Nailfold Videocapillaroscopy Parameters Research Articles

Microvascular status in juvenile Sjögren’s disease: the first nailfold videocapillaroscopy investigation

IntroductionJuvenile Sjögren’s disease (jSjD) is a rare autoimmune disease characterized by exocrine gland involvement and systemic manifestations, including small vessel vasculitis and Raynaud’s phenomenon (RP). We aimed to investigate the microvascular status in jSjD patients by nailfold videocapillaroscopy (NVC) and the potential correlations with clinical and serological features.MethodsClinical data from thirteen consecutive jSjD patients (11 females and 2 males), with a mean age of 16 ± 4 years, diagnosed before 16 years of age (mean age at diagnosis 12 ± 3) according to the 2016 American College of Rheumatology/EULAR criteria for adult SjD, were collected including age- and sex-matched healthy controls (HCs). Clinical, laboratory, and instrumental data were collected, together with NVC examination. Non-specific and specific NVC parameters were investigated, such as capillary density, capillary dilations, giant capillaries, microhaemorrhages and abnormal shapes. Associations between NVC findings and clinical/serological features were explored and analysed using parametrical and non-parametrical tests.ResultsCapillary density reduction correlated significantly with articular involvement (arthralgias) (p = 0.024). Microhaemorrhages correlated with lower C3 levels (p = 0.034). No specific NVC pattern for jSjD was identified, whereas abnormal capillary shapes were significantly higher in jSjD patients than HCs (p = 0.005). NVC abnormalities were not associated with SjD-specific instrumental tests (biopsy, imaging, Schirmer’s test). RP was present in 8% of jSjD patients.ConclusionsThe reduction of capillary density, as well as microhaemorrhages at NVC analysis, are significantly associated with some clinical aspects like articular involvement and serum biomarkers (C3 reduction). The NVC is suggested as safe and further analysis in jSjD patients.Key Points• Juvenile Sjögren’s disease (jSjD) exhibits a higher rate of abnormal shapes at nailfold videocapillaroscopy (NVC) compared to matched healthy controls.• Articular involvement in jSjD is significantly associated with a lower capillary number at NVC.• Microhaemorrhages on NVC are associated with lower C3 levels, prompting this finding as a putative novel negative biomarker/prognostic factor for jSjD.

Asymmetric dimethylarginine correlates with worsening peripheral microangiopathy in systemic sclerosis.

Systemic sclerosis (SSc) is a connective tissue disease characterized primarily by micro-angiopathy and endothelial dysfunction which stimulate a fibrotic process. Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide (NO) inhibitor and represents a novel biomarker for vascular dysfunction. Nailfold video capillaroscopy (NVC) represents a non-invasive and reliable technique for the evaluation of microvasculopathy in SSc. The aim of this study was to examine the possible association between ADMA and microvascular involvement in patients with SSc. This was a cross-sectional study including consecutive SSc patients attending the Scleroderma Outpatient Clinic. ADMA was measured in serum samples using a commercial enzyme immunoassay. Participants underwent NVC with qualitative and semi-quantitative assessment and all NVC parameters were measured in the distal row of each finger. The findings were classified in one of the three qualitative NVC patterns: early, active, and late. Eighty-one (92,6% women) SSc individuals with mean age 55.44±13.4years were included in this analysis. Within-groups comparisons revealed a trend between higher ADMA levels and progressive micro-vasculopathy (1,29 [2,1] vs 1,57 [1,95] vs 2,41 [3,87]; for early, active and late patterns respectively, p=0.039). Furthermore, ADMA concentration was significantly associated with the number of capillaries/mm (r=-0.235; p=0.035). Serum ADMA levels were significantly associated with advancing stages of microcirculatory abnormalities suggesting that ADMA may have a role in promoting microvascular endothelial dysfunction in SSc individuals.

