Early Diagnosis Of Systemic Sclerosis Research Articles

Early Diagnosis of Systemic Sclerosis by Skin Ultrasonography.

Early Diagnosis of Systemic Sclerosis by Skin Ultrasonography.

AB0582 DIAGNOSING SYSTEMIC SCLEROSIS WITH PHOTOACOUSTIC AND HIGH-FREQUENCY ULTRASOUND IMAGING

Background:Vasculopathy is already evident in early systemic sclerosis (SSc); Raynaud’s phenomenon and typical nailfoldcapillaroscopic findings are part of the criteria of very early diagnosis of SSc (VEDOSs) (1). As not all early SSc patients have alterations in their nailfoldcapillaries, there is need for other diagnostic tools. Photoacoustics(PA) and high-frequency ultrasound (HFUS) might be able to fulfill this need (2). The former can measure the oxygen saturation of hemoglobin by using short pulsed laser light while the latter can provide high-resolution images that allow measuring skin thickening distal from DIP joint, which could be used to determine skin involvement early.Objectives:We hypothesize that photoacoustics and high-frequency ultrasound can distinguish (early) SSc patients from individuals with primary Raynaud’s phenomenon (PR) by measuring the oxygenation (by PA) of the fingertip and skin thickening (by HFUS).Methods:In our cross-sectional study, we compared measurements of the third finger in (early)SSc patients with individuals with PR and healthy volunteers. Smoking and beta-blockage were exclusion criteria. The level of oxygenation (by PA) and skin thickness (by HFUS) were compared between groups. Nailfoldcapillaroscopy was performed on all subjects and analyzed for the pattern.Results:Thirty-one adult subjects participated in this study: twelve patients with SSc, 5 patients with early SSc, 5 volunteers with PR and 9 healthy controls.We found a significant difference in median (IQR) oxygen saturation between earlySSc patients 75.9% (IQR 75.1%-86.6%) and subjects with PR 94.1% (IQR 93.1%-94.5%) (p=0.0002) using the Wilcoxon rank-sum test (figure 1).Figure 1.Boxplot of saturation (%) per group.Measurements of skin thickening also showed a significant difference in early SSc patients compared to subjects with PR, respectively 0.5mm (IQR 0.4mm-0.5mm) vs. 0.3mm (IQR 0.3mm-0.3mm), P=0.0002 (figure 2).Figure 2.Boxplot of skin thickness (mm) per group.Conclusion:Our results demonstrate that photoacoustic and high-frequency ultrasound can distinguish between (early)SSc and PR in both oxygenation saturation and skin thickening. In a larger prognostic study we want to determine the value of photoacoustic and high frequency ultrasound in diagnosing earlySSc.

P161 Optical coherence tomography of the skin detects scleroderma changes in clinically unaffected skin: an opportunity for early detection of systemic sclerosis

Abstract Background The Very Early Diagnosis Of Systemic Sclerosis (VEDOSS) study has shown that 82% of patients with Raynaud’s phenomenon, specific ANA positivity and scleroderma pattern at nailfold video capillaroscopy will fulfill classification criteria within 5 years. This is suggesting that there is a sub-clinical window of opportunity to diagnose systemic sclerosis (SSc) before clinical manifestations occur. In this scenario, a non-invasive tool to diagnose SSc in clinically unaffected skin might improve the early detection of disease in at risk-patients. Optical coherence tomography (OCT) of the skin has been shown to be a sensitive and accurate biomarker of skin fibrosis in SSc. Here we aimed to assess the ability of skin OCT to detect SSc in clinically unaffected skin from a multicentre cohort. Methods Dorsal forearm skin of SSc patients and matched-healthy controls (HC) was evaluated using VivoSight scanner (Michelson Diagnostics). Mean A-scans (mean OCT signal plotted against depth-in-tissue) were derived as previously described. Minimum Optical Density (MinOD), Maximum OD (MaxOD) and OD at 300 micron-depth (OD300) were calculated. Clinical involvement was assessed by an operator blinded to OCT findings using the mRSS. Receiver-operating characteristic (ROC) curve analysis was carried out for MinOD, MaxOD, and OD300 to evaluate their ability to discriminate between SSc and HC. Statistical analysis was performed using GraphPad Prism software V.7.0. Results One hundred seventy four OCT images were collected from 87 subjects [43 SSc (39 Female, mean age 49.7±9.1 years) and 44 gender/age-matched healthy controls (HC) (36 Female, mean age 50.2±8.3 years)] in two different SSc centres. All patients fulfilled classification criteria for SSc. OCT measures demonstrated discriminative ability in SSc skin detection with any clinical skin involvement (0-3 at site of analysis) with an AUC of 0.73 (MinOD, 95%CI 0.64-0.81), 0.77 (MaxOD, 95%CI 0.7-0.85) and 0.82 (OD300, 95%CI 0.76-0.89); p < 0.0001 for all as previously indicated. Most importantly, all three measures showed comparable performance in detecting scleroderma also in clinically unaffected skin (mRss=0 at site of analysis), with an AUC of 0.7 (95%CI 0.6-0.81, p = 0.001), 0.72 (95%CI 0.61-0.83, p = 0.0003) and 0.72 (95%CI 0.61-0.83, p = 0.0003) for MinOD, MaxOD and OD300 respectively. Conclusion Virtual biopsy by OCT recognises clinically unaffected skin of SSc patients from the HC skin. This is consistent with gene array data showing that scleroderma specific signatures are consistent in affected and clinically unaffected skin. These results inform future studies on at risk patients with clinically unaffected skin which may define a role for OCT in detecting subclinical SSc. Disclosures G. Abignano None. D. Temiz Karadag None. O. Gundogdu None. G. Lettieri None. M. Padula None. A.A. Padula None. P. Emery None. S. D'Angelo None. F. Del Galdo None.

