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Systemic 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). A 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. A 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). In 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. [ABSTRACT FROM AUTHOR]

Background: Janus kinase (JAK) inhibitors constitute a novel class of oral biologic disease-modifying antirheumatic drugs for patients with rheumatoid arthritis (RA). However, their use has been associated with increased risk of major cardiovascular events. We investigated whether treatment with JAK inhibitors exerts significant alterations in the micro- and microvasculature in RA patients. Methods: Thirteen patients with RA initiating treatment with JAK inhibitors were prospectively studied. Eventually, data from 11 patients who completed the study were analyzed. Procedures were performed at baseline and 3 months after treatment. Nailfold videocapillaroscopy was applied to detect alterations of the dermal capillary network. Participants underwent 24 h ambulatory blood pressure monitoring (Mobil-O-Graph device) for the assessment of blood pressure (both brachial and aortic) and markers of large artery stiffening [pulse wave velocity (PWV), augmentation index] throughout the whole 24 h and the respective day- and nighttime periods. Carotid intima–media thickness was assessed with ultrasound. Results: Three-month treatment with JAK inhibitors was not associated with any differences in brachial and aortic blood pressure, arterial stiffness, and carotid atherosclerosis, with the only exception of nighttime PWV, which was significantly elevated at follow-up. However, three-month treatment with JAK inhibitors induced significant microvascular alterations and increased the total number of capillaroscopic abnormalities. Conclusions: Three-month treatment with JAK inhibitors may exert significant effects on microcirculation as assessed with nailfold videocapillaroscopy, whereas macrovascular structure and function appears largely unaffected. Further research toward this direction may add substantial information to the available literature regarding cardiovascular aspects of JAK inhibitors in RA. [ABSTRACT FROM AUTHOR]

Purpose: Idiopathic macular telangiectasia type 2 (IMT) is a neurodegenerative disease characterized by bilateral, idiopathic, and perifoveal retinal telangiectatic vessel formations. We aimed to compare proximal nailfold videocapillaroscopy (NV) findings between patients with IMT and healthy individuals and evaluate the optical coherence tomography angiography (OCTA) parameters of the patients with IMT according to their NV findings. Methods: The study included 43 patients with IMT and 92 healthy controls of similar age and gender without any additional diseases. The OCTA and NV findings of the patients and controls were examined. Results: The mean age was 59.76 ± 5.73 years in the IMT group and 58.23 ± 4.96 years in the control group. Of the 43 patients with IMT, 19 were found to have increased capillary tortuosity, six had microhemorrhage, and 18 had bizarre capillaries (P < 0.001). In the IMT group, the total vascular density value of the superficial capillary plexus was higher among the patients with capillary microhemorrhage (P = 0.001), and the subfoveal choroidal thickness was lower among those with increased capillary tortuosity and bizarre capillaries (P = 0.04 and P = 0.07, respectively). Conclusion: This is the first study in which the NV findings of patients with IMT were compared with those of a control group. We found higher rates of increased capillary tortuosity, microhemorrhage, and bizarre capillaries in the IMT group compared to the controls. We consider that this situation is caused by microvascular damage. We also think that IMT is a systemic disease that affects both proximal nailfold capillaries and eye vessels.

Introduction: Juvenile 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. Methods: Clinical 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. Results: Capillary 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. Conclusions: The 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. [ABSTRACT FROM AUTHOR]

Purpose: Idiopathic macular telangiectasia type 2 (IMT) is a neurodegenerative disease characterized by bilateral, idiopathic, and perifoveal retinal telangiectatic vessel formations. We aimed to compare proximal nailfold videocapillaroscopy (NV) findings between patients with IMT and healthy individuals and evaluate the optical coherence tomography angiography (OCTA) parameters of the patients with IMT according to their NV findings. Methods: The study included 43 patients with IMT and 92 healthy controls of similar age and gender without any additional diseases. The OCTA and NV findings of the patients and controls were examined. Results: The mean age was 59.76 ± 5.73 years in the IMT group and 58.23 ± 4.96 years in the control group. Of the 43 patients with IMT, 19 were found to have increased capillary tortuosity, six had microhemorrhage, and 18 had bizarre capillaries (P < 0.001). In the IMT group, the total vascular density value of the superficial capillary plexus was higher among the patients with capillary microhemorrhage (P = 0.001), and the subfoveal choroidal thickness was lower among those with increased capillary tortuosity and bizarre capillaries (P = 0.04 and P = 0.07, respectively). Conclusion: This is the first study in which the NV findings of patients with IMT were compared with those of a control group. We found higher rates of increased capillary tortuosity, microhemorrhage, and bizarre capillaries in the IMT group compared to the controls. We consider that this situation is caused by microvascular damage. We also think that IMT is a systemic disease that affects both proximal nailfold capillaries and eye vessels. [ABSTRACT FROM AUTHOR]

Purpose: Idiopathic macular telangiectasia type 2 (IMT) is a neurodegenerative disease characterized by bilateral, idiopathic, and perifoveal retinal telangiectatic vessel formations. We aimed to compare proximal nailfold videocapillaroscopy (NV) findings between patients with IMT and healthy individuals and evaluate the optical coherence tomography angiography (OCTA) parameters of the patients with IMT according to their NV findings. Methods: The study included 43 patients with IMT and 92 healthy controls of similar age and gender without any additional diseases. The OCTA and NV findings of the patients and controls were examined. Results: The mean age was 59.76 ± 5.73 years in the IMT group and 58.23 ± 4.96 years in the control group. Of the 43 patients with IMT, 19 were found to have increased capillary tortuosity, six had microhemorrhage, and 18 had bizarre capillaries (P < 0.001). In the IMT group, the total vascular density value of the superficial capillary plexus was higher among the patients with capillary microhemorrhage (P = 0.001), and the subfoveal choroidal thickness was lower among those with increased capillary tortuosity and bizarre capillaries (P = 0.04 and P = 0.07, respectively). Conclusion: This is the first study in which the NV findings of patients with IMT were compared with those of a control group. We found higher rates of increased capillary tortuosity, microhemorrhage, and bizarre capillaries in the IMT group compared to the controls. We consider that this situation is caused by microvascular damage. We also think that IMT is a systemic disease that affects both proximal nailfold capillaries and eye vessels. [ABSTRACT FROM AUTHOR]

Chiara Alfia Ferrara,1 Gaetano La Rocca,2 Giuseppe Ielo,1 Alessandro Libra,1 Gianluca Sambataro1 1Department of Clinical and Experimental Medicine, Regional Referral Centre for Rare Lung Diseases, A.O.U. “Policlinico-San Marco”, University of Catania, Catania, Italy; 2Department of Rheumatology, University of Pisa, Pisa, ItalyCorrespondence: Gianluca Sambataro, Regional Referral Center for Rare Lung Disease, University of Catania, via S. Sofia 68, Catania, 95123, Italy, Email dottorsambataro@gmail.comAbstract: Mixed Connective Tissue Disease (MCTD) is an autoimmune disease first described by Sharp et al in 1972, characterized by the presence of anti-Ribonucleoprotein antibodies directed against the U1 complex (anti-U1RNP). The condition shares clinical characteristics with Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Systemic Sclerosis. Diagnosis is quite difficult due to its rarity, the lack of validated classification criteria, and its heterogeneous clinical presentation. While in the early stages its nuanced clinical features might lead to it being incorrectly classified as other Connective Tissue Diseases (CTDs) or even not recognized, in cases of longstanding disease its classification as a CTD is clear but challenging to discriminate from overlap syndromes. MCTD should be considered a distinct entity due to the presence of a specific genetic substrate and the presence of the high titer of a specific autoantibody, anti-U1RNP, present in all the commercial kits for Extractable Nuclear Antigens, and almost always associated with Antinuclear Antibody positivity with a coarse speckled pattern. Except for anti-U1RNP, no specific biomarkers are available to guide clinicians to a correct classification of MCTD, which is arrived at by the association of clinical, serological and instrumental evaluation. In the first stages, the disease is mainly characterized by Raynaud’s phenomenon, inflammatory arthritis, puffy fingers, myalgia and/or myositis, and rarely, trigeminal neuropathy. Longstanding disease is generally associated with the development of Pulmonary Hypertension and Interstitial Lung Disease, which are the two main causes of mortality in MCTD. The aim of this review is to summarize current knowledge on the early recognition of MCTD.Keywords: mixed connective tissue disease, diagnosis, Raynaud’s phenomenon, nailfold videocapillaroscopy, anti-RNP, inflammatory arthritis

Background: Janus kinase (JAK) inhibitors constitute a novel class of oral biologic disease-modifying antirheumatic drugs for patients with rheumatoid arthritis (RA). However, their use has been associated with increased risk of major cardiovascular events. We investigated whether treatment with JAK inhibitors exerts significant alterations in the micro- and microvasculature in RA patients. Methods: Thirteen patients with RA initiating treatment with JAK inhibitors were prospectively studied. Eventually, data from 11 patients who completed the study were analyzed. Procedures were performed at baseline and 3 months after treatment. Nailfold videocapillaroscopy was applied to detect alterations of the dermal capillary network. Participants underwent 24 h ambulatory blood pressure monitoring (Mobil-O-Graph device) for the assessment of blood pressure (both brachial and aortic) and markers of large artery stiffening [pulse wave velocity (PWV), augmentation index] throughout the whole 24 h and the respective day- and nighttime periods. Carotid intima–media thickness was assessed with ultrasound. Results: Three-month treatment with JAK inhibitors was not associated with any differences in brachial and aortic blood pressure, arterial stiffness, and carotid atherosclerosis, with the only exception of nighttime PWV, which was significantly elevated at follow-up. However, three-month treatment with JAK inhibitors induced significant microvascular alterations and increased the total number of capillaroscopic abnormalities. Conclusions: Three-month treatment with JAK inhibitors may exert significant effects on microcirculation as assessed with nailfold videocapillaroscopy, whereas macrovascular structure and function appears largely unaffected. Further research toward this direction may add substantial information to the available literature regarding cardiovascular aspects of JAK inhibitors in RA.

Aim: This study seeks to evaluate the results of nailfold videocapillaroscopies (NVCs) among patients with central serous chorioretinopathy (CSC) and their correlation with the choroid and retinal parameters. Material and Methods: The examined group included 152 patients with acute, recurrent, chronic and neovascular CSC (34 F, 118 M, mean age 45.9 ± 8.9) and 41 healthy controls (12 F, 29 M, mean age 47 ± 11.5). The NVC examination, ophthalmoscopy, angio-OCT and OCT were performed. In addition, the medical history regarding chronic general disorders and known risk factors were recorded. Results: Abnormal NVC patterns and the dilated apical part of capillaries were found only in CSC patients (p = 0.000). Neoangiogenesis was observed in 25 acute (58.14%), 22 recurrent (42.31%), 16 chronic (36.36%) and 5 neovascular patients (45.45%) and 2 control subjects (4.88%) (p = 0.000). Glomerular capillaries were found in 8 acute (18.6%), 17 recurrent (31.48%), 25 chronic (56.82%) and 8 neovascular patients (72.73%) (p = 0.000). Meandering capillaries were more common in acute and recurrent CSC and glomerular capillaries were more common in chronic and aneurysmal dilations in neovascular CSC. Conclusions: The observed digital microcirculation abnormalities in patients with CSC, such as dilation, meandering, tortuosity and glomerular, may confirm systemic micro-vasculopathy. The potential role of the NVC examination in assessing the CSC prognosis requires further evaluation. [ABSTRACT FROM AUTHOR]

Nailfold videocapillaroscopic alterations have been described in COVID-19, but their correlations with biomarkers of inflammation, coagulation and endothelial perturbation are still unclear, and no information is available on nailfold histopathology. Nailfold videocapillaroscopy was performed on fifteen patients with COVID-19 in Milan, Italy and the signs of microangiopathy were correlated with plasma biomarkers of inflammation (C reactive protein [CRP], ferritin), coagulation (D-dimer, fibrinogen), endothelial perturbation (Von Willebrand factor [VWF]) and angiogenesis (vascular endothelial growth factor [VEGF]) along with genetic drivers of COVID-19 susceptibility. Histopathological analysis of autoptic nailfold excisions was performed on fifteen patients who died for COVID-19 in New Orleans, United States. All COVID-19 patients studied with videocapillaroscopy showed alterations rarely seen in healthy individuals consistent with microangiopathy, such as hemosiderin deposits (sign of microthrombosis and microhemorrhages) and enlarged loops (sign of endotheliopathy). The number of hemosiderin deposits correlated both with ferritin and CRP levels (r = 0.67, p = 0.008 for both) and the number of enlarged loops significantly correlated with the levels of VWF (r = 0.67, p = 0.006). Ferritin levels were higher in non-O groups, determined by the rs657152 C > A cluster, (median 619, min–max 551–3266 mg/dL) than in the O group (373, 44–581 mg/dL, p = 0.006). Nailfold histology revealed microvascular damage, i.e., mild perivascular lymphocyte and macrophage infiltration and microvascular ectasia in the dermal vessels of all cases, and microthrombi within vessels in five cases. Alterations in nailfold videocapillaroscopy and elevated biomarkers of endothelial perturbation that match histopathologic findings open new perspectives in the possibility of non-invasively demonstrating microangiopathy in COVID-19. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the nailfold videocapillaroscopic examination results from patients with pseudoexfoliative glaucoma (XFG) and to assess the relationship between the results of this examination and the patient's clinical status in the XFG group. Material and Methods: The studied group consisted of 39 Caucasian patients with XFG and 32 patients in a control group. The patients were classified into two subgroups: the hypertensive pseudoexfoliative glaucoma (hXFG) subgroup and the normotensive pseudoexfoliative glaucoma (nXFG) subgroup. The nailfold videocapillaroscopy (NVC) was performed on all participants. The results of each NVC were classified as having a normal or abnormal pattern. Results: There was no statistical difference between the results of an abnormal NVC pattern in the study group vs. the control group (p = 0.8773). Microhemorrhages were shown in 30.0% of patients with nXFG vs. the control group (6.25%) (p = 0.0520). Microhemorrhages tended to be more frequent in the XFG group (p = 0.1221). A prevalent number of tortuous capillaries was observed in hXFG patients with advanced glaucomatous neuropathy. Dilatation in the capillaries and microbleedings were observed in the group of patients with lower IOP values. Tortuosity in the capillaries was significantly more frequent in PEXG patients (XFG vs. control: p = 0.0386). No relationships between the results of NVC and age, c/d, BCVA, time of treatment, and visual field defect were found. Conclusions: Specific features of NVC examination differentiate nXFG from hXFG patients. Some capillaroscopic features may correlate with the patient's clinical status of XFG. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to evaluate nailfold videocapillaroscopy (NVC) as a useful tool for assessing the disease activity of ANCA-associated vasculitis (AAV). Methods This study enrolled 51 patients with AAV and 21 healthy controls. We scored NVC findings semiquantitatively, and compared them between AAV patients and controls. We examined the association of NVC findings with disease activity indicators, histopathological findings of skin biopsies, and high-resolution CT (HRCT) scores in AAV. Additionally, we repeatedly rated the NVC findings 3 months after immunosuppressive therapy. Results Of the 51 enrolled patients, 36 (70.6%) showed a microangiopathy pattern and 4 (7.8%) showed a scleroderma pattern in AAV. The scores for microhaemorrhage, capillary loss, neoangiogenesis, and tortuosity were significantly higher in the AAV group than in the control group. NVC abnormalities correlated with the severity of skin, lung and kidney involvement. The scores of giant capillaries significantly correlated with the total BVAS and the chest BVAS; the scores of capillary loss correlated with the chest BVAS and the renal BVAS. The scores of microhaemorrhage significantly correlated with perivascular inflammatory cell infiltrations in the upper dermis of the purpura and tended to correlate with the total ground-glass opacity and consolidation scores on HRCT. In addition, capillary loss scores had a significant positive correlation with serum creatinine levels. Additionally, the microhaemorrhage scores were significantly reduced after 3 months of immunosuppressive therapy. Conclusion In AAV patients, NVC abnormalities are significantly associated with disease severity. This result suggests that NVC is a useful tool for assessing the disease activity and treatment response in AAV. [ABSTRACT FROM AUTHOR]

