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      Automated structure and flow measurement — a promising tool in nailfold capillaroscopy

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          Abstract

          Objectives

          Despite increasing interest in nailfold capillaroscopy, objective measures of capillary structure and blood flow have been little studied. We aimed to test the hypothesis that structural measurements, capillary flow, and a combined measure have the predictive power to separate patients with systemic sclerosis (SSc) from those with primary Raynaud's phenomenon (PRP) and healthy controls (HC).

          Methods

          50 patients with SSc, 12 with PRP, and 50 HC were imaged using a novel capillaroscopy system that generates high-quality nailfold images and provides fully-automated measurements of capillary structure and blood flow (capillary density, mean width, maximum width, shape score, derangement and mean flow velocity). Population statistics summarise the differences between the three groups. Areas under ROC curves (A Z) were used to measure classification accuracy when assigning individuals to SSc and HC/PRP groups.

          Results

          Statistically significant differences in group means were found between patients with SSc and both HC and patients with PRP, for all measurements, e.g. mean width (μm) ± SE: 15.0 ± 0.71, 12.7 ± 0.74 and 11.8 ± 0.23 for SSc, PRP and HC respectively. Combining the five structural measurements gave better classification (A Z = 0.919 ± 0.026) than the best single measurement (mean width, A Z = 0.874 ± 0.043), whilst adding flow further improved classification (A Z = 0.930 ± 0.024).

          Conclusions

          Structural and blood flow measurements are both able to distinguish patients with SSc from those with PRP/HC. Importantly, these hold promise as clinical trial outcome measures for treatments aimed at improving finger blood flow or microvascular remodelling.

          Highlights

          • Novel system allows rapid capture of high-quality capillary structure and flow images.

          • Nailfold capillary structure and flow can be measured automatically.

          • Combining capillary structure and flow strongly discriminates disease from normality.

          • Flow, significantly reduced in SSc, shows potential as a functional outcome measure.

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          Most cited references19

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          Criteria for the classification of early systemic sclerosis.

          We propose criteria for the early diagnosis and classification of systemic sclerosis that reflect the vascular and serological advances of the last 2 decades.
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            Preliminary criteria for the very early diagnosis of systemic sclerosis: results of a Delphi Consensus Study from EULAR Scleroderma Trials and Research Group.

            To identify a core set of preliminary items considered as important for the very early diagnosis of systemic sclerosis (SSc). 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. 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. 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.
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              The challenge of early systemic sclerosis for the EULAR Scleroderma Trial and Research group (EUSTAR) community. It is time to cut the Gordian knot and develop a prevention or rescue strategy.

              Early diagnosis of systemic sclerosis (SSc) may allow the start of treatment that could slow disease progression. For this reason early diagnosis of the disease is of pivotal importance. However, the lack of diagnostic criteria and valid predictors significantly limit patient evaluation and the use of potentially effective drugs in the earliest phase of SSc. Early SSc may be suspected on the basis of Raynaud's phenomenon, puffy fingers, autoantibodies and SSc capillaroscopic pattern. In practice, the aim is to have criteria for the diagnosis of very early SSc. The criteria that are proposed are obviously provisional and need to be validated: (a) initially through a Delphi technique; (b) thereafter perhaps using already available datasets; but (c) of critical importance, through prospective studies. Only after prospective studies can these potential criteria be considered validated. The consensus on criteria for the classification of very early SSc might be part of the evolving EULAR/ACR project of reclassification of SSc.
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                Author and article information

                Contributors
                Journal
                Microvasc Res
                Microvasc. Res
                Microvascular Research
                Academic Press
                0026-2862
                1095-9319
                1 July 2018
                July 2018
                : 118
                : 173-177
                Affiliations
                [a ]Centre for Imaging Sciences, Division of Informatics, Imaging & Data Sciences, The University of Manchester, Manchester, UK
                [b ]Division of Musculoskeletal & Dermatological Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
                [c ]Salford Royal NHS Foundation Trust, Salford, UK
                [d ]NIHR Manchester Musculoskeletal Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
                Author notes
                [* ]Corresponding author at: The University of Manchester, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK. ariane.herrick@ 123456manchester.ac.uk
                Article
                S0026-2862(17)30266-2
                10.1016/j.mvr.2018.03.016
                5956308
                29605552
                e53d1ccf-0fc2-44f7-8c47-657e66590f15
                © 2018 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 7 December 2017
                : 8 March 2018
                : 28 March 2018
                Categories
                Article

                Cardiovascular Medicine
                systemic sclerosis,nailfold capillaroscopy,red blood cell velocity,microcirculation

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