Novel instrumental markers of proximal scleroderma provided by imaging photoplethysmography

Objective: Instrumental identification of proximal scleroderma, which is necessary for the early diagnosis of systemic sclerosis (SSD), has not yet been developed. The aim of this study was to assess the potential diagnostic value of the imaging photoplethysmography (IPPG) method in patients with SSD. Approach: The study enrolled 19 patients with SSD and 21 healthy subjects matched by age and sex with the patients. Spatial distribution of capillary-blood-flow parameters and their dynamics was estimated in the facial area of patients and subjects. In the IPPG system, a 40 s video of the subject’s face illuminated by green polarized light was recorded with a monochrome digital camera in synchronization with the electrocardiogram. Experimental data were processed using custom software allowing assessment of an arrival time of the blood pressure wave (PAT), an amplitude of pulsatile component (APC) of the photoplethysmographic (PPG) waveform, and their variability. Main results: Our study has revealed a significant increase in PAT variability in patients with SSD compared to the control group: 52 ± 47 ms vs 24 ± 13 ms (P =0.01). Similarly, the variability of the PPG-pulse shape was larger in patients with SSD: 0.13 ± 0.07% vs 0.09 ± 0.02% (P < 0.001). In addition, patients with scleroderma showed a significantly greater degree of asymmetry of the APC parameter than the control group: 17.7 ± 9.7 vs 7.9 ± 5.0 (P < 0.001). At the same time, no correlation was found between the PPG waveform parameters and either the form or duration of the disease. Also, no relationship between the characteristics of the PPG waveform and the modified Rodnan skin score was found. Significance: Novel instrumental markers found in our pilot study showed that the IPPG method can be used for diagnosing SSD in the early stages of the disease.

Nailfold capillaroscopy: a useful instrument for early diagnosis of systemic sclerosis in patients with primary biliary cholangitis

Introduction: Primary Biliary Cholangitis (PBC) is a cholestatic autoimmune disease affecting small bile ducts. PBC is often associated with Systemic Sclerosis (SSc). SSc prevalence is about 5–12% in PBC patients and diagnosis is often delayed due to lack of specific recommendations. Aim: We assessed the utility of Nailfold Capillaroscopy (NC) in anticipating SSc diagnosis in PBC patients.

Recent advances in the workup and management of Raynaud’s phenomenon

Raynaud phenomenon (RP) is defined as recurrent, reversible episodes of vasospasm involving peripheral small vessels, typically in the fingers and toes. Primary (idiopathic) RP is common (it occurrs in about 5% of the general population) and is usually benign. Secondary RP accounts for 10% to 20% of all RP cases and may be associated with complications such as tissue loss, ulcers, and gangrene. Systemic sclerosis (SSc) or, more rarely, other connective tissue diseases are the main underlying conditions. A detailed clinical history and careful physical examination may be helpful in identifying the cause. Routine investigations include a full blood count, measurement of erythrocyte sedimentation rate, C‑reactive protein, antinuclear antibody levels, biochemical profile, thyroid function tests, protein electrophoresis, chest X‑ray, and nailfold capillaroscopy. Capillaroscopy can facilitate a very early diagnosis of SSc. Doppler ultrasound is recommended to evaluate the risk of pathologies in large to medium-sized arteries. Lifestyle modifications may be sufficient to control primary RP, but some patients, and most with secondary RP, require pharmacologic treatment. Several medications are proposed to manage RP and its complications, such as calcium channel blockers, phosphodiesterase type 5 inhibitors, intravenous prostanoids, and topical nitrates. However, scientific evidence for the use of these drugs is still weak to moderate. Despite the lack of efficacy of bosentan in RP treatment, this medication is approved for the secondary prevention of digital ulcers in patients with SSc. In conclusion, the management of RP still represents a challenge. Collaboration between healthcare professionals, patient organizations, and the society could encourage earlier medical assessment of people at risk of SSc.

Very early systemic sclerosis.

The early diagnosis of systemic sclerosis (SSc) can be very difficult, when most of the typical signs and symptoms are absent. For this reason, the approach to SSc has changed during the last decades because the importance of an early diagnosis and treatment has been widely understood. "Very early SSc" is identified as a condition characterized by Raynaud's phenomenon, puffy fingers, disease-specific autoantibodies, and microvascular alterations at capillaroscopy. However, reliable biomarkers able to predict the disease evolution are missing, and decision whether to treat or not to treat in the earliest phase of the disease remains a dilemma. Presently, the only feasible clinical strategy in very early SSc remains a tight follow-up program to detect in "real time" the onset of internal organ involvement, which may thus allow an aggressive therapeutic agenda.

The usefulness of capillaroscopy for assessment of microcirculation disturbances during treatment

Capillaroscopy is a non-invasive method enabling the assessment of microcirculation in patients with Raynaud`s phenomenon. The examination has been used for early diagnosis of systemic sclerosis and diseases from the scleroderma spectrum and for assessment of systemic sclerosis activity as well as for monitoring and evaluation of the efficacy of therapy. Vasodilators applied in the treatment of vascular disorders during systemic sclerosis were demonstrated to significantly improve the capillaroscopy images, expressed as an increased number of capillaries and reduced disorganisation of vascular drawings. Forum Reumatol. 2019, tom 5, nr 2: 65–69

Nailfold capillaroscopy in systemic sclerosis - state of the art: The evolving knowledge about capillaroscopic abnormalities in systemic sclerosis.

Capillaroscopy is a unique method for morphological evaluation of the nailfold capillaries that plays a crucial role for early diagnosis of systemic sclerosis. The first description of the pathological capillaroscopic changes in systemic sclerosis was made by Brown and O'Leary in 1925. Several decades later they have been validated and accepted as a diagnostic criterion in the current 2013 EULAR/ACR classification criteria. This article summarizes the evolving knowledge about the use of nailfold capillaroscopy in systemic sclerosis. Initially, Maricq et al. suggested two major categories of capillaroscopic findings in systemic sclerosis - an 'active'and 'slow' capillaroscopic pattern. Their description and terminology suggested a correlation between capillaroscopic changes and disease activity and progression. In the later classification of Cutolo et al., three phases were defined, i.e. 'early', 'active' and 'late' that reflect the time-related evolution of the capillaroscopic changes suggesting their association with disease duration. Current knowledge about the microvascular changes in systemic sclerosis supports both associations with disease activity and disease duration. The general opinion about the association of capillaroscopic findings with clinical involvement and disease activity in systemic sclerosis is not uniform. This is supposedly because the phase changes of systemic sclerosis-related microangiopathy are almost a universal feature in scleroderma and are not specific for a certain type of an accompaning clinical manifestation. Thus, the speed of progression of microvascular alterations might be a decisive criterion, and in cases of rapid dynamics of capillaroscopic findings, it could be considered as an indicator of disease activity. Interestingly, vascular 'recovery' has been observed after treatment with immunosuppressive drugs, haematopoietic stem cell transplantation, and the endothelin receptor antagonist - bosentan. The evolving knowledge about nailfold capillaroscopy in systemic sclerosis will further spread its application from a mainly diagnostic tool to an established, reliable method for evaluation of disease activity, prognosis and therapeutic response.

Lysyl oxidase-a possible role in systemic sclerosis-associated pulmonary hypertension: a multicentre study.

Lysyl oxidase (LOX) is an extracellular enzyme that cross-links collagen fibrils. LOX was found to be increased in serum of SSc patients and was suggested to be related to skin fibrosis, yet a vascular source of LOX has been demonstrated in idiopathic pulmonary arterial hypertension (iPAH). We aimed to validate elevated LOX serum levels in SSc and to study its correlation with clinical characteristics and investigate its main source at the tissue level. A total of 86 established SSc patients were compared with 86 patients with very early diagnosis of systemic sclerosis (VEDOSS), 110 patients with primary RP (PRP) and 80 healthy controls. LOX serum levels were determined by ELISA. Five lung and 12 skin biopsies from SSc patients were stained for LOX and compared with controls. Serum levels of LOX in SSc were significantly higher than in VEDOSS, PRP and healthy controls (P < 0.001). LOX inversely correlated with the diffusing capacity of the lung for carbon monoxide diffusing capacity (DLCO) in diffuse SSc (r = -0.376, P = 0.02). Patients with moderate to severe estimated systolic PAH had higher LOX levels (P < 0.01). Lung biopsies demonstrated intense LOX staining in SSc patients with PAH that was predominantly located in the endothelium of the remodelled pulmonary vessels. Serum LOX levels are increased in established SSc and inversely correlate with the DLCO. LOX is elevated in patients with moderate to severe PAH and is located in the proliferating endothelium in lung arterioles, suggesting a possible role for LOX in SSc-associated PAH.

Position article and guidelines 2018 recommendations of the Brazilian Society of Rheumatology for the indication, interpretation and performance of nailfold capillaroscopy

Nailfold capillaroscopy (NFC) is a reproducible, simple, low-cost, and safe imaging technique used for morphological analysis of nail bed capillaries. It is considered to be extremely useful for the investigation of Raynaud’s phenomenon and for the early diagnosis of systemic sclerosis (SSc). The capillaroscopic pattern typically associated with SSc, scleroderma (“SD”) pattern, is characterized by dilated capillaries, microhemorrhages, avascular areas and/or capillary loss, and distortion of the capillary architecture. The aim of these recommendations is to provide orientation regarding the relevance of NFC, and to establish a consensus on the indications, nomenclature, the interpretation of NFC findings and the technical equipments that should be used. These recommendations were formulated based on a systematic literature review of studies included in the database MEDLINE (PubMed) without any time restriction.

Stressful life events at the onset and during the evolution of systemic sclerosis

Objective: Stressful life events, such as Childhood Adverse Events (CAE) and Recent Stressful Events (RSE) may play a role in the pathogenesis of autoimmune disorders. The present study investigated their occurrence in Systemic Sclerosis (SSc). Methods: 110 SSc patients and 110 controls were enrolled. Stressful events assessment included a semi-structured interview and the Childhood Experience of Care and Abuse Questionnaire (CECA-Q). A normative evaluation of RSE was made by means of the Paykel’s scoring of life events. The clinical status of patients with a very early diagnosis of Systemic Sclerosis (VEDOSS) during the first year after the diagnosis was evaluated in order to detect patients with a significant clinical worsening. Results: All investigated CAE were more frequently reported in SSc patients compared to controls, although with a significant difference only for the events “loss of mother” (p<0.05) and “sexual abuse” (p<0.05). SSc patients reported higher occurrence of at least one RSE (p<0.01), number of RSE (p<0.01), and stress load (mean total Paykel’s score) (p<0.01) in the year prior to the diagnosis compared to the year prior to the interview for controls. This was particularly true for severe and independent RSE (p<0.001). VEDOSS subjects who worsened during the first year after the diagnosis, compared to those who did not, reported a higher impact of severe and independent RSE in the same year (p<0.05). Conclusions: CAE may represent potential predisposing factors for SSc, while the occurrence of RSE may play a role in the onset and worsening of the disease.

Slit2/Robo4 axis may contribute to endothelial cell dysfunction and angiogenesis disturbance in systemic sclerosis

ObjectiveIn systemic sclerosis (SSc), early microvascular injury is followed by impaired angiogenesis and peripheral capillary loss. Here, we investigated the possible contribution of the neurovascular guidance molecule Slit2 and its...

Early diagnosis and management of systemic sclerosis

Systemic sclerosis (SSc) is a rare but potentially life-threatening rheumatological condition with a wide range of signs and symptoms. This article describes the GP's key role in the early diagnosis of SSc and discusses the current and emerging treatment options.

The role of nailfold capillary dropout on mortality in systemic sclerosis.

