Graham Dinsdale

A study comparing videocapillaroscopy and dermoscopy in the assessment of nailfold capillaries in patients with systemic sclerosis–spectrum disorders

OBJECTIVES Nailfold videocapillaroscopy (NVC), the current gold standard for detection of capillary abnormalities suggestive of an SSc-spectrum disorder, is not widely available: a key question is whether lower-magnification, easy-to-use dermoscopy compares favourably. This is especially relevant given the inclusion of capillaroscopic abnormality within the 2013 classification criteria for SSc. Our objectives were to examine the ability to classify capillaries and to evaluate abnormality (severity), by both NVC and dermoscopy, to determine whether these differ between general and specialist rheumatologists, and to compare intra- and interrater reliability of both techniques. METHODS NVC and dermoscopy images were acquired from all 10 nailbeds of 32 subjects with a range of capillary abnormalities. Images were graded (using a web-based interface) on a 0-3 scale of severity: normal (0), mildly (1), definitely (2) and grossly abnormal (3), and an unclassifiable category. Raters graded images from four subjects (40 nailbeds) using each technique, with five repeated images to estimate intrarater reliability. RESULTS Forty-eight rheumatologists from 12 countries participated in the study (22 generalists, 26 specialists). While most images could be graded by both techniques, more were graded by NVC (84% vs 70%) and were systematically scored higher by NVC (mean difference 0.43 between the ratings). Agreement between the techniques was moderate. Intra- and interrater reliability were comparable for the two techniques in the classifiability of images and the grading of severity. CONCLUSION Our results suggest that dermoscopy is comparable to NVC, although NVC images were more likely to be classifiable and were graded more severely.

An Automated System for Detecting and Measuring Nailfold Capillaries

Nailfold capillaroscopy is an established qualitative technique in the assessment of patients displaying Raynauds phenomenon. We describe a fully automated system for extracting quantitative biomarkers from capillaroscopy images, using a layered machine learning approach. On an unseen set of 455 images, the system detects and locates individual capillaries as well as human experts, and makes measurements of vessel morphology that reveal statistically significant differences between patients with (relatively benign) primary Raynauds phenomenon, and those with potentially life-threatening systemic sclerosis.

A comparison of intense pulsed light and laser treatment of telangiectases in patients with systemic sclerosis: a within-subject randomized trial

OBJECTIVE Cutaneous telangiectases are a characteristic and psychologically distressing feature of SSc. Our aim was to assess the efficacy of two light-based treatments: pulsed dye laser (PDL) and intense pulsed light (IPL). METHODS Nineteen patients with facial or upper limb telangiectases underwent three treatments with PDL and IPL (randomly assigned to left- and right-sided lesions). Outcome measures were clinical photography (assessed by two clinicians), dermoscopy (assessed by two observers), laser Doppler imaging (LDI) and observer and patient opinion, including patient self-assessment psychological questionnaires [Hospital Anxiety and Depression Scale (HADS), Adapted Satisfaction with Appearance Scale (ASWAP)]. RESULTS Comparison between 16-week follow-up and baseline photography scores (from -2 to +2 on a Likert scale, with >0 being improvement) were a mean score for PDL of 1.7 (95% CI 1.4, 2.0) and for IPL 1.4 (0.9, 1.8), with a mean difference between PDL and IPL of -0.3 (-0.5, -0.1) (P = 0.01). Dermoscopy scores also improved with both therapies: PDL 1.3 (1.1, 1.5) and IPL 0.8 (0.5, 1.1), again greater with PDL (P = 0.01). LDI showed decreases in blood flow at 16 weeks, indicating a response to both therapies. All patients reported benefit from treatment (more preferred PDL at 16 weeks). Psychological questionnaires also indicated improvement after therapy with mean change in ASWAP of -13.9 (95% CI -20.5, -7.4). No side effects were reported for IPL; PDL caused transient bruising in most cases. CONCLUSION Both PDL and IPL are effective treatments for SSc-related telangiectases. Outcome measures indicate that PDL has better outcomes in terms of appearance, although IPL had fewer side effects.