Objective MCTD manifests with microvasculopathy and overlapping clinical features of SLE, SSc and idiopathic inflammatory myopathies (IIM). The aim of this study was to investigate the clinical significance of microvasculopathy in patients with MCTD using nailfold videocapillaroscopy (NVC). Methods Fifty patients with newly diagnosed and untreated MCTD were enrolled in this multicentre, prospective and observational study. Clinical features and NVC findings were assessed at baseline and after 1 year post-intervention, along with disease controls [SLE (n  = 40), SSc (n  = 70) and IIM (n  = 50)]. Results All MCTD patients presented Raynaud's phenomenon and were positive for anti-U1 RNP antibodies, and 22.0% (11/50) had pulmonary arterial hypertension (PAH). The prevalence of NVC scleroderma patterns in MCTD was 38.0%, which was lower than SSc (88.6%) but higher than SLE (10.0%). In addition, when we divided MCTD patients into two groups by presence or absence of NVC scleroderma patterns, we found a higher prevalence of PAH in patients with NVC scleroderma patterns. Namely, NVC scleroderma patterns were observed in all MCTD patients with PAH, and in 21.0% of those without PAH. After intensive immunosuppressive therapy, NVC scleroderma patterns disappeared in half of the MCTD patients but were not changed in SSc patients. Conclusions MCTD differed from SLE, SSc and IIM in terms of the prevalence and responsiveness of NVC scleroderma patterns to immunosuppressive therapy. Detection of nailfold microvascular abnormalities in MCTD could contribute to predicting PAH and help us to understand further aspects of the pathogenesis of MCTD. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives: Diabetic nephropathy is a microvascular complication of diabetes and the most common cause of end-stage renal failure throughout the world. Videocapillaroscopy is a simple and noninvasive method that can display capillaries in the nail bed at the micron level. A few studies have been conducted on detecting retinopathy, another important diabetic microvascular complication, with videocapillaroscopy; however, no comprehensive study has been performed on diabetic nephropathy. We aimed to determine the relationship between nephropathy and capillaroscopic changes. Subjects and methods: Capillaroscopic findings of 144 patients with type 2 diabetes and 88 healthy controls were assessed prospectively by nailfold videocapillaroscopy. Twelve capillaroscopic findings were evaluated in all subjects. Results: Patients with albuminuria had more capillary aneurysms (15.5%), more microhemorrhages (15.5%), greater tortuosity (76.3%), more neoformations (29.9%), more bizarre capillaries (49.5%) and more bushy capillaries (20.6%) than the control group. In logistic regression analysis, tortuosity was significantly correlated with albuminuria (OR: 2.451, p = 0.048). Conclusions: Our findings show that the application of nailfold videocapillaroscopy can detect microvascular abnormalities in the nail bed that occur in diabetes mellitus patients compared to healthy people. Although there was no difference in the microvascular changes among the stages of diabetic nephropathy, a relationship between tortuosity and albuminuria was identified by logistic regression analysis. Nailfold videocapillaroscopy may be a new application that can be used to screen the microvascular changes that occur in diabetes mellitus.

Systemic sclerosis (SSc) is a complex autoimmune connective-tissue disease, characterised by vasculopathy and fibrosis of the skin and internal organs. Activation of microvascular endothelial cells (ECs) causes the intimal hyperplasia that characterises the vascular remodelling in SSc. The most frequent complication of SSc is the development of digital ulcers (DUs). Thymic stromal lymphopoietin (TSLP) may trigger fibrosis and sustain vascular damage. Aim of this study was to evaluate the correlation between serum level of TSLP and DUs. 75 consecutive SSc patients were enrolled and serum TSLP levels were measured. The presence of history of DUs (HDU) was evaluated. Recurrent new DUs were defined as the presence of at least 3 episodes of DUs in a 12-months follow up period. The risk of developing new DUs was calculated by applying the capillaroscopic skin ulcer risk index (CSURI). The median value of TSLP was higher in patients with HDU than patients without HDU [181.67 pg/ml (IQR 144.67; 265.66) vs 154.67 pg/ml (IQR 110.67; 171.33), p < 0.01]. The median value of TSLP was higher in patients with an increased CSURI index than patients without an increased CSURI [188 pg/ml (IQR 171.33; 246.33) vs 159.33 pg/ml (IQR 128.67; 218), p < 0.01]. Kaplan-Meier curves demonstrated that free survival from new DUs was significantly (p < 0.01) lower in SSc patients with increased TSLP serum levels. TSLP might have a key role in digital microvascular damage of SSc patients. • SSc patients with history of DUs have higher serum level of TSLP. • TSLP is higher in SSc patient with recurrent new DUs. • TSLP is higher in SSc patient with CSURI≥2.96. • Free survival from new DUs is significantly lower in SSc patients with increased TSLP. [ABSTRACT FROM AUTHOR]

ObjectivesTo assess performance of interstitial pneumonia (IP) with autoimmune features (IPAF) criteria in clinical practice and describe the utility of additional workup in identifying patients with underlying connective tissue diseases (CTD).MethodsWe set a retrospective study of our patients with autoimmune IP, who were allocated to CTD-IP, IPAF or undifferentiated autoimmune IP (uAIP) subgroups according to the updated classification criteria. Presence of the process-related variables comprising IPAF defining domains was scrutinized in all patients, and, when available, the results of nailfold videocapillaroscopy (NVC) were recorded.ResultsThirty nine out of 118 patients, accounting for 71% of former undifferentiated cases, fulfilled IPAF criteria. Arthritis and Raynaud’s phenomenon were prevalent in this subgroup. While systemic sclerosis-specific autoantibodies were restricted to CTD-IP patients, anti-tRNA synthetase antibodies were also present in IPAF. In contrast, rheumatoid factor, anti-Ro antibodies and ANA nucleolar patterns could be found in all subgroups. Usual interstitial pneumonia (UIP) / possible UIP were the most frequently observed radiographic patterns Therefore, the presence of thoracic multicompartimental findings as also performance of open lung biopsies were useful in characterizing as IPAF those UIP cases lacking a clinical domain. Interestingly, we could observe NVC abnormalities in 54% of IPAF and 36% of uAIP tested patients, even though many of them did not report Raynaud’s phenomenon.ConclusionBesides application of IPAF criteria, distribution of IPAF defining variables along with NVC exams help identify more homogeneous phenotypic subgroups of autoimmune IP of potential relevance beyond clinical diagnosis.