Semi-quantitative wide-field nailfold capillaroscopy (NFC) is a simple technique with proven utility in the early diagnosis of systemic sclerosis (SSc). Its role in prognosis, however, remains uncertain. To investigate the possible utility of NFC in predicting survival. Patients with SSc listed on the South Australian Scleroderma Register (SASR) with prior NFC performed at Flinders Medical Centre from 1991 to 2015 were included in this study. Baseline demographic data, diagnosis, scleroderma antibody status and mortality status were also collected for each patient. The cohort consisted of 99 patients with limited cutaneous SSc, 30 patients with diffuse cutaneous SSc and 23 with an overlap scleroderma syndrome. Fifty-six patients died during the period of study (censured end June 2015). Patients with diffuse scleroderma had significantly greater capillary dropout compared with limited and overlap scleroderma (P < 0.001). In univariate analysis, both capillary dropout scores (log-rank χ2 = 8.75, P = 0.003) and antibody status (log-rank χ2 = 13.94, P = 0.003) were associated with mortality. ANOVA showed a significant association between antibody status and capillary dropout (P < 0.001). In Cox regression, adjustment for capillary dropout attenuated the impact of autoantibody group on survival. Nailfold capillary dropout was significantly associated with mortality and the severity of dropout attenuates survival dictated by antibody status. Together these observations support the hypothesis that capillary dropout is on the causal pathway between induction of scleroderma associated autoantibodies and mortality.

Skin manifestations of patients with systemic sclerosis and their clinical significance

Objective To investigate features of skin lesions of patients with systemic sclerosis (SSc) , and to analyze the relationship of skin manifestations with clinical classification, autoantibodies and internal organ involvement. Methods Clinical data were collected from 120 patients with SSc in Department of Dermatology of Zhongshan Hospital Affiliated to Fudan University and Department of Scleroderma of Shanghai TCM-integrated Hospital between 2012 and 2014, and analyzed retrospectively. Results Among the 120 patients with SSc, 118 (98.3%) had Raynaud′s phenomenon, 116 (96.7%) had skin sclerosis, including 101 (84.2%) with sclerosis of skin over the dorsum of fingers, 90 (75%) had swollen skin, including 84 (70%) with swollen fingers, 77 (64.2%) had poikiloderma, 75 (62.5%) had thinned lip, 74 (61.7%) had telangiectasia, 63 (52.5%) had radial furrowing around the mouth, 57 (47.5%) had mask-like face, 49 (40.8%) had hyperplasia of nail cuticle, 35 (29.2%) had petechiae of the nailfolds, 25 (20.8%) had depressed fingertip, 24 (20.0%) had atrophy of the finger pulp, 24 (20.0%) had distal finger shortening, and 15 (12.5%) had fingertip ulcer. Anti-Scl-70 antibody and anti-centromere antibody (ACA) were positive in 42 (35.0%) and 31 (25.8%) patients respectively. The incidence of swollen fingers, fingertip ulcer, atrophy of the finger pulp was significantly higher in the anti-Scl-70 antibody- positive group than in the-negative group (P < 0.05) , and the incidence of sclerosis of skin over the dorsum of fingers, poikiloderma, fingertip ulcer and atrophy of the finger pulp was all significantly higher in the anti-Scl-70 antibody-positive group than in the ACA-positive group (P < 0.05) . The main internal organ involvement included interstitial lung disease (50%, 44/88) , cardiac involvement (47.8%, 55/115) , pulmonary arterial hypertension (35.7%, 41/115) , esophageal involvement (28.3%, 34/120) and kidney involvement (9.2%, 11/120) . Patients with diffuse cutaneous systemic sclerosis (dcSSc) showed significantly higher incidence of cardiac involvement and poikiloderma compared with those with limited cutaneous systemic sclerosis (lcSSc) (P < 0.01) . Swollen fingers, sclerosis of skin over the dorsum of fingers, poikiloderma, telangiectasia, lip thinning, and radial furrowing around the mouth most commonly occurred in patients with early SSc, and swollen fingers and sclerosis of skin over the dorsum of fingers were highly correlated with the occurrence of pulmonary arterial hypertension. Telangiectasia, depressed fingertip and fingertip ulcer were significantly correlated with the occurrence of interstitial lung disease, and atrophy of the finger pulp was significantly correlated with the occurrence of cardiac involvement (both P < 0.05) . Conclusions Raynaud′s phenomenon, swollen fingers, sclerosis of skin over the dorsum of fingers, poikiloderma, telangiectasia, lip thinning and radial furrowing around the mouth can be helpful for the early diagnosis of SSc. Pulmonary arterial hypertension commonly occurs in the early stage of SSc. Depressed fingertip and fingertip ulcer indicate the occurrence of interstitial lung disease, and the atrophy of the finger pulp indicates cardiac involvement. Key words: Scleroderma, systemic; Skin manifestations; Antoantibodies; Early diagnosis; Fibrosis; Internal organs

