title: Stiff skin syndrome: evidence for an inflammation-independent fibrosis?
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of BioMedicine, Division of Rheumatology, DENOthe Centre, University of Florence, AOUC, Florence, Italy. serena16@libero.it
authors.forename: Serena
authors.initials: S
authors.lastname: Guiducci
authors.forename: Joerg H W
authors.initials: JH
authors.lastname: Distler
authors.forename: Anna Franca
authors.initials: AF
authors.lastname: Milia
authors.forename: Irene
authors.initials: I
authors.lastname: Miniati
authors.forename: Veronica
authors.initials: V
authors.lastname: Rogai
authors.forename: Mirko
authors.initials: M
authors.lastname: Manetti
authors.forename: Fernanda
authors.initials: F
authors.lastname: Falcini
authors.forename: Lidia
authors.initials: L
authors.lastname: Ibba-Manneschi
authors.forename: Steffen
authors.initials: S
authors.lastname: Gay
authors.forename: Oliver
authors.initials: O
authors.lastname: Distler
authors.forename: Marco
authors.initials: M
authors.lastname: Matucci-Cerinic
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000235:genetics; D003094:Collagen / Q000235:genetics; D024042:Collagen Type I; D020405:Dermis / Q000378:metabolism / Q000473:pathology; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000032:analysis / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics; D005355:Fibrosis; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D012871:Skin Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D013577:Syndrome; D019700:Thrombospondin 1 / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D053583:Interleukin-1beta; D015850:Interleukin-6; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D003094:Collagen; D051498:Receptor, Fibroblast Growth Factor, Type 3