Microvascular changes on nailfold capillaroscopy in acute stage of Kawasaki disease: a new diagnostic paradigm for an enigmatic condition.

OBJECTIVES: Kawasaki disease (KD) is a medium vessel vasculitis with a predilection to involve coronary arteries. However, there is a paucity of literature on microvascular changes in patients with KD. METHODS: Children diagnosed with KD based on American Heart Association guidelines 2017 were enrolled prospectively. Demographic details and echocardiographic changes in coronaries were recorded. Nailfold capillaries were assessed using Optilia Video capillaroscopy and data were analysed using Optilia Optiflix Capillaroscopy software at acute (prior to IVIG administration) and subacute/convalescent phase. RESULTS: We enrolled 32 children with KD (17 boys) with a median age of 3 years. Nailfold capillaroscopy (NFC) was performed in 32 patients in the acute phase (compared with 32 controls) and in 17 during the subacute/convalescent phase at a median follow-up of 15 (15-90) days after IVIG treatment. The following findings were seen in NFC in the acute phase of KD: reduced capillary density (n = 12, 38.6%), dilated capillaries (n = 3, 9.3%), ramifications (n = 3, 9.3%) and capillary haemorrhages (n = 2, 6.2%). Capillary density was reduced significantly in the acute phase of KD (38.6%) as compared with the subacute/convalescent phase (25.4%) (P-value <0.001) and controls (0%) (P-value = 0.03). We observed no correlation between coronary artery involvement and mean capillary density (P = 0.870). CONCLUSION: Results show that patients with KD have significant nailfold capillary changes in the acute phase. These findings may provide a new diagnostic paradigm for KD and a window to predict coronary artery abnormalities.

Artificial intelligence for nailfold capillaroscopy analyses - a proof of concept application in juvenile dermatomyositis.

BACKGROUND: Biomarkers for idiopathic inflammatory myopathies are difficult to identify and may involve expensive laboratory tests. We assess the potential for artificial intelligence (AI) to differentiate children with juvenile dermatomyositis (JDM) from healthy controls using nailfold capillaroscopy (NFC) images. We also assessed the potential of NFC images to reflect the range of disease activity with JDM. METHODS: A total of 1,120 NFC images from 111 children with active JDM, diagnosed between 1990 and 2020, and 321 NFC images from 31 healthy controls were retrieved from the CureJM JDM Registry. We built a lightweight and explainable deep neural network model called NFC-Net. Images were downscaled by interpolation techniques to reduce the computational cost. RESULTS: NFC-Net achieved high performance in differentiating patients with JDM from controls, with an area under the ROC curve (AUROC) of 0.93 (0.84, 0.99) and accuracy of 0.91 (0.82, 0.92). With sensitivity (0.85) and specificity (0.90) resulted in model precision of 0.95. The AUROC and accuracy for predicting clinical disease activity from inactivity were 0.75 (0.61, 0.81) and 0.74 (0.65, 0.79). CONCLUSION: The good performance of the NFC-Net demonstrates that NFC images are sufficient for detecting often unrecognized JDM disease activity, providing a reliable indicator of disease status. IMPACT: Proposed NFC-Net can accurately predict children with JDM from healthy controls using nailfold capillaroscopy (NFC) images. Additionally, it predicts the scores to JDM disease activity versus no activity. Equipped with gradients, NFC-Net is explainable and gives visual information beside the reported accuracies. NFC-Net is computationally efficient since it is applied to substantially downscaled NFC images. Furthermore, the model can be wrapped within an edge-based device like a mobile application that is accessible to both clinicians and patients.

Raynaud phenomenon and microvasculopathy in systemic sclerosis: multi-modality imaging for diagnosis and evaluation.