Reduced perfusion in systemic sclerosis digital ulcers (both fingertip and extensor) can be increased by topical application of glyceryl trinitrate

Objectives In patients with systemic sclerosis (SSc), fingertip digital ulcers (DUs) are believed to be ischaemic, and extensor surface DUs a result of mechanical factors/microtrauma. Our aim was to assess blood flow response to topical glyceryl trinitrate (GTN) compared to placebo in SSc DUs, looking for differences in pathophysiology between fingertip and extensor lesions. Method This was a double-blind, randomised, crossover, placebo-controlled study. Sixteen (6 fingertip, 10 extensor) DUs were each studied twice (one day apart): once with GTN and once with placebo ointment. Perfusion at the DU centre (‘DUCore’) and periphery (‘DUPeriphery’), as measured by laser Doppler imaging was performed before and immediately after ointment application, then every 10 min, up to 90 min post-application. We calculated the area under the response curve (AUC) and the ratio of peak perfusion to baseline, then compared these between GTN and placebo. Results Perfusion was lower in the DUCore compared to the DUPeriphery (ratio of 0.52). The microvessels of the DUCore were responsive to GTN, with an increase in perfusion, with a similar effect in both fingertip and extensor DUs. The AUC and peak/baseline perfusion difference in means (ratio, 95% confidence interval) between GTN and placebo at the DUCore were 1.2 (1.0–1.6) and 1.2 (1.0–1.5) respectively, and at the DUPeriphery were 1.1 (0.8–1.6) and 1.0 (0.9–1.2) respectively. Conclusion DUs (both fingertip and extensor) were responsive to topical GTN, with an increase in perfusion to the ischaemic DU centre. If both fingertip and extensor DUs have a (potentially reversible) ischaemic aetiology, this has important treatment implications.

Does the clinical context improve the reliability of rheumatologists grading digital ulcers in systemic sclerosis

Digital ulcers (DUs) are often a primary end point in systemic sclerosis (SSc; scleroderma) clinical trials, although the reliability of rheumatologists grading DUs is poor to moderate at best. DU assessment in recent trials has been based upon visual inspection alone, which potentially misses “real‐world” clinical contextual information. Our aim was to investigate whether this clinical information improves the reliability of rheumatologists grading DUs. A secondary aim was to assess agreement between patients and rheumatologists.

Thermographic Abnormalities are Associated with Future Digital Ulcers and Death in Patients with Systemic Sclerosis

Objective. Capillaroscopic abnormalities are predictive of future digital ulcers (DU). Our aim was to investigate whether functional digital vascular disease (thermographically assessed) is also associated with future DU. Methods. A retrospective case note review of patients with systemic sclerosis (SSc) undergoing thermography and who were followed for up to about 3 years. Results. There were 138 patients (equal mixture of normal/abnormal thermography). Patients with abnormal thermography were more likely to develop DU (clinician-observed and/or patient-reported, OR 2.84, p = 0.021), including multiple episodes, and more likely to die (OR 5.42, p = 0.050). Conclusion. Abnormal thermography is associated with DU and disease severity in patients with SSc.

A Multicenter Study of the Validity and Reliability of Responses to Hand Cold Challenge as Measured by Laser Speckle Contrast Imaging and Thermography: Outcome Measures for Systemic Sclerosis–Related Raynaud's Phenomenon

Reliable and objective outcome measures to facilitate clinical trials of novel treatments for systemic sclerosis (SSc)–related Raynauds phenomenon (RP) are badly needed. Laser speckle contrast imaging (LSCI) and thermography are noninvasive measures of perfusion that have shown excellent potential. This multicenter study was undertaken to determine the reliability and validity of a hand cold challenge protocol using LSCI, standard thermography, and low‐cost cell phone/mobile phone thermography (henceforth referred to as mobile thermography) in patients with SSc‐related RP.

Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study

Objectives Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs). Methods The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. ‘Progressors’ were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV). Results 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%. Conclusions Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years. Trial registration number NCT02339441.

Simulating nailfold capillaroscopy sequences to evaluate algorithms for blood flow estimation

The effects of systemic sclerosis (SSc) - a disease of the connective tissue causing blood flow problems that can require amputation of the fingers - can be observed indirectly by imaging the capillaries at the nailfold, though taking quantitative measures such as blood flow to diagnose the disease and monitor its progression is not easy. Optical flow algorithms may be applied, though without ground truth (i.e. known blood flow) it is hard to evaluate their accuracy. We propose an image model that generates realistic capillaroscopy videos with known flow, and use this model to quantify the effect of flow rate, cell density and contrast (among others) on estimated flow. This resource will help researchers to design systems that are robust under real-world conditions.

Digital ulcers in systemic sclerosis are associated with microangiopathic abnormalities of perilesional skin as assessed by capillaroscopy

Centre for Musculoskeletal Research, The University of Manchester, Manchester Academic Health Science Centre, Salford Royal NHS Foundation Trust, Manchester, Department of Rheumatology, Salford Royal NHS Foundation Trust, Salford, Photon Science Institute, The University of Manchester, Manchester, and NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK