Significant nailfold capillary loss and late capillaroscopic pattern are associated with pulmonary arterial hypertension in systemic sclerosis.

OBJECTIVES: To evaluate differences in nailfold videocapillaroscopy (NVC) findings between systemic sclerosis-SSc patients with and without a diagnosis of pulmonary arterial hypertension (PAH). METHODS: 110 SSc patients were enrolled in this cross-sectional, case-control, multi-centre study. Patients were divided into cases (SSc-PAH confirmed by right hearth catheterization-RHC) and controls (SSc-nonPAH with low probability of PAH). NVC patterns (early, active, and late) and morphological parameters (microvascular density, non-specific abnormalities, giant capillaries, micro-haemorrhages, avascular areas) were considered using a semiquantitative scoring system. RESULTS: SSc-PAH patients showed higher frequencies of late pattern (p < 0.01), non-specific abnormalities (p < 0.01), lower capillary density (p < 0.01), higher avascular areas (p < 0.01), and a higher mean NVC score (p < 0.01). Contrarily, the early/active pattern (p < 0.01) and a higher rate of micro-haemorrhages (p = 0.04) were more frequent in non-PAH patients. By the multivariate analysis, SSc-PAH patients, compared to non-PAH, had more non-specific abnormalities (27/55, 49.1% vs 10/55, 18.2%, adjusted OR: 16.89, 95%CI: 3.06-93.16), a lower capillary density (grade 3, 20/55, 36.4% vs 5/55, 9.1%, adjusted OR: 38.33, 95%CI: 2.34-367.80), and avascular areas (18/55, 32.7% vs 10/55, 18.2%, adjusted OR: 16.90, 95%CI: 2.64-44.35). A correlation was found between the mean pulmonary arterial pressure-mPAP and avascular areas (p < 0.01), capillary density (p < 0.01), and non-specific abnormalities (p < 0.01). A clinical model including the NVC variables may be able to predict the diagnosis of PAH. CONCLUSIONS: Our results indicate that the distinctive peripheral microcirculatory injury of SSc, i.e capillary loss and morphological abnormalities, appear more severe and pronounced in patients with SSc-PAH.

Standardized nailfold capillaroscopy in children with rheumatic diseases: a worldwide study.

OBJECTIVES: To standardly assess and describe nailfold videocapillaroscopy (NVC) assessment in children and adolescents with juvenile rheumatic and musculoskeletal diseases (jRMD) vs healthy controls (HCs). MATERIAL AND METHODS: In consecutive jRMD children and matched HCs from 13 centres worldwide, 16 NVC images per patient were acquired locally and read centrally per international consensus standard evaluation of the EULAR Study Group on Microcirculation in Rheumatic Diseases. A total of 95 patients with JIA, 22 with JDM, 20 with childhood-onset SLE (cSLE), 13 with juvenile SSc (jSSc), 21 with localized scleroderma (lSc), 18 with MCTD and 20 with primary RP (PRP) were included. NVC differences between juvenile subgroups and HCs were calculated through multivariable regression analysis. RESULTS: A total of 6474 images were assessed from 413 subjects (mean age 12.1 years, 70.9% female). The quantitative NVC characteristics were significantly lower or higher in the following subgroups compared with HCs: for density: lower in jSSc, JDM, MCTD, cSLE and lSc; for dilations: higher in jSSc, MCTD and JDM; for abnormal shapes: higher in JDM and MCTD; for haemorrhages: higher in jSSc, MCTD, JDM and cSLE. The qualitative NVC assessment of JIA, lSc and PRP did not differ from HCs, whereas the cSLE and jSSc, MCTD, JDM and cSLE subgroups showed more non-specific and scleroderma patterns, respectively. CONCLUSIONS: This analysis resulted from a pioneering registry of NVC in jRMD. The NVC assessment in jRMD differed significantly from HCs. Future prospective follow-up will further elucidate the role of NVC in jRMD.

Systemic sclerosis associated interstitial lung disease: a conceptual framework for subclinical, clinical and progressive disease.

