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Objectives EULAR supports the use of nailfold videocapillaroscopy (NVC) for identifying disease patterns (DPs) associated with SSc and RP. Recently, EULAR proposed an easy-to-manage procedure, a so-called Fast Track algorithm, for differentiating SSc patterns from non-SSc patterns in NVC specimens. However, subjectivity among capillaroscopists remains a limitation. Our aim was to perform a software-based analysis of NVC peculiarities in a cohort of samples from SSc and RP patients and, subsequently, build a Fast Track–inspired algorithm for identifying DPs without the constraint of interobserver variability. Methods NVCs were examined by 9 capillaroscopists. Those NVCs whose DPs were consensually agreed upon (by ≥2 out of 3 interobservers) were subsequently analysed using in-house–developed software. The results for each variable were grouped according to the consensually agreed-upon DPs in order to identify useful hallmarks for categorizing them. Results A total of 851 NVCs (21 957 images) whose DPs had been consensually agreed upon were software-analysed. Appropriate cut-offs set for capillary density and percentage of abnormal and giant capillaries, tortuosities and haemorrhages allowed DP categorization and the development of the CAPI-score algorithm. This consisted of four rules: Rule 1, SSc vs non-SSc, accuracy 0.88; Rules 2 and 3, SSc-early vs SSc-active vs SSc-late, accuracy 0.82; Rule 4, non-SSc normal vs non-SSc non-specific, accuracy 0.73. Accuracy improved when the analysis was limited to NVCs whose DPs had achieved full consensus between the interobservers. Conclusion The CAPI-score algorithm may become a tool that is useful in assigning DPs by overcoming the limitations of subjectivity. [ABSTRACT FROM AUTHOR]

Objective Patients with secondary RP show a wide range of symptoms depending on the condition of vascular structures. If the symptoms are localized to specific fingers and angiography reveals a discrete segment of occlusion of a proper digital artery, we perform proper digital artery reconstruction with an interposition vein graft. The objective of this study was to evaluate the results of the surgery in patients with chronic hand ischaemia. Methods A retrospective chart review was performed on patients who underwent proper digital artery reconstruction. Each digit that underwent grafting was analysed separately. The results of surgical intervention and recurrence based on patient symptoms were evaluated. Cox proportional hazards regression models were used to identify independent risk factors associated with recurrence, and the Kaplan–Meier method was used to predict the 5-year recurrence-free rate. Results A total of 79 digits from 57 patients were included in this study. The majority of patients demonstrated resolution of ischaemic pain and ulceration (97.5% and 95.3%, respectively). Recurrence occurred in 16 (20.3%) patients during the follow-up period. In two cases (2.5%) surgery had no effect. In the multivariate Cox regression analysis, smoking and concomitant periarterial sympathectomy were significant factors associated with recurrence. In the Kaplan–Meier analysis, the 5-year recurrence-free rate in the total study population was 69.3%. Conclusions Digital artery reconstruction using an interposition vein graft is an effective procedure for improving ischaemic pain and ulceration in patients with RP. Smoking and concomitant periarterial sympathectomy were significantly associated with recurrence. [ABSTRACT FROM AUTHOR]

Objectives To compare clinical characteristics, including the frequency of cutaneous, extramuscular manifestations and malignancy, between adults with anti-synthetase syndrome (ASyS) and DM. Methods Using data regarding adults from the MYONET registry, a cohort of DM patients with anti-Mi2/-TIF1γ/-NXP2/-SAE/-MDA5 autoantibodies, and a cohort of ASyS patients with anti-tRNA synthetase autoantibodies (anti-Jo1/-PL7/-PL12/-OJ/-EJ/-Zo/-KS) were identified. Patients with DM sine dermatitis or with discordant dual autoantibody specificities were excluded. Sub-cohorts of patients with ASyS with or without skin involvement were defined based on presence of DM-type rashes (heliotrope rash, Gottron's papules/sign, violaceous rash, shawl sign, V-sign, erythroderma, and/or periorbital rash). Results In total 1054 patients were included (DM, n  = 405; ASyS, n  = 649). In the ASyS cohort, 31% (n  = 203) had DM-type skin involvement (ASyS-DMskin). A higher frequency of extramuscular manifestations, including Mechanic's hands, Raynaud's phenomenon, arthritis, interstitial lung disease and cardiac involvement differentiated ASyS-DMskin from DM (all P  < 0.001), whereas higher frequency of any of four DM-type rashes—heliotrope rash (n  = 248, 61% vs n  = 90, 44%), violaceous rash (n  = 166, 41% vs n  = 57, 9%), V-sign (n  = 124, 31% vs n  = 28, 4%), and shawl sign (n  = 133, 33% vs n  = 18, 3%)—differentiated DM from ASyS-DMskin (all P  < 0.005). Cancer-associated myositis (CAM) was more frequent in DM (n  = 67, 17%) compared with ASyS (n  = 21, 3%) and ASyS-DMskin (n  = 7, 3%) cohorts (both P  < 0.001). Conclusion DM-type rashes are frequent in patients with ASyS; however, distinct clinical manifestations differentiate these patients from classical DM. Skin involvement in ASyS does not necessitate increased malignancy surveillance. These findings will inform future ASyS classification criteria and patient management. [ABSTRACT FROM AUTHOR]

Objectives Measurement of digital perfusion, sometimes coupled with a cold challenge, has been widely used as an objective outcome in trials evaluating drug therapies in RP, in addition to patient-reported outcomes or to establish the proof-of-concept in preliminary studies. However, whether digital perfusion is a valid surrogate for clinical outcomes in RP trials has never been explored. The principal aim of this study was to evaluate the potential surrogacy of digital perfusion, by combining individual-level and trial-level data. Methods We used individual data from a series of n -of-1 trials, and trial data from a network meta-analysis. We estimated individual-level surrogacy through coefficients of determination between digital perfusion and clinical outcomes (R 2ind). We further calculated the coefficients of determination between treatment effect on the clinical outcomes and on digital perfusion, at the individual level (R 2TEind) and at the trial level (R 2trial), using non-weighted linear regression, with their 95% CI calculated through bootstrapping. Results Results from 33 patients and 24 trials were included in the final analysis. At the individual level, there was no correlation between digital perfusion and clinical outcomes at rest and in response to various cooling tests (the highest R 2ind was 0.03 [−0.07, 0.09]), and R 2TEind was also very low 0.07 (0, 0.29). At the trial level, the highest value of R 2trial was 0.1 (0, 0.477). Conclusions Digital perfusion, at rest or in response to a cold challenge, and whatever the method used, does not fulfil the criteria of a valid surrogate for existing patient-reported outcomes in RP trials. [ABSTRACT FROM AUTHOR]