The microcirculation is composed of blood vessels with mean internal diameter smaller than 100 μm. This structure is responsible for survival of cells and in the last 50 years its study has become increasingly interesting because it often participates in the pathophysiology of several diseases or can determine better or worse prognosis for them. Due to the growing importance of knowing more about the microcirculation, several techniques have been developed and now it is possible to study its structure or function. In the last 25 years, the cutaneous microcirculation has emerged as an accessible and representative portion of generalized vascular bed allowing the examination of mechanisms of microcirculatory function and dysfunction. This mini review presents several techniques used for non-invasive access to skin microcirculation, such as Nailfold Videocapillaroscopy, Orthogonal Polarization Spectral Imaging, Sidestream Dark Field Imaging, Incident Dark field Illumination, Laser Doppler Flowmetry, and Laser Speckle Contrast Imaging applied. The techniques presented will describe which types of variables (structural or functional) can be evaluated, their limitations and potential uses.

Objectives Nailfold videocapillaroscopy (NVC) plays a well-established role in differentiating primary from secondary RP due to SSc. However, the association of NVC with novel severe organ involvement/progression in SSc has never been evaluated in a multicentre, multinational study, which we now perform for the first time. Methods Follow-up data from 334 SSc patients [265 women; 18 limited SSc (lSSc)/203 lcSSc/113 dcSSc] registered between November 2008 and January 2016 by seven tertiary centres in the EUSTAR-database, were analysed. Novel severe organ involvement/progression was defined as new/progressive involvement of the peripheral vasculature, lungs, heart, skin, gastrointestinal tract, kidneys, musculoskeletal system, or death, at the 12- or 24-month follow-up. NVC images at enrolment were quantitatively and qualitatively evaluated according to the standardized definitions of the EULAR Study Group on Microcirculation in Rheumatic Diseases. Uni- and multivariable logistic regression modelling (ULR, MLR) was performed. Results Of the 334 included SSc patients, 257 (76.9%) developed novel overall severe organ involvement/progression. Following MLR, normal capillary density was associated with less-frequent novel overall severe organ involvement/progression [odds ratio (OR) = 0.77, P  < 0.001] and novel peripheral vascular involvement (OR = 0.79, P   =  0.043); microhaemorrhages were associated with less novel pulmonary hypertension (OR = 0.47, P   =  0.029); and a 'severe' (active/late) NVC pattern was associated with novel overall severe organ involvement/progression (OR = 2.14, P   =  0.002) and skin progression (OR = 1.70, P   =  0.049). Conclusions Our results suggest that NVC may be a promising biomarker in SSc, certainly warranting further investigation. Despite the participation of tertiary centres, which follow their patients in a standardized way, we were underpowered to detect associations with infrequent severe organ involvement/progression. [ABSTRACT FROM AUTHOR]

Introduction: Newly developed Doppler techniques enable the sampling of slow vascular flows and the extrapolation of spectral parameters in distal arterioles. The aim of this study was to investigate the role of spectral analysis performed by means of ultra‐high frequency ultrasound (US) in the evaluation of the peripheral vascular bed of systemic sclerosis (SSc) patients. Methods: Both hands of 33 patients affected by diffuse cutaneous SSc and 34 volunteers were evaluated with a US machine equipped with 33‐9 MHz and 18‐5 MHz transducers. Proximal resistive index and the peak systolic velocity (pRI and pPSV, respectively), were calculated at the level of the second interdigital artery. The distal resistive index (dRI) was calculated at the level of a nailfold arteriole of the third finger. All SSc patients had been previously divided into 4 subgroups according to their nailfold videocapillaroscopic (NVC) patterns following accepted criteria. Results: SSc patients showed a significantly slower systolic velocity at the level of the second interdigital artery (pPSV [SD] = 8.38 [3] cm/s vs pPSV [SD] = 11.14 [4.5] cm/s; P =.005) and a higher dRI (dRI [SD] = 0.65 (0.14) vs dRI [SD] = 0.57 [0.11); P =.0115). No differences were found between the pRI values measured in the SSc patients and those of the controls (pRI [SD] = 0.76 [0.11] vs pRI [SD] = 0.73 [0.12]; P =.359]. The subgroup analysis did not show any significant difference when pPSV, pRI and dRI were compared among NVC morphological patterns. Conclusion: High‐resolution Doppler analysis of digital distal arterioles may disclose subtle abnormalities in the downstream microvasculature of SSc patients that could be missed when the examination is performed at a more proximal level and/or using lower Doppler frequencies. [ABSTRACT FROM AUTHOR]

Background: Systemic sclerosis (SSc) is a complex connective tissue disease characterized by microangiopathy, immune dysregulation, and fibrosis. Early detection of microvascular abnormalities using nailfold videocapillaroscopy (NVC) is crucial in assessing disease progression and associated disease's involvement such as interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH)., Objective: This study aims to explore the relationships correlation between NVC patterns, clinical manifestations, and systemic complications in SSc., Methods: We analyzed the data of 63 patients, predominantly female (95%), with a mean age of 49 years and an average disease duration of 42 months. Patients were categorized into early, active, and late patterns based on NVC findings. Clinical features, including digital ulcers (DU), ILD, and PAH, were assessed. Pearson correlation analyses were performed to evaluate the relationships between capillary loss, neoangiogenesis, ILD, and PAH., Results: The early pattern group (mean mRSS 2.36) exhibited minimal microvascular damage and systemic involvement, with no DUs. In the active pattern group (mean mRSS 10.40), 34.38% had diffuse cutaneous SSc (dcSSc), with 15.63% presenting DUs, 65.63% ILD, and 37.5% PAH. The late pattern group (mean mRSS 18.00) showed the most severe disease, with 80% having DUs, 70% dcSSc, 90% ILD, and 70% PAH. Pearson correlation analyses revealed strong correlations between capillary loss and ILD (r = 0.7255) and PAH (r = 0.6369). A moderate correlation was found between neoangiogenesis and PAH (r = 0.5592)., Conclusion: The study demonstrates that progressive microvascular damage in SSc, as visualized by NVC, correlates strongly with the severity of systemic complications. Early detection of capillary loss and neoangiogenesis using NVC is critical for timely interventions, which could improve patient outcomes by mitigating the progression of ILD and PAH., (© 2024 Camelia Palici et al., published by Sciendo.)

Rheumatoid arthritis (RA) is a chronic and refractory autoimmune joint disease that affects multiple organs. Several methods have been applied for the study of microvascular endothelial dysfunction, which is considered an important component of vascular disease in RA. Implementation of nailfold videocapillaroscopy (NVC) represents a viable choice, as the skin is an easily accessible window for the non-invasive, real-time assessment of subtle microcirculation abnormalities. Although NVC is routinely used in the rheumatology field, especially for the diagnostic workout of Raynaud's phenomenon, accumulating evidence suggests a role in the evaluation of systemic vasculopathy associated with autoimmune rheumatic disorders. The current paper aims to provide an overview of NVC as a valuable clinical aid for the assessment of peripheral microcirculation in RA. Previous studies characterizing the capillaroscopic pattern in RA are summarized, along with associations with disease-related characteristics. Most available reports have mainly focused on the descriptions of non-specific morphological alterations that may reflect endothelial injury over the course of the disease. Still, the exact pattern of structural and functional capillaroscopic alterations and their clinical significance in RA remains a subject of ongoing research. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc, scleroderma) is a complex connective tissue disease whose earliest clinical manifestations are microvascular tone dysregulation and peripheral microcirculatory abnormalities. Following previous evidence of an association between circulating neurovascular guidance molecules and SSc disturbed angiogenesis, here, we measured the levels of soluble neuropilin 1 (sNRP1), semaphorin 3E (Sema3E), and Slit2 by enzyme-linked immunosorbent assay in serum samples from a large case series of 166 SSc patients vs. 110 healthy controls. We focused on their possible correlation with vascular disease clinical features and applied logistic regression analysis to determine which of them could better reflect disease activity and severity. Our results demonstrate that, in SSc: (i) sNRP1 is significantly decreased, with lower sNRP1 serum levels correlating with the severity of nailfold videocapillaroscopy (NVC) abnormalities and the presence of ischemic digital ulcers (DUs); (ii) both Sema3E and Slit2 are increased, with Sema3E better reflecting early NVC abnormalities; and (iii) higher Sema3E correlates with the absence of DUs, while augmented Slit2 associates with the presence of DUs. Receiver operator characteristics curve analysis revealed that both circulating sNRP1 and Sema3E show a moderate diagnostic accuracy. Moreover, logistic regression analysis allowed to identify sNRP1 and Sema3E as more suitable independent biomarkers reflecting the activity and severity of SSc-related peripheral microvasculopathy. [ABSTRACT FROM AUTHOR]