PURPOSE OF REVIEW: To describe the clinical significance of and the diagnostic approach to Raynaud phenomenon (RP) in the peripheral extremities and the heart. RECENT FINDINGS: Nailfold capillaroscopy has recently been standardized in an expert consensus paper. Abnormal capillaroscopy in combination with specific autoantibody profiles and clinical signs are highly predictive of progression of RP to systemic sclerosis (SSc). Magnetic resonance imaging (MRI) can also perform tissue characterization of both the extremities and the heart. Microvascular wall abnormalities detected using nailfold capillaroscopy in patients with SSc may lead to deposition of erythrocyte-derived iron, due to microhemorrhages, which may predispose to fibrosis. MRI can assess the presence of iron using T2∗ measurements. SUMMARY: RP is a hallmark of the microvasculopathy in SSc and can affect both the peripheral extremities and the heart. Nailfold capillaroscopy is the current gold standard for the evaluation of the peripheral microvasculature. Other imaging modalities include thermography, laser Doppler-derived methods, 99m Tc-pertechnetate hand perfusion scintigraphy, power Doppler ultrasonography, dynamic optical coherence tomography, MRI, and photoacoustic imaging, but these are currently not widely used. Cardiac RP can be investigated with positron emission tomography or cardiovascular magnetic resonance, with the latter offering the additional possibility of tissue characterization and iron content quantification secondary to microhemorrhages.

Standardized nailfold capillaroscopy in children with rheumatic diseases: a worldwide study.

OBJECTIVES: To standardly assess and describe nailfold videocapillaroscopy (NVC) assessment in children and adolescents with juvenile rheumatic and musculoskeletal diseases (jRMD) vs healthy controls (HCs). MATERIAL AND METHODS: In consecutive jRMD children and matched HCs from 13 centres worldwide, 16 NVC images per patient were acquired locally and read centrally per international consensus standard evaluation of the EULAR Study Group on Microcirculation in Rheumatic Diseases. A total of 95 patients with JIA, 22 with JDM, 20 with childhood-onset SLE (cSLE), 13 with juvenile SSc (jSSc), 21 with localized scleroderma (lSc), 18 with MCTD and 20 with primary RP (PRP) were included. NVC differences between juvenile subgroups and HCs were calculated through multivariable regression analysis. RESULTS: A total of 6474 images were assessed from 413 subjects (mean age 12.1 years, 70.9% female). The quantitative NVC characteristics were significantly lower or higher in the following subgroups compared with HCs: for density: lower in jSSc, JDM, MCTD, cSLE and lSc; for dilations: higher in jSSc, MCTD and JDM; for abnormal shapes: higher in JDM and MCTD; for haemorrhages: higher in jSSc, MCTD, JDM and cSLE. The qualitative NVC assessment of JIA, lSc and PRP did not differ from HCs, whereas the cSLE and jSSc, MCTD, JDM and cSLE subgroups showed more non-specific and scleroderma patterns, respectively. CONCLUSIONS: This analysis resulted from a pioneering registry of NVC in jRMD. The NVC assessment in jRMD differed significantly from HCs. Future prospective follow-up will further elucidate the role of NVC in jRMD.

Vision transformer assisting rheumatologists in screening for capillaroscopy changes in systemic sclerosis: an artificial intelligence model.

OBJECTIVES: The first objective of this study was to implement and assess the performance and reliability of a vision transformer (ViT)-based deep-learning model, an 'off-the-shelf' artificial intelligence solution, for identifying distinct signs of microangiopathy in nailfold capilloroscopy (NFC) images of patients with SSc. The second objective was to compare the ViT's analysis performance with that of practising rheumatologists. METHODS: NFC images of patients prospectively enrolled in our European Scleroderma Trials and Research group (EUSTAR) and Very Early Diagnosis of Systemic Sclerosis (VEDOSS) local registries were used. The primary outcome investigated was the ViT's classification performance for identifying disease-associated changes (enlarged capillaries, giant capillaries, capillary loss, microhaemorrhages) and the presence of the scleroderma pattern in these images using a cross-fold validation setting. The secondary outcome involved a comparison of the ViT's performance vs that of rheumatologists on a reliability set, consisting of a subset of 464 NFC images with majority vote-derived ground-truth labels. RESULTS: We analysed 17 126 NFC images derived from 234 EUSTAR and 55 VEDOSS patients. The ViT had good performance in identifying the various microangiopathic changes in capillaries by NFC [area under the curve (AUC) from 81.8% to 84.5%]. In the reliability set, the rheumatologists reached a higher average accuracy, as well as a better trade-off between sensitivity and specificity compared with the ViT. However, the annotators' performance was variable, and one out of four rheumatologists showed equal or lower classification measures compared with the ViT. CONCLUSIONS: The ViT is a modern, well-performing and readily available tool for assessing patterns of microangiopathy on NFC images, and it may assist rheumatologists in generating consistent and high-quality NFC reports; however, the final diagnosis of a scleroderma pattern in any individual case needs the judgement of an experienced observer.

