The Impact of Nailfold Capillaroscopy in the Approach of Microcirculation

Nailfold capillaroscopy (NFC) is a simple, validated, and noninvasive method to assess the microcirculation, through direct visualization of the capillaries. Main patterns are classified, according to Cutolo et al., as scleroderma, further divided into early, active, or late patterns, or nonscleroderma. NFC findings include dilated loops, tortuosities, meandering or bushy capillaries, hemorrhage, or architectural distortion. NFC use has been indicated for the evaluation of Raynaud’s phenomenon (RP), once it permits the distinction between primary and secondary RP. NFC results accounts for diagnostic criteria of systemic sclerosis, but they can also be useful in staging other connective tissue autoimmune diseases, like systemic lupus erythematosus, inflammatory myositis, or vasculitis. The CSURI index uses NFC for prediction of digital ulcer relapse. Recent evidence revealed NFC can also be applied in systemic disorders with vascular involvement

Raynaud’s phenomenon: a mirror of autoimmune disease

Raynaud’s phenomenon is a discoloration of the hands and feet provoked by cold or emotional stress. In some patients it is the first symptom of an underlying autoimmune disease (secondary), however, in most patients it is without an underlying disease (primary). Because it is important to treat patients with an autoimmune disease in an early stage, it is important to differentiate between the primary and secondary Raynaud’s. Furthermore, Raynaud’s can give complaints such as pain, which can reduce the patients’ quality of life.In this thesis the mechanisms which lead to this phenomenon are addressed, differentiators between primary and secondary Raynaud’s are assessed, and treatment options are studied. The most important conclusions are that there is a relation between damage to the nailfold capillaries and the degree of the attacks, and also with body mass index. Furthermore, changes in the capillaries seem to predict the presence of abnormal pulmonary function tests in patients with different autoimmune diseases. When the thumb is uninvolved and after a Raynaud’s attack there is a quick recovery, an underlying disease is unlikely. Regarding to treatment, bosentan seems to improve the stiffness of the forearm arteries. Lastly, the ‘SPTS’, a procedure to treat Raynaud’s, seems to be effective on short-term and has minimal burden

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

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

No effects of bosentan on microvasculature in patients with limited cutaneous systemic sclerosis

The endothelium-derived vasoconstrictor molecule endothelin-1 (ET-1) has been suggested to play a role in the pathogenesis of Raynaud's phenomenon (RP) and systemic sclerosis (SSc). We studied the effect of bosentan on microvascular structure and function in patients with RP secondary to limited cutaneous SSc in a mechanistic pilot study. In this single center, open study, 15 patients with limited cutaneous SSc were treated with bosentan for 16 weeks with a follow-up period of 4 weeks. Changes in microvascular structure and function were studied with assessment of vasodilatory microvascular responses using laser Doppler fluxmetry combined with iontophoresis, capillary permeability using fluorescence videomicroscopy, nailfold capillary microscopy, and serological markers of endothelial activation. No significant changes were seen in vasodilator responses to acetylcholine and sodium nitroprusside following bosentan treatment. No effect was noted on capillary permeability during treatment. The number of nailfold capillaries remained unchanged. The endothelial activation marker vascular cell adhesion molecule did not change during treatment, but levels of thrombomodulin significantly decreased after 12 weeks of treatment. Bosentan did not induce significant changes in vasodilator responses, capillary permeability, and capillary density during treatment, so no evidence was obtained for structural improvement of microvascular structure and function in this short-time mechanistic pilot study in patients with lcSSc

Systematic analysis of the literature in search of defining systemic sclerosis subsets

OBJECTIVE: Systemic sclerosis (SSc) is a multisystem disease with heterogeneity in presentation and prognosis. An international collaboration to develop new SSc subset criteria is underway. Our objectives were to identify systems of SSc subset classification and synthesize novel concepts to inform development of new criteria. METHODS: Medline, Cochrane MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, EMBASE, and Web of Science were searched from their inceptions to December 2019 for studies related to SSc subclassification, limited to humans and without language or sample size restrictions. RESULTS: Of 5686 citations, 102 studies reported original data on SSc subsets. Subset classification systems relied on extent of skin involvement and/or SSc-specific autoantibodies (n = 61), nailfold capillary patterns (n = 29), and molecular, genomic, and cellular patterns (n = 12). While some systems of subset classification confer prognostic value for clinical phenotype, severity, and mortality, only subsetting by gene expression signatures in tissue samples has been associated with response to therapy. CONCLUSION: Subsetting on extent of skin involvement remains important. Novel disease attributes including SSc-specific autoantibodies, nailfold capillary patterns, and tissue gene expression signatures have been proposed as innovative means of SSc subsetting