Objectives 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). Methods 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. Results 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. Conclusion 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. [ABSTRACT FROM AUTHOR]

Nailfold Videocapillaroscopy (NVC) is a valuable tool in the differential diagnosis of Raynaud's phenomenon (RP), present in certain Rheumatic diseases (RD). Knowing that many people have cardiovascular risk factors (CVRF), the main objective was to demonstrate that CVRF and carotid plaques produce NVC alterations. Cross-sectional unicentric study carried out from 2020 to 2023. Four groups were formed: subjects with RD and RP, participants with RD without RP, subjects with RP without RD and finally participants without RP or RD (study group). Each subject exhibiting CVRF presented only a single risk factor. The variables collected were: sociodemographic, CVRF (diabetes, tobacco, alcohol (ALC), obesity (OBE), dyslipidemia and arterial hypertension (AH)), diseases, RP, treatments, tortuosities and NVC alterations (ramified capillaries, enlarged capillaries, giant capillaries, haemorrhages and density loss) and carotid ultrasound (CU). 402 subjects were included (76 % women, mean age 51 ± 16 years), 67 % had CVRF, 50 % RP and 38 % RD. Tortuosities were present in 100 % of CVRF participants. A statistically significant association was found between the presence of CVRF and all the NVC alterations: ramified capillaries (OR = 95.6), enlarged capillaries (OR = 59.2), giant capillaries (OR = 8.32), haemorrhages (OR = 17.6) and density loss (OR = 14.4). In particular, an association was found between giant capillaries with AH (p = 0,008) and OBE (p 〈0,001), and haemorrhages and density loss with ALC and OBE (p < 0,001). On the other hand, 40 subjects presented CU plaques (9.9 %), associated with enlarged capillaries (OR = 8.08), haemorrhages (OR = 4.04) and ramified capillaries (OR = 3.01). The pathological intima-media thickness was also associated with haemorrhages (OR = 3.14). There is a clear association between CVRF and ultrasound atherosclerotic findings in carotid with NVC alterations. These findings are of special interest for a correct NVC interpretation and to avoid false positives in the diagnosis of primary and secondary RP. • There is a clear association between capillaroscopy's alterations and cardiovascular risk factors. • Special interest to avoid false positives in the diagnosis of Rheumatic diseases related with Raynaud's phenomenon. • Tortuosities, ramified and enlarged capillaries are associated with all the cardiovascular risk factors. • Haemorrhages, giant capillaries and loss of density are more associated with alcohol abuse and obesity. • First study relating capillaroscopy with carotid ultrasound findings in subjects with all the cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the nailfold videocapillaroscopic examination results from patients with pseudoexfoliative glaucoma (XFG) and to assess the relationship between the results of this examination and the patient’s clinical status in the XFG group. Material and Methods: The studied group consisted of 39 Caucasian patients with XFG and 32 patients in a control group. The patients were classified into two subgroups: the hypertensive pseudoexfoliative glaucoma (hXFG) subgroup and the normotensive pseudoexfoliative glaucoma (nXFG) subgroup. The nailfold videocapillaroscopy (NVC) was performed on all participants. The results of each NVC were classified as having a normal or abnormal pattern. Results: There was no statistical difference between the results of an abnormal NVC pattern in the study group vs. the control group (p = 0.8773). Microhemorrhages were shown in 30.0% of patients with nXFG vs. the control group (6.25%) (p = 0.0520). Microhemorrhages tended to be more frequent in the XFG group (p = 0.1221). A prevalent number of tortuous capillaries was observed in hXFG patients with advanced glaucomatous neuropathy. Dilatation in the capillaries and microbleedings were observed in the group of patients with lower IOP values. Tortuosity in the capillaries was significantly more frequent in PEXG patients (XFG vs. control: p = 0.0386). No relationships between the results of NVC and age, c/d, BCVA, time of treatment, and visual field defect were found. Conclusions: Specific features of NVC examination differentiate nXFG from hXFG patients. Some capillaroscopic features may correlate with the patient’s clinical status of XFG.

BACKGROUND: In patients with ischemia and no obstructive coronary artery disease (INOCA), coronary microvascular dysfunction is associated with higher rate of major adverse cardiovascular events. OBJECTIVE: To demonstrate if microvascular dysfunction present in coronary microcirculation of patients with INOCA may be detected noninvasively in their peripheral circulation. METHODS: 25 patients with INOCA and 25 apparently healthy individuals (controls) were subjected to nailfold videocapillaroscopy (NVC) and venous occlusion plethysmography (VOP) to evaluate peripheral microvascular function and blood collection for biomarkers analysis, including soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelin-1 (ET-1) and C-reactive protein (CRP). RESULTS: Red blood cell velocity (RBCV) before and after ischemia (RBCVmax) were significantly lower in patients with INOCA (p = 0.0001). Time to reach maximal red blood cell velocity (TRBCVmax) was significantly longer in INOCA group (p = 0.0004). Concerning VOP, maximal blood flow (p = 0.004) and its relative increment were significantly lower in patients with INOCA (p = 0.0004). RBCVmax showed significant correlations with sVCAM-1 (r = –0.38, p < 0.05), ET-1 (r = –0.73, p < 0.05) and CRP (r = –0.33, p < 0.05). Relative increment of maximal post-ischemic blood flow was significantly correlated with sVCAM-1 (r = –0.42, p < 0.05) and ET-1 (r = –0.48, p < 0.05). CONCLUSIONS: The impairment of microvascular function present in coronary microcirculation of patients with INOCA can be also detected in peripheral microcirculation. [ABSTRACT FROM AUTHOR]

Abstract Background Nailfold videocapillaroscopy (NVC) is a feasible method that allows the observation of the microvascular changes that mark the course of systemic sclerosis (SSc). In previous studies, we demonstrated that the NEMO score, i.e. the cumulative number of microhaemorrhages and microthromboses, is a good indicator of the steady-state level and overtime changes of disease activity (DA) in SSc. Objectives To verify whether high NEMO scores, which mirror a very active microvascular derangement in the fingers, may be associated with the subsequent development of ischaemic digital ulcers (IDUs). Methods The NEMO score was assessed at baseline (T0) in 98 patients with SSc, all classified according to the ACR-EULAR criteria. Of them, 90 were females, 48 had the limited and 50 had the diffuse cutaneous variant of SSc. Afterwards, the patients were closely followed up for 2 years, and the appearance of new IDUs recorded at any time of the follow-up. The T0-NEMO score values of patients who developed IDUs were compared to those of patients who did not. A receiver operating curve (ROC) was constructed, and the area under the curve (AUC) calculated by plotting the sensitivity and 1-specificity of the different NEMO score values in predicting the subsequent development of IDUs. Results During the follow-up, 38 out of 98 patients developed one or more IDUs. The NEMO score at T0 was significantly higher in those who developed IDUs with respect to those who did not [median 14.5 (95% CI 11.0–21.5) and 4.5 (95% CI 4.0–6.0), respectively, p