Objectives Assessment of construct validity and reliability of a novel patient-reported outcome (PRO) instrument for assessing the severity and impact of RP in SSc. Methods An international multicentre study validation study of the 27-item Assessment of Systemic Sclerosis-Associated Raynaud's Phenomenon (ASRAP) and 10-item short-form (ASRAP-SF) questionnaires. The relationship between ASRAP questionnaires and demographics, clinical phenotype and legacy instruments for assessing SSc-RP severity, disability and pain was assessed. Repeatability was evaluated at 1 week. Anchor-based statements of health status facilitated assessment of ASRAP thresholds of meaning. Results A total of 420 SSc subjects were enrolled. There was good correlation between ASRAP (and ASRAP-SF) with RP visual analogue scale (VAS) and Scleroderma Health Assessment Questionnaire RP VAS (rho range 0.648–0.727, P  < 0.001). Correlation with diary-based assessment of SSc-RP attack frequency and duration was lower (rho range 0.258–0.504, P  < 0.001). ASRAP questionnaires had good correlation with instruments for assessing disability, hand function, pain and global health assessment (rho range 0.427–0.575, P  < 0.001). Significantly higher ASRAP scores were identified in smokers, patients with active digital ulceration (DU), previous history of DU and calcinosis (P  < 0.05 for all comparisons). There was excellent repeatability at 1 week among patients with stable SSc-RP symptoms (intra-class coefficients of 0.891 and 0.848, P  < 0.001). Patient-acceptable symptom state thresholds for ASRAP and ASRAP-SF were 45.34 and 45.77, respectively. A preliminary Minimally Important Clinical Difference threshold of 4.17 (95% CI 0.53, 7.81, P  = 0.029) was estimated. Conclusion ASRAP and ASRAP-SF questionnaires are valid and reliable novel PRO instruments for assessing the severity and impact of SSc-RP. [ABSTRACT FROM AUTHOR]

The authors discuss the study "CAPI-score: a quantitative algorithm for identifying disease patterns in nailfold videocapillaroscopy," by B. C. Gracia Tello and colleagues, published in the issue. Topics include impact of the emergence of artificial intelligence (AI) on the medical landscape, challenges in AI's application in nailfold videocapillaroscopy (NVC), and advantages regarding previous AI studies.

The article presents a study which examined the Myoton's ability to assess cutaneous systemic sclerosis (SSc) and compared the results to modified Rodnan skin score (mRSS) and high-frequency ultrasound thickness measurements. Topics discussed include description of Myoton, the use of Myoton to measure the skin stiffness of three SSc patients, and details of the case of each patient.

The article describes the case of Raynaud's phenomenon (RP), digital ischaemia, and paradoxical arthritis as a result of ixekizumab treatment and discusses the potential pathogenesis of these suspected adverse events. Topics include her symptoms that developed after taking ixekizumab, reason for prescribing anticoagulation with low-molecular weight heparin, and proposed hypothesis to explain the underlying mechanisms of paradoxical reactions like arthritis and psoriasis.

Objectives Silver fibre gloves transport heat from the palm to the fingers, possibly reducing the burden of RP in SSc patients. We aim to evaluate the clinical efficiency of this intervention. Methods A multicentre, double-blind, randomized trial was performed, accounting for interindividual differences and external factors using a crossover design. Patients were randomized in two groups: group 1 wore 8% silver fibre gloves in period 1 and normal gloves in period 2 and group 2 vice versa. Each period lasted 6 weeks. The primary outcome was the Raynaud Condition Score (RCS) over time (minimal clinical important difference 1.4), assessed three times per week using an online questionnaire. Secondary outcomes included vascular complications and Scleroderma-Health Assessment Questionnaire (SHAQ). Outcomes were evaluated before unblinding using linear mixed models. Results A total of 85 SSc patients were included, with 76 completing the study. The mean RCS during 2 weeks before the study (i.e. without gloves) was 6.4 (s. d. 1.6). Both with silver fibre gloves and normal gloves the mean RCS decreased to 3.9 (s. d. 2.3) with a similar course over time. There was no difference in mean RCS over time between the type of gloves [β = 0.067 (95% CI −0.006, 0.19)]. Of secondary outcomes, total SHAQ [β = 0.036 (95% CI 0.026, 0.046)] was slightly higher with silver fibre gloves, which is clinically irrelevant. Three patients developed new digital ulcers with normal gloves vs one patient with silver fibre gloves [odds ratio 3.2 (95% CI 0.32, 31.1)]. Conclusions Wearing gloves in SSc patients clearly decreases the RP burden. Our results do not support the hypothesis that increased heat transport of 8% silver fibre gloves is associated with less disease burden as measured in this study by the RCS compared with normal gloves. Clinical trial registration number Netherlands Trial register (https://www.trialregister.nl/) NL7904 [ABSTRACT FROM AUTHOR]

Objective Our main aim was to investigate the effect of a single oral dose of C21, a selective angiotensin II type 2 receptor agonist, on cold-induced vasoconstriction in SSc-related RP. Methods This was a phase IIa, randomized, double-blind, cross-over, single-dose, placebo-controlled, single-centre study. Twelve female patients with SSc (median age 58.5 years, median duration of RP 19.0 years) attended on four occasions: screening, treatment visits 1 and 2 (separated by 3–7 days) and follow-up. At the first treatment visit, patients were randomized to receive either a single oral dose of C21 (200 mg) or placebo, then the opposite treatment on the second visit. Forty min after each treatment, each patient underwent a standard hand cold challenge. The primary end point was the area under the curve (AUC) for rewarming for each finger (eight fingers) over 15 min. Secondary end points included the maximum finger temperature after rewarming (MAX). Statistical analyses were performed by multiplicative ANCOVA models. Results For all eight fingers combined, mean AUC for rewarming was higher after treatment with C21 than after placebo (geometric mean 20 046°C*s vs 19 558°C*s), but not significantly (P  = 0.380) and MAX (at 15 min) was also higher (geometric mean 23.5°C vs 22.5°C; P  = 0.036). C21 was well tolerated. Conclusion Despite the small trial size, a signal emerged suggesting that even in patients with established SSc, C21 may confer benefit for RP and deserves further investigation. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov , NCT04388176. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective MCTD manifests with microvasculopathy and overlapping clinical features of SLE, SSc and idiopathic inflammatory myopathies (IIM). The aim of this study was to investigate the clinical significance of microvasculopathy in patients with MCTD using nailfold videocapillaroscopy (NVC). Methods Fifty patients with newly diagnosed and untreated MCTD were enrolled in this multicentre, prospective and observational study. Clinical features and NVC findings were assessed at baseline and after 1 year post-intervention, along with disease controls [SLE (n  = 40), SSc (n  = 70) and IIM (n  = 50)]. Results All MCTD patients presented Raynaud's phenomenon and were positive for anti-U1 RNP antibodies, and 22.0% (11/50) had pulmonary arterial hypertension (PAH). The prevalence of NVC scleroderma patterns in MCTD was 38.0%, which was lower than SSc (88.6%) but higher than SLE (10.0%). In addition, when we divided MCTD patients into two groups by presence or absence of NVC scleroderma patterns, we found a higher prevalence of PAH in patients with NVC scleroderma patterns. Namely, NVC scleroderma patterns were observed in all MCTD patients with PAH, and in 21.0% of those without PAH. After intensive immunosuppressive therapy, NVC scleroderma patterns disappeared in half of the MCTD patients but were not changed in SSc patients. Conclusions MCTD differed from SLE, SSc and IIM in terms of the prevalence and responsiveness of NVC scleroderma patterns to immunosuppressive therapy. Detection of nailfold microvascular abnormalities in MCTD could contribute to predicting PAH and help us to understand further aspects of the pathogenesis of MCTD. [ABSTRACT FROM AUTHOR]

