Late Scleroderma Pattern Research Articles

Retinal Microvasculature in Systemic Sclerosis Patients and the Correlation between Nailfold Capillaroscopic Findings and Optical Coherence Angiography Results.

Background: The comparison of retinal perfusion in the eyes of patients with systemic sclerosis (SSc) and in healthy controls using optical coherence tomography angiography (OCTA). The correlation between nailfold capillaroscopy results and OCTA findings among SSc. Methods: The study enrolled 31 patients with systemic sclerosis and 41 healthy controls. OCTA was performed in both groups to assess the retinal vasculature in the superficial (SCP) and deep (DCP) capillary plexuses and the foveal avascular zone (FAZ) area. Nailfold capillaroscopy (NC) was performed in SSc patients and compared to the FAZ area and the superficial and the deep vessel density. Results: In the SSc group, the parafoveal vessel density in DCP was significantly higher in relation to the mean value (p < 0.0001) and in each quadrant of the macula (p < 0.0001) compared to healthy subjects (p < 0.0001). The patients with early scleroderma patterns in capillaroscopy had a larger superficial and deep FAZ (p = 0.0104, p = 0.0076, respectively) than those with active and late patterns. There was a statistically significant difference in the FAZ when comparing early to active (p < 0.0001) and early to late scleroderma patterns (p < 0.0001). A statistically significant difference was found in the type of interstitial lung disease and the deep FAZ area (p = 0.0484). SSc patients with nonspecific interstitial pneumonia (NSIP) had a larger FAZ than those with usual interstitial pneumonia (UIP) (p = 0.0484). Moreover, NSIP cases had a higher parafoveal mean superficial vessel density than those with UIP (p = 0.0471). Conclusions: Our investigation showed that the peripheral microvascular system correlates with ocular microcirculatory impairment. The results indicate the important role of OCTA in the diagnosis, monitoring, and prognosis of microvascular changes in SSc.

Nail involvement in connective tissue diseases: an epidemiological, clinical, and dermoscopic study.

The assessment of nail changes in connective tissue diseases (CTD) has been rarely explored in previous studies. The use of dermoscopy to study vascular changes in nailfolds is an interesting diagnostic technique. The aim of the study was to describe the epidemiological, clinical, and dermoscopic features of nail lesions in CTD. A prospective study was performed at the Dermatology Department of Habib Thameur Hospital (Tunis, Tunisia) in collaboration with the Internal Medicine Department over a period of 15 months, from July 2020 to September 2021, including patients diagnosed with systemic sclerosis (SS), systemic lupus erythematosus (SLE) and dermatomyositis (DM). Our study included 48 patients. Nail involvement was found in 44 cases. Dermoscopic nailfold abnormalities were identified in 37 cases. The most common clinical features were ragged cuticle, nailfold erythema, and onycholysis. Additionally, splinter hemorrhage, longitudinal ridging, lunula abnormalities, melanonychia, trachyonychia, leukonychia, increase in transverse curvature, parrot beak nail, half and half nails, and onychorrhexis were described. Nailfold dermoscopy showed a normal pattern in 10 cases, a nonspecific pattern in nine cases (SLE), and a scleroderma pattern in 29 cases (SS and DM). The scleroderma pattern was further categorized into an early pattern (6), an active pattern (14), and a late pattern (9). Normal pattern was observed solely in patients in remission. The late scleroderma pattern was associated with disease duration and systemic involvement. In SLE, disease activity correlated with onycholysis, nailfold erythema, and pathologic pattern in dermoscopy. However, patients with DM displayed a positive correlation between pulmonary involvement and scleroderma pattern. Nail involvement in CTD includes a diverse range of abnormalities. Despite being nonspecific, it can provide crucial clues for establishing a diagnosis. Nailfold dermoscopy serves as a mirror for microangiopathy, enabling the detection of changes at an initial stage, and thus, it becomes a diagnostic and prognostic tool.

Can microvascular damage predict disease severity in patients with systemic sclerosis?