A deep learning system for quantitative assessment of microvascular abnormalities in nailfold capillary images.

OBJECTIVES: Nailfold capillaroscopy is key to timely diagnosis of SSc, but is often not used in rheumatology clinics because the images are difficult to interpret. We aimed to develop and validate a fully automated image analysis system to fill this gap. METHODS: We mimicked the image interpretation strategies of SSc experts, using deep learning networks to detect each capillary in the distal row of vessels and make morphological measurements. We combined measurements from multiple fingers to give a subject-level probability of SSc.We trained the system using high-resolution images from 111 subjects (group A) and tested on images from subjects not in the training set: 132 imaged at high-resolution (group B); 66 imaged with a low-cost digital microscope (group C). Roughly half of each group had confirmed SSc, and half were healthy controls or had primary RP ('normal'). We also estimated the performance of SSc experts. RESULTS: We compared automated SSc probabilities with the known clinical status of patients (SSc versus 'normal'), generating receiver operating characteristic curves (ROCs). For group B, the area under the ROC (AUC) was 97% (94-99%) [median (90% CI)], with equal sensitivity/specificity 91% (86-95%). For group C, the AUC was 95% (88-99%), with equal sensitivity/specificity 89% (82-95%). SSc expert consensus achieved sensitivity 82% and specificity 73%. CONCLUSION: Fully automated analysis using deep learning can achieve diagnostic performance at least as good as SSc experts, and is sufficiently robust to work with low-cost digital microscope images.

Non-invasive detection of early microvascular changes in juveniles with type 1 diabetes.

AIMS/HYPOTHESIS: The study aimed to assess the usefulness of capillaroscopy and photoplethysmography in the search for early vascular anomalies in children with type 1 diabetes. METHODS: One hundred sixty children and adolescents aged 6-18, 125 patients with type 1 diabetes, and 35 healthy volunteers were enrolled in the study. We performed a detailed clinical evaluation, anthropometric measurements, nailfold capillaroscopy, and photoplethysmography. RESULTS: Patients with diabetes had more often abnormal morphology in capillaroscopy (68.60%, p = 0.019), enlarged capillaries (32.6%, p = 0.006), and more often more over five meandering capillaries (20.90%, p = 0.026) compared to healthy controls. Meandering capillaries correlated with higher parameters of nutritional status. In a photoplethysmography, patients with diagnosed neuropathy had a higher percentage of flow disturbance curves (p < 0.001) with a reduced frequency of normal curves (p = 0.050). CONCLUSIONS: Capillaroscopic and photoplethysmographic examinations are non-invasive, painless, fast, and inexpensive. They are devoid of side effects, and there are no limitations in the frequency of their use and repetition. The usefulness of capillaroscopy and photoplethysmography in the study of microcirculation in diabetic patients indicates the vast application possibilities of these methods in clinical practice.

Automated nailfold capillary density measurement method based on improved YOLOv5.

