Quantitative nailfold capillaroscopy-update and possible next steps.
TL;DR: In this article, the potential for precise discrimination between normal and abnormal capillaries and for reliable measurement of disease progression and treatment response is discussed. And the potential of automated analysis could facilitate large-scale prospective studies using capillaroscopic parameters as possible biomarkers of systemic sclerosis spectrum disorders.
Abstract: We review the exciting potential (and challenges) of quantitative nailfold capillaroscopy, focusing on its role in systemic sclerosis. Quantifying abnormality, including automated analysis of nailfold images, overcomes the subjectivity of qualitative/descriptive image interpretation. First we consider the rationale for quantitative analysis, including the potential for precise discrimination between normal and abnormal capillaries and for reliable measurement of disease progression and treatment response. We discuss nailfold image acquisition and interpretation, and describe how early work on semi-quantitative and quantitative analysis paved the way for semi-automated and automated analysis. Measurement of red blood cell velocity is described briefly. Finally we give a personal view on 'next steps'. From a clinical perspective, increased uptake of nailfold capillaroscopy by general rheumatologists could be achieved via low-cost hand-held devices with cloud-based automated analysis. From a research perspective, automated analysis could facilitate large-scale prospective studies using capillaroscopic parameters as possible biomarkers of systemic sclerosis-spectrum disorders.
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TL;DR: A review of non-invasive tools for analyzing microvascular changes is presented in this article, and the clinical roles of validated or tested imaging methods are discussed for autoimmune rheumatic diseases.
Abstract: Morphological and functional analysis of the microcirculation are objective outcome measures that are recommended for use in the presence of clinical signs of altered peripheral blood flow (such as Raynaud phenomenon), which can occur in systemic sclerosis (SSc) and other autoimmune rheumatic diseases. Several advanced non-invasive tools are available for monitoring the microcirculation, including nailfold videocapillaroscopy, which is the best-studied and most commonly used method for distinguishing and quantifying microvascular morphological alterations in SSc. Nailfold videocapillaroscopy can also be used alongside laser Doppler techniques to assist in the early diagnosis and follow-up of patients with dermatomyositis or mixed connective tissue disease. Power Doppler ultrasonography, which has been used for many years to evaluate the vascularity of synovial tissue in rheumatoid arthritis, is another promising tool for the analysis of skin and nailbed capillary perfusion in other autoimmune rheumatic diseases. Other emerging methods include raster-scanning optoacoustic mesoscopy, which offers non-invasive high-resolution 3D visualization of capillaries and has been tested in psoriatic arthritis and SSc. The principle functions and operative characteristics of several non-invasive tools for analysing microvascular changes are outlined in this Review, and the clinical roles of validated or tested imaging methods are discussed for autoimmune rheumatic diseases.
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TL;DR: The growing interest in the visualization of psoriatic nail unit changes has led to the discovery of an abundance of image characteristics across various modalities.
Abstract: The growing interest in the visualization of psoriatic nail unit changes has led to the discovery of an abundance of image characteristics across various modalities.
7 citations
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TL;DR: An automated image analysis method for segmentation and mapping of capillary flow dynamics captured using nailfold video capillaroscopy (NVC) is developed and compared between young and middle‐aged healthy controls.
Abstract: 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.
3 citations
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TL;DR: In this article , the performance and reliability of a vision transformer (ViT)-based deep-learning model for identifying distinct signs of microangiopathy in nailfold capilloroscopy (NFC) images of patients with SSc was compared with that of practising rheumatologists.
Abstract: Abstract 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.
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TL;DR: The challenges, challenges, provides tips, and highlights the exciting potential of nailfold capillaroscopy in standard practice are presented.