OBJECTIVES: To establish a framework by which experts define disease subsets in systemic sclerosis associated interstitial lung disease (SSc-ILD). METHODS: A conceptual framework for subclinical, clinical and progressive ILD was provided to 83 experts, asking them to use the framework and classify actual SSc-ILD patients. Each patient profile was designed to be classified by at least four experts in terms of severity and risk of progression at baseline; progression was based on 1-year follow-up data. A consensus was reached if ≥75% of experts agreed. Experts provided information on which items were important in determining classification. RESULTS: Forty-four experts (53%) completed the survey. Consensus was achieved on the dimensions of severity (75%, 60 of 80 profiles), risk of progression (71%, 57 of 80 profiles) and progressive ILD (60%, 24 of 40 profiles). For profiles achieving consensus, most were classified as clinical ILD (92%), low risk (54%) and stable (71%). Severity and disease progression overlapped in terms of framework items that were most influential in classifying patients (forced vital capacity, extent of lung involvement on high resolution chest CT [HRCT]); risk of progression was influenced primarily by disease duration. CONCLUSIONS: Using our proposed conceptual framework, international experts were able to achieve a consensus on classifying SSc-ILD patients along the dimensions of disease severity, risk of progression and progression over time. Experts rely on similar items when classifying disease severity and progression: a combination of spirometry and gas exchange and quantitative HRCT.

Disease activity and disease-related factors are drivers of patient global assessment in rheumatoid arthritis: a real-life cross-sectional study.

Despite that the Patient Global Assessment (PGA) is widely used for measuring Rheumatoid Arthritis (RA) disease activity to define the remission state of the disease, the primary contributors influencing patients' ratings are still debated. This study aims to determine which clinical, sociodemographic and lifestyle-related contextual factors might be key drivers of PGA in RA. This single-center cross-sectional study recruited 393 consecutive adult RA patients. Median age 60 years, females 306 (77.9%). Data related to disease activity were assessed by using Simplified Disease Activity Index (SDAI), severity by Health Assessment Questionnaire (HAQ), and impact by RA Impact of Disease (RAID). Sociodemographic/lifestyle features were collected. Disease remission was calculated using Boolean-based criteria 1.0 and 2.0. Quantile regression models were used for univariate and multivariate analysis. The remission rate progressively increased from 15% by using SDAI with a Boolean 1.0-based definition to 43.5% using a Boolean 2.0-based remission. Among factors related to disease activity, the use of low-dose corticosteroids, the RAID items pain and sleep difficulties were predictive for worse PGA scores (p = 0.01). Among factors related to disease severity HAQ score and RAID total were independent factors associated with higher median PGA (p = 0.02 and p < 0.001). RAID's physical well-being was related to PGA scores (p = 0.01). An increasing trend in PGA was observed in longstanding diseases (> 15 years). Our results confirmed that there is no unambiguous interpretation of the PGA score. It is a measure related to some disease activity parameters, but it is also influenced by contextual factors related to disease severity and impact. These data highlighted that PGA should have a broad interpretation, thus supporting the proposal of a dual targets (biological and impact) approach to obtain a more accurate estimate of disease activity.

Nailfold capillaroscopy in SSc: innocent bystander or promising biomarker for novel severe organ involvement/progression?

OBJECTIVES: Nailfold videocapillaroscopy (NVC) plays a well-established role in differentiating primary from secondary RP due to SSc. However, the association of NVC with novel severe organ involvement/progression in SSc has never been evaluated in a multicentre, multinational study, which we now perform for the first time. METHODS: Follow-up data from 334 SSc patients [265 women; 18 limited SSc (lSSc)/203 lcSSc/113 dcSSc] registered between November 2008 and January 2016 by seven tertiary centres in the EUSTAR-database, were analysed. Novel severe organ involvement/progression was defined as new/progressive involvement of the peripheral vasculature, lungs, heart, skin, gastrointestinal tract, kidneys, musculoskeletal system, or death, at the 12- or 24-month follow-up. NVC images at enrolment were quantitatively and qualitatively evaluated according to the standardized definitions of the EULAR Study Group on Microcirculation in Rheumatic Diseases. Uni- and multivariable logistic regression modelling (ULR, MLR) was performed. RESULTS: Of the 334 included SSc patients, 257 (76.9%) developed novel overall severe organ involvement/progression. Following MLR, normal capillary density was associated with less-frequent novel overall severe organ involvement/progression [odds ratio (OR) = 0.77, P < 0.001] and novel peripheral vascular involvement (OR = 0.79, P = 0.043); microhaemorrhages were associated with less novel pulmonary hypertension (OR = 0.47, P = 0.029); and a 'severe' (active/late) NVC pattern was associated with novel overall severe organ involvement/progression (OR = 2.14, P = 0.002) and skin progression (OR = 1.70, P = 0.049). CONCLUSIONS: Our results suggest that NVC may be a promising biomarker in SSc, certainly warranting further investigation. Despite the participation of tertiary centres, which follow their patients in a standardized way, we were underpowered to detect associations with infrequent severe organ involvement/progression.

Nailfold video capillaroscopy as a useful diagnostic tool in systemic vasculitis.

BACKGROUND: Nailfold video capillaroscopy (NVC) enables us a direct view of the microvasculature. Only several capillaroscopy studies in adult patients with vasculitis have been reported. AIM: To characterize NVC changes in vasculitis. METHODS: Vasculitis patients and healthy controls were evaluated by NVC. NVC changes associated with vasculitis were assessed retrospectively in a cohort of 100 patients with Raynaud's phenomenon (RP). RESULTS: 17 patients with active vasculitis and 8 patients with vasculitis in remission were compared to 25 age and sex-matched healthy controls. Active vasculitis patients demonstrated higher rates of neoangiogenesis and capillary loss in comparison to other groups. Two novel NVC abnormalities were observed in patients with vasculitis: "Rolling" (slow capillary flow) and "peri-capillary stippling" (PCS), small deposits that may represent capillary leak. PCS was observed exclusively in 5 of 17 patients with active vasculitis. Retrospectively, we were able to detect PCS also in 14 % of 100 patients that were evaluated for RP, of whom 64 % were diagnosed with scleroderma or a related disorder. CONCLUSIONS: Patients with active vasculitis demonstrate frequent capillary abnormalities. Although these abnormalities are non-specific, we suggest that their combination may aid the diagnosis of vasculitis. Future studies are needed to validate our findings.

Patient Perception of Depressive Symptoms in Rheumatic Diseases: A Cross-sectional Survey.

OBJECTIVES: The presented study aimed to explore the presence and the self-identification of depressive symptoms among patients with rheumatic musculoskeletal diseases (RMDs) through the use of the Patient Health Questionnaire (PHQ-9). METHODS: Between June and October 2019, patients from the regional association for people with RMDs in Lombardy, Italy (ALOMAR), were invited to participate in a cross-sectional online survey. Participants completed PHQ-9 along with a survey about their perception of depressive symptoms. Patients were stratified according to PHQ-9 score as follows: not depressed (<4), subclinical or mild depression (5-9), moderate depression (10-14), moderately severe depression (10-14), and severe depression (20-27). Descriptive statistics and analyses of variance were used to explore data. RESULTS: Of the 192 RMD patients who completed PHQ-9, 35 (18.2%) were not depressed, 68 (35.4%) had subclinical or mild depression, 42 (21.9%) had moderate depression, 30 (15.6%) had moderately severe depression, and 17 (8.9%) had severe depression. Contrary to the above findings, only 16 respondents (8.3%) reported that they experienced depressive symptoms, and only 7 of the 16 were being followed by a psychiatrist. Respondents with higher PHQ-9 scores tended to have concomitant fibromyalgia, to be younger, and to be overweight. CONCLUSIONS: The current results indicate the overall burden of depressive symptoms in RMD patients. While clinical depression (PHQ-9 >10) was detected in 41.2% of respondents, only 8.3% reported that they experience depressive symptoms. Routine screening of RMD patients for depression is therefore critical.

Reporting items for capillaroscopy in clinical research on musculoskeletal diseases: a systematic review and international Delphi consensus.

OBJECTIVES: The level of detail included when describing nailfold videocapillaroscopy (NVC) methods varies among research studies, making interpretation and comparison of results challenging. The overarching objective of the present study was to seek consensus on the reporting standards in NVC methodology for clinical research in rheumatic diseases and to propose a pragmatic reporting checklist. METHODS: Based on the items derived from a systematic review focused on this topic, a three-step web-based Delphi consensus on minimum reporting standards in NVC was performed among members of the European League against Rheumatism (EULAR) Study Group on Microcirculation in Rheumatic Diseases and the Scleroderma Clinical Trials Consortium. RESULTS: A total of 319 articles were selected by the systematic review, and 46 items were proposed in the Delphi process. This Delphi exercise was completed by 80 participants from 31 countries, including Australia and countries within Asia, Europe, North America and South America. Agreement was reached on items covering three main areas: patient preparation before NVC (15 items), device description (5 items) and examination details (13 items). CONCLUSION: Based on the available evidence, the description of NVC methods was highly heterogeneous in the identified studies and differed markedly on several items. A reporting checklist of 33 items, based on practical suggestions made (using a Delphi process) by international participants, has been developed to provide guidance to improve and standardize the NVC methodology to be applied in future clinical research studies.

The clinical phenotype of systemic sclerosis patients with anti-PM/Scl antibodies: results from the EUSTAR cohort.

OBJECTIVE: To evaluate clinical associations of anti-PM/Scl antibodies in patients with SSc in a multicentre international cohort, with particular focus on unresolved issues, including scleroderma renal crisis (RC), malignancies, and functional outcome of interstitial lung disease (ILD). METHODS: (1) Analysis of SSc patients from the EUSTAR database: 144 anti-PM/Scl+ without SSc-specific autoantibodies were compared with 7202 anti-PM/Scl-, and then to 155 anti-Pm/Scl+ with SSc-specific antibodies. (2) Case-control study: additional data were collected for 165 anti-PM/Scl+ SSc patients (85 from the EUSTAR registry) and compared with 257 anti-PM/Scl- SSc controls, matched for sex, cutaneous subset, disease duration and age at SSc onset. RESULTS: Patients with isolated anti-PM/Scl+, as compared with anti-Pm/Scl-, had higher frequency of muscle involvement, ILD, calcinosis and cutaneous signs of DM, but similar frequency of SRC and malignancies (either synchronous with SSc onset or not). The presence of muscle involvement was associated with a more severe disease phenotype. Although very frequent, ILD had a better functional outcome in cases than in controls. In patients with both anti-PM/Scl and SSc-specific antibodies, a higher frequency of typical SSc features than in those with isolated anti-PM/Scl was observed. CONCLUSION: The analysis of the largest series of anti-PM/Scl+ SSc patients so far reported helps to delineate a specific clinical subset with muscle involvement, cutaneous DM, calcinosis and ILD characterized by a good functional outcome. SRC and malignancies do not seem to be part of this syndrome.

COVID-19 related poor mental health and sleep disorders in rheumatic patients: a citizen science project.

BACKGROUND: Patients with chronic rheumatic diseases (RDs) are more vulnerable and the containment measures related to the COVID-19 pandemic might have severe psychological consequences. We investigated the presence of and risk factors associated with poor mental health, sleep disorders among RDs during the pandemic. METHODS: This cross-sectional Italian citizen science project evaluated the psychological impact of the COVID-19 pandemic in patients with RDs. Between May and September 2020, eleven RD patients' associations sent the survey by using their mailing list and the related webpage and social network. 507 RD patients completed an ad-hoc anonymous online survey including the Perceived Stress Scale (PSS) and Impact Event Scale-Revised (IES-R). RESULTS: The mean scores on the PSS-10 and the IES-R were 18.1 and 29.7, respectively. Higher PSS scores were associated with younger age (p <  0.01), female gender (p <  0.01), overweight/obesity (p = 0.01), psychiatric pharmacotherapy (p <  0.01), and anxiety for loss of income (p <  0.01). Higher IES-R scores were associated with female gender (p <  0.01), intestinal diseases (p = 0.03), anxiety (p <  0.01), and health concern (p <  0.01). Among 375 patients with inflammatory arthritis, 246 (65.6%) had trouble staying asleep, 238 (63.5%) falling asleep, and 112 (29.9%) had dreams about the pandemic. Older age (OR = 1.038, CI 1.002-1.076), psychiatric pharmacotherapy (OR = 25.819, CI 11.465-58.143), and COVID infection (OR = 2.783, CI 1.215-6.372) were predictive of insomnia during the pandemic. CONCLUSIONS: A considerable COVID-19 related psychosocial burden has been detected in RDs. Different factors were predictive of poor mental health and sleep disorders in these patients. Focused supportive strategies should be implemented to improve the psychological well-being of fragile patients during pandemics.

Systemic sclerosis Progression INvestiGation (SPRING) Italian registry: demographic and clinico-serological features of the scleroderma spectrum.

OBJECTIVES: Systemic sclerosis (SSc) is a severe multiple-organ disease characterised by unpredictable clinical course, inadequate response to treatment, and poor prognosis. National SSc registries may provide large and representative patients cohorts required for descriptive and prognostic studies. Therefore, the Italian Society for Rheumatology promoted the registry SPRING (Systemic sclerosis Progression INvestiGation). METHODS: The SPRING is a multi-centre rheumatological cohort study encompassing the wide scleroderma spectrum, namely the primary Raynaud's phenomenon (pRP), suspected secondary RP, Very Early Diagnosis of Systemic Sclerosis (VEDOSS), and definite SSc. Here we describe the demographic and clinical characteristics of a population of 2,028 Italian patients at the initial phase of enrolment, mainly focusing on the cohort of 1,538 patients with definite SSc. RESULTS: Definite SSc showed a significantly higher prevalence of digital ulcers, capillaroscopic 'late' pattern, oesophageal and cardio-pulmonary involvement compared to VEDOSS, as expected on the basis of the followed classification criteria. The in-depth analysis of definite SSc revealed that male gender, diffuse cutaneous subset, and anti-Scl70 seropositivity were significantly associated with increased prevalence of the most harmful disease manifestations. Similarly, patients with very short RP duration (≤1 year) at SSc diagnosis showed a statistically increased prevalence of unfavourable clinico-serological features. CONCLUSIONS: Nationwide registries with suitable subsetting of patients and follow-up studies since the prodromal phase of the disease may give us valuable insights into the SSc natural history and main prognostic factors.

The burden of air pollution and temperature on Raynaud's phenomenon secondary to systemic sclerosis.

OBJECTIVES: to evaluate the effect of air pollution (ozone - O3 and particulate matter <=10 µm and <=2.5 µm - PM10 and PM2.5) on the severity of Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc). DESIGN: cross-sectional, observational, and single centre study. SETTING AND PARTICIPANTS: all consecutive SSc patients residing in Lombardy (Northern Italy) were enrolled. PM10, PM2.5, and O3 concentrations were calculated for each patient at municipality resolution in the week before the evaluation. Similar considerations were made for meteorological variables (temperature and humidity). MAIN OUTCOME MEASURES: patients were asked to assess RP severity during the week before the evaluation according to a visual analogue scale (VAS). Ordinal logistic regression models were fitted to evaluate the short-term effect of temperature and air pollution with respect to RP. A univariate linear regression model was created to consider the association between temperature and pollutants. RESULTS: in this study, 87 SSc patients were enrolled. Temperature was confirmed to strongly influence RP severity. PM10 and PM.5 were found to significantly worsen RP severity for the first four days before the evaluation, including the day of the visit, and as mean up to six days before the evaluation. O3 seemed to exert a protective effect on RP severity that was significant for the first four days before the evaluation, including the day of the visit, and as mean up to seven days before the evaluation. CONCLUSIONS: since the overwhelming effect of temperature on RP, final conclusions about the exact contribution of pollutants on RP severity cannot be drawn because of the strong inter-correlation between air pollution and temperature.

The patient experience of Raynaud's phenomenon in systemic sclerosis.

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.

Lysyl oxidase-a possible role in systemic sclerosis-associated pulmonary hypertension: a multicentre study.

OBJECTIVE: Lysyl oxidase (LOX) is an extracellular enzyme that cross-links collagen fibrils. LOX was found to be increased in serum of SSc patients and was suggested to be related to skin fibrosis, yet a vascular source of LOX has been demonstrated in idiopathic pulmonary arterial hypertension (iPAH). We aimed to validate elevated LOX serum levels in SSc and to study its correlation with clinical characteristics and investigate its main source at the tissue level. METHODS: A total of 86 established SSc patients were compared with 86 patients with very early diagnosis of systemic sclerosis (VEDOSS), 110 patients with primary RP (PRP) and 80 healthy controls. LOX serum levels were determined by ELISA. Five lung and 12 skin biopsies from SSc patients were stained for LOX and compared with controls. RESULTS: Serum levels of LOX in SSc were significantly higher than in VEDOSS, PRP and healthy controls (P < 0.001). LOX inversely correlated with the diffusing capacity of the lung for carbon monoxide diffusing capacity (DLCO) in diffuse SSc (r = -0.376, P = 0.02). Patients with moderate to severe estimated systolic PAH had higher LOX levels (P < 0.01). Lung biopsies demonstrated intense LOX staining in SSc patients with PAH that was predominantly located in the endothelium of the remodelled pulmonary vessels. CONCLUSION: Serum LOX levels are increased in established SSc and inversely correlate with the DLCO. LOX is elevated in patients with moderate to severe PAH and is located in the proliferating endothelium in lung arterioles, suggesting a possible role for LOX in SSc-associated PAH.

Evidence of macro- and micro-angiopathy in scleroderma: An integrated approach combining 22-MHz power Doppler ultrasonography and video-capillaroscopy.