Nailfold capillary density is an essential physiological parameter for analyzing nailfold health; however, clinical images of the nailfold are taken in many situations, and most clinicians subjectively analyze nailfold images. Therefore, based on the improved "you only look once v5" (YOLOv5) algorithm, this study proposes an automated method for measuring nailfold capillary density. The improved technique can effectively and rapidly detect distal capillaries by incorporating methods or structures such as 9mosaic, spatial pyramid pooling cross-stage partial construction, bilinear interpolation, and efficient intersection over union. First, the modified YOLOv5 algorithm was used to detect nailfold capillaries. Subsequently, the number of distal capillaries was filtered using the 90° method. Finally, the capillary density was calculated. The results showed that the Average Precision (AP)@0.5 value of the proposed approach reached 85.2 %, which was an improvement of 4.93 %, 5.24 %, and 107 % compared with the original YOLOv5, YOLOv6, and simple-faster rapid-region convolutional network (R-CNN), respectively. For different nailfold images, using the density calculated by nailfold experts as a benchmark, the calculated results of the proposed method were consistent with the manually calculated results and superior to those of the original YOLOv5.

Asymmetric dimethylarginine correlates with worsening peripheral microangiopathy in systemic sclerosis.

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

Peripheral nailfold capillary microscopic abnormalities in rheumatoid arthritis are associated with arterial stiffness: Results from a cross-sectional study.

Vascular injury eventually resulting in the establishment of cardiovascular disease is a serious complication in rheumatoid arthritis (RA). Nailfold videocapillaroscopy (NVC) is a non-invasive imaging modality that enables the quantitative and qualitative assessment of the peripheral microvasculature. Nevertheless, capillaroscopic patterns remain inadequately defined in RA, especially regarding their clinical significance as potential markers of systemic vascular impairment. Consecutive RA patients underwent NVC using a standardized protocol, to assess the following parameters: capillary density, avascular areas, capillary dimensions, microhemorrhages, subpapillary venous plexus, and presence of ramified, bushy, crossed and tortuous capillaries. Carotid-femoral pulse wave velocity (PWV) and pulse pressure were measured as well-acknowledged markers of large artery stiffening. The vast majority of our cohort (n = 44) presented a combination of non-specific and abnormal capillaroscopic parameters. Capillary ramification was associated with both PWV and pulse pressure, even after adjustment for cardiovascular risk factors and systemic inflammation. Our study highlights the high prevalence of a wide range of capillaroscopic deviations from the normal patterns in RA. Furthermore, it provides for the first time evidence of an association between structural disorders of the microcirculation and markers of macrovascular dysfunction, suggesting that NVC might have a role as an index of generalised vascular impairment in RA.

Nailfold capillaroscopy reveals early peripheral microcirculation abnormalities in children affected by heterozygous familial hypercholesterolemia.

BACKGROUND: nailfold capillaroscopy (NCF) is a non-invasive imaging technique to seek peripheral microcirculation abnormalities in children and adults. Familial hypercholesterolemia is a genetic disorder caused by mutations capable of increasing blood levels of low-density lipoproteins cholesterol (LDL-C), thus triggering early atherosclerosis. The study aims at evaluating peripheral microcirculation in children with heterozygous familial hypercholesterolemia (HeFH) by means of NFC in comparison with healthy peers and at searching for possible correlations between these abnormalities and patients' lipid panel. METHODS: thirty-six HeFH patients were enrolled (13 males and 23 females. Mean age 8 ± 3 years; age range 3-13 years). They had increased levels of total cholesterol (237.9 ± 34.2 mg/dl) and LDL-C (154.2 ± 37.6 mg/dl). Both values were ≥95th gender and age specific centile. All the subjects in the study underwent NFC. RESULTS: In 69.4 % of HeFH children nailfold capillaries were tortuous (p < 0.00001 compared to healthy controls). In 41.6 % the number of capillaries was markedly reduced (<7 capillaries/mm). The mean number of capillaries was 8.4 ± 2.6/mm in HeFH and 12.2 ± 1.4/mm in healthy controls (p < 0.00001). In 100 % of the sample size capillary blood flow was slowed down (p < 0.00001). In 50 % of the sample size a blood "sludge" phenomenon was seen (p < 0.00001). No gender differences were detected. Sludge phenomenon was seen only in those with LDL-C over 99th centile (p < 0.00001). CONCLUSION: NCF allows the identification of an early peripheral microvascular dysfunction in HeFH children which is similar to that already seen in atherosclerotic disease. Prompt identification of these capillary abnormalities may be crucial in implementing early prevention measures.

