Progression of nailfold capillaroscopic patterns and correlation with organ involvement in systemic sclerosis: a 12 year study

Sulli, Alberto; Paolino, Sabrina; Pizzorni, Carmen; Ferrari, G.; Pacini, G.; Carmisciano, Luca; Smith, Vanessa; Cutolo, Maurizio

doi:10.1093/rheumatology/kez374

Cited by 34 publications

(30 citation statements)

References 49 publications

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“…However, the progressive systemic fibrosis in ILD positive patients was also confirmed by the concomitant presence of the most advanced “Late” NVC pattern of microvascular damage that characterizes SSc patients with intensive fibrosis [ 26 ]. Based on these clinical considerations, the downregulatory effect of nintedanib on the transition of fibrocytes isolated from Scl70 + ILD + patients into myofibroblasts and their ECM overproduction might be a further supporting element for the beneficial effects exerted by nintedanib in reducing the progression of the ILD in SSc [ 15 , 16 , 27 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

Nintedanib downregulates the transition of cultured systemic sclerosis fibrocytes into myofibroblasts and their pro-fibrotic activity

et al. 2021

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Background Circulating fibrocytes are an important source of fibroblasts and myofibroblasts, which are involved in fibrotic processes, including systemic sclerosis (SSc). The study aimed to investigate the effect of nintedanib (a tyrosine kinase inhibitor) in inhibiting the in vitro transition of circulating SSc fibrocytes into myofibroblasts and their pro-fibrotic activity. Methods Circulating fibrocytes were obtained from 18 SSc patients and 5 healthy subjects (HSs). Cultured SSc fibrocytes were maintained in growth medium (untreated cells) or treated with nintedanib 0.1 and 1 μM for 3 and 24 h. Fibroblast-specific protein-1 (S100A4) and α-smooth muscle actin (αSMA), as markers of fibroblast/myofibroblast phenotype, together with type I collagen (COL1) and fibronectin (FN), were investigated by qRT-PCR and Western blotting. Non-parametric tests were used for statistical analysis. Results Significantly elevated gene and protein expressions of αSMA, S100A4, COL1, and FN were observed in SSc fibrocytes compared to HS fibrocytes (gene: αSMA p < 0.001; others p < 0.0001; protein: all p < 0.05). Interestingly, an increased gene and protein expression of αSMA and S100A4 was found in fibrocytes from SSc patients positive for anti-Scl70 and with interstitial lung disease (ILD) (Scl70+ILD+) compared to Scl70−ILD− patients (S100A4: gene: p < 0.01; protein: p < 0.05), whereas no differences were observed for COL1 and FN. Nintedanib reduced gene and protein expression of αSMA, S100A4, COL1, and FN in SSc fibrocytes compared to untreated ones with different statistical significance. Noteworthy, nintedanib significantly downregulated gene and protein expression of αSMA, S100A4, COL1, and FN in Scl70+ILD+ fibrocytes (all p < 0.05), whereas only that of S100A4 and FN was significantly downregulated (p < 0.05) in Scl70−ILD− fibrocytes compared to the related untreated cells. Conclusions Nintedanib seems to downregulate in vitro the transition of fibrocytes into myofibroblasts and their pro-fibrotic activity, particularly in cells isolated from Scl70+ILD+ SSc patients.

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Section: Discussionmentioning

confidence: 99%

Nintedanib downregulates the transition of cultured systemic sclerosis fibrocytes into myofibroblasts and their pro-fibrotic activity

et al. 2021

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“…Microvasculopathy represents a fundamental part of SSc pathogenesis, leading to several clinical manifestations such as Raynaud's phenomenon and digital ulcers [45]. Multiple cohort studies have postulated that nailfold capillaroscopic abnormalities correlate with the severity of organ involvement including PAH [13,41,42,46]. Indeed, in a 3-year longitudinal study, progressive loss of capillaries, presence of angiogenesis, and late scleroderma pattern were identified as markers for the occurrence of PAH [42].…”

Section: Discussionmentioning

confidence: 99%

“…SSc-PAH has also been associated with higher scores for capillary loss and capillary disorganization [41]. Additionally, it has been reported that increasing echocardiographically derived systolic pulmonary arterial pressure correlates with the severity of scleroderma pattern [46]. Furthermore, a diagnostic accuracy meta-analysis assessing the value of NVC in the diagnosis of SSc-PAH demonstrated that lower capillary density and increased capillary loop width could potentially detect patients with SSc-PAH [18].…”

Section: Discussionmentioning

confidence: 99%

Nailfold Capillaroscopy in Systemic Sclerosis Patients with and without Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis

Minopoulou

Theodorakopoulou

Boutou

et al. 2021

JCM

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Systemic sclerosis (SSc)-related pulmonary arterial hypertension (SSc-PAH) is a leading cause of mortality in SSc. The extent of peripheral microvasculopathy assessed through nailfold capillaroscopy might correlate with the presence of PAH in SSc patients. We searched the PubMed, Cochrane Library, Scopus, and Web of Science databases and performed a random effects meta-analysis of observational studies comparing nailfold capillaroscopic alterations in SSc-PAH versus SSc-noPAH patients. Weighted mean differences (WMD) with the corresponding confidence intervals (CIs) were estimated. The quality of the included studies was evaluated using a modified Newcastle–Ottawa scale. Seven studies with 101 SSc-PAH and 277 SSc-noPAH participants were included. Capillary density was marginally reduced in the SSc-PAH group (WMD: −1.0, 95% CI: −2.0 to 0.0, I2 = 86%). This effect was strengthened once PAH diagnosis was confirmed by right heart catheterization (WMD: −1.2, 95% CI: −2.3 to −0.1, I2 = 85%). An increase in capillary loop width was observed in SSc-PAH compared to SSc-noPAH patients (WMD: 10.9, 95% CI: 2.5 to 19.4, I2 = 78%). Furthermore, SSc-PAH patients had a 7.3 times higher likelihood of active or late scleroderma pattern (95% CI: 3.0 to 18.0, I2 = 4%). SSc-PAH patients presented with worse nailfold capillaroscopic findings compared to SSc-noPAH patients.

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“…NVC is to date the best tool to analyze microvascular abnormalities in CTDs [ 17 , 18 ]. Additionally, NVC alterations in course of SSc are well-defined and correlate with organ involvement and disease progression, in contrast to other CTDs—such as in SLE, SjS, MCTD, and IIM—in which NVC alteration is less disease-specific [ 19 – 24 ].…”

Section: Discussionmentioning

confidence: 99%

Antiphospholipid antibodies and anticoagulant therapy: capillaroscopic findings

et al. 2021

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Background Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by specific vascular and obstetric manifestations and by antiphospholipid antibodies (aPL) positivity. Microvascular damage in the course of APS and “aPL carrier” patients without symptoms is poorly investigated. Objectives This study aims to compare nailfold videocapillaroscopy (NVC) microvascular parameters in APS patients and non-symptomatic "aPL carriers" and to investigate their possible correlations with different aPL subtypes. Methods NVC was performed during standard evaluations in 18 APS patients (mean age 50 ± 13.8 years), 24 "aPL carriers" without symptoms (mean age 46.4 ± 16.4 years), and 18 control patients (CTR) (mean age 74 ± 12.5 years) taking oral anticoagulants for non-immunological indications (i.e., cardiovascular accidents). All patients were investigated for the presence of dilated capillaries, giant capillaries, microhemorrhages, capillary loss, and further non-specific/specific abnormalities (i.e., branched “bushy” capillaries, sign of neoangiogenesis) by NVC. Every alteration was also classified according to a semi-quantitative score. Lupus anticoagulant, anticardiolipin antibodies, and antibeta2 glycoprotein I antibodies were tested in each patient. Results APS patients showed at NVC increased frequency of microhemorrhages (p = 0.039)—particularly a “comb-like” pattern (parallel hemorrhages) (p = 0.002)—than "aPL carriers". Of note, there were no significant differences concerning the isolated number of microhemorrhages between APS and the CTR group (p = 0.314), but “comb-like” hemorrhages were significantly more frequent in the APS group (p = 0.034). Not any significant correlation was found between the aPL subtypes and NVC parameters. Conclusions APS patients showed significantly a greater number of non-specific NVC abnormalities than "aPL carriers", particularly the “comb-like” NVC pattern. Oral anticoagulants may represent a confounding factor for isolated microhemorrhages. Not any correlation was found between aPL subtypes and NVC parameters. Further investigations are needed to better characterize the microvascular endothelium damage induced by aPL.

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Progression of nailfold capillaroscopic patterns and correlation with organ involvement in systemic sclerosis: a 12 year study

Cited by 34 publications

References 49 publications

Nintedanib downregulates the transition of cultured systemic sclerosis fibrocytes into myofibroblasts and their pro-fibrotic activity

Nintedanib downregulates the transition of cultured systemic sclerosis fibrocytes into myofibroblasts and their pro-fibrotic activity

Nailfold Capillaroscopy in Systemic Sclerosis Patients with and without Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis

Antiphospholipid antibodies and anticoagulant therapy: capillaroscopic findings

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