Nailfold capillary scleroderma pattern may be associated with disease damage in childhood-onset systemic lupus erythematosus:important lessons from longitudinal follow-up

OBJECTIVES: To observe if capillary patterns in childhood-onset SLE (cSLE) change over time and find associations between a capillary scleroderma pattern with disease activity, damage or scleroderma-like features. METHODS: Clinical and (yearly) capillaroscopy data from a longitudinal cohort of patients with cSLE (minimum of four Systemic Lupus International Collaborating Clinics (SLICC) criteria, onset <18 years) were analysed. Disease activity was measured by Systemic Lupus Erythematosus Activity Index (SLEDAI) and disease damage by SLICC Damage Index. A scleroderma pattern was defined according to the ‘fast track algorithm’ from the European League Against Rheumatism Study Group on Microcirculation in Rheumatic Diseases. An abnormal capillary pattern, not matching a scleroderma pattern, was defined as ‘microangiopathy’. RESULTS: Our cohort consisted of 53 patients with cSLE with a median disease onset of 14 years (IQR 12.5–15.5 years), median SLEDAI score at diagnosis was 11 (IQR 8–16), median SLEDAI at follow-up was 2 (IQR 1–6). A scleroderma pattern (ever) was seen in 18.9%, while only 13.2% of patients had a normal capillary pattern. Thirty-three patients had follow-up capillaroscopy of which 21.2% showed changes in type of capillary pattern over time. Type of capillary pattern was not associated with disease activity. Raynaud’s phenomenon (ever) was equally distributed among patients with different capillaroscopy patterns (p=0.26). Anti-ribonucleoprotein antibodies (ever) were significantly more detected (Χ(2), p=0.016) in the scleroderma pattern subgroup (n=7 of 10, 70%). Already 5 years after disease onset, more than 50% of patients with a scleroderma pattern had SLE-related disease damage (HR 4.5, 95% CI 1.1 to 18.8, p=0.034), but they did not develop clinical features of systemic sclerosis at follow-up. Number of detected fingers with a scleroderma pattern was similar between cSLE, juvenile systemic sclerosis and juvenile undifferentiated connective tissue disease. CONCLUSION: This longitudinal study shows that the majority of capillary patterns in cSLE are abnormal and they can change over time. Irrespective of disease activity, a capillary scleroderma pattern in cSLE may be associated with higher risk of SLE-related disease damage

Nailfold Videocapillaroscopic Features and Other Clinical Risk Factors for Digital Ulcers in Systemic Sclerosis: A Multicenter, Prospective Cohort Study

OBJECTIVE: To identify nailfold videocapillaroscopic and other clinical risk factors for new digital ulcers (DUs) in a 6-month period in patients with systemic sclerosis (SSc), the videoCAPillaroscopy (CAP) study. METHODS: Overall 623 patients with SSc from 59 centers (14 countries) were stratified into two groups: "DU History" and "No-DU History". At enrollment, patients underwent detailed nailfold videocapillaroscopic evaluation and an assessment of demographics, DU status, and clinical and SSc characteristics. Risk factors for developing new DUs were assessed using univariable and multivariable logistic regression analyses. RESULTS: Of the "DU History" group (n = 468), 79.5% were female, the mean age was 54.0 ± 13.7 years, 59.8% had limited cutaneous SSc, and 22% developed a new DU during follow-up. The strongest risk factors for new DUs identified by multivariable logistic regression (MLR) in the "DU History" group included: mean number of capillaries/mm in the middle finger of the dominant hand, number of DUs (0, 1, 2, ≥3), and presence of critical digital ischemia. The receiver operating characteristic area under the curve (ROC-AUC) (95% confidence interval [CI]) of the final MLR model was 0.738 (0.681-0.795). Internal validation through bootstrap generated a ROC-AUC (95% CI) of 0.633 (0.510-0.756). CONCLUSION: This international, prospective study including detailed nailfold videocapillaroscopic evaluation and extensive clinical characterization of patients with SSc identified the mean number of capillaries/mm in the middle finger of the dominant hand, number of DUs and presence of critical digital ischemia at enrollment as risk factors for the development of new DUs. This article is protected by copyright. All rights reserved