External clinical validation of automated software to identify structural abnormalities and microhaemorrhages in nailfold videocapillaroscopy images.

OBJECTIVES: Automated systems to analyse nailfold videocapillaroscopy (NVC) images are needed to promptly and comprehensively characterise patients with systemic sclerosis (SSc) or Raynaud's phenomenon (RP). We previously developed, and validated in-house, a deep convolutional neural network-based algorithm to classify NVC-captured images according to the presence/absence of structural abnormalities and/or microhaemorrhages. We present its external clinical validation. METHODS: A total of 1,164 NVC images of RP patients were annotated by 5 trained capillaroscopists according to the following categories: normal capillary; dilation; giant capillary; abnormal shape; tortuosity; microhaemorrhage. The images were also presented to the algorithm. Matches and discrepancies between algorithm predictions and those annotations obtained by consensus of ≥3 or ≥4 interobservers were analysed. RESULTS: Consensus among ≥3 capillaroscopists was achieved in 86.9% of images, 75.8% of which were correctly predicted by the algorithm. Consensus among ≥4 experts occurred in 52.0% of cases, in which 87.1% of the algorithm's results matched with those of the expert panel. The algorithm's positive predictive value was >80% for microhaemorrhages and unaltered, giant or abnormal capillaries. Sensitivity was >75% for dilations and tortuosities. Negative predictive value and specificity were >89% for all categories. CONCLUSIONS: This external clinical validation suggests that this algorithm is useful to assist in the diagnosis and follow-up of SSc or RP patients in a timely manner. It may also be helpful in the management of patients with any pathology presenting with microvascular changes, as the algorithm has been designed to also be useful for research aiming at extending the usage of nailfold capillaroscopy to more conditions.

Clinical utility of nailfold capillaroscopy.

Nailfold capillaroscopy (NFC) is a simple noninvasive microscopic technique used to identify characteristic morphological abnormalities in the nailfold capillaries. The presence of this microvasculopathy appears to be of fundamental importance in the pathological processes that underlie the scleroderma spectrum disorders (including dermatomyositis and antisynthetase myositis). This review discusses the different methodologies and techniques in performing NFC and stresses the diagnostic utility achieved with simple 'bedside' techniques utilising the ophthalmoscope, dermatoscope or smart phone. Recent advances in reporting abnormal microvascular patterns and vascular metrics (e.g. capillary density and dropout) are discussed. The aetiopathogenesis of the microvasculopathy is currently unknown but its close association with Raynaud Phenomena and specific autoantibodies together with recent observations from sequential NFC allows speculations on its possible mechanism. Finally, future developments in the use of NFC as a possible biomarker in the management of the scleroderma spectrum disorders are discussed, with a recommendation that NFC becomes more widely available, particularly in rheumatological, immunological and dermatological practice. NFC provides a clinically accessible window on the pathologic process fundamental to scleroderma-related disease.

Role of short courses on nailfold capillaroscopy in obtaining abilities for the identification of microvasculopathy in patients with Raynaud's phenomenon.

INTRODUCTION: An early distinction between "normal" and "abnormal" capillaroscopic pattern during the first visit to a dermatologist has a crucial significance for a diagnostic management of Raynaud's phenomenon (RP). There exists a question about the level of expertise sufficient to evaluate the microcirculation. AIM: To evaluate the utility of short courses on NFC among dermatologists and medical students in obtaining sufficient abilities for the identification of microvasculopathy in patients with RP using videocapillaroscope and handheld dermoscope. METHODS: Both groups participated in 1-h course on NFC. Before the course, participants were asked to classify 20 videocapillaroscopic and 10 dermoscopic capillaroscopic pictures into "normal" or "abnormal" pattern. Each picture was displayed on a separate slide MS PowerPoint for 10 s. The evaluation was repeated soon after the course. RESULTS: A total of 36 dermatologists and 49 medical students were enrolled. The rate of properly classified dermoscopic and videodermoscopic pictures increased after the course in both groups, but students improved the accuracy of classification on dermoscopic pictures to the greater extent than dermatologists. The rate of correctly recognized pictures with "abnormal" pattern was significantly greater than ones with "normal" pattern at the baseline and after the course, independently of imagining tool. CONCLUSIONS: Short courses on NFC may improve the classification of capillaroscopic images, even in medical staff with no previous experience in NFC. The recognition of capillaroscopic abnormalities seems to be easier than obtaining the confidence that evaluated picture has "normal pattern."

