Cutaneous chronic graft-versus-host disease does not have the abnormal endothelial phenotype or vascular rarefaction characteristic of systemic sclerosis.
BACKGROUND
The clinical and histologic appearance of fibrosis in cutaneous lesions in chronic graft-versus -host disease (c-GVHD) resembles the appearance of fibrosis in scleroderma (SSc). Recent studies identified distinctive structural changes in the superficial dermal microvasculature and matrix of SSc skin. We compared the dermal microvasculature in human c-GVHD to SSc to determine if c-GVHD is a suitable model for SSc.


RESULTS
We analyzed skin biopsies of normal controls (n = 24), patients with SSc (n = 30) and c-GVHD with dermal fibrosis (n = 133)). Immunostaining was employed to identify vessels, vascular smooth muscle, dermal matrix, and cell proliferation. C-GVHD and SSc had similar dermal matrix composition and vascular smooth muscle pathology, including intimal hyperplasia. SSc, however, differed significantly from c-GVHD in three ways. First, there were significantly fewer (p = 0.00001) average vessels in SSc biopsies (9.8) when compared with c-GVHD (16.5). Second, in SSc, endothelial markers were decreased significantly (19/19 and 12/14 for VE cadherin and vWF (p = <0.0001 and <0.05), respectively). In contrast, 0/13 c-GVHD biopsies showed loss of staining with canonical endothelial markers. Third, c-GVHD contained areas of microvascular endothelial proliferation not present in the SSc biopsies.


CONCLUSIONS
The sclerosis associated with c-GVHD appears to resemble wound healing. Focal capillary proliferation occurs in early c-GVHD. In contrast, loss of canonical endothelial markers and dermal capillaries is seen in SSc, but not in c-GVHD. The loss of VE cadherin in SSc, in particular, may be related to microvascular rarefaction because VE cadherin is necessary for angiogenesis. C-GVHD is a suitable model for studying dermal fibrosis but may not be applicable for studying the microvascular alterations characteristic of SSc.
Fleming
Jo Nadine
JN
Department of Pathology, University of Washington, Seattle, Washington, USA. flemij@u.washington.edu
Shulman
Howard M
HM
Nash
Richard A
RA
Johnson
Pamela Y
PY
Wight
Thomas N
TN
Gown
Allen
A
Schwartz
Stephen M
SM
D002908:Chronic Disease; D004727:Endothelium / Q000473:pathology*; D006086:Graft vs Host Disease / Q000473:pathology*; D006801:Humans; D010641:Phenotype; D012595:Scleroderma, Systemic / Q000473:pathology*; D012871:Skin Diseases / Q000473:pathology*