| Vascular leak is a central feature in the pathogenesis of systemic sclerosis. | |
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MedLine Citation:
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PMID: 22660809 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: The main histopathological focus of systemic sclerosis (SSc) has concentrated on fibrotic changes. We investigated the microvasculature alterations in the skin of patients with SSc at various stages of disease duration with whole-field digital microscopy. METHODS: Twenty consecutive patients with SSc, 1 with Raynaud's phenomenon (RP) without SSc, and 4 healthy controls underwent punch biopsy on the medial forearm. Eighteen patients were included in the primary analysis. Two with recent-onset diffuse cutaneous disease, 1 repeat SSc biopsy, and 1 patient with RP without SSc were also evaluated. All specimens were processed with histochemical stains and immunohistochemistry. We analyzed microvasculature abnormalities in an objective and systematic manner taking advantage of recent advances in whole-field digital microscopy. This analysis was coupled with ultrastructural evaluation performed with transmission electron microscopy (TEM). RESULTS: Whole-field digital microscopy and TEM of SSc skin biopsies revealed that endothelial abnormalities are a universal feature regardless of clinical features and/or duration of disease. These features were not seen in any healthy control specimens or in the single RP patient samples. Whole-field digital microscopy identified increased interstitial edema (31.0% ± 9.6% vs 17.6% ± 3.3% in controls; p = 0.009) and fibrosis (75.6% ± 5.7% vs 66.1% ± 9.8% in controls; p = 0.02) in all patients with SSc. Lower CD34 staining was seen in SSc compared to healthy controls (0.32% ± 0.22% vs 1.31% ± 0.34%; p < 0.0001) and within the SSc population with interstitial lung disease (0.55% ± 0.22% vs 0.15% ± 0.16%; p = 0.01). Perivascular and interstitial infiltrate of mast cells was present in all SSc specimens. CONCLUSION: Whole-field digital microscopy offers a means of rapidly carrying out objective, fully quantitative, and reproducible measurements of microscopic features of SSc microvascular change. The universal morphologically abnormal endothelial cells and interstitial edema in all patients with SSc biopsied suggests that SSc may be intrinsically a disease of the endothelium characterized by vascular leak. |
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Authors:
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Tracy M Frech; Monica P Revelo; Stavros G Drakos; Maureen A Murtaugh; Boaz A Markewitz; Allen D Sawitzke; Dean Y Li |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2012-06-01 |
Journal Detail:
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Title: The Journal of rheumatology Volume: 39 ISSN: 0315-162X ISO Abbreviation: J. Rheumatol. Publication Date: 2012 Jul |
Date Detail:
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Created Date: 2012-07-03 Completed Date: 2012-11-26 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 7501984 Medline TA: J Rheumatol Country: Canada |
Other Details:
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Languages: eng Pagination: 1385-91 Citation Subset: IM |
Affiliation:
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Division of Rheumatology, Department of Internal Medicine, University of Utah, 4B200 SOM, 30 N 1900 E, Salt Lake City, Utah 84132, USA.. tracy.frech@hsc.utah.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Antigens, CD34 / analysis Capillary Leak Syndrome / pathology* Edema / pathology Endothelium, Vascular / pathology*, ultrastructure Female Humans Lung Diseases, Interstitial / pathology Male Mast Cells Microscopy Microvessels Middle Aged Raynaud Disease / pathology Scleroderma, Systemic / pathology* Severity of Illness Index Skin / blood supply*, pathology |
| Grant Support | |
ID/Acronym/Agency:
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R01 HL077671/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD34 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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