Automated Stabilization, Enhancement and Capillaries Segmentation in Videocapillaroscopy.

Oral capillaroscopy is a critical and non-invasive technique used to evaluate microcirculation. Its ability to observe small vessels in vivo has generated significant interest in the field. Capillaroscopy serves as an essential tool for diagnosing and prognosing various pathologies, with anatomic-pathological lesions playing a crucial role in their progression. Despite its importance, the utilization of videocapillaroscopy in the oral cavity encounters limitations due to the acquisition setup, encompassing spatial and temporal resolutions of the video camera, objective magnification, and physical probe dimensions. Moreover, the operator's influence during the acquisition process, particularly how the probe is maneuvered, further affects its effectiveness. This study aims to address these challenges and improve data reliability by developing a computerized support system for microcirculation analysis. The designed system performs stabilization, enhancement and automatic segmentation of capillaries in oral mucosal video sequences. The stabilization phase was performed by means of a method based on the coupling of seed points in a classification process. The enhancement process implemented was based on the temporal analysis of the capillaroscopic frames. Finally, an automatic segmentation phase of the capillaries was implemented with the additional objective of quantitatively assessing the signal improvement achieved through the developed techniques. Specifically, transfer learning of the renowned U-net deep network was implemented for this purpose. The proposed method underwent testing on a database with ground truth obtained from expert manual segmentation. The obtained results demonstrate an achieved Jaccard index of 90.1% and an accuracy of 96.2%, highlighting the effectiveness of the developed techniques in oral capillaroscopy. In conclusion, these promising outcomes encourage the utilization of this method to assist in the diagnosis and monitoring of conditions that impact microcirculation, such as rheumatologic or cardiovascular disorders.

Imaging techniques for assessment of vascular involvement in systemic sclerosis.

PURPOSE OF REVIEW: Vascular assessment in systemic sclerosis (SSc) is included in classification criteria for this disease, thus routinely used in the evaluation of patients in which this diagnosis is being considered. In this review, imaging techniques for assessment of vascular involvement in SSc hands and skin are discussed. RECENT FINDINGS: Longitudinal use of imaging techniques has important implications for understanding the progressive vasculopathy and fibrotic transition in SSc. Nailfold and oral capillaroscopy as well as laser speckle contrast analysis are established techniques for vascular functional assessment, but longitudinal use is challenged by equipment costs and clinical time constraints. Ultrasound techniques are well described but require technical training. Advances in mobile infrared thermography and optical coherence tomography could potentially provide a point-of-care, quantitative outcome measure in clinical trials and practice. SUMMARY: The equipment cost, technical training, data standardization, and invasiveness of vascular assessment techniques that quantify morphological (microangiopathy) and functional (blood flow reduction) are critical for implementation into SSc clinical trials and practice to understand progressive vasculopathy, such as wound development.

Automated capillary flow segmentation and mapping for nailfold video capillaroscopy.

