Stiff skin syndrome: evidence for an inflammation-independent fibrosis?

Rheumatology (Oxford). 2009 Jul;48(7):849-52. doi: 10.1093/rheumatology/kep118. Epub 2009 May 25.

Abstract

Objectives: Stiff skin syndrome (SSS) is a rare scleroderma-like syndrome of unknown aetiology. A 16-year-old boy presented with thoracic and abdominal asymmetry, and 'orange peel' cutaneous lesions, with fibrotic stone-hard indurations at the buttocks, thighs and arms leading to secondary joint contractures of the extremities. Our aim was to analyse the expression of extracellular matrix (ECM) molecules and pro-fibrotic cytokines in the dermis and epidermis of SSS.

Methods: The diagnosis of SSS was confirmed by clinical and histopathological examination. Collagen type 1 alpha-2 chain (Col1A2), fibronectin-1, thrombospondin-1, TGF-beta, connective tissue growth factor (CTGF), IL-6, -1beta, ET-1, Fibroblast growth factor receptor 3 (FGFR-3) and MCP-1 expression was analysed in SSS and age- and sex-matched healthy control skin by real-time PCR. VEGF expression was also studied.

Results: Histopathological examination showed flattened dermal papillae, a scarce presence of sub-epidermal microvessels and mild dermal fibrosis, but no inflammatory infiltrates. In the SSS dermis, the expression of IL-1beta, -6 and MCP-1 was low, whereas VEGF was intensively expressed. No differences were observed for TGF-beta, CTGF and ET-1. In contrast, col1A2, fibronectin-1 and thrombospondin-1 were overexpressed in the SSS dermis.

Conclusion: In our SSS patient, an overexpression of ECM proteins was detected, whereas no inflammatory infiltrates or up-regulation of pro-fibrotic cytokines were found. The data suggest that fibrosis in SSS might be independent from inflammation.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Case-Control Studies
  • Chemokine CCL2 / genetics
  • Collagen / genetics
  • Collagen Type I
  • Dermis / metabolism
  • Dermis / pathology
  • Epidermis / metabolism
  • Epidermis / pathology
  • Extracellular Matrix Proteins / analysis
  • Extracellular Matrix Proteins / metabolism
  • Fibronectins / genetics
  • Fibrosis
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Interleukin-1beta / genetics
  • Interleukin-6 / genetics
  • Male
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin / immunology
  • Skin / metabolism
  • Skin / pathology*
  • Skin Diseases / immunology
  • Skin Diseases / metabolism
  • Skin Diseases / pathology*
  • Syndrome
  • Thrombospondin 1 / genetics
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • CCL2 protein, human
  • Chemokine CCL2
  • Collagen Type I
  • Extracellular Matrix Proteins
  • Fibronectins
  • Interleukin-1beta
  • Interleukin-6
  • Thrombospondin 1
  • Vascular Endothelial Growth Factor A
  • Collagen
  • Receptor, Fibroblast Growth Factor, Type 3