title: An abnormality in glucocorticoid receptor expression differentiates steroid responders from nonresponders in keloid disease.
abstract: BACKGROUND
  Glucocorticoids (GCs) are first-line treatment for keloid disease (KD) but are limited by high incidence of resistance, recurrence and undesirable side-effects. Identifying patient responsiveness early could guide therapy.
  
  
  METHODS
  Nineteen patients with KD were recruited at week 0 (before treatment) and received intralesional steroids. At weeks 0, 2 and 4, noninvasive imaging and biopsies were performed. Responsiveness was determined by clinical response and a significant reduction in vascular perfusion following steroid treatment, using full-field laser perfusion imaging (FLPI). Responsiveness was also evaluated using (i) spectrophotometric intracutaneous analysis to quantify changes in collagen and melanin and (ii) histology to identify changes in epidermal thickness and glycosaminoglycan (GAG) expression. Biopsies were used to quantify changes in glucocorticoid receptor (GR) expression using quantitative reverse transcriptase polymerase chain reaction, immunoblotting and immunohistochemistry.
  
  
  RESULTS
  At week 2, the FLPI was used to separate patients into steroid responsive (n = 12) and nonresponsive groups (n = 7). All patients demonstrated a significant decrease in GAG at week 2 (P < 0.05). At week 4, responsive patients exhibited significant reduction in melanin, GAG, epidermal thickness (all P < 0.05) and a continued reduction in perfusion (P < 0.001) compared with nonresponders. Steroid-responsive patients had increased GR expression at baseline and showed autoregulation of GR compared with nonresponders, who showed no change in GR transcription or protein.
  
  
  CONCLUSIONS
  This is the first demonstration that keloid response to steroids can be measured objectively using noninvasive imaging. FLPI is a potentially reliable tool to stratify KD responsiveness. Altered GR expression may be the mechanism gating therapeutic response.
authors.affiliation: Institute of Inflammation and Repair, Manchester Institute of Biotechnology, University of Manchester, Manchester, U.K.
authors.forename: D
authors.initials: D
authors.lastname: Rutkowski
authors.affiliation: Institute of Inflammation and Repair, Manchester Institute of Biotechnology, University of Manchester, Manchester, U.K.
authors.forename: F
authors.initials: F
authors.lastname: Syed
authors.affiliation: Manchester Centre for Nuclear Hormone Research in Disease, Institute of Human Development, University of Manchester, Manchester, U.K.
authors.forename: L C
authors.initials: LC
authors.lastname: Matthews
authors.affiliation: Manchester Centre for Nuclear Hormone Research in Disease, Institute of Human Development, University of Manchester, Manchester, U.K.
authors.forename: D W
authors.initials: DW
authors.lastname: Ray
authors.affiliation: Institute of Inflammation and Repair, Manchester Institute of Biotechnology, University of Manchester, Manchester, U.K.
authors.forename: D A
authors.initials: DA
authors.lastname: McGrouther
authors.affiliation: Institute of Inflammation and Repair, Manchester Institute of Biotechnology, University of Manchester, Manchester, U.K.
authors.forename: R E B
authors.initials: RE
authors.lastname: Watson
authors.affiliation: Institute of Inflammation and Repair, Manchester Institute of Biotechnology, University of Manchester, Manchester, U.K.
authors.forename: A
authors.initials: A
authors.lastname: Bayat
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D002921:Cicatrix / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007627:Keloid / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013256:Steroids / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D011965:Receptors, Glucocorticoid; D013256:Steroids