An abnormality in glucocorticoid receptor expression differentiates steroid responders from nonresponders in keloid disease.Citation formats

  • External authors:
  • David Rutkowski
  • F Syed
  • Duncan A Mcgrouther

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An abnormality in glucocorticoid receptor expression differentiates steroid responders from nonresponders in keloid disease. / Rutkowski, David; Syed, F; Matthews, Laura C; Ray, DW; Mcgrouther, Duncan A; Watson, Rachel E; Bayat, A.

In: British Journal of Dermatology, Vol. 173, No. 3, 09.2015, p. 690-700.

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Rutkowski, David ; Syed, F ; Matthews, Laura C ; Ray, DW ; Mcgrouther, Duncan A ; Watson, Rachel E ; Bayat, A. / An abnormality in glucocorticoid receptor expression differentiates steroid responders from nonresponders in keloid disease. In: British Journal of Dermatology. 2015 ; Vol. 173, No. 3. pp. 690-700.

Bibtex

@article{92dfbb41a07d4b6db7ac539408dbc757,
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.",
keywords = "wound healing, dermal fibrosis, keloid disease, skin scarring, steroid responsiveness, glucocorticoid sensitivity",
author = "David Rutkowski and F Syed and Matthews, {Laura C} and DW Ray and Mcgrouther, {Duncan A} and Watson, {Rachel E} and A. Bayat",
year = "2015",
month = "9",
doi = "10.1111/bjd.13752",
language = "English",
volume = "173",
pages = "690--700",
journal = "British Journal of Dermatology",
issn = "0007-0963",
publisher = "John Wiley & Sons Ltd",
number = "3",

}

RIS

TY - JOUR

T1 - An abnormality in glucocorticoid receptor expression differentiates steroid responders from nonresponders in keloid disease.

AU - Rutkowski, David

AU - Syed, F

AU - Matthews, Laura C

AU - Ray, DW

AU - Mcgrouther, Duncan A

AU - Watson, Rachel E

AU - Bayat, A.

PY - 2015/9

Y1 - 2015/9

N2 - 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.

AB - 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.

KW - wound healing

KW - dermal fibrosis

KW - keloid disease

KW - skin scarring

KW - steroid responsiveness

KW - glucocorticoid sensitivity

U2 - 10.1111/bjd.13752

DO - 10.1111/bjd.13752

M3 - Article

VL - 173

SP - 690

EP - 700

JO - British Journal of Dermatology

JF - British Journal of Dermatology

SN - 0007-0963

IS - 3

ER -