Very Early Systemic Sclerosis and Pre-systemic Sclerosis: Definition, Recognition, Clinical Relevance and Future Directions

The approach to systemic sclerosis (SSc) has changed over the years with an increasing focus on the very early diagnosis of the disease. The terminology identifying patients in the early phase of SSc has been significantly confusing in the last three decades. The purpose of this article is to analyze how the concept of "very early SSc" has evolved over the years, which is the role of an early diagnosis and how early treat patients. Several attempts have been made over time, to create more sensitive and specific classification criteria to include the largest number of SSc patients, also in the earliest phase. An algorythm for the very early diagnosis of SSc was identified, diagnostic preliminary criteria proposed, and new 2013 ACR/EULAR SSc classification criteria published, including new items and adding emphasis to the vasculopathic manifestations. True biomarkers that could predict the disease evolution are still missing. Treat or not to treat patients in the earliest phases still remain a dilemma. For the moment, the only feasible clinical strategy in very early SSc remains a tight follow up program to detect in "real time" the early internal organ involvement which may allow an aggressive therapeutic agenda.

EULAR 2017: Annual European Congress of Rheumatology, June 14–17, 2017, Madrid, Spain

EULAR 2017: Annual European Congress of Rheumatology, June 14–17, 2017, Madrid, Spain

Evidence for a Derangement of the Microvascular System in Patients with a Very Early Diagnosis of Systemic Sclerosis.

To investigate whether patients with a very early diagnosis of systemic sclerosis (VEDOSS) may already present circulating markers and in vitro signs of microvascular dysfunction. Serum samples were obtained from 55 patients with systemic sclerosis (SSc), 25 patients with VEDOSS, and 55 matched healthy controls (HC). Serum levels of pan-vascular endothelial growth factor (VEGF) and soluble neuropilin-1 (sNRP-1) were measured by ELISA. Human dermal microvascular endothelial cells (H-MVEC) were cultured and stimulated with SSc, VEDOSS, and HC sera. Protein expression of NRP-1 was analyzed by Western blotting, cell proliferation by 5'-bromodeoxyuridine assay, migration capacity by wound-healing assay, and capillary-like tube formation by Matrigel assay. Serum levels of pan-VEGF were increased in patients with VEDOSS and SSc versus HC (p = 0.05 and p = 0.003, respectively). Serum levels of sNRP-1 were significantly reduced in patients with VEDOSS and SSc compared with controls (p = 0.012 and p = 0.027, respectively). NRP-1 expression was decreased in H-MVEC stimulated with VEDOSS sera (p < 0.001 vs HC). Proliferation was reduced in H-MVEC stimulated either with VEDOSS or SSc sera in comparison with HC sera (p = 0.015 and p = 0.043, respectively). Wound healing was compromised in H-MVEC stimulated with VEDOSS and SSc sera versus HC sera (p < 0.01 for both). Capillarogenesis was decreased in H-MVEC stimulated with VEDOSS sera (p < 0.01) and SSc sera (p < 0.001) compared with cells stimulated with HC sera. Similar to patients with SSc, patients with VEDOSS already present biological signs of endothelial dysfunction. Our data demonstrate that VEDOSS sera significantly modify endothelial cell behavior and impair the angiogenic potential of the microvascular system.

Capillaroscopy in systemic sclerosis: A narrative literature review

Abstract Nailfold capillaroscopy is relatively little known tool outside the areas of rheumatology and dermatology. It is used to observe the shape, number and organization of the capillaries in the nail bed. It has not been widely used in the past, partly as it required specialized training and equipment, as well as the poor standardization of this diagnostic method. However, in recent years, thanks to renewed interest and research effort of the academic community, these problems have been able to be overcome, turning capillaroscopy into real resource for the study of microcirculation, being especially useful in differentiating primary from secondary Raynaud's phenomenon. These benefits have enabled capillaroscopy to gain importance in the rheumatology field, specifically in the early diagnosis of systemic sclerosis, a disease with significant microcirculation involvement, where the change in capillaroscopy pattern also helps to predict the onset of complications, such as digital ulcers and organ compromise.