IntroductionSystemic sclerosis (SSc) is characterized by progressive fibrosis of the skin and internal organs, microvascular damage and cellular and humoral immunity abnormalities. Microvascular damage can be easily detected through nailfold videocapillaroscopy (NVC). Materials and methodsA retrospective study of patients with SSc and a NVC performed within the first 6 months after diagnosis was conducted. Visceral involvement in the first 3 years of the disease and NVC findings were collected. The severity of microvascular damage was classified into four categories, according to the worsening of the NVC patterns. The severity of organ involvement was assessed by the disease severity scale of Medsger for each organ and as a global measure of disease severity, the simple summation was used. ResultsA total of 86 patients with SSc were included. A moderate correlation was found between the severity of microvascular damage and the global measure of disease severity (r=0.55, p<0.001), the severity of peripheral vascular involvement (r=0.43, p<0.001) and the severity of skin involvement (r=0.34, p=0.001).The presence of a late scleroderma pattern in NVC were predictive in univariate analysis of digital ulcers (OR 6.03, 95% CI 1.52–23.86, p=0.01), muscular involvement (OR 13.09, 95% CI 1.09–156.78, p=0.04), calcinosis (OR 27.22, 95% CI 5.56–133.33, p<0.001) and worse global disease severity score (OR 1.67, 95% CI 1.17–2.38, p=0.005). Multivariate analysis adjusted for disease duration and gender confirmed late pattern as an independent predictor of calcinosis (OR 42.89, 95% CI 5.53–332.85, p<0.001). Discussion and conclusionIn this study, the worsening of NVC pattern in SSc was associated with the overall disease severity, the severity of peripheral vascular involvement and extension of skin involvement. This study highlights the importance of NVC as a prognostic tool and a possible predictor of systemic visceral involvement.

Nailfold capillaroscopy in Egyptian systemic lupus erythematosus (SLE) patients: correlation with demographic features and serum levels of IL 17A and IFNs I

BackgroundIn SLE patients, cytokines are linked to endothelial cell damage. Nailfold capillaroscopy (NFC) is a simple method for evaluating micro-vascular abnormalities in different connective tissue diseases (CTDs). The study aimed to detect the levels of interleukin 17A (IL 17A), type I interferons (IFNs I) in the serum, and NFC changes in Egyptian SLE patients compared to a control group and to correlate NFC findings with patients’ demographic features and serum levels of IL 17A and IFNs I.ResultsSerum levels of IL 17A, IFN α, and IFN β were significantly higher in SLE patients than in control group (P < 0.0001). About thirty nine patients (73.6%) of the 53 SLE patients showed abnormal NFC changes. Egyptian SLE patients had a high prevalence of the NFC non-specific pattern, with 32 (60.4%) patients showing non-specific changes and 7 (13.2%) patients showing scleroderma pattern, including 3 (5.6%) patients with active scleroderma pattern and 4 (7.55%) patients with late scleroderma pattern. Furthermore, Raynaud’s phenomenon (RP) was observed in 8 (15.1%) SLE patients, with 3 (5.6%) having normal NFC pattern and 5 (9.4%) having scleroderma pattern. All controls (n = 20) showed normal hairpin shape capillaries. Except for SLEDAI (P = 0.03) and the presence of RP (P < 0.0001), there were no significant differences in demographic and laboratory parameters between the three NFC patterns (normal, non-specific, and scleroderma); additionally, NFC score correlated significantly with SLEDAI (P = 0.021).ConclusionAs a result of the high disease activity, Egyptian SLE patients had elevated serum levels of IL 17A and IFNs I. The most common NFC pattern in Egyptian SLE patients was a non-specific pattern. NFC abnormalities in Egyptian SLE patients were correlated with disease activity but not with patients’ ages, disease duration, or serum levels of IL 17A and IFNs I. SLE patients with scleroderma NFC pattern and RP should be closely followed for the possibility of appearance of anti-U1 RNP antibodies and MCTDS.