The article describes the case of a 60-year-old man with 12-month history of discolouration of the fingers after cold exposure or emotional distress. Topics discussed include his medical history, symptoms that appeared after cold exposure or emotional stress, which was compatible with his history of Raynaud's phenomenon (RP), and conclusion on the recurrence of RP.

Objective This study analysed the very early disease of SSc (VEDOSS) characteristics in a group of 217 patients with RP and at least one manifestation of SSc in search of predictors for the progression to SSc. Methods This was a cross-sectional single-centre analysis of patients presenting with RP with a specific SSc clinical manifestation or SSc autoantibody or SD pattern at nailfold capillaroscopy (SD-NFC), without skin involvement, who attended a scleroderma outpatient clinic between 2010 and 2019. The performance of VEDOSS and the importance of the combination of VEDOSS characteristics to predict the progression to SSc were evaluated. Results Among 217 patients, 153 (70.5%) were classified as SSc, including 65 (30%) in the first investigation; 69.3% of the SSc patients met VEDOSS criteria compared with 6.3% of patients who did not progress to SSc. The combinations most associated with progression to SSc were RP + puffy fingers (PF) + positive ANA + SD-NFC and/or SSc-specific antibody (VEDOSS level 2), with an odds ratio (OR) of 19.52 (95% CI 4.48, 85.06; P  < 0.001) and RP + PF + positive ANA (VEDOSS level 1; 'red flags') (OR 15.45; P  < 0.001), while combinations without non-RP clinical symptoms, as RP + SD-NFC (OR 0.03; P  < 0.001) and RP + anticentromere + SD-NFC (OR 0.06; P  = 0.006) were associated with non-progression to SSc. Conclusion Among patients with RP with at least one manifestation of SSc, without skin involvement, combinations of VEDOSS characteristics were the strongest predictors of progression to SSc at a median follow-up of 4 years. [ABSTRACT FROM AUTHOR]

Objective In patients with RP, capillaroscopy is useful for discriminating primary from secondary causes. There are certain capillaroscopy and lab values as predictive factors leading to a known CTD. We conducted the present study to evaluate the causes of RP in our area and followed the studied subjects to find prognostic factors indicating a definite CTD or remaining a UCTD. Methods In this retrospective cohort study we included all adult patients with RP who were referred for capillaroscopy from 2010 to 2019. All the patients with primary and secondary RP with follow-up were evaluated for demography, laboratory results and capillaroscopy to find the risk factors of their progression to a CTD. Results A total of 760 of 776 patients were included, with 679 being female (89.3%) and 81 (10.7%) male. There were 660 subjects (90.8%) with secondary RP [mostly UCTD (48.2%) and then SSc (16.4%)] and 67 (9.2%) with primary RP; 109 patients were followed up and 42 (42%) of those with secondary RP developed a definite CTD. The scleroderma pattern and some capillary changes on capillaroscopy and/or positive ANA had statistically significant differences for CTD transition. Conclusion We had a small number of patients with primary RP. The most prevalent causes of secondary RP in our patients were UCTD and SSc. Some capillaroscopy and laboratory results alone or in combination could be used as a predictive marker for the transition of patients with UCTD to CTD. [ABSTRACT FROM AUTHOR]

Objective Anti-NOR90 antibodies are usually found in patients with SSc; however, their clinical relevance remains obscure. We developed an ELISA for measuring them to investigate the clinical features of patients with anti-NOR90 antibodies. Methods Serum samples from 1252 patients with various conditions from Nagoya University Hospital and 244 patients with idiopathic interstitial pneumonia (IIP) from Tosei General Hospital were included. Anti-NOR90 antibodies were assayed by an ELISA using the recombinant protein produced by in vitro transcription/translation. Results Five (0.4%) patients in the Nagoya University Hospital cohort had anti-NOR90 antibodies. One patient with diffuse cutaneous SSc, three with limited cutaneous SSc, and one with Raynaud's disease were positive for anti-NOR90 antibodies. Anti-NOR90 antibodies were found more frequently in patients with systemic scleroderma-spectrum disorders (SSDs) than without SSDs (5/316 vs 0/936, P <0.00101) and were found more frequently in patients with SSc than without SSc (4/249 vs 0/528, P <0.0104) in the systemic autoimmune rheumatic diseases cohort. Three of the four anti-NOR90-positive SSc patients had interstitial lung disease (ILD), and two of those four had cancer. Three (1.2%) patients in the Tosei General Hospital cohort had anti-NOR90 antibodies. All three of the anti-NOR90-positive IIP patients had gastrointestinal tract involvement, and two of those three had cancer or skin lesions observed in SSc. Conclusions Although anti-NOR90 antibodies are rarely found in clinics, our ELISA is useful for their detection. Further studies are needed to confirm the association of anti-NOR90 antibodies with ILD and cancer in SSc and IIP patients. [ABSTRACT FROM AUTHOR]

Objective SSc is a complex CTD affecting mental and physical health. Fatigue, hand function loss, and RP are the most prevalent disease-specific symptoms of systemic sclerosis. This study aimed to develop consensus and evidence-based recommendations for non-pharmacological treatment of these symptoms. Methods A multidisciplinary task force was installed comprising 20 Dutch experts. After agreeing on the method for formulating the recommendations, clinically relevant questions about patient education and treatments were inventoried. During a face-to-face task force meeting, draft recommendations were generated through a systematically structured discussion, following the nominal group technique. To support the recommendations, an extensive literature search was conducted in MEDLINE and six other databases until September 2020, and 20 key systematic reviews, randomized controlled trials, and published recommendations were selected. Moreover, 13 Dutch medical specialists were consulted on non-pharmacological advice regarding RP and digital ulcers. For each recommendation, the level of evidence and the level of agreement was determined. Results Forty-one evidence and consensus-based recommendations were developed, and 34, concerning treatments and patient education of fatigue, hand function loss, and RP/digital ulcers-related problems, were approved by the task force. Conclusions These 34 recommendations provide guidance on non-pharmacological treatment of three of the most frequently described symptoms in patients with systemic sclerosis. The proposed recommendations can guide referrals to health professionals, inform the content of non-pharmacological interventions, and can be used in the development of national and international postgraduate educational offerings. [ABSTRACT FROM AUTHOR]