Microvascular capillaroscopic abnormalities and occurrence of antinuclear autoantibodies in patients with sarcoidosis

We described nailfold videocapillaroscopy (NVC) findings and estimated the prevalence of serum anti-nuclear (ANA) and extractable nuclear antigen autoantibodies (ENA) in a cohort of sarcoidosis patients, comparing them with adequate healthy controls (HCs) and with primary Raynaud’s phenomenon patients (PRPs). NVC findings were also correlated with the occurrence of autoantibodies, current treatment, laboratory parameters, variables of lung function and whole-body imaging data. Twenty-six patients with sarcoidosis were assessed through NVC, laboratory parameters, pulmonary function tests, chest-X ray and 18- fluorodeoxyglucose positron emission tomography/computed tomography. The NVC parameters and ANA/ENA dosage were recorded also in 30 PRPs and 30 HCs. Sarcoidosis patients showed a higher rate of capillary dilations and nonspecific abnormalities and a lower mean capillary absolute number than PRPs and HCs (p < 0.01 for all comparisons). The prevalence of ANA positivity was higher in patients with sarcoidosis compared with PRPs and HCs (p < 0.02 for both), whereas ENA positivity was detected in one sarcoidosis patient (Ro52). Among sarcoidosis patients, the mean capillary absolute number negatively correlated with the C-reactive protein concentrations and was positively associated with the forced vital capacity percentage. Instead, a negative correlation was detected between serum ACE levels and the presence of capillary dilations (all p < 0.05). Our findings suggest a microvascular involvement in sarcoidosis whose investigation by NVC might be useful for the follow-up of patients displaying RP. Autoantibody positivity in sarcoidosis might suggest autoimmune implications in the disease or the production of autoantibodies reactive to tissue damage.

Peripheral Microangiopathy Changes in Pulmonary Arterial Hypertension Related to Systemic Sclerosis: Data From a Multicenter Observational Study

Systemic sclerosis (SSc) is a connective tissue disease characterized by immune-system alterations, fibrosis involving the skin and internal organs and diffuse microangiopathy. Pulmonary arterial hypertension (PAH) is a severe complication of SSc affecting about 10–15% of the patients and it is a leading cause of mortality. Due to the devastating nature of SSc-PAH, there is a clear need to systematically adopt appropriate screening programs. Nail fold videocapillaroscopy (NVC) studies have shown a more severe peripheral microvascular dysfunction in SSc patients with PAH suggesting that abnormalities in peripheral microcirculation may correlate with pulmonary microangiopathy. This is a cross-sectional study involving four tertiary University Rheumatology Units in the Center-North of Italy. Seventy patients, 35 adults with SSc and PAH confirmed by RHC (F/M 34/1; median age 65.2 ± 8.9 SD yrs), and 35 SSc patients without PAH were enrolled (F/M 3471; median age 63.3 ± 10.3 SD yrs). Clinical, laboratoristic and instrumental data were collected and NVC was performed in all patient. Specific NVC parameters were evaluated and a semi-quantitative rating scale was adopted to score these changes. Finally, patients were distributed into the suitable NVC pattern belonging to the scleroderma pattern. Our aim was to compare the peripheral microangiopathy changes in SSc patients with and without PAH, and to investigate the relationship between NVC findings and the main hemodynamic parameters of pulmonary vasculopathy. Patients with SSc-PAH+ showed a significant higher frequency of interstitial lung disease (ILD). No significant differences regarding clinical and laboratoristic parameters were observed. NVC abnormalities, avascular areas were more frequent in SSc patients with PAH, respect to those without (p = 0.03), and capillary density was significantly lower when considering grade 3 (p = 0.02). A higher NVC semiquantitative mean was found in SSc-PAH+ patients and a greater rate of the “late” pattern was detected in SSc-PAH+ subjects in respect to PAH- (57.1% vs. 25.7%) (p = 0.03). A significant correlations between pulmonary pressure values (sPAP by TTE and mPAP by RHC) and the capillary density (Spearman's rho 0.35, p = 0.04 for both). Our findings provide additional evidence to the literature data, confirming that a higher degree of peripheral nailfold microangiopathy is more common in SSc-PAH patients, and further strengthening the concept that NVC changes may run parallel with similar abnormalities inside pulmonary microcirculation.

Is There a Link Between Nailfold Videocapillaroscopy and Pulmonary Function Tests in Systemic Sclerosis Patients?: A 24-Month Follow-up Monocentric Study.