The relationship of nailfold capillaroscopy patterns with clinical features, functional status, pain and fatigue in patients with systemic sclerosis

Aim: To identify the frequency of scleroderma-type capillaroscopic patterns and evaluate the association of capillaroscopic patterns with clinical parameters, functional status, fatigue, and pain in systemic sclerosis (SSc).&#x0D; Material and Method: This cross-sectional study included SSc patients consecutively between January 2017 and January 2019. Cutaneous involvement was evaluated with the modified Rodnan skin score (mRSS). The presence of digital ulcers, Raynaud phenomenon, interstitial lung disease, pulmonary hypertension, cardiac, gastrointestinal system (GIS), renal, joint and muscle involvement were recorded. The severity of the Raynaud phenomenon, fatigue, pain, and patient global assessment (PGA) was assessed on the Visual Analogue Scale (VAS). The Health Assessment Questionnaire (HAQ) and the Duruoz Hand Index (DHI) were used to assess physical disability and hand function, respectively. Nailfold videocapillaroscopic examinations of the patients were performed, and they were classified into four groups, including normal/non-specific, early, active, and late scleroderma patterns.&#x0D; Results: The mean age of 32 patients with SSc (31 female, one male) was 48.93±12.77. Anormal capillaroscopic examination findings were detected in 93.7% of the patients, and the most common capillaroscopic pattern was the active pattern. The comparison of scleroderma pattern groups revealed no difference in age (p=0.224), but disease duration was shorter in the early pattern group (p=0.005). The duration and severity of the Raynaud phenomenon, and mean mRSS were lower in the early pattern group (p=0.004, p=0.009, and p=0.001, respectively). The digital ulcer (p=0.011) and diffuse cutaneous SSc (p=0.016) were more common in the late pattern group. The percentage of pulmonary hypertension (p=0.011), GIS involvement (p

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.

Assessing the role for nailfold videocapillaroscopy in interstitial lung disease classfication: a systematic review and meta-analysis.

The nailfold videocapillaroscopy (NVC) has been known to assist with interstitial lung disease (ILD) classification. However, evidence on its diagnostic efficacy is limited, particularly in some connective tissue disease-related interstitial lung diseases (CTD-ILD), and in interstitial pneumonia with autoimmune features (IPAF). This study aimed to address this limitation by conducting a meta-analysis on the efficacy of the NVC in ILD subgroups of CTD-ILD, IPAF and idiopathic pulmonary fibrosis (IPF). MEDLINE, EMBASE, CENTRAL were screened from inception to December 2020 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies that report prevalence of nailfold abnormalities (NVC+) in CTD-ILD, IPAF and IPF cohorts were included. Data were presented as prevalence ratio (PR) with 95% CI using a random-effects model. Quality of evidence was assessed using GRADE criteria. Twenty-one studies were eligible. Prevalence of NVC+ was highest in CTD-ILD; PR (95 CI%) 80.4% (74.3%, 85.3%), followed by IPAF; 27.4% (10.9%, 53.7%), and IPF; 13.8% (5.7%, 29.9%). Late scleroderma pattern was the most prevalent nailfold pattern; 40.4% (28.1%, 54.1%) in our CTD-ILD cohort. Quality of evidence was low for CTD-ILD, IPAF and IPF cohorts, moderate for the late scleroderma pattern cohort. NVC can increase the diagnostic accuracy of ILD when used in a multi-disciplinary setting, and appears to have greatest utility in CTD-ILD, followed by IPAF and IPF. The Late Scleroderma Pattern was the most frequent nailfold capillary pattern in SSc-ILD. Future research will allow for greater understanding of the prognostic value of the NVC in ILD.

Nailfold capillaroscopy in systemic diseases: short overview for internal medicine.