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References
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Radboud University Nijmegen Medical Centre1, University of Michigan2, Radboud University Nijmegen3, University of Toronto4, McGill University5, University of Basel6, University of Florence7, Auckland City Hospital8, University of Pittsburgh9, Charité10, University of California, Los Angeles11, University College London12, University of Zurich13, University of Paris14, Marche Polytechnic University15, University of Texas Health Science Center at Houston16, Newcastle University17, University of Pécs18, Georgetown University19, Istanbul University20, Medical University of Białystok21, University of Giessen22, Seconda Università degli Studi di Napoli23, University College Dublin24, Stanford University25, University of Colorado Denver26, National Health Service27, Medical College of Wisconsin28, University of Alabama at Birmingham29, University of Manchester30, Rutgers University31, Thomas Jefferson University32, Amgen33, University of Toledo34, Boston University35, Medical University of South Carolina36, University of Pennsylvania37, Northwestern University38
TL;DR: The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria and should allow for more patients to be classified correctly as having the disease.
Abstract: OBJECTIVE: The 1980 American College of Rheumatology (ACR) classification criteria for systemic sclerosis (SSc) lack sensitivity for early SSc and limited cutaneous SSc. The present work, by a joint committee of the ACR and the European League Against Rheumatism (EULAR), was undertaken for the purpose of developing new classification criteria for SSc. METHODS: Using consensus methods, 23 candidate items were arranged in a multicriteria additive point system with a threshold to classify cases as SSc. The classification system was reduced by clustering items and simplifying weights. The system was tested by 1) determining specificity and sensitivity in SSc cases and controls with scleroderma-like disorders, and 2) validating against the combined view of a group of experts on a set of cases with or without SSc. RESULTS: It was determined that skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for the patient to be classified as having SSc; if that is not present, 7 additive items apply, with varying weights for each: skin thickening of the fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynaud's phenomenon, and SSc-related autoantibodies. Sensitivity and specificity in the validation sample were, respectively, 0.91 and 0.92 for the new classification criteria and 0.75 and 0.72 for the 1980 ACR classification criteria. All selected cases were classified in accordance with consensus-based expert opinion. All cases classified as SSc according to the 1980 ACR criteria were classified as SSc with the new criteria, and several additional cases were now considered to be SSc. CONCLUSION: The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria for SSc and should allow for more patients to be classified correctly as having the disease.
2,743 citations
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TL;DR: In RP evolving to definite SSc, microvascular damage is dynamic and sequential, while SSc-specific autoantibodies are associated with the course and type of capillary abnormalities.
Abstract: Objective
To identify in patients with Raynaud's phenomenon (RP) independent markers that predict progression to definite systemic sclerosis (SSc) and to determine in patients with progression to SSc the type and sequence of microvascular damage and its relationship to SSc-specific autoantibodies.
Methods
Consecutive patients referred for evaluation of RP who had no definite connective tissue disease were evaluated for microvascular damage by nailfold capillary microscopy (NCM) and for anticentromere (anti–CENP-B), anti-Th/To, anti–topoisomerase I, and anti–RNA polymerase III (anti–RNAP III) autoantibodies by specific assays. Patients were studied prospectively.
Results
Of the 586 patients who were followed up for 3,197 person-years, 74 (12.6%) developed definite SSc. A characteristic sequence of microvascular damage was identified, starting with enlarged capillaries, followed by capillary loss, and then by capillary telangiectases. Definite SSc was diagnosed in close temporal relationship to capillary loss. Enlarged capillaries, capillary loss, and SSc-specific autoantibodies independently predicted definite SSc. Anti–CENP-B and anti-Th/To antibodies predicted enlarged capillaries; these autoantibodies and anti–RNAP III predicted capillary loss. Each autoantibody was associated with a distinct time course of microvascular damage. At followup, 79.5% of patients with 1 of these autoantibodies and abnormal findings on NCM at baseline had developed definite SSc. Patients with both baseline predictors were 60 times more likely to develop definite SSc. The data validated the proposed criteria for early SSc.
Conclusion
In RP evolving to definite SSc, microvascular damage is dynamic and sequential, while SSc-specific autoantibodies are associated with the course and type of capillary abnormalities. Abnormal findings on NCM at baseline together with an SSc-specific autoantibody indicate a very high probability of developing definite SSc, whereas their absence rules out this outcome.
