Rapid handheld measurements of skin and subcutaneous tissue stiffness in systemic sclerosis.
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ABSTRACT:
SUBMITTER: Ghosh S
PROVIDER: S-EPMC10765152 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Rapid handheld measurements of skin and subcutaneous tissue stiffness in systemic sclerosis.
Ghosh Shramana S O'Connell Katie A KA Kwun Shinwho S Smith Hayden B HB Phillips Catherine H CH Silaphet Tyra T Jiang Bohan B McNeil Andrew J AJ Saknite Inga I Frech Tracy M TM Tkaczyk Eric R ER
Rheumatology (Oxford, England) 20240101 1
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Project description:Systemic sclerosis (SSc) is a connective tissue disease that results in excessive accumulation of collagen in the skin and internal organs. Overall, SSc has a rare morbidity (276 cases per million adults in the United States), but has a 10-year survival rate of 55%. Currently, the modified Rodnan skin score (mRSS) is assessed by palpation on 17 sites on the body. However, the mRSS assessed score is subjective and may be influenced by the experience of the rheumatologists. In addition, the inherent elasticity of skin may bias the mRSS assessment in the early stage of SSc, such as oedematous. Optical coherence elastography (OCE) is a rapidly emerging technique, which can assess mechanical contrast in tissues with micrometer spatial resolution. In this work, the OCE technique is applied to assess the mechanical properties of skin in both control and bleomycin (BLM) induced SSc-like disease noninvasively. Young’s modulus of the BLM-SSc skin was found be significantly higher than that of normal skin, in both the in vivo and in vitro studies (p<0.05 p<0.05 ). Thus, OCE is able to differentiate healthy and fibrotic skin using mechanical contrast. It is a promising new technology for quantifying skin involvement in SSc in a rapid, unbiased, and noninvasive manner.
| S-EPMC4837197 | biostudies-literature
Project description:BackgroundUltrasound is a useful tool to evaluate and quantify skin lesions. Few studies have assessed the criterion validity of skin ultrasound in systemic sclerosis (SSc). The aims of the study were to investigate skin thickness and stiffness using ultrasound and shear wave elastography (SWE) in SSc and to validate skin ultrasound measurements against histological skin thickness.MethodsA total of 22 patients with diffuse cutaneous SSc (dcSSc), 22 with limited cutaneous SSc (lcSSc), and 22 age- and gender-matched healthy controls were enrolled. Skin thickness and stiffness were measured by B-mode ultrasound with SWE imaging on the bilateral fingers and hands. Additional ultrasound evaluation was carried out in 13 patients (9 dcSSc and 4 lcSSc) on their dorsal forearms, followed by skin biopsy conducted in the same skin areas. Correlations between ultrasound measurements and histological skin thickness and modified Rodnan skin score (mRSS) were investigated using Spearman's correlation.ResultsCompared with controls, ultrasound-measured skin thickness and skin stiffness were significantly higher in patients with SSc (p < 0.001) and even higher in those with dcSSc. No clear correlation could be established between ultrasound-determined skin thickness and stiffness at the same site. Ultrasound-measured skin thickness correlated well with histological skin thickness (r = 0.6926, p = 0.009). A weaker association was also observed between histological skin thickness and local mRSS (r = 0.5867, p = 0.050).ConclusionsUltrasound is a reliable tool for quantifying skin involvement in SSc. Ultrasound-measured skin thickness showed good agreement with histological skin thickness.
| S-EPMC7448329 | biostudies-literature
Project description:This data article contains complementary figures related to the research article entitled, "Transforming growth factor-β-induced CUX1 isoforms are associated with fibrosis in systemic sclerosis lung fibroblasts" (Ikeda et al. (2016) [2], http://dx.doi.org/10.1016/j.bbrep.2016.06.022), which presents that TGF-β increased CUX1 binding in the proximal promoter and enhancer of the COL1A2 and regulated COL1. Further, in the scleroderma (SSc) lung and diffuse alveolar damage lung sections, CUX1 localized within the α- smooth muscle actin (α-SMA) positive cells (Fragiadaki et al., 2011) [1], "High doses of TGF-beta potently suppress type I collagen via the transcription factor CUX1" (Ikeda et al., 2016) [2]. Here we show that CUX1 isoforms are localized within α-smooth muscle actin-positive cells in SSc skin and idiopathic pulmonary fibrosis (IPF) lung tissue sections. In particular, at the granular and prickle cell layers in the SSc skin sections, CUX1 and α-SMA are co-localized. In addition, at the fibrotic loci in the IPF lung tissue sections, CUX1 localized within the α-smooth muscle actin (α-SMA) positive cells.