Nailfold capillaroscopy (NFC) is now one of the main imaging tools in systemic sclerosis and imposed over time as an easy, non-invasive method for the nailfold microvascular bed assessment. In qualitative NFC normal pattern is characterized by homogeneous, parallel fashion arrangement of the last capillaries row as well as by capillaries with hairpin or non-specific variations like tortuous and/ or crossing shape. Nailfold capillaroscopy is strongly recommended for evaluation of all patients with Raynaud phenomenon. Appearance of giant capillaries is chronologically the first relevant finding for scleroderma spectrum disorders development (systemic sclerosis, dermatomyositis, undifferentiated and mixed connective tissue disease). Collapses of the giant loops generate microhemorrhages and further capillary loss with subsequent hypoxia, and neoangiogenesis seen as ramified/ bushy capillaries. Nailfold capillaroscopy is indicated especially in systemic sclerosis, being also included in the classification criteria. Based on these major NFC pathologic findings (giant capillaries, microhemorrhages, avascularity and neoangiogenesis), three evolutive stages were described in systemic sclerosis, namely the early, active, and late scleroderma pattern. In other connective tissue diseases than those scleroderma-related, like systemic lupus erythematosus, psoriatic arthritis, or antiphospholipid syndrome, the interest for capillaroscopy is growing, but the attempts of defining specific characteristics failed until now. Besides qualitative NFC, semiquantitative and quantitative capillaroscopic assessments were proposed for more accurate evaluation. Lately, automated systems are under development. There is still need of more studies to sustain the nailfold capillaroscopy validity as diagnostic and prognostic test.

Relation between nailfold capillaroscopic pattern (assessed using a dermoscope) and organ involvement in systemic sclerosis

Objectives: The objectives of the study were: (1) To document the nailfold capillary changes (using a dermoscope) in patients with systemic sclerosis attending a tertiary care center, (2) to study the relation between nailfold capillaroscopic pattern and skin sclerosis assessed by modified Rodnan skin score (mRSS), and (3) to study the relation between nailfold capillaroscopic pattern and organ involvement in systemic sclerosis. Materials and Methods: A cross-sectional study was conducted among 40 patients with systemic sclerosis who attended the dermatology outpatient department of a tertiary care center from January 1, 2018, to December 31, 2018. Nailfold capillaries were examined with the help of dinolite dermoscope AM4113ZT at 50× and 200× magnification, under polarized light. Results: Study participants included 34 (85%) females and 6 males (15%). The nailfold capillaroscopy showed “early scleroderma pattern” in 3 (7.5%) “active pattern” in 28 (70%) and “late pattern” in 9 (22.5%) patients. “Late scleroderma pattern” showed a significant association with disease duration, mRSS, and mean number of organs affected. Limitations: The study participants may be over-representing advanced cases since the study was conducted among patients attending a tertiary referral center. Conclusion: We found dermoscope to be a useful tool to study the nailfold capillary changes in patients with systemic sclerosis as reported by others. Late scleroderma pattern may serve as an indicator of high mRSS and involvement of more number of organs in systemic sclerosis.

Color Doppler Ultrasonography of digital arteries and digital ulcers development in systemic sclerosis

BackgroundThe aim of this study was to evaluate the role of Color Doppler Ultrasonography (CDUS) of proper palmar digital arteries (PPDA) as predictive marker of new digital ulcers (DUs) in systemic sclerosis (SSc) patients during 5 years follow-up. Methods36 SSc patients were examined using nailfold videocapillaroscopy (NVC) and CDUS of PPDA. ResultsFourteen (38.9%) patients had chronic or acute occlusions (C and D pattern) on CDUS evaluation. Using a cut-off of 0.70, 21 (58.3%) patients had a Resistive Index (RI) ≥0.70. Nineteen (52.8%) patients developed new DUs during the follow-up. The median value of RI was higher in SSc patients with DUs than in SSc patients without DUs [0.73 (IQR 0.70–0.81) vs 0.67 (IQR 0.57–0.70), p < 0.0001].The Kaplan-Meier analysis showed a free survival from new DUs higher (p < 0.01) in SSc patients with Pattern A and B than SSc patients with Pattern C and D. The Kaplan-Meier curves showed that free survival from new DUs is lower (p < 0.001) in SSc patients with increased RI (≥0.70) than in SSc patients with normal RI.In multivariate analysis with two co-variates, RI ≥ 0.70 [HR 5.197 (1.471–18.359), p < 0.01] and NVC late scleroderma pattern [HR 7.087 (1.989–25.246), p < 0.01] were predictive markers of new DUs. ConclusionsRI of PPDA in association with NVC could be used to evaluate SSc patients with increased risk of new DUs development.