Buerger's disease is characterized by peripheral ischemia due to occlusion of small- and medium-sized arteries in the extremities. This report describes a case of Buerger's disease in a 51-year-old male who presented with findings resembling systemic sclerosis. The patient exhibited Raynaud's phenomenon in year X-3, which developed to skin hardening, nail avulsion, and ulceration of the right fingers in year X. Diagnostic testing showed positive microvasculopathy on nailfold videocapillaroscopy (NVC) and positive fibrosis on skin biopsy. Although the patient fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for systemic sclerosis, several findings in this case were atypical for systemic sclerosis, including left-right asymmetry in finger involvement, nail loss, and negative autoantibody tests. Contrast-enhanced computed tomography showed poor perfusion of the right ulnar artery, and a heavy smoking history was established in the patient case. Therefore, based on Shionoya's criteria, he was diagnosed with a case of Buerger's disease confined to the upper extremity. Smoking cessation and vasodilator therapy resulted in the prompt resolution of ischemic symptoms, skin hardening, and ulcerations. Furthermore, NVC abnormalities improved, and ulnar artery occlusion showed reperfusion on repeat testing. The present case suggests that hypoxemia-driven microvasculopathy may contribute to vascular occlusion and skin fibrosis observed in this atypical presentation., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Pulmonary arterial hypertension (PAH) represents one of the most devastating complications in connective tissue diseases (CTDs). The aim of this study was to investigate the presence of peripheral microangiopathy in patients with PAH associated with CTDs (CTD-PAH) by exploring nailfold videocapillaroscopic (NVC) changes and identify possible associations of NVC characteristics with markers of disease severity. Α cross-sectional study was performed in 18 CTD-PAH patients [13 PAH due to systemic sclerosis (SSc-PAH) and 5 with other types of CTD-PAH], 14 patients with SSc without PAH (SSc-non-PAH) and 20 healthy controls. NVC quantitative and qualitative parameters were evaluated using Optilia Digital Capillaroscope. To ensure inter-observer repeatability, capillaroscopic images were reviewed by two independent investigators. When compared to healthy controls, patients with CTD-PAH (77.8% women, mean age 65.9 years) presented reduced capillary density (6.5 ± 1.6 loops/mm vs. 9.7 ± 0.7 loops/mm, p < 0.001) and increased capillary loop width (23.3 ± 10.1 μm vs. 11.2 ± 2.5 μm, p < 0.001). SSc-PAH patients presented lower capillary density in comparison with other CTD-PAH patients and SSc-non-PAH subjects and abnormal and disorganized capillaries compared to controls. Patients with other CTD-PAH had also reduced capillary density and increased loop diameter compared to controls. A significant linear correlation was identified between capillary density and estimated glomerular filtration rate in the total CTD-PAH population (r = 0.63, p = 0.007). In SSc-PAH group, capillary loop diameter was positively correlated to cardiac index (r = 0.61, p = 0.02). Significant NVC microvascular changes were detected in patients with various types of CTD-PAH, suggesting an impaired peripheral microcirculation parallel to pulmonary vasculopathy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Background In previous studies, we demonstrated that the NEMO score, i.e. the cumulative number of microhaemorrhages (MHEs) and microthromboses (MTs), observed in nailfold videocapillaroscopy was a good indicator of the steady state level of disease activity (DA) in patients with systemic sclerosis (SSc) when the European Scleroderma Study Group (EScSG) index was considered the gold standard. Aim of the study To verify whether the NEMO score could be (i) a valid tool to assess DA, even when the modified European Scleroderma Trials and Research (EUSTAR) index was considered to be the comparator, and (ii) a sensitive method to capture the DA overtime changes. Patients and methods The NEMO score and the EScSG and EUSTAR indices were contemporarily assessed at baseline (T0) and after a follow-up of 4–56 months (T1) in 98 patients with SSc. The differences (Δ) between the T1 and T0 values of the NEMO score and the EScSG and EUSTAR indices were calculated and compared to each other. Results NEMO score values were very closely correlated with the corresponding values of the EScSG and EUSTAR indices both at T0 and T1 observations (p

Rheumatoid arthritis (RA) is a chronic and refractory autoimmune joint disease that affects multiple organs. Several methods have been applied for the study of microvascular endothelial dysfunction, which is considered an important component of vascular disease in RA. Implementation of nailfold videocapillaroscopy (NVC) represents a viable choice, as the skin is an easily accessible window for the non-invasive, real-time assessment of subtle microcirculation abnormalities. Although NVC is routinely used in the rheumatology field, especially for the diagnostic workout of Raynaud’s phenomenon, accumulating evidence suggests a role in the evaluation of systemic vasculopathy associated with autoimmune rheumatic disorders. The current paper aims to provide an overview of NVC as a valuable clinical aid for the assessment of peripheral microcirculation in RA. Previous studies characterizing the capillaroscopic pattern in RA are summarized, along with associations with disease-related characteristics. Most available reports have mainly focused on the descriptions of non-specific morphological alterations that may reflect endothelial injury over the course of the disease. Still, the exact pattern of structural and functional capillaroscopic alterations and their clinical significance in RA remains a subject of ongoing research.

Abstract Background To determine whether lung involvement is related to microvascular perturbations, nailfold videocapillaroscopy (NVC) was performed in patients with systemic sclerosis (SSc). Methods A cross-sectional study was consecutively accomplished in 152 SSc patients. NVC, a pulmonary function test and echocardiography were undergone within a 3-month period. Finally, 134 patients with at least eight NVC (200× magnification) images were selected for quantitative and qualitative examinations. Results Patients with interstitial lung disease presented lower median capillary density (4.86/mm vs 5.88/mm, p = 0.005) and higher median of neoangiogenesis (0.56/mm vs 0.31/mm, p = 0.005). A higher quantity of neoangiogenesis capillaries was found in patients with pulmonary arterial hypertension (0.70/mm vs 0.33/mm, p = 0.008). Multivariate linear regression analysis established a correlation between neoangiogenesis and decreased forced vital capacity (FVC) (p

BACKGROUND: Microvascular dysfunction is one of the pathophysiological mechanisms in heart failure. Nailfold videocapillaroscopy is a noninvasive technique used to examine the microvasculature. OBJECTIVE: In this study, we aimed to investigate the nailfold capillaroscopic abnormalities in heart failure patients with reduced and preserved ejection fraction and compare those with control group. METHODS: Three groups of patients were recruited for the study: HFrEF group includes the patients with heart failure with reduced ejection fraction (HFrEF), HFpEF group, patients with heart failure with preserved ejection fraction (HFpEF) and control group, healthy asymptomatic individuals. Nailfold videocapillaroscopy was performed with a videodermatoscope and all nailfold images were evaluated for enlargement and hemorrhages. RESULTS: Abnormal videocapillaroscopic findings including enlargement and/or hemorrhages were present in 7 (24%) patients in HFrEF group, 19 (66%) patients in HFpEF group and 11 (37%) in control group. The number of patients with abnormal videocapillaroscopic findings were significantly greater in HFpEF group compared to HFrEF (p < 0.05) and control groups (p < 0.05). However, no significant difference was observed in videocapillaroscopic findings between HFrEF and control groups. CONCLUSIONS: Our study showed that microvascular abnormalities demonstrated by videodermatoscopic examination of nailfold capillaries are considerably more common in HFpEF patients compared to HFrEF and control groups. [ABSTRACT FROM AUTHOR]