The aim of this study was to explore the associations between nailfold videocapillaroscopy (NVC) and pulmonary function tests (PFTs) in systemic sclerosis (SSc) patients. This was a longitudinal study with follow-up of unselected Brazilian SSc patients. Baseline clinical examination, serological workup, high-resolution chest tomography, and NVC were performed. Pulmonary function test was performed at baseline and after 24 months. Pulmonary function test worsening over time was defined as either a ΔFVC decline ≥10% or a ΔFVC decline ≥5% and <9%, combined with a ΔDLCO decline ≥15%, at 24 months. The NVC parameters were quantitatively (capillary density number, dimension, morphology, and hemorrhages) and qualitatively (NVC pattern) evaluated according to the consented standardized definitions of the EULAR Study Group on Microcirculation in Rheumatic Diseases. Seventy-nine patients were included. Fifty-nine were rated to have a scleroderma pattern (6 "early"/16 "active"/37 "late"). The mean FVC and DLCO were 76.8% and 67.2% at baseline and 73.8% and 64.3% at 24 months, respectively. After multivariate analysis, we found that a reduced baseline FVC was associated with reduced capillary density (odds ratio [OR], 11; 95% confidence interval [CI], 1.5-90.7; p = 0.03) and a reduced baseline DLCO associated with the late scleroderma pattern (OR, 6.75; 95% CI, 1.09-42; p = 0.03). No association between worsening of PFT over time and NVC was found. The association between NVC and PFTs might corroborate the link between microangiopathy and interstitial lung disease in patients with SSc. This finding might strengthen the idea of incorporating NVC as a tool to predict progressive interstitial lung disease in these patients in the future.

Antiphospholipid antibodies and anticoagulant therapy: capillaroscopic findings

BackgroundAntiphospholipid 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.ObjectivesThis 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.MethodsNVC 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.ResultsAPS 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.ConclusionsAPS 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.

AB0330 ANTIPHOSPHOLIPID ANTIBODIES AND ANTICOAGULANT TREATMENT: CAPILLAROSCOPIC FINDINGS

Background:Antiphospholipid syndrome (APS) is an autoimmune condition characterized by arterial and/or venous thrombosis and/or obstetric morbidity, associated with the presence in the serum of antiphospholipid antibodies (aPL) [1]. Subjects with confirmed positivity of aPL in absence of thrombotic/obstetric manifestations are identified as aPL carriers [2] The microangiopathy detected by nailfold videocapillaroscopy (NVC) in APS and in aPL-carrier patients is poorly investigated, as well as the possible interference of anticoagulant drugs [3].Objectives:To compare microvascular damage in APS, aPL carriers and a group of patients (CTR) without aPL positivity and on regular warfarin therapy for cardiovascular indicationsMethods:NVC investigations were performed as part of standard procedures in APS patients (18, mean age 50.0±12.8 years), aPL carriers (24, mean age 46.4±16.4 years) and CTR without aPL (18, mean age 74±12.5 years) in therapy with oral anticoagulant (warfarin) for non-immunological vascular complications (atrial fibrillation, mechanical heart valve, deep venous thrombosis). Only patients affected by primary APS form were selected from data files (2006 Sapporo classification criteria). The following NVC parameters were availble: dilated capillaries, giant capillaries, microhemorrhages (with particular attention to linear and thin hemosiderin deposits, arranged perpendicularly and parallel to the nailfold bed, “comb-like”), abnormal shape (i.e. brunched “bushy” capillaries) and capillary number reduction. Those parameters were scored according to a semi-quantitative scale [4,5]. Statistical analysis was performed by non-parametric tests. Any p values equal or lower than 0.05 was considered statistically significant.Results:APS patients showed a higher score for dilated capillaries (p=0.001), more frequent microhemorrhages (p=0.03), in particular “comb-like” microhemorrhages (p=0.007) than simply aPL carriers. Of note, there wasn’t a statistically significant difference in the number of microhemorrhages between APS and CTR group (p=0.23), but again the number of “comb-like” hemorrhages, was almost absent in the CTR group (p=0.03). No significant correlation was found between the different aPL subtypes and the NVC parameters.Conclusion:APS patients showed significantly higher number of non-specific NVC abnormalities than aPL carriers. Anticoagulant treatment could represent a further risk factor for the appearance of microhemorrhages in all the patients, being the NVC “comb-like“ pattern mainly associated with the APS. Further investigations with larger cohorts of patients are needed for the definition of a possible APS specific NVC-pattern.

Does sublingual microscopy correlate with nailfold videocapillaroscopy in systemic sclerosis?