518 citations
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University of Paris1, Radboud University Nijmegen2, University of Basel3, Sapienza University of Rome4, Ghent University5, Federal University of Paraná6, University of Florence7, University of Giessen8, University of Genoa9, University of Zurich10, Seconda Università degli Studi di Napoli11, University of Pécs12, University of California, Los Angeles13, Medical University of Białystok14, Charité15, Iuliu Hațieganu University of Medicine and Pharmacy16, Charles University in Prague17, Istanbul University18, Complutense University of Madrid19, University of Geneva20, Medical University of Silesia21, University of Düsseldorf22, University of Ljubljana23, Marche Polytechnic University24, Medical University of Vienna25, Lund University26, University of Cologne27, University of Pisa28, University College London29, University of Tübingen30, James Cook University Hospital31, University of Coimbra32, University of Copenhagen33, University of Münster34, Russian Academy35, Carol Davila University of Medicine and Pharmacy36, Hanyang University37, Thomas Jefferson University38, Utrecht University39, University of Connecticut40, Katholieke Universiteit Leuven41, University of Zagreb42, Heidelberg University43, University of Cagliari44, University of São Paulo45, University College Dublin46, University of Verona47, Wrocław Medical University48, Université catholique de Louvain49, Dresden University of Technology50
TL;DR: A core set of preliminary items considered as important for the very early diagnosis of systemic sclerosis were identified in a Delphi exercise among 110 experts in the field of SSc.
Abstract: Objective: To identify a core set of preliminary items considered as important for the very early diagnosis of systemic sclerosis (SSc). Methods: A list of items provided by European League Against Rheumatism (EULAR) Scleroderma Trial and Research(EUSTAR) centres were subjected to a Delphi exercise among 110 experts in the field of SSc. In round 1, experts were asked to choose the items they considered as the most important for the very early diagnosis of SSc. In round 2, experts were asked to reconsider the items accepted after the first stage. In round 3, the clinical relevance of selected items and their importance as measures that would lead to an early referral process were rated using appropriateness scores. Results: Physicians from 85 EUSTAR centres participated in the study and provided an initial list of 121 items. After three Delphi rounds, the steering committee, with input from external experts, collapsed the 121 items into three domains containing seven items, developed as follows: skin domain (puffy fingers/puffy swollen digits turning into sclerodactily);vascular domain (Raynaud's phenomenon, abnormal capillaroscopy with scleroderma pattern) and laboratory domain (antinuclear, anticentromere and antitopoisomerase-I antibodies). Finally, the whole assembly of EUSTAR centres ratified with a majority vote the results in a final face-to-face meeting. Conclusion: The three Delphi rounds allowed us to identify the items considered by experts as necessary for the very early diagnosis of SSc. The validation of these items to establish diagnostic criteria is currently ongoing in a prospective observational cohort.
334 citations
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TL;DR: The fingers of 75 patients with connective tissue disorders were examined by “wide-field” capillary microscopy and 3 distinct groups were recognized among these patients: increased visibility of nailfold subpapillary plexus in rheumatoid arthritis, massive capillary dilatation in scleroderma-dermatomyositis, and focal loss of capillaries in systemic lupus erythematosus.
Abstract: The fingers of 75 patients with connective tissue disorders were examined by “wide-field” capillary microscopy Four diagnostic groups were included in this study: rheumatoid arthritis—28, scleroderma—22, dermatomyositis—8, and systemic lupus erythematosus—17On the basis of different patterns of elementary microvascular abnormalities and their distribution, 3 distinct groups were recognized among these patients: 1) increased visibility of nailfold subpapillary plexus in rheumatoid arthritis, 2) massive capillary dilatation in scleroderma-dermatomyositis, and 3) focal loss of capillaries and prominence of subpapillary vessels with “punched-out” lesions in systemic lupus erythematosus
308 citations
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307 citations