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

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.

Value of Nailfold Capillaroscopy as A Screening Method for Pulmonary Arterial Hypertension in Patients with Systemic Sclerosis

Background: Pulmonary arterial hypertension (PAH) represents one of the main clinical pictures of microvascular damage in systemic sclerosis (SSc). Objective: To assess the role of nailfold capillaroscopy (NFC) changes as a screening tool for the existence of PAH in patients with systemic sclerosis. Patients and methods: Forty SSc patients were studied, included: 20 patients with PAH (diagnosed by transthoracic echocardiography and confirmed by right heart catheterization) and another 20 without PAH. History taking, clinical examination, and laboratory investigations including serological biomarkers (anti-centromere and anti-topoisomerase1 antibodies) have been recorded. NFC was performed for all patients according to the standard method. Results: Scleroderma patients with PAH had significantly a longer disease duration (p=0.002) and higher frequencies of positive anticentromere and anti-topoisomerase 1 antibodies (p=0.011 and p=0.010 respectively). As regard NFC picture, SSc patients without PAH had significantly higher frequencies of early scleroderma pattern changes in 73.7% (p= 0.003), avascular area score 0 in 52.6% (p=0.014) and total NFC score 0 in 57.9% (p=0.022). In contrast, SSc patients with PAH showed higher frequencies of late scleroderma pattern changes in 50% (p=0.005) with lower capillary density (p <0.001), increased number of dilated mega-capillaries (p=0.049) together with more advanced avascular area of score 3 in 47.6% (p=0.007) and total NFC of score 3 in 45% (p=0.003). A significant negative correlation between mean pulmonary arterial pressure and capillary density (r=-0.57, p<0.001) was reported. Conclusion: Low capillary density together with wide avascular areas and more severe NFC scores have a clear association with the presence of PAH.

Value of Nailfold Capillaroscopy as A Screening Method for Pulmonary Arterial Hypertension in Patients with Systemic Sclerosis

Background: Pulmonary arterial hypertension (PAH) represents one of the main clinical pictures of microvascular damage in systemic sclerosis (SSc). Objective: To assess the role of nailfold capillaroscopy (NFC) changes as a screening tool for the existence of PAH in patients with systemic sclerosis. Patients and methods: Forty SSc patients were studied, included: 20 patients with PAH (diagnosed by transthoracic echocardiography and confirmed by right heart catheterization) and another 20 without PAH. History taking, clinical examination, and laboratory investigations including serological biomarkers (anti-centromere and anti-topoisomerase1 antibodies) have been recorded. NFC was performed for all patients according to the standard method. Results: Scleroderma patients with PAH had significantly a longer disease duration (p=0.002) and higher frequencies of positive anticentromere and anti-topoisomerase 1 antibodies (p=0.011 and p=0.010 respectively). As regard NFC picture, SSc patients without PAH had significantly higher frequencies of early scleroderma pattern changes in 73.7% (p= 0.003), avascular area score 0 in 52.6% (p=0.014) and total NFC score 0 in 57.9% (p=0.022). In contrast, SSc patients with PAH showed higher frequencies of late scleroderma pattern changes in 50% (p=0.005) with lower capillary density (p <0.001), increased number of dilated mega-capillaries (p=0.049) together with more advanced avascular area of score 3 in 47.6% (p=0.007) and total NFC of score 3 in 45% (p=0.003). A significant negative correlation between mean pulmonary arterial pressure and capillary density (r=-0.57, p<0.001) was reported. Conclusion: Low capillary density together with wide avascular areas and more severe NFC scores have a clear association with the presence of PAH.

