title: Dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy): study of inflammatory cells and transforming growth factor beta1 expression in affected skin.
abstract: OBJECTIVE
  Nephrogenic fibrosing dermopathy (NFD) is a newly recognized cutaneous fibrotic disorder occurring in individuals with end-stage renal disease (ESRD). The aim of the present study was to describe the clinical and histopathologic features of 9 new cases and to characterize the inflammatory cells and expression of transforming growth factor beta1 (TGFbeta1) in affected skin.
  
  
  METHODS
  Clinical and laboratory assessments, including serology and pulmonary function studies, were performed in 9 patients undergoing long-term dialysis (8 hemodialysis; 1 peritoneal dialysis) for ESRD of diverse etiologies. Skin, fascia, striated muscles, lungs, and heart were examined by histopathology. Inflammatory cells were characterized by immunophenotyping using specific monoclonal antibodies. TGFbeta1 expression was determined by in situ hybridization.
  
  
  RESULTS
  All patients displayed cutaneous features resembling both systemic sclerosis and diffuse fasciitis, with severe loss of motion and flexion contractures in multiple joints. Six patients displayed woody induration of the muscles of the legs, thighs, and forearms. Five of the 6 patients with lung involvement had a reduced diffusion capacity for carbon monoxide on pulmonary function testing. Marked elevations of the erythrocyte sedimentation rate and/or C-reactive protein level were found in 6 patients. Antinuclear antibodies were present at low titers in 4 patients. Histopathologic studies indicated that in addition to the dermis, the fibrotic process affected the subcutaneous tissue, fascia, striated muscles, lungs, and myocardium. Large numbers of CD68+/factor XIIIa+ dendritic cells and increased expression of TGFbeta1 were found in affected skin and muscle.
  
  
  CONCLUSIONS
  Our findings indicate that the fibrotic process of NFD affects not only the dermis, but also the subcutaneous tissues, fascia, and other organs, including striated muscles, heart, and lungs. We therefore believe this is a systemic fibrosing process, and we suggest that dialysis-associated systemic fibrosis would be a better term for the condition.
authors.affiliation: Division of Rheumatology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5541, USA. Sergio.Jimenez@jefferson.edu
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Jiménez
authors.forename: Carol M
authors.initials: CM
authors.lastname: Artlett
authors.forename: Nora
authors.initials: N
authors.lastname: Sandorfi
authors.forename: Chris
authors.initials: C
authors.lastname: Derk
authors.forename: Kevin
authors.initials: K
authors.lastname: Latinis
authors.forename: Heloisa
authors.initials: H
authors.lastname: Sawaya
authors.forename: Richard
authors.initials: R
authors.lastname: Haddad
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Shanahan
mesh_terms: D000328:Adult; D000368:Aged; D005205:Fascia / Q000473:pathology; D005260:Female; D005355:Fibrosis; D006801:Humans; D016130:Immunophenotyping; D017403:In Situ Hybridization; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D006435:Renal Dialysis; D012867:Skin / Q000737:chemistry* / Q000473:pathology; D012871:Skin Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D016212:Transforming Growth Factor beta / Q000032:analysis*; D053773:Transforming Growth Factor beta1
chemical_list: C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1