinically affected and nonaffected skin samples. In 10 of 11 patients whose condition was getting worse, endothelial and fibroblast activation preceded fibrosis. Endothelial and fibroblast activation are more widespread in the skin of scleroderma patients than is evident by inspection on physical examination. What appears to be "normal" skin in diffuse scleroderma is already pathologic, as shown by abnormal endothelial activation and procollagen production.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / immunology
  • Biopsy
  • Cell Adhesion Molecules / analysis
  • Cell Adhesion Molecules / immunology
  • Cell Adhesion Molecules / metabolism
  • E-Selectin
  • Endothelium, Vascular / chemistry
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology*
  • Female
  • Fibroblasts / chemistry
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Humans
  • Immunohistochemistry
  • Intercellular Adhesion Molecule-1
  • Male
  • Middle Aged
  • Procollagen / analysis
  • Procollagen / immunology
  • Procollagen / metabolism
  • Scleroderma, Systemic / metabolism
  • Scleroderma, Systemic / pathology*
  • Skin / chemistry
  • Skin / metabolism
  • Skin / pathology*


  • Antibodies, Monoclonal
  • Cell Adhesion Molecules
  • E-Selectin
  • Procollagen
  • Intercellular Adhesion Molecule-1