Objective Digital pitting scars (DPS) are frequent, but little studied in SSc to date. Methods An analysis of SSc patients enrolled in the EUSTAR database. Primary objectives were to (i) examine DPS prevalence; (ii) examine whether DPS are associated with digital ulcers (DUs) and active digital ischaemia (DUs or gangrene); and (iii) describe other associations with DPS including internal organ complications. Secondary objectives were whether DPS are associated with (i) functional impairment; (ii) structural microvascular disease; and (iii) mortality. Descriptive statistics and parametric/non-parametric tests were used. Binary logistic regression was used to examine the association between DPS and DUs, active digital ischaemia and mortality. Results A total of 9671 patients were included with reported DPS at any time point (n  = 4924) or 'never' DPS (n  = 4747). The majority (86.9%) were female and mean age was 55.7 years. DPS were associated with longer disease and Raynaud's duration (both P  ≤ 0.001). DPS were associated with interstitial lung disease, pulmonary hypertension, conduction blocks, telangiectases, calcinosis (all P  ≤ 0.001) and joint synovitis (P  = 0.021). Patients were more likely to have more severe capillaroscopic abnormality and greater hand functional impairment. Multivariable logistic regression analyses showed that DPS were associated (odds ratio) with DUs: 22.03 (19.51–24.87), active digital ischaemia: 6.30 (5.34–7.42) and death: 1.86 (1.48–2.36). Conclusion DPS are associated with a severe disease course including death. The impact of DPS on hand function and ischaemia is significant. The presence of DPS should alert the clinician to a poor prognosis and need to optimize the therapeutic strategy. [ABSTRACT FROM AUTHOR]

Objectives In SSc patients, disease specific determinants that influence health-related quality of life (HRQoL) over time have not been described. We aim to, in patients with SSc, (i) evaluate if and how HRQoL changes over time, and (ii) assess how different SSc domains and functional impairments contribute to changes in HRQoL over time. Methods All SSc patients from the Leiden SSc cohort were included; patients with disease duration <24 months were classified as incident cases. HRQoL was assessed prospectively on an annual basis using the EQ-5D and the SF36. To assess baseline associations between clinical characteristics and HRQoL, linear regressions were performed. To identify possible associations between SSc characteristics and HRQoL change over time, linear mixed models were performed in both incident and prevalent cases. Results In total, 492 SSc patients were included (n  = 202 incident cases), with a median follow-up duration of 3.4 years. At baseline, presence of organ involvement was independently associated with a worse SF36 physical component score and lower EQ-5D score. Over time, gastrointestinal symptoms, Raynaud and digital ulcers were independently associated with deterioration of HRQoL in both incident and prevalent cases. In prevalent cases, pulmonary arterial hypertension (PAH) was associated with a decrease in HRQoL over time. Worse functioning as measured by six-min walking distance, mouth-opening, finger-to-palm distance and grip-strength contributed significantly to deterioration of HRQoL over time. Conclusion In SSc, key clinical burdens that contribute to worsening of HRQoL over time include digital ulcers, Raynaud and gastrointestinal involvement. In addition, PAH is a significant burden in prevalent disease. [ABSTRACT FROM AUTHOR]

Objectives To identify clinical factors associated with cancer risk in the idiopathic inflammatory myopathies (IIMs) and to systematically review the existing evidence related to cancer screening. Methods A systematic literature search was carried out on Medline, Embase and Scopus. Cancer risk within the IIM population (i.e. not compared with the general population) was expressed as risk ratios (RR) for binary variables and weighted mean differences (WMD) for continuous variables. Evidence relating to cancer screening practices in the IIMs were synthesized via narrative review. Results Sixty-nine studies were included in the meta-analysis. DM subtype (RR 2.21), older age (WMD 11.19), male sex (RR 1.53), dysphagia (RR 2.09), cutaneous ulceration (RR 2.73) and anti-transcriptional intermediary factor-1 gamma positivity (RR 4.66) were identified as being associated with significantly increased risk of cancer. PM (RR 0.49) and clinically amyopathic DM (RR 0.44) subtypes, Raynaud's phenomenon (RR 0.61), interstitial lung disease (RR 0.49), very high serum creatine kinase (WMD −1189.96) or lactate dehydrogenase (WMD −336.52) levels, and anti-Jo1 (RR 0.45) or anti-EJ (RR 0.17) positivity were identified as being associated with significantly reduced risk of cancer. Nine studies relating to IIM-specific cancer screening were included. CT scanning of the thorax, abdomen and pelvis appeared to be effective in identifying underlying asymptomatic cancers. Conclusion Cancer risk factors should be evaluated in patients with IIM for risk stratification. Screening evidence is limited but CT scanning could be useful. Prospective studies and consensus guidelines are needed to establish cancer screening strategies in IIM patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

It is 120 years since 'angiomyositis' was included alongside 'polymyositis' and 'dermatomyositis' in an attempt to propose a taxonomy that reflected the major clinical characteristics of idiopathic inflammatory myopathy (IIM). Endothelial injury, perivascular inflammation and capillary loss are important histological findings in affected tissues in IIM. Overt vascular clinical features including RP and abnormal nailfold capillaroscopy (NC) are also common in IIM. Despite the presence of endothelial injury, perivascular inflammation and capillary loss in affected tissues in IIM, and the presence of clinical features such as RP and NC abnormalities, the pathogenic and therapeutic implications of vasculopathy in IIM have been somewhat overlooked. RP and NC abnormalities are not always present, providing a valuable opportunity to explore aetiopathogenic factors driving vasculopathy within autoimmune rheumatic disease. The present review examines the aetiopathogenic, prognostic and therapeutic significance of vasculopathy in IIM. We describe the prevalence and clinical relevance of vasculopathy in IIM, and consider how vasculopathy may be better utilized to support improved IIM diagnosis and disease classification. Areas of unmet research need are highlighted where relevant. [ABSTRACT FROM AUTHOR]

Objective To assess the minimally invasive single-port thoracoscopic sympathicotomy feasibility and efficacy in patients with treatment-resistant RP. Methods Single-port thoracoscopic sympathicotomy was performed unilaterally on the left side in eight patients with RP (six males, two females, with a median age of 45.2 years). Five patients had primary and three had secondary RP. Perfusion effects in the hands were assessed at baseline and after 1 month by using a cooling and recovery procedure, and by using laser speckle contrast analysis. Number and duration of RP attacks were reported over a 2-week period. Results Patient satisfaction was 100% after surgery. After surgery, a unilateral improvement in perfusion was observed in the left hand compared with the right hand, with cooling and recovery (P = 0.008) and with laser speckle contrast analysis (P = 0.023). In addition, the number and duration of the attacks in the left hand decreased compared with the right hand (both P = 0.028). No serious adverse events occurred in a follow-up period of at least 10 months. Conclusion Single-port thoracoscopic sympathicotomy is feasible and can be effective in improving hand perfusion in patients with RP. However, long-term efficacy needs to be established. Clinical trial registration number NCT02680509. [ABSTRACT FROM AUTHOR]

The article discusses the results of a study on the application of mobile phone thermal imaging as an ambulatory test for the management of Raynaud's phenomenon (RP). Topics mentioned include the ability of patients to capture RP attacks, the advantage of detecting temperature differences due to RP episodes to community monitoring and clinical trials in the management of RP, and the correlation of results using mobile phone thermography and a thermocouple.