Serum klotho concentrations inversely correlate with the severity of nailfold capillaroscopic patterns in patients with systemic sclerosis.

Klotho is a transmembrane and soluble glycoprotein that governs vascular integrity. Previous studies have demonstrated reduced serum klotho concentrations in patients with systemic sclerosis (SSc), and it is known that klotho deficiency can impair the healing of digital ulcers related to microvessel damage. The aim of this study was to evaluate the association between serum klotho levels and nailfold capillaroscopic abnormalities in SSc patients. We retrospectively enrolled 54 consecutive patients with SSc diagnosed on the basis of the 2013 EULAR/ACR criteria [11 with diffuse SSc; 47 females; median age 68.0 years (IQ 18); median disease duration 11.0 years (IQ 7)]. Serum klotho concentrations were determined by means of an enzyme-linked immunosorbent assay. On the basis of the 2000 classification of Cutolo et al., 14 patients had normal nailfold capillaroscopic findings, 8 had an early scleroderma pattern, 21 an active scleroderma pattern, and 11 a late scleroderma pattern. The median serum klotho concentration was 0.29 ng/mL (IQ 1). Regression analysis of variation showed an inverse correlation between serum klotho concentrations and the severity of the capillaroscopic pattern (p=0.02; t -2.2284), which was not influenced by concomitant treatment. Logistic regression did not reveal any significant association between the risk of developing digital ulcers and nailfold capillaroscopic patterns, serum klotho levels, or concomitant medications. The presence of avascular areas significantly correlated with calcinosis (p=0.006). In line with previous studies, our findings confirm that klotho plays a role in preventing microvascular damage detected with nailfold capillaroscopy.

Association Between Nailfold Capillary Density and Pulmonary and Cardiac Involvement in Medium to Longstanding Juvenile Dermatomyositis.

To explore the associations between microvascular abnormalities as assessed by nailfold capillaroscopy (NFC) and pulmonary and cardiac involvement in patients with juvenile dermatomyositis (DM) who are assessed after medium- to long-term follow-up. Fifty-eight patients with juvenile DM were examined a mean ± SD of 17.0 ± 10.6 years after symptom onset. Nailfold capillary density (NCD) and a neovascular pattern (defined as an active or late scleroderma pattern) were analyzed, with blinding to clinical data. Pulmonary involvement was assessed by pulmonary function tests including spirometry, diffusing capacity for carbon monoxide (DLco), and body plethysmography. High-resolution computed tomography (HRCT) was also performed. Cardiac involvement was assessed by electrocardiography, Holter monitoring (heart rate variability), and echocardiography. Patients with low NCD (<6 capillaries/mm) (n = 21), compared to patients with normal NCD (≥6 capillaries/mm) (n = 37) had lower forced vital capacity (89.7% versus 98.5% predicted), total lung capacity (87.8% versus 94.5% predicted), and more often had low DLco values (15 [71%] of 21 patients versus 14 [38%] of 37 controls) (all P < 0.05). Use of HRCT to assess airway disease was more frequent in the group with low NCD (6 [30%] of 20 patients versus 3 [8%] of 36 patients in the normal NCD group; P = 0.034). No associations between NCD and cardiac parameters or between neovascular pattern and pulmonary or cardiac parameters were observed. In patients with juvenile DM, low NCD was associated with lung involvement, which was mostly subclinical. No significant associations with cardiac involvement were observed. These results shed light on possible mechanisms underlying organ involvement, but further and preferably larger studies are needed to identify NCD as a potential biomarker for lung and cardiac involvement in juvenile DM.