OBJECTIVE: This study aimed to develop an automated image analysis method for segmentation and mapping of capillary flow dynamics captured using nailfold video capillaroscopy (NVC). Methods were applied to compare capillary flow structures and dynamics between young and middle-aged healthy controls. METHODS: NVC images were obtained in a resting state, and a region of the vessel in the image was extracted using a conventional U-Net neural network. The approximate length, diameter, and radius of the curvature were calculated automatically. Flow speed and its fluctuation over time were mapped using the Radon transform and frequency spectrum analysis from the kymograph image created along the vessel's centerline. RESULTS: The diameter of the curve segment (14.4 µm and 13.0 µm) and the interval of two straight segments (13.7 µm and 32.1 µm) of young and middle-aged subjects, respectively, were significantly different. Faster flow was observed in older subjects (0.48 mm/s) than in younger subjects (0.26 mm/s). The power spectral analysis revealed a significant correlation between the high-frequency power spectrum and the flow speed. CONCLUSIONS: The present method allows a spatiotemporal characterization of capillary morphology and flow dynamics with NVC, allowing a wide application such as large-scale health assessment.

Nailfold capillaroscopy in SSc: innocent bystander or promising biomarker for novel severe organ involvement/progression?

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.

Nailfold capillaroscopy: a survey of current UK practice and 'next steps' to increase uptake among rheumatologists.

OBJECTIVES: To identify barriers to the use of nailfold capillaroscopy as a diagnostic tool for patients presenting with Raynaud's phenomenon in UK rheumatology centres and to obtain rheumatologists' views on a proposed internet-based standardized system for clinical reporting of nailfold capillaroscopy images. METHODS: An online survey was developed using expert opinion from clinicians, scientists and health service researchers. The survey was piloted and sent to UK-based rheumatologists using established electronic mailing lists between October 2020 and March 2021. Survey data were analysed using descriptive statistics. RESULTS: A total of 104 rheumatologists representing rheumatology centres across the UK responded to the survey. Wide variations in terms of workloads and practices were described. Thirty-four (33%) respondents reported using nailfold capillaroscopy only at their own centre, 33 (32%) referred to other centres, 9 (9%) did both and 28 (27%) did not use capillaroscopy at all. Of the 43 respondents using capillaroscopy on site, 25 (58%) used either a dermatoscope or universal serial bus microscope and 9 (21%) used videocapillaroscopy. Among the 61 respondents not undertaking capillaroscopy on site, barriers included lack of equipment (85%), lack of experience in acquiring images (69%) and lack of expertise in interpreting images (67%). Sixty-six respondents (63%) expressed interest in an internet-based, standardized automated system for reporting images. CONCLUSION: Most UK rheumatologists currently do not perform nailfold capillaroscopy on site. An internet-based nailfold capillaroscopy system for use with low-cost microscopes as well as with videocapillaroscopy could help increase uptake of capillaroscopy and thereby facilitate early diagnosis of SSc across the UK.

Full longitudinal nailfold videocapillaroscopy analysis of microvascular changes during normal pregnancy.

BACKGROUND: Microvascular remodeling is one major responsible for vascular adaptation in pregnancy, still it is not routinely evaluated in the obstetric field. This pilot study aimed to explore the role of nailfold capillaroscopy (NCV) in detecting microvascular changes during normal pregnancy. METHODS: A population of 30 healthy pregnant women was longitudinally followed performing clinical assessment and NVC evaluation at each trimester and post-partum. Thirty non-pregnant age-matched healthy women having received at least two NVCs with a minimum 9 to 12-month interval were selected as controls. All NVC images were evaluated by a qualitative and semi-quantitative assessment using current standardised approach. Statistical analyses were conducted to assess NVC trend throughout gestation and its possible association with pregnancy course. RESULTS: A progressive significant increase of NVC neoangiogenesis and a specular reduction in capillary dilations was observed during pregnancy (p < 0.05). These variations were not found in age-matched controls, who showed stable NVC parameters over a similar time frame (p < 0.05). Additionally, a significant inverse correlation was found between NVC neoangiogenesis rate and maternal systemic BP (rho = -0.72, p < 0.005). CONCLUSION: This first comprehensive longitudinal NVC evaluation during normal pregnancy reports significant but physiological microvascular variations throughout gestation, suggesting NVC as a safe and promising technique for further investigate and define patterns of microvascular changes also in pathological pregnancies.