Objectives This study aimed to assess the potential role of the TNF superfamily member lymphocyte T-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells (LIGHT) in SSc through evaluation of: skin expression of LIGHT and its receptors, herpesvirus entry mediator and lymphotoxin ß-related receptor, and serum concentration of LIGHT in SSc patients. Methods Expression of LIGHT and its receptors was investigated by immunohistochemistry and evaluated semi-quantitatively in skin biopsies from 19 SSc patients and 9 healthy controls. Serum levels of LIGHT were measured using ELISA in 329 patients with SSc and 50 control subjects. Results Expression of LIGHT and both receptors was higher in SSc patients compared with controls (P < 0.05 for all comparisons). Patients with early SSc (⩽ 3 years from the first non-Raynaud's phenomenon symptom) showed higher expression of LIGHT and herpesvirus entry mediator compared with patients with longer disease duration (P < 0.05 for both comparisons). The mean serum concentration of LIGHT was significantly higher in SSc patients compared with the controls (P < 0.05). High serum concentration of LIGHT was associated with male sex, presence of digital ulcers, muscle involvement (defined by elevated serum creatine kinase levels), steroid treatment and lack of ACA. However, in multivariate regression analysis only presence of digital ulcers and creatine kinase elevation were independently associated with serum concentration of LIGHT. Conclusion These data provide the first evidence of overexpression of LIGHT and its receptors in SSc and suggest that the LIGHT axis might contribute to the pathogenesis of SSc. Increased serum concentrations of LIGHT seem to reflect vascular injury in SSc. [ABSTRACT FROM AUTHOR]

The article describes the case of a 49-year-old Caucasian male who developed relapsing polychondritis (RP) and took the initiative to take consecutive photographs of his digital ulcers (DU) before being seen at the rheumatology clinic. Topics covered include the medical history of the patient, the potential of smartphone photographs in allowing the remote diagnosis and monitoring of systemic sclerosis (SSc)-related DU, and how the images helped in the assessment of treatment response.

The authors discuss drug initiation and escalation strategies of vasodilator therapies for Raynaud's phenomenon (RP). Topics include basis of the decision to initiate and assess treatment response in RP, factor attributed to the success of treat to target (T2T) strategies in inflammatory arthritis, and key initial steps to the successful development of a T2T strategy for systemic sclerosis (SSc)-RP and digital vasculopathy.

Objectives Nailfold capillaroscopy is being increasingly used by rheumatologists in the diagnosis of SSc. However, assessment of all nailfolds can be time-consuming in a busy outpatient clinic. Our aim was to answer the question as to how many (and which) fingers a clinician should routinely assess to capture accurately the true state. Methods A total of 2994 assessments (by an international panel of expert observers) of 1600 images from 173 participants (101 with SSc, 22 with primary RP and 50 healthy controls) were included in this analysis. Seven single-finger or finger combinations (derived from the middle and ring fingers) were then tested for sensitivity for the presence of two markers of capillary abnormality [presence of giant capillaries and an SSc grade (early, active or late)] compared with assessment of all eight fingers. Results For the eight-finger gold standard, sensitivity against the diagnostic criteria was 74.6% (53.0% for the presence of giants alone and 73.1% for image grade alone). Examining only one finger gave low sensitivity (ranging from right middle 31.7% to left ring 46.6%). Examining both ring fingers gave a sensitivity of 59.8%, whereas examining the four-finger combination of both ring and both middle fingers gave a sensitivity of 66.7%. Conclusion During routine capillaroscopic examination, ideally all eight nailbeds (excluding thumbs) should be examined, otherwise some abnormalities will be missed. Examining only four fingers reduces capillaroscopy sensitivity. [ABSTRACT FROM AUTHOR]

RP is the most common manifestation of SSc and a major cause of disease-related morbidity. This review provides a detailed appraisal of the patient experience of SSc-RP and potential implications for disease classification, patient-reported outcome instrument development and SSc-RP clinical trial design. The review explores the clinical features of SSc-RP, the severity and burden of SSc-RP symptoms and the impact of SSc-RP on function, work and social participation, body image dissatisfaction and health-related quality of life in SSc. Where management of SSc-RP is concerned, the review focuses on the 'patient experience' of interventions for SSc-RP, examining geographic variation in clinical practice and potential barriers to the adoption of treatment recommendations concerning best-practice management of SSc-RP. Knowledge gaps are highlighted that could form the focus of future research. A more thorough understanding of the patient experience could support the development of novel reported outcome instruments for assessing SSc-RP. [ABSTRACT FROM AUTHOR]

There is an important unmet need for clinically validated non-invasive biomarkers for SSc diagnosis, assessment of disease activity, extent of internal organ involvement, therapeutic response and prognosis. There is also an unmet need for biomarkers to accurately differentiate primary RP from recent onset RP evolving into SSc. The lack of sensitive and specific biomarkers for SSc and SSc-associated RP is a limitation for the optimal clinical management of these patients. The development of highly sensitive and specific proteomic analysis employing aptamers and the expansion in the number of proteins that can be specifically identified by aptamer proteomics have opened new horizons for biomarker discovery. Here, we review the background and rationale for aptamer proteomic analysis for the identification of novel non-invasive biomarkers for SSc and recent onset RP evolving into SSc. Large scale application of aptamer proteomic platforms for this purpose will be of substantial value for the precision and personalized medical care of SSc patients. These studies will be placed in context by comparison with proteomic biomarker studies performed for other rheumatological inflammatory and autoimmune diseases. [ABSTRACT FROM AUTHOR]

Objectives. The aim of this work was to study inter- and intra-observer agreement for the diagnosis of scleroderma pattern by wide-field capillaroscopy. Methods. Images were taken from 50 patients known to have SSc and 50 controls consulting for RP who did not have SSc. These images were rated simultaneously by 11 experienced vascular medicine physicians as scleroderma pattern or not. Two weeks later, 7 of the 11 observers again rated the same images. Results. Inter-observer agreement was almost perfect between the 11 observers (κ 0.86 ± 0.01), and the proportion of concordant observations was 79% (70-87). When each observer was compared with the reference, agreement was also almost perfect: κ coefficient 0.92 ± 0.03 and proportion of concordant observations 79% (70-87). Intra-observer agreement was also almost perfect: median κ coefficient 0.94 (0.78-0.96) and median proportion of concordant observations 97% (89-98). Conclusion. Excellent inter- and intra-observer agreement was obtained in experienced vascular physicians for the diagnosis of capillaroscopic landscape by wide-field nailfold capillary microscopy. [ABSTRACT FROM AUTHOR]

RP is an exaggerated vasospastic response to cold or emotion. Randomized, double-blind, placebocontrolled trials with either parallel group or cross-over trials should be mainly considered. Cross-over design, which is good for early phase trials of immediate or very short-term outcomes, is important in a condition as heterogeneous as RP: a wash-out period between treatment arms should always be included to minimize the possibility of a period (carry-over) effect. Duration of RP trials is usually constrained by the need to complete these over a single season, usually winter when the weather is colder. For cross-over trials, each treatment arm tends to be 4 weeks or less. Frequency and duration of attacks, and the Raynaud's Condition Score are widely used outcome measures. There is increasing interest in physiological laboratory endpoints, for example laser Doppler imaging at least for early phase trials. [ABSTRACT FROM AUTHOR]

Objective. The aim of the study was to assess the association between plethysmographically measured vasospasms during stepwise cooling and recovery, as an index for digital ischaemia, and nailfold capillaroscopic pattern (NCP) severity in patients with primary or secondary RP, including SSc. Methods. In 381 consecutive patients with suspected RP without a history of digital ulcers, NCP (assessed by widefield videocapillaroscopy), fingertip photoelectric plethysmography during cooling and recovery and clinical characteristics were analysed. NCPs were graded as follows: normal, non-specific, early and active. The mean ischaemic time was defined as the mean time of perfusion loss during cooling and recovery of five fingers. Results. In the patients with loss of perfusion during cooling and recovery, the NCP was normal in 152, non-specific in 96, early in 61 and active in 39 patients. The mean ischaemic time was positively associated with the severity of NCP, with P < 0.05 for each two- or three-grade increase and independent of underlying SSc. The difference was most pronounced during recovery. Conclusion. We demonstrate that the degree of vasospasm and ischaemia provoked by stepwise cooling and recovery are positively associated with NCP in patients with RP of different aetiologies and without a history of digital ulcers. [ABSTRACT FROM AUTHOR]

Objective. To evaluate whether patients can predict attacks of RP (if so, this would have implications for developing new treatments) and to evaluate the impact of RP attacks on quality of life (QoL). Methods. Individuals with RP were invited through international patient associations to participate in an online survey. Results. Responses from 443 subjects with self-reported RP from 15 countries were evaluable. The mean age of subjects was 41 years (91% female). Fifty-eight per cent of subjects reported they could predict at least 51 % of RP attacks, and 57% could predict attack severity either fairly well or better [with 43% predicting severity only poorly (30%) or very poorly (13%)]. Sixty-four per cent of subjects reported a poor or very poor current ability to prevent/control RP attacks. One hundred and eighty-two subjects (41 %) reported current or previous use of medications for RP: 82% reported at least one currently used medication being tolerated, but only 16% reported at least one current medication being effective. Most subjects (78%) reported making at least one life adjustment due to RP, with more in subjects with secondary RP compared with primary RP (87% vs 71%, P = 0.001). Current QoL with RP was impaired [mean = 6/10 (10 best imaginable)] and secondary RP subjects reported a greater absolute improvement when asked to imagine their QoL without RP (2.3 vs 3.3 P = 0.0002). Conclusion. Subjects' ability to predict RP attacks is limited. Treatments were generally considered tolerable but seldom fully effective. Our results confirm an unmet need for new treatments. RP significantly impacts on QoL in all subjects. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to determine the frequency and characteristics of antisynthetase syndrome (ASS) revealed by polyarthritis. Methods. First we conducted a retrospective single-centre study to assess the frequency of ASS patients who presented with polyarthritis without pulmonary and/or muscle symptoms. Secondly, we conducted a larger, multicentre study in order to describe the clinical characteristics of these patients. Exclusion criteria were the presence of RF, the presence of ACPA and overlap with another CTD. Results. In the single-centre study, polyarthritis was the first manifestation in 12 of 45 ASS patients (27%). An additional 28 patients were collected for the multicentre study, resulting in a total population of 40 ASS patients who presented with polyarthritis. The mean delay from polyarthritis onset to ASS diagnosis was 27 months (S.D. 40). Pulmonary and muscle symptoms were uncommon at ASS diagnosis (40% and 32.5%, respectively) and were dramatically delayed [mean delay after polyarthritis onset of 41 months (S.D. 53) and 21 months (S.D. 14), respectively]. Mechanic's hands and cutaneous signs of DM occurred in 25% and 22.5%, respectively, with a mean delay of 10 months (S.D. 10) and 31 months (S.D. 21), respectively. When present (32%), RP was the earliest non-articular manifestation [mean delay 3 months (S.D. 23) after polyarthritis onset]. On HEp-2 cells, antinuclear and/or cytoplasmic fluorescence was found in 70% of cases, with specificity for various anti-aminoacyl tRNA synthetase (anti-ARS) antibodies. Conclusion. ASS may be revealed by polyarthritis. To decrease the delay in diagnosis of ASS, pulmonary and muscle symptoms and anti-ARS antibodies might usefully be searched for in seronegative polyarthritis patients, especially in those with RP. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to identify cold-associated autoantibodies in patients with RP secondary to CTDs.Methods. Indirect immunofluorescence staining was performed on non-permeabilized cold-stimulated normal human dermal microvascular endothelial cells (dHMVECs), using patients’ sera. Cold-induced alterations in cell surface proteomes were analysed by isobaric tag for relative and absolute quantitation (iTRAQ) analysis. Serological proteome analysis (SERPA) was applied to screen cold-associated autoantigens. The prevalence of the candidate autoantibody was determined by ELISA in 290 patients with RP secondary to CTDs (SSc, SLE or MCTD), 10 patients with primary RP and 27 healthy controls.Results. Enhanced cell surface immunoreactivity was detected in cold-stimulated dHMVECs when incubated with sera from patients with secondary RP. By iTRAQ analysis, many proteins, including heterogeneous nuclear ribonucleoprotein K (hnRNP-K), were found to be increased on the cell surface of dHMVECs after cold stimulation. By the SERPA approach, hnRNP-K was identified as a candidate autoantigen in patients with secondary RP. Cold-induced translocation of hnRNP-K to the cell surface was confirmed by immunoblotting and flow cytometry. By ELISA analysis, patients with secondary RP show a significantly higher prevalence of anti-hnRNP-K autoantibody (30.0%, 61/203) than patients without RP (9.2%, 8/87, P = 0.0001), patients with primary RP (0%, 0/10, P = 0.0314) or healthy controls (0%, 0/27, P = 0.0001).Conclusion. By comprehensive proteomics, we identified hnRNP-K as a novel cold-associated autoantigen in patients with secondary RP. Anti-hnRNP-K autoantibody may potentially serve as a biomarker for RP secondary to various CTDs. [ABSTRACT FROM PUBLISHER]

Objective. Multisite photoplethysmography (PPG) cardiovascular assessments can evaluate endothelial, peripheral autonomic and arterial dysfunction. The aim of this pilot study was to investigate the potential clinical utility of the technology in assessing patients with SSc and primary RP (PRP).Methods. Multisite PPG pulse measurements, a reference ankle brachial pressure index (ABPI) and a full clinical assessment were undertaken for three subject groups: SSc, PRP and controls. Endothelial and autonomic function and arterial disease measures were obtained using pulse wave analysis.Results. Nineteen SSc, 19 PRP and 23 control subjects were assessed and compared. Endothelial function was significantly impaired in SSc (P < 0.02), but with no difference between controls and PRP. Receiver operating characteristic–based classification accuracy was 81% (sensitivity 90%, specificity 74%) for separating SSc from controls and 82% (sensitivity 84%, specificity 79%) for separating SSc from PRP. SSc patients with digital ulcers had significantly lower endothelial function compared with those without ulcers (P < 0.05). Autonomic dysfunction was suggested in both SSc and PRP and was most exaggerated in patients with diffuse SSc. All groups had overall normal ABPI and arterial stiffness timing measures. Bilateral timing differences at the toes, which represents peripheral occlusive arterial disease, did show increased asymmetry in SSc (P < 0.02).Conclusion. Multisite PPG pulse technology showed potential diagnostic ability. By using measures of endothelial function, it differentiated SSc from control and PRP subjects with an accuracy of at least 81%. Objective pulse-derived measures of autonomic function and arterial disease in SSc have also been reported in this pilot study. [ABSTRACT FROM PUBLISHER]

Objective. RP is a reversible vasoconstriction of digital arteries that causes pain and skin discoloration. This study compared the efficacy of the new phosphodiesterase type 5 inhibitor udenafil with that of the calcium channel blocker amlodipine in the treatment of secondary RP.Methods. A total of 29 patients with secondary RP associated with connective tissue diseases were enrolled in this double-blind, randomized, cross-over study. The patients were randomized to receive udenafil 100 mg/day or amlodipine 10 mg/day for 4 weeks. After a washout period they were crossed over to the other drug for another 4 weeks. The primary outcome was RP frequency before and after treatment. The secondary outcomes were RP condition scores, RP duration, number of digital ulcers, HAQ, physician global assessment and digital artery flow before and after treatment.Results. Amlodipine and udenafil both decreased the rate of RP attack significantly. The drugs did not differ in terms of RP frequency or any of the secondary outcomes except for digital blood flow; udenafil improved it significantly better than amlodipine (P = 0.021). Udenafil was well tolerated without serious adverse effects.Conclusion. Udenafil and amlodipine have comparable efficacy in improving RP attacks. In addition, udenafil improves the blood flow in digital arteries compared with amlodipine.Trial registration. www.clinicaltrials.gov, protocol number NCT01280266. [ABSTRACT FROM PUBLISHER]

The article presents a case of a 31-year-old female Indian who was rushed to the outpatient rheumatology clinic due to Raynaud's phenomenon, joint pain and rashes to discuss dorsal papules as feature of anti-EJ positive anti-synthetase syndrome (ASSD). Her examination showed the papules in her knuckles and distal phalanges and cutaneous desquamation on the toes. Also cited is the association of ASSD with conditions like myositis, arthritis and interstitial lung disease.

Objectives. The objectives of this study were to evaluate the dynamic behaviour of digital skin microvascular blood flow before and after cold stimulation using laser Doppler imaging (LDI) in children and adolescents with RP secondary to juvenile systemic sclerosis (JSS), primary RP (PRP) and healthy controls and to compare functional abnormalities measured by LDI with structural microvascular abnormalities evaluated by nailfold capillaroscopy (NFC).Methods. Five JSS patients, five children and adolescents with PRP and five healthy controls matched for gender and age were included. All subjects had NFC performed. Finger blood flow (FBF) was measured using the LDI system (Moor Instruments) at baseline and after cold stimulus (CS).Results. There were a decreased number of capillaries, a greater number of enlarged capillaries and a higher deletion score in JSS patients compared with controls and patients with PRP. The mean baseline FBF was significantly lower in JSS patients compared with controls. There was no difference between the mean baseline FBF in JSS patients compared with patients with PRP. There was a significant decrease in FBF 1 min after CS in all groups followed by blood flow recovery at 20 min after CS in comparison with basal FBF values in controls, but not in JSS and PRP patients.Conclusion. In JSS patients, LDI showed a lower FBF before and after CS compared with healthy controls and may be an objective and sensitive method for the measurement of digital skin blood flow in RP children. [ABSTRACT FROM PUBLISHER]

Capillaroscopy is a non-invasive and safe tool to morphologically study the microcirculation. In rheumatology it has a dual use. First, it has a role in differential diagnosis of patients with RP. Second, it may have a role in the prediction of clinical complications in CTDs. In SSc, pilot studies have shown predictive associations with peripheral vascular and lung involvement hinting at a role of capillaroscopy as putative biomarker. Also and logically, in SSc, microangiopathy, as assessed by capillaroscopy, has been associated with markers of the disease such as angiogenic/static factors and SSc-specific antibodies. Moreover, morphological assessments of the microcirculation (capillaroscopy) seem to correlate with functional assessments (such as laser Doppler). Because of its clinical and research role, eyes are geared in Europe to expand the knowledge of this tool. Both the European League Against Rheumatism (EULAR) and the ACR are stepping forward to this need. [ABSTRACT FROM PUBLISHER]

Objective. To assess patients with SSc who present without circulating ANAs or RP.Methods. Five thousand three hundred and ninety patients who fulfilled the ACR criteria for SSc and were enrolled in the EULAR Scleroderma Trials and Research (EUSTAR) database were screened for the absence of both RP and circulating ANA. To differentiate SSc from its mimics, additional information was gathered using a standardized questionnaire.Results. Five thousand three hundred and seventy-eight (99.8%) of the 5390 SSc patients in the EUSTAR database had either detectable ANA or a history of RP. Twelve (0.2%) patients lacked both circulating ANA and RP. Details of the medical history could be obtained for seven patients. Three cases were compatible with ANA-negative and RP-negative SSc and were not typical of any known SSc mimic. Four patients had a malignancy: two had breast cancer, one had multiple myeloma with possible scleromyxoedema and one had bladder carcinoma. There was no temporal relationship between the onset of skin fibrosis and that of the tumour. Although no patient with confirmed nephrogenic systemic fibrosis was identified among the cases of ANA-negative and RP-negative SSc, the presentation of one patient could be compatible with that of nephrogenic systemic fibrosis other than for the absence of chronic kidney disease or of known prior gadolinium exposure.Conclusion. We have identified a very small subgroup of SSc patients who lack both circulating ANA and RP, none of whom fulfils the diagnostic criteria for any known SSc mimic. Prospective studies are needed to elucidate the clinical presentation, evolution and outcome of such patients. [ABSTRACT FROM AUTHOR]

Objectives. Acro-osteolysis (bony resorption of the terminal digital tufts) is a well-recognized, but under-researched, manifestation of SSc. Our aim was to investigate the hypothesis that acro-osteolysis is associated with (i) the severity of digital ischaemia and (ii) the presence of calcinosis.Methods. This was a retrospective study of 101 patients with SSc in whom hand radiographs taken between 2001 and May 2008 were available for review. These radiographs were graded for severity of acro-osteolysis on a 0–4-point scale for each finger (0 = normal bone structure, 4 = severe pencilling of the terminal phalanges). From these scores, patients were subdivided into the following two groups: normal/minimal acro-osteolysis and moderate/severe acro-osteolysis. The presence or absence of calcinosis (mild, moderate or severe) was also documented.Results. Of the 101 patients, 68 were grouped as normal/minimal acro-osteolysis and 33 as moderate/severe acro-osteolysis. Forty-five had severe digital ischaemia: 25 (76%) of the patients with moderate/severe acro-osteolysis compared with 20 (29%) of those with normal/minimal acro-osteolysis (multifactorial analysis: P < 0.001). Patients with moderate/severe acro-osteolysis were more likely to have severe calcinosis (33% vs 13%), but this was not statistically significant after adjustment for potential confounders.Conclusion. Acro-osteolysis was strongly associated with severe digital ischaemia. The potential association with severe calcinosis merits further study. Prospective studies are required to investigate acro-osteolysis as a marker of digital vascular disease progression and of treatment response. [ABSTRACT FROM PUBLISHER]

Objective. To investigate the inter- and intra-observer reliability of both qualitative and quantitative parameters used in the assessment of nail-fold capillaroscopy images.Methods. Fifty mosaic nail-fold images of healthy controls (n = 10), patients with primary RP (n = 10) and SSc (n = 30) were assessed in random order by two blinded observers on two occasions at centres in Sweden, UK and The Netherlands. Each image was therefore scored by six observers twice.Results. Inter- and intra-observer reliability of quantitative parameters showed substantial to almost perfect agreement [inter- and intra-observer weighted κ's for the number of widened capillaries was 0.75 and 0.87 and giant capillaries was 0.84 and 0.92, intra-class correlation coefficients (ICCs) for capillary density was 0.87 and 0.92 and total loop width was 0.94 and 0.98, respectively]. Qualitative parameters including architecture, avascularity, haemorrhage, crossed, ramified and bushy capillaries showed moderate to substantial inter-observer reproducibility (weighted κ ranging from 0.47 to 0.73), and substantial intra-observer repeatability (weighted κ ranging from 0.71 to 0.80), whereas the scoring of tortuous and bizarre capillaries showed poor inter-observer and substantial intra-observer agreement (inter-observer weighted κ's was 0.39 and 0.21 and intra-observer weighted κ's was 0.68 and 0.76, respectively).Conclusion. All quantitative and certain qualitative parameters are highly reliable in terms of inter- and intra-observer agreement. A combination of parameters with the highest reliability should be incorporated into future capillaroscopic scoring systems in studies of prediction and monitoring of SSc spectrum disorders. [ABSTRACT FROM PUBLISHER]

Objective. We sought to evaluate the use of high-resolution three-dimensional time of flight (3D TOF) magnetic resonance angiography (MRA) at 3 Tesla in the visualization of digital arteries in SSc patients.Methods. A total of 33 patients with SSc [32 females and 1 male; mean (s.d.) age 37.0 (10.2) years; median number of years since onset of RP 3.4 (2.8) years] and 7 healthy controls [6 females and 1 male; mean (s.d.) age 30.7 (3.5) years] were examined on a 3T MR system. A modified high spatial resolution (voxel size = 0.35 × 0.35 × 0.5 mm3) 3D TOF MRA (repetition time/echo time = 19/4.4 ms, flip angle = 15°, slice thickness = 1 mm) was performed during a total scan time of 8 min 22 s. The source images and maximum intensity projection reconstruction were studied; the digital arteries count and lumen area of the selective section of the vessel were measured independently by two experienced radiologists and compared with that of the control ones; and a four-level grading system was made according to the severity. Statistical analysis was performed with t-test and P < 0.05 was used as the criterion.Results. We detected the eight digital arteries in the four fingers (without the thumb) of each case and got a 47.58% presentation in general in the SSc group, and artery No. 5 had the highest presentation rate (70.97%). Statistics showed that the digital arteries No. 1 (P = 0.058) and No. 3 (P = 0.093) had no difference in the lumen area (P > 0.05). We finally got 3 cases in Grade 1, 14 cases in Grade 2, 9 cases in Grade 3 and 5 cases in Grade 4.Conclusion. MRA of the digital arteries in the described technique is a promising method for us to judge the severity of microvascular involvement in finger vessels of SSc patients. [ABSTRACT FROM PUBLISHER]

Objective. To evaluate the efficacy of tadalafil as add-on therapy in secondary RP resistant to vasodilators.Methods. Patients with scleroderma and MCTD having four or more RP attacks per week despite being on vasodilators were randomized to receive either placebo or tadalafil (20 mg) on alternate days as add-on therapy to their current vasodilators for 6 weeks. After a 7-day washout, patients were crossed over to the other arm. Primary endpoints were improvement in the daily frequency and duration of RP episodes and RP condition score (RCS). Secondary outcome measures were healing of existing and appearance of new digital ulcers (DUs) and improvement in scleroderma-specific HAQ (SHAQ), quality of life (QoL), flow-mediated dilatation (FMD), patient and physician global assessment.Results. Twenty-four of 25 recruited patients completed the study. All the patients were receiving calcium channel blockers and in addition 18 were receiving other vasodilators. During tadalafil therapy significant improvement in mean daily frequency, mean daily duration of RP and mean daily RCS were observed as compared with baseline and placebo. All the 24 digital lesions healed during tadalafil therapy as compared with 3/13 during the placebo treatment (P < 0.0001). One new DU was reported during tadalafil therapy vs 13 during placebo therapy (P = 0.0005). QoL, SHAQ, FMD, patient and physician global assessment significantly improved while on tadalafil. No serious adverse event was observed.Conclusion. Tadalafil as add-on therapy improves symptoms of RP, heals and prevents new DUs and improves QoL in patients with resistant secondary RP.Trial Registration. Clinicaltrials.gov, http://clinicaltrials.gov/, identifier: NCT00626665. [ABSTRACT FROM PUBLISHER]