Capillaroscopic findings and vascular biomarkers in systemic sclerosis: Association of low CD40L levels with late scleroderma pattern

ObjectiveTo determine the relationship between vascular biomarkers reflecting the vascular injury and neoangiogenesis with capillaroscopic changes in systemic sclerosis (SSc). MethodsNailfold video-capillaroscopy (NVC) was performed qualitatively (early, active and late scleroderma patterns) in 72 SSc patients (66 female) fulfilling ACR/EULAR (2013) criteria. Serum samples of patients were collected and analysed by flow cytometer with multiplex kits of sCD40L, tPA, MCP-1, sE-selectin, IL-8, IL-6, VEGF, sP-selectin, TGF-β1 and VCAM at the same time with NVC. ResultsCompared to healthy subjects; tPA (p=0.02), MCP-1 (p=0.001), sE-selectin (p=0.008) and TGF-β1 (p=0.001) levels were significantly higher, however sP-selectin (p=0.011) and IL-8 (p=0.001) levels were lower in SSc patients. SSc patients were defined according to NVC patterns as ‘early’ (n=10), ‘active’ (n=37) and ‘late’ (n=25). According to NVC patterns of SSc patients, only sCD40L levels were significantly lower in the ‘late’ group (p=0.039). The other markers were similar among NVC groups. ConclusionsNVC is a useful method for investigating the vascular pathogenesis and severity of SSc. Although the levels were similar to healthy controls in patients with early/active NVC patterns, there were lower sCD40L serum levels in patients with late NVC pattern. CD40L may have a role in the early/active phase of vascular involvement.

Serum vascular endothelial growth factor (VEGF), soluble VEGF receptor-1 (sVEGFR-1) and sVEGFR-2 in systemic sclerosis patients: Relation to clinical manifestations and capillaroscopy findings

IntroductionThe role of angiogenesis in the pathogenesis of systemic sclerosis (SSc) is well known. The imbalance between vascular endothelial growth factor (VEGF) and their anti-angiogenic soluble receptors (sVEGFR-1 and VEGFR-2) has been proposed as a possible cause of microangiopathy. Aim of the workTo determine the levels of VEGF, sVEGFR-1 and sVEGFR-2 and the VEGF/sVEGFR1 and VEGF/sVEGFR2 ratios in SSc patients and to study their relation with clinical manifestations and capillaroscopy findings. Patients and methodsThe study included 44 SSc patients and 44 controls. The sclerosis severity was assessed by the modified Rodnan skin score (mRss) and capillaroscopy performed in patients. Serum VEGF, sVEGFR-1 and sVEGFR-2 were measured in patients and control. ResultsSSc patients had a mean age of 40.7±12.8years, M:F (1:9) and disease duration was 56.2±60.6months. 27 patients (61.4%) had diffuse-SSc and 17 (38.6%) limited. The mean VEGF was significantly higher (363.4±133.9pg/ml) and sVEGFR-2 lower (2039.6±109pg/ml) in patients compared to control (93.9±25.2pg/ml and 2366±116.5pg/ml; p=0.05 and p=0.04, respectively). Serum levels of sVEGFR-2 in patients with early, active and nonspecific scleroderma pattern of capillaroscopy was higher in comparison to patients with late scleroderma pattern (p=0.05). There were no significant differences in the studied parameters between those patients with and without digital ulcerations and interstitial pulmonary fibrosis. A significant correlation was found between mRss and VEGF (p=0.04). ConclusionAn overproduction of VEGF, a potent angiogenic molecule or down regulated production of its natural inhibitors (sVEGFR-2) might be involved in the development of vasculopathy in SSc patients.

A comparison between nailfold capillaroscopy patterns in adulthood in juvenile and adult-onset systemic sclerosis: A EUSTAR exploratory study