| S-EPMC4993856 | biostudies-literature
Project description: Not available
| S-EPMC10038878 | biostudies-literature
Project description:IL-1 has been implicated in various fibrotic diseases. This randomized, Placebo-Controlled trial we examine the effect of il1-b inhibition on skin expression. We used microarrays to explore gene expression changes in the Rilonacept clinical trial
2019-09-12 | GSE119939 | GEO
Project description:BackgroundSkin thickness is a prominent clinical feature of systemic sclerosis (SSc), but there is no consensus on the cut-off for a positive tuberculin skin test (TST) size and the limitation of the TST for a diagnosis of tuberculosis in SSc. We aimed to identify the cut-off size of an indurated TST and the sensitivity and specificity of the test for the diagnosis of tuberculosis in SSc patients.MethodsA cross-sectional study of 168 adult Thai SSc patients was conducted. The TST was done using 0.1 ml of purified protein derivatives via intradermal injection. The test was interpreted 72 h after testing.ResultsThe median age was 57.2 years. The majority (71.8%) had the diffuse cutaneous SSc subset. All the patients had a BCG vaccination at birth, and 17 (10.1%) had a tuberculosis infection. An indurated skin reaction size of 20 mm had the highest specificity for tuberculosis (99.3%: 95%CI 96.4-100) (ROC 0.53). The skin thickness-assessed using the modified Rodnan skin score (mRSS)-had a significant negative correlation with the reaction size (Rho -0.23; p = 0.003).ConclusionThe TST is not sufficiently sensitive for detecting TB infection in SSc patients, albeit a skin induration of ≥ 15 mm indicates a high specificity for tuberculosis infection. A high mRSS resulted in a smaller skin reaction size when using the TST, which has limited utility as a diagnostic for tuberculosis among SSc patients with severe skin thickness. The manuscript was presented as a poster presentation at the Annual European Congress of Rheumatology EULAR 2019 Madrid 12-15 June 2019. (Ann Rheum Dis. 2019;78(suppl 2): abstract FRI0347) http://dx.doi.org/10.1136/annrheumdis-2019-eular.1456.
| S-EPMC9375415 | biostudies-literature
Project description:The protective effects of lower body subcutaneous adiposity are linked to the depot functioning as a "metabolic sink" receiving and sequestering excess lipid. This postulate, however, is based on indirect evidence. Mechanisms that mediate this protection are unknown. Here we directly examined this with progressive subcutaneous adipose tissue removal. Ad libitum chow fed mice underwent sham surgery, unilateral or bilateral removal of inguinal adipose tissue or bilateral removal of both inguinal and dorsal adipose tissue. Subsequently mice were separated into 5 week chow or 5 or 13 week HFD groups (N = 10 per group). Primary outcome measures included adipocyte distribution, muscle and liver triglycerides, glucose tolerance, circulating adipocytokines and muscle insulin sensitivity. Subcutaneous adipose tissue removal caused lipid accumulation in femoral muscle proximal to excision, however, lipid accumulation was not proportionally inverse to adipose tissue quantity excised. Accumulative adipose removal was associated with an incremental reduction in systemic glucose tolerance in 13 week HFD mice. Although insulin-stimulated pAkt/Akt did not progressively decrease among surgery groups following 13 weeks of HFD, there was a suppressed pAkt/Akt response in the non-insulin stimulated (saline-injected) 13 week HFD mice. Hence, increases in lower body subcutaneous adipose removal resulted in incremental decreases in the effectiveness of basal insulin sensitivity of femoral muscle. The current data supports that the subcutaneous depot protects systemic glucose homeostasis while also protecting proximal muscle from metabolic dysregulation and lipid accumulation. Removal of the "metabolic sink" likely leads to glucose intolerance because of decreased storage space for glucose and/or lipids.