In this study, we examine sublingual videomicroscopy and nailfold videocapillaroscopy (NVC) features in systemic sclerosis (SSc) patients presenting for routine care. Consented participants met classification criteria for SSc. Sublingual videomicroscopy testing was performed in each subject, followed by a NVC assessment. Sublingual assessment provided a density measurement, red blood cell fraction (RBC fract), and perfused boundary region (PBR) score. NVC evaluator defined nailfold findings as normal; specific changes for "early," "active," and "late" scleroderma pattern; or "non-specific" changes. Microangiopathy evolution score was calculated for each participant. Statistical evaluation was performed by non-parametric tests to assess the correlation of the two tools. Thirty-nine SSc patients with limited cutaneous disease participated in this study. Most participants had late pattern NVC. There was a highly significant association between the total sublingual microvascular density and number of capillaries measured by NVC (r = 0.569, P = 0.0002), and statistically significant negative correlation between sublingual total microvascular density and microangiopathy evolution score (r = 0.532, P = 0.0006). There was significant, negative correlation between the total sublingual microvascular density and disorganization of vascular array and capillary ramification (r = 0.461, P = 0.003) and degree of giant capillaries (r = 0.387, P = 0.01). There was no correlation between RBC fract and PBR with NVC parameters. This study showed a significant correlation between sublingual videomicroscopy and NVC in terms of sublingual total microvascular density and microangiopathy evolution score. These preliminary results further support the serial use of a non-invasive and automated sublingual microvascular function testing and glycocalyx measurement in the clinical setting. KEY POINTS: • Tools that longitudinally assess microvascular function and morphologic features are important for monitoring SSc vasculopathy. • Nailfold and sublingual microscopy can identify a loss of capillary density in SSc patients.

May capillaroscopy be a candidate tool in future algorithms for SSC-ILD: Are we looking for the holy grail? A systematic review.

To investigate whether nailfold videocapillaroscopy (NVC), an increasingly worldwide used non-invasive tool to reliably evaluate the peripheral microcirculation, may be an outcome measure in future screening algorithms for systemic sclerosis related interstitial lung disease (SSc-ILD). A systematic review to identify original research papers documenting an association between NVC and SSc-ILD was performed in 3 electronic databases according to the PRISMA guidelines. Subsequently, NVC parameters were subdivided according to the consented standardised capillaroscopic definitions of the EULAR Study Group on Microcirculation in Rheumatic Diseases / Scleroderma Clinical Trials Consortium on Capillaroscopy, into quantitative (capillary density, capillary dimension, capillary morphology and haemorrhages) and qualitative assessment (NVC pattern). The systematic search identified 310 unique search results, of which 2 cross-sectional and 1 longitudinal study were retained. In both cross-sectional studies, the presence of SSc-ILD was found to be inversely associated with capillary density (p=.008 and p=.005). The presence of a severe (active/late) NVC pattern was evaluated and associated with the presence of SSc-ILD in one of the cross-sectional studies. In the longitudinal study, incident SSc-ILD was associated with progressive capillary loss (p=.03) and the conversion to a worse (active/late) NVC pattern (p=.001/p=.003). This first systematic literature review investigating the role of NVC in SSc-ILD using standardised capillaroscopic definitions uncovered associations between NVC and (incident) SSc-ILD. If large prospective studies further corroborate and elucidate these findings, NVC might possibly be a candidate outcome measure to be integrated in screening algorithms for incident/progressive SSc-ILD.

Association between coronary artery disease severity and videocapillaroscopic findings of nail fold capillary circulation

Aim: Endothelial dysfunction plays a significant role in the etiology of coronary artery disease (CAD), which develops due to atherosclerosis, and is a major cause of morbidity and mortality. Nail fold videocapillaroscopy (NVC) assessment is a surrogate marker of endothelial dysfunction. To the best of our knowledge, the relationship between the microcirculation features on NVC and the severity of coronary atherosclerosis has not previously been investigated. In this study, we aimed to investigate the relationship between severity of coronary atherosclerosis (shown by SYNTAX and Gensini scores) and NVC findings which is an indirect indicator of systemic endothelial damage.Methods: The study was designed as a retrospective cohort. One-hundred consecutive patients who underwent coronary angiography (CAG) and had at least one lesion in the epicardial coronary arteries, narrowing the lumen by more than 50%, were included. Coronary angiographic images of the patients were evaluated by two experienced interventional cardiologists and SYNTAX and Gensini scores were calculated. Patients were divided into three groups according to the SYNTAX scores (SYNTAX score ≤22, between 23-32, and ≥33) and two groups according to Gensini scores (Gensini score ≥30 and ˂30). The NVC examinations were performed by a rheumatologist who was experienced in this field, and the reduction in capillary density, presence of dilated capillaries, giant capillary, microhemorrhage, branching, disorganization, tortuosity, avascular area, extravasation, and neoangiogenesis were investigated.Results: Dilated capillary vessels were more common in diabetic patients (85%) than in non-diabetics (66.7%) (P=0.041). Besides, there was no significant difference in NVC parameters between patients with and without diabetes mellitus (P>0.05 for all), with and without hypertension (P>0.05 for all). There was no significant difference between the SYNTAX groups in terms of NVC findings (P>0.05 for all). The NVC findings were similar between Gensini groups (P>0.05 for all). Conclusion: The severity of atherosclerosis surrogated by SYNTAX and Gensini scores was not related to the NVC findings. Therefore, NVC is inappropriate for determining the severity of CAD.