Nailfold video-capillaroscopy (NVC) is a useful diagnostic tool, used to early detect abnormalities in micro-circulation, providing a qualitative description of microvascular anomalies in Raynaud's phenomenon. NVC role in the diagnosis of Systemic Sclerosis is well known. In other rheumatic conditions such as connective tissue diseases, vasculitis, and arthritis, the NVC anomalies are often included in a scleroderma like pattern. The use of NVC in non-rheumatic diseases (NRD), with remarkable microvascular damage, as diabetes, is not standardized yet, although several research studies are carrying on. The aim of this article is to provide a resume of published results in order to lay the groundwork for the employment of NVC both in the diagnosis and follow up of microvascular complication in NRD. Furthermore, we mention NVC findings in pathologies without well recognize microvascular damages in their pathogenesis: micro-vessels abnormalities may suggest a different point of view. [ABSTRACT FROM AUTHOR]

Objectives: The European Alliance of Associations for Rheumatology (EULAR) supports the use of nailfold videocapillaroscopy (NVC) to identify disease patterns (DPs) associated with systemic sclerosis (SSc) and Raynaud's phenomenon (RP). Recently, EULAR proposed an easy-to-manage procedure, a so-called Fast Track algorithm, to differentiate SSc from non-SSc patterns in NVC specimens. However, subjectivity among capillaroscopists remains a limitation. Our aim was to perform a software-based analysis of NVC peculiarities in a cohort of samples from SSc and RP patients and, subsequently, build a Fast Track-inspired algorithm to identify DPs without the constraint of interobserver variability., Methods: NVCs were examined by 9 capillaroscopists. Those NVCs whose DPs were consensually agreed (≥2 out of 3 interobservers) were subsequently analysed with an in-house developed software. Each variable's results were grouped according to the consensually agreed DPs in order to identify useful hallmarks to categorise them., Results: Eight-hundred and fifty-one NVCs (21 957 images) whose DPs had been consensually agreed were software-analysed. Appropriate cut-offs set in capillary density and percentage of abnormal and giant capillaries, tortuosities and hemorrhages allowed DP categorization and the development of the CAPI-Score algorithm. This consisted of 4 rules: Rule 1, SSc vs non-SSc, accuracy 0.88; Rules 2 and 3, SSc-early vs SSc-active vs SSc-late, accuracy 0.82; Rule 4, non-SSc normal vs non-SSc non-specific, accuracy 0.73. Accuracy improved when the analysis was limited to NVCs whose DPs had achieved full consensus among interobservers., Conclusions: The CAPI-Score algorithm may become a useful tool to assign DPs by overcoming the limitations of subjectivity., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Systemic sclerosis (SSc) is a connective tissue disease, characterized by vascular damage and progressive fibrosis, affecting the skin and internal organs. The vascular changes include functional and structural abnormalities in the microcirculation, which play a central role not only in diagnosis but also in the prognosis and follow‐up of systemic sclerosis patients. Nailfold videocapillaroscopy (NVC) is a safe, validated, noninvasive, inexpensive, reliable, and reproducible method that allows for the evaluation of structural changes in scleroderma microangiopathy. However, capillary blood flow/perfusion cannot be measured by NVC under standard conditions and, consequently, must rely on various laser techniques and thermography for the assessment and quantification of cutaneous blood perfusion. Other emerging technologies, such as optical Doppler tomography and spectroscopy, may be used to evaluate the skin flow. This review updates current knowledge on the use of microvascular evaluation techniques in SSc, including complications such as digital ulcers and pulmonary arterial hypertension. [ABSTRACT FROM AUTHOR]

Objectives Urinary tract involvement is a seldom-reported manifestation of SSc that could compromise patients' quality of life. This study compares lower urinary tract symptoms (LUTS) in SSc patients and in healthy subjects and their association with clinical and diagnostic parameters. Methods LUTS were assessed through self-reported questionnaires in 42 SSc patients and 50 matched healthy subjects. Statistical analyses were performed to explore LUTS in the two populations and their association with SSc variables, including nailfold videocapillaroscopy patterns, SSc-related antibodies and DXA parameters. Results SSc patients showed significantly higher prevalence and severity of urinary incontinence (UI) and overactive bladder (OAB) than healthy controls (P < 0.005, P < 0.01). SSc was a strong predictor of LUTS, independent of demographic data, comorbidities and treatments (odds ratio 5.57, 95% CI 1.64–18.88). In SSc patients OAB positively correlated with sarcopenia (P < 0.001), and both OAB and UI significantly correlated with reduced BMD (P < 0.05, P = 0.001). UI positively correlated with Scl70 antibodies (P < 0.05) and ciclosporin treatment (P = 0.001) and negatively with RNA polymerase III antibodies (P < 0.05); OAB positively correlated with calcinosis (P < 0.005) and negatively with methotrexate treatment (P < 0.05). Nailfold videocapillaroscopy 'active' and 'late' patterns were predominant among SSc patients presenting urinary symptoms, although no statistical correlation was found. Conclusion For the first time urinary tract involvement was found to be significantly higher in SSc patients than in healthy matched controls. In addition, sarcopenia, bone damage and calcinosis appeared significantly correlated with LUTS, suggesting a possible interplay. [ABSTRACT FROM AUTHOR]

Objective: Pulmonary arterial hypertension (PAH) is one of the leading causes of death in systemic sclerosis (SSc). Current screening algorithms are hampered by low positive predictive values. Outcome measures that could add to performance characteristics would be welcome. We aim to evaluate the role of nailfold videocapillaroscopy (NVC) using standardized definitions, in SSc-related PAH (SSc-PAH).Methods: A systematic review to identify original research papers documenting an association between NVC and right heart catheterization-defined SSc-PAH was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Subsequently, NVC characteristics were subdivided into quantitative (capillary density, dimension, morphology, and hemorrhages), semiquantitative, and qualitative assessment (NVC pattern), according to the definitions of the European League Against Rheumatism Study Group on Microcirculation in Rheumatic Diseases.Results: The systematic search identified 316 unique search results, of which 5 were included in the final qualitative analysis. The occurrence of incident SSc-PAH unequivocally associated in 2 longitudinal studies with progressive capillary loss (p = 0.04 and p = 0.033) and the progression to a severe (active/late) NVC pattern (p = 0.05/0.01 and HR = 5.12, 95% CI 1.23-21.27). In 3 cross-sectional studies, SSc-PAH was found to be unequivocally inversely associated with capillary density (p = 0.001 and p < 0.05) and associated with the presence of a severe NVC pattern (p = 0.03 and p < 0.05).Conclusion: This is the first systematic literature review investigating the role of NVC in SSc-PAH using standardized description, to our knowledge. Unequivocal associations were found between (incident) SSc-PAH and capillary density and NVC pattern. Integration of NVC into current screening algorithms to boost their performance may be a future step. [ABSTRACT FROM AUTHOR]