| S-EPMC6768251 | biostudies-literature
Project description:Systemic sclerosis (SSc) is an autoimmune disease characterized by clinical heterogeneity, multi-organ involvement, and complex genetic risk. Here, we report the first multi-tissue meta-analysis of ten independent SSc gene expression datasets. We identify a common immune-fibrotic expression axis across all tissues that is associated with the most severe disease phenotypes. The coexpression patterns conserved across tissues and phenotypes were used to query functional genomic networks, which allowed us to identify common and tissue-specific disease drivers. We find evidence of pro-fibrotic macrophages (MØs) in SSc end-target organs. Prominent genes in the skin functional genomic network are associated with SSc genetic risk and are modulated by immunosuppressive treatment in clinical improvers. These data suggest the interactions between T lymphocytes and MØs are a critical driver of disease and implicate MØs as central to SSc pathogenesis. In total, this study presents a mechanism for fibrosis in SSc end-target tissues, a set of putative therapeutic targets for modulating SSc, and a framework for multi-tissue functional genomic studies of complex human disease.
2017-01-01 | GSE76806 | GEO
Project description:AimsEpicardial adipose tissue (EAT) has emerged as a mediator between systemic inflammatory disorders and cardiovascular disease, and may therefore play a role in the pathophysiology of cardiac involvement in systemic sclerosis (SSc). The aim of this study was to assess the correlation between EAT and left ventricular (LV) function, and to determine the prognostic value of EAT in patients with SSc.Methods and resultsConsecutive patients with SSc who underwent non-contrast thorax computed tomography and echocardiography were included. EAT mass was quantified using dedicated software. The study endpoint was all-cause mortality. A total of 230 SSc patients (age 53 ± 15 years, 14% male) were included. The median value of EAT mass was 67 g (interquartile range: 45-101 g). Patients with increased EAT mass (≥67 g) showed more impaired LV diastolic function as compared with patients with less EAT mass (<67 g), and even after adjusting for age and comorbidities, EAT mass was independently associated with LV diastolic function parameters. During a median follow-up of 8 years, 42 deaths occurred. Kaplan-Meier analysis showed that patients with increased EAT mass had higher all-cause mortality rate as compared with patients with less EAT mass (29% vs. 7%; P < 0.001). In the multivariable analysis, EAT was independently associated with all-cause mortality after adjusting for important covariates (HR: 1.006; 95% CI: 1.001-1.010).ConclusionIn patients with SSc, EAT is independently associated with LV diastolic dysfunction and higher mortality rate.
| S-EPMC11195713 | biostudies-literature
Project description:Systemic sclerosis (SSc) is a rare, severe, auto-immune disease characterized by inflammation, vasculopathy and fibrosis. Activated (myo)fibroblasts are crucial drivers of this fibrosis. By exploiting their expression of fibroblast activation protein (FAP) to perform targeted photodynamic therapy (tPDT), we can locoregionally deplete these pathogenic cells. In this study, we explored the use of FAP-tPDT in primary skin fibroblasts from SSc patients, both in 2D and 3D cultures. Method: The FAP targeting antibody 28H1 was conjugated with the photosensitizer IRDye700DX. Primary skin fibroblasts were obtained from lesional skin biopsies of SSc patients via spontaneous outgrowth and subsequently cultured on plastic or collagen type I. For 2D FAP-tPDT, cells were incubated in buffer with or without the antibody-photosensitizer construct, washed after 4 h and exposed to λ = 689 nm light. Cell viability was measured using CellTiter Glo®®. For 3D FAP-tPDT, cells were seeded in collagen plugs and underwent the same treatment procedure. Contraction of the plugs was followed over time to determine myofibroblast activity. Results: FAP-tPDT resulted in antibody-dose dependent cytotoxicity in primary skin fibroblasts upon light exposure. Cells not exposed to light or incubated with an irrelevant antibody-photosensitizer construct did not show this response. FAP-tPDT fully prevented contraction of collagen plugs seeded with primary SSc fibroblasts. Even incubation with a very low dose of antibody (0.4 nM) inhibited contraction in 2 out of 3 donors. Conclusions: Here we have shown, for the first time, the potential of FAP-tPDT for the treatment of fibrosis in SSc skin.
| S-EPMC8657852 | biostudies-literature