Systemic sclerosis patients with and without pulmonary arterial hypertension: a nailfold capillaroscopy study

Pulmonary arterial hypertension (PAH) is a complication of SSc due to increased vascular resistance, and abnormal vascularity is a well-known feature of the disease as shown by nailfold videocapillaroscopy (NVC). This study investigated for specific NVC changes in SSc patients with and without PAH to assess any useful difference. Twenty-four SSc patients, 12 with PAH and 12 without, entered the study. Evidence of PAH was defined as increased systolic pulmonary artery pressure (PAP) (≥35 mmHg), indirectly assessed by echocardiography and confirmed by right heart catheterization (mPAP > 25 mmHg). NVC was performed, and a semi-quantitative rating scale, a rating system for avascular areas and a specific NVC pattern evaluation, namely early, active and late, were used. An NVC score >1 was more frequently found in patients with PAH than those without, 11 cases (92%) vs 5 cases (42%) (P = 0.03); an avascular areas grade >1 was present in 10 (83%) and 2 (17%) cases, respectively (P = 0.003); and a more severe NC pattern (active/late) was described in 11 (92%) and 5 (42%) patients, respectively (P = 0.03). When we compared the mPAP with NVC parameters, we found significant correlations between mPAP values and the NVC score (P < 0.005) and with the avascular areas score (P < 0.001). Our results underline the relevance of early microvascular assessment in patients at risk of developing a severe complication such as PAH that can amplify the systemic microvascular impairment in SSc. More severe NVC abnormalities should lead to strict cardiopulmonary surveillance and a complete NVC study is indicated.

Nailfold videocapillaroscopy in systemic sclerosis: diagnostic and follow-up parameters and correlation with both specific serum autoantibodies and subsets of skin involvement

The aim of the present study was to demonstrate, by nailfold videocapillaroscopy (NVC), the existence of diagnostic and follow-up parameters of microvascular damage in systemic sclerosis (SS) (grouped in the "early", "active" and "late" NVC patterns). The presence of the different subsets of skin involvement (limSS and difSS), as well as the role of some specific serum autoantibodies in the expression of the NVC parameters were investigated. 245 consecutive SS patients were recruited and clinical data assessed. Antinuclear (ANA), antitopoisomerase I (Scl70) and anticentromere (ACA) antibodies were investigated in all patients. Giant capillaries and hemorrhages were confirmed to be the earliest NVC finding in SS (diagnostic parameters). The loss of capillaries, along with ramified capillaries and vascular architectural disorganization were validated as parameters of progression of SS microangiopathy. Really, both Raynaud's phenomenon (RP) and SS duration were detected longer in patients with the "late" than in those with the "active" or the "early" NVC pattern. Patients affected by limSS were found to have shorter disease duration, as well as showed more frequently the "early" or the "active" NVC patterns. Conversely, patients affected by the difSS showed longer disease duration and mostly the presence of the "active" or "late" NVC pattern. The Scl70 positivity was lower in the patients showing the "early" than in those with the "active" and the "late" NVC patterns, whereas no significant correlation was found between the Scl70 presence and both RP and SS duration. The ACA positivity was higher in patients showing the "early" NVC pattern, as well as in patients with longer disease duration. This study confirms that the identification of distinct NVC patterns may be useful to evaluate the severity and the stage of the SS microvascular damage. The presence of the Scl70 antibodies seems related to a more rapid progression of the SS microangiopathy. On the contrary, the presence of the ACA seems to be related to a slower progression of the SS microvascular damage. The SS peripheral microangiopathy is similar as in patients with limSS, as in those affected by difSS.