Objective The aim of this observational study was to investigate the evolution of scleroderma microangiopathy throughout different nailfold videocapillaroscopy (NVC) patterns ('early', 'active', 'late') as well as the prevalence of organ involvement in SSc patients during a 12-year follow-up. Methods Thirty-four SSc patients showing at baseline (first capillaroscopic analysis) the 'early' NVC pattern of microangiopathy were enrolled and followed for 12 years (s. d. 2). Complete NVC analysis and clinical and serological findings were collected. Patients were in a standard therapeutic care setting. Statistical analysis was carried out by non-parametric tests. Results After a 12-year follow-up, the 'early' NVC pattern changed from baseline in 76% of the patients. The NVC pattern was found to be 'active' in 9 patients (26%), 'late' in 13 (38%) and characterized by non-specific capillary abnormalities in 4 (12%). In the subgroup whose microangiopathy progressed from the 'early' to the 'late' NVC pattern, the median time of progression from the 'early' to the 'active' pattern was significantly shorter (11 months) when compared with patients who progressed from the 'early' to the 'active' NVC pattern (55 months) (P = 0.002). The median time of progression between NVC patterns was significantly shorter in SSc patients showing either a nucleolar ANA pattern or Scl70 autoantibodies (P = 0.048). Organ involvement was progressively greater in SSc patients with 'early', 'active' and 'late' NVC patterns, respectively. Conclusions This longitudinal study confirms over a 12-year follow-up the evolution of specific NVC patterns associated with the progressive severity of organ involvement in SSc patients in a standard clinical care setting. [ABSTRACT FROM AUTHOR]

Microvascular damage and a decrease in peripheral blood perfusion are typical features of systemic sclerosis (SSc) with serious clinical implications, not only for a very early diagnosis, but also for disease progression. Nailfold videocapillaroscopy is a validated and safe imaging technique able to detect peripheral capillary morphology, as well as to classify and to score any nailfold abnormalities into different microangiopathy patterns. Capillaroscopic analysis is now included in the ACR/EULAR classification criteria for SSc. The decrease in peripheral blood perfusion is usually associated with microvascular damage in SSc, which may be studied by different methods. Several of these make use of safe laser technologies. This paper focuses on these new clinical aspects to assess SSc microvascular impairment.

Objective The pathological changes in SSc include immune system dysregulation and microvascular damage. However, the association of immune cell phenotype heterogeneity and microvascular abnormalities is unclear. The aim of this study is to elucidate this association in SSc. Methods Peripheral blood mononuclear cells obtained from 150 SSc patients were used for comprehensive flow cytometric analysis based on the Human Immunology Project. Hierarchical cluster analysis was used to classify SSc patients into subgroups and their association with microvascular abnormalities, as assessed by nailfold videocapillaroscopy (i.e. 'early', 'active' and 'late' patterns), was analysed. Results The proportions of activated CD4+ T cells, T cells re-expressing CD45RA, activated Th1 and Th17 cells and IgD−CD27− B cells were higher in SSc patients than in healthy individuals. Hierarchical cluster analysis stratified SSc patients into three groups: patients with few immune abnormalities (fewer abnormalities group), patients with high proportions of activated T and Treg cells (Treg-dominant group) and patients with high proportions of Tfh and plasmablasts (Tfh-dominant group). Age and disease duration were comparable among the groups. On the other hand, microvascular abnormalities, especially the 'late' nailfold videocapillaroscopy pattern, correlated with internal organ involvement. Among the groups stratified according to immune cell phenotype, the progression to the 'late' nailfold videocapillaroscopy pattern was more frequent in the Tfh-dominant group. Conclusion Our study confirmed the presence of immunophenotypic abnormalities in SSc. Immunological abnormalities were not uniform but rather limited to subpopulations, particularly the Tfh-dominant group, where they were highly associated with microvascular abnormalities and organ involvement. [ABSTRACT FROM AUTHOR]

Classified as a distinct subset of idiopathic inflammatory myopathies, anti-synthetase syndrome is an orphan autoimmune disease characterized by the presence of anti-aminoacyl-tRNA synthetase antibodies associated with a spectrum of clinical features including interstitial lung disease, myositis or dermatomyositis, chronic polyarthritis, fever, mechanic‘s hands and Raynaud‘s phenomenon. The main objective of our study was to evaluate nailfold capillary abnormalities in a series of cases diagnosed with anti-synthetase syndrome, aiming to describe capillaroscopy findings and to identify potential relation with clinical and functional outcomes. Irrespective of clinical and serological disease subtype, significant capillaroscopic changes may help diagnosis and identify negative prognostic factors, advancing the role of routine capillaroscopy in the decisional algorithm of anti-synthetase syndrome. Nailfold videocapillaroscopy is able to provide valuable information in patients with anti-tRNA synthetase myositis, suggesting that diffuse microangiopathy represents an early pathobiologic event.

Abstract Background Some abnormalities in nailfold videocapillaroscopy (NVC), such as the presence of micro-haemorrhages (MHEs), micro-thromboses (MTs), giant capillaries (GCs) and reduction in the number of capillaries (nCs), suggest a disease activity (DA) phase in systemic sclerosis (SSc). In a previous paper, we showed that the number of micro-haemorrhages and micro-thromboses (the so-called NEMO score) was the NVC feature more closely associated with DA. The present study was aimed at validating the NEMO score as a measure of DA in patients with SSc. Methods Two cohorts of 122 and 97 patients with SSc who were referred to two different rheumatology units, one in Milan and one in Naples, respectively, constituted the validation cohorts. The NEMO score, the total number of GCs and the mean nCs per digit were the parameters defined in each patient by eight-finger NVC. An expert operator analysed the NVCs in each of the participating units. The European Scleroderma Study Group (ESSG) index was used to define the DA level in each patient at the time of NVC examination. Results The NEMO score was the NVC parameter more strictly correlated with the ESSG score in both the Milan and Naples cohorts (p

Objectives: Raynaud’s phenomenon (RP) is characterized by intense vasospasm of the digital arteries that causes characteristic color changes in fingers. There are two main types of RP: Primary RP (PRP) and Secondary RP (SRP). PRP is a benign condition. Whilst SRP is associated with several connective tissue diseases (CTD), in particular systemic sclerosis (SSc). The objectives of this report were: to present a short review on morphological (nailfold videocapillaroscopy, NVC) and functional techniques (laser tools and thermography) that allow for a correct diagnosis and treatment of RP and to investigate blood perfusion (BP) by laser speckle contrast analysis (LASCA) in different skin areas of hands and face in PRP, SRP to SSc, and healthy subjects (CNT).Methods: 31 PRP patients (LeRoy criteria), 70 SRP to SSc (ACR/EULAR criteria) and 68 CNT were enrolled. BP was assessed by LASCA at the level different areas of hands and face. NVC was performed to distinguish between PRP and SRP, and to detect the proper pattern of nailfold microangiopathy in SSc patients.Results: Both PRP and SRP showed a statistically significant lower BP than CNT at the level of fingertips (p < 0.0001), periungual (p < 0.0001), palmar aspect of 3rd finger (p < 0.0001), and palm areas (p < 0.0001). Moreover, BP was significantly lower in PRP than in SRP to SSc with the “Early” pattern of microangiopathy in the same areas as above (p < 0.04).Conclusion: By considering a small cohort of patients, BP of hands was found lower in PRP than in SSc patients with the “Early” NVC pattern of microangiopathy.

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.

A 57-year-old woman with a diagnosis of antisynthetase syndrome (ASSD) underwent a nailfold videocapillaroscopy (NVC) showing a scleroderma pattern. Alterations in capillary morphology have been reported in adults with inflammatory myositis (IM) but only recently have the differences in NVC findings between these two diseases been established. ASSD is currently classified as a subset of IM, for which reason only a few studies in literature evaluate its specific hallmarks, showing nonspecific features of NVC in patients with polymyositis and dermatomyositis (DM) and antisynthetase antibodies. To our knowledge, this is the first description of ASSD capillaroscopy features, and the first report of NVC in ASSD with evidence of scleroderma pattern. Further studies are needed to define clearly frequency, typical features, and possible correlation with clinical and serological data of NVC changes in ASSD, differences between microangiopathy in ASSD and systemic sclerosis or DM.