ObjectiveQualitative capillaroscopy patterns in juvenile- and adult-onset systemic sclerosis (SSc) were studied in adulthood using data from the EULAR Scleroderma Trials and Research (EUSTAR) database. MethodsData collected between June 2004 and April 2013 were examined with focus on capillaroscopy. In this retrospective exploratory study, series of patients with juvenile-onset SSc were matched with series of adult-onset SSc having the same gender and autoantibody profile. Results30 of 123 patients with juvenile-onset and 2108 of 7133 with adult-onset SSc had data on capillaroscopy. Juvenile-onset SSc showed scleroderma pattern more frequently than adult-onset SSc (93.3% and 88%). The OR was 2.44 and 95% CI 0.57–10.41. An active scleroderma pattern was present in 58% of juvenile- and 61% of adult-onset SSc. The OR was 0.91 and 95% CI 0.28–2.93. The late scleroderma pattern was present in 61% of juvenile- and 55.5% of adult-onset SSc. The OR was 1.06 and 95% CI 0.34–3.56. ConclusionThis is the first exploratory study on the comparison of capillaroscopy between juvenile- and adult-onset SSc in adulthood. Juvenile-onset SSc had an increase prevalence of scleroderma pattern, but a similar distribution of the three patterns was suggested. Further studies are needed to define this issue.

Endothelial Dysfunction and Nailfold Videocapillaroscopy Pattern as Predictors of Digital Ulcers in Systemic Sclerosis: a Cohort Study and Review of the Literature.

Raynaud's phenomenon and digital ulcers (DUs) are frequent among systemic sclerosis (SSc) patients. Our aim was to investigate the diagnostic and predictive value for DU of endothelial dysfunction biomarkers (flow-mediated dilatation (FMD), serum levels of endothelin-1 (ET-1), and ADMA), angiogenic/angiostatic biomarkers (vascular endothelial growth factor (VEGF), endoglin, and endostatin), and nailfold videocapillaroscopy (NVC). We compared our results with a literature review. In a cohort study of 77 SSc patients, we followed two groups of patients: (i) naïve DU patients (39) and (ii) active DU at baseline (38 patients) for 3 years. Telangiectasia (p < 0.001) and diffuse disease subset (p = 0.001) were significantly more frequent in patients with active DU at enrolment. Additionally, NVC late scleroderma pattern (AUC 0.846, 95%CI 0.760-0.932), lower values of FMD (AUC 0.754, 95%CI 0.643-0.864), increased serum levels of ET-1 (AUC 0.758, 95%CI 0.649-0.866), ADMA (AUC 0.634, 95%CI 0.511-0.757), and endoglin as well as low VEGF serum levels (AUC 0.705, 95%CI 0.579-0.830) were significantly associated to new DU events in the 3-year follow-up. Cox regression analysis showed that FMD > 9.41 % (HR 0.37, 95%CI 0.14-0.99); ET-1 >11.85 pmol/L (HR 3.81, 95%CI 1.41-10.26) and late NVC pattern (HR 2.29, 95%CI 0.97-5.38) were independent predictors of DU recurrence. When estimating the probability of occurrence of first DU in naïve DU patients, only late NVC pattern (HR 12.66, 95%CI 2.06-77.89) was an independent predictor factor. In conclusion, late scleroderma patterns in NVC are the best independent predictors of SSc patients who are at risk of developing DU. Endothelial dysfunction assessed by FMD and ET-1 was also found to be an independent predictor of DU recurrence in a 3-year follow-up.

Anti-nuclear antibodies as predictor of outcome in a multi-center cohort of Italian children and adolescents with Raynaud's phenomenon.

A retrospective multi-center data collection of clinical, laboratory, and treatment characteristics of 94 Caucasian children and adolescents with Raynaud's phenomenon (RP) started at a mean age of 12.8 ± 5years, with variable involvement of hands, feet, and face, was performed for a period of 3years. Collected data included nailfold videocapillaroscopy (NVC), lung function tests, and different laboratory tests finalized to characterize an eventual connective tissue disease (CTD), disclosed by RP itself. Twelve patients presented an early-scleroderma pattern at NVC, 1 a late-scleroderma pattern, and 58 a nonspecific pattern. Laboratory data results showed the positivity of anti-nuclear antibodies (ANA) in 29% of patients. After this 3-year period of observation, 8 patients had developed a CTD. Our data examined by multivariate analysis, though limited to a multi-center cohort of pediatric patients with RP, strongly suggest that ANA positivity is a significant predictor of progression of RP towards a CTD.