OBJECTIVE: We aimed to study in SSc patients macrovascular involvement by using power Doppler ultrasound (PDUS) and microvascular one by PDUS and nailfold video-capillaroscopy (NVC) and to examine the association between history of digital ulcers (HDU) and imaging (PDUS and NVC) parameters. METHODS: NVC and PDUS were systematically performed in 106 consecutive SSc patients at the 3rd and 4th finger of the dominant hand after exclusion of ulnar artery occlusion (UAO). 22 MHz PDUS measurements included nailbed and fingertip qualitatively graded, and resistivity index (RI) of ulnar and radial proper digital arteries. Capillary number/mm was calculated by NVC on the same digits examined by PDUS. RESULTS: Vascularization at fingertip and nailbed showed a good correlation between them and to capillary number. RI, representative of macrovascular involvement, did not correlate to microvascular involvement as assessed by PDUS and NVC. RI and capillary number at NVC showed significant correlation to HDU while fingertip and nailbed vascularization as assessed by PDUS did not. As such, PDUS and NVC provide different and potentially complementary information on SSc-related peripheral macro- and micro-vascular involvement. CONCLUSION: Macro- and micro-vascular involvement in SSc patients are different processes and are not present at the same time in every patient. Thus, both these aspects should be carefully evaluated in SSc patients.

Acute and chronic effects of two different intravenous iloprost regimens in systemic sclerosis: a pragmatic non-randomized trial.

OBJECTIVES: I.v. iloprost (ILO) may be used in the treatment of refractory RP and digital ulcers. We aim to evaluate the acute and chronic effects of two different ILO regimens by power Doppler US (PDUS) and nailfold videocapillaroscopy. METHODS: In this 3-month single-centre pragmatic non-randomized trial, 96 SSc patients were included and stratified according to ILO treatment as: no ILO (group A), ILO once monthly (group B) and ILO for five consecutive days (group C). Resistivity index (RI), finger pulp blood flow and periungual vascularization by PDUS, and sum of capillaries apex width in 1 mm by nailfold videocapillaroscopy were evaluated. Results were adjusted for the average outdoor temperature at the place of residence. RESULTS: An acute ILO effect was observed for only finger pulp blood flow in groups B and C (P < 0.001 and P < 0.005, respectively). An acute effect was observed for RI and periungual vascularization only in group B. A progressive increase was observed for other parameters without statistical difference. ILO effects were not observed any longer before the following infusion. Some parameters (finger pulp blood flow in group B and RI in group C) showed a statistically higher increase the lower the outdoor temperature was. CONCLUSION: ILO had an acute effect as assessed by PDUS, especially in group B. By contrast, an ILO chronic effect was not detectable before the following infusion in both treatment groups. More studies are needed to define how often ILO should be administered.

Mapping and predicting mortality from systemic sclerosis.

OBJECTIVES: To determine the causes of death and risk factors in systemic sclerosis (SSc). METHODS: Between 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database. Candidate prognostic factors were tested by Cox proportional hazards regression model by single variable analysis, followed by a multiple variable model stratified by centres. The bootstrapping technique was used for internal validation. RESULTS: We identified 2719 French certificates of deaths related to SSc, mainly from cardiac (31%) and respiratory (18%) causes, and an increase in SSc-specific mortality over time. Over a median follow-up of 2.3 years, 1072 (9.6%) of 11 193 patients from the EUSTAR sample died, from cardiac disease in 27% and respiratory causes in 17%. By multiple variable analysis, a risk score was developed, which accurately predicted the 3-year mortality, with an area under the curve of 0.82. The 3-year survival of patients in the upper quartile was 53%, in contrast with 98% in the first quartile. CONCLUSION: Combining two complementary and detailed databases enabled the collection of an unprecedented 3700 deaths, revealing the major contribution of the cardiopulmonary system to SSc mortality. We also developed a robust score to risk-stratify these patients and estimate their 3-year survival. With the emergence of new therapies, these important observations should help caregivers plan and refine the monitoring and management to prolong these patients' survival.

Detection of early endothelial damage in patients with Raynaud's phenomenon.

OBJECTIVES: Raynaud's phenomenon (RP) can be the first manifestation of systemic sclerosis (SSc) or other connective tissue diseases (CTDs), often preceding an overt disease by years. It is not known if markers of endothelial damage are detectable in those RP patients who subsequently develop a CTD. METHODS: We studied 82 RP patients at their first evaluation to correlate the levels of endothelial markers with the subsequent development of an overt disease 36months later. We measured plasma levels of tissue-type plasminogen activator (t-PA) and von Willebrand factor (vWF), two markers of endothelial damage, and interleukin-6 (IL-6), a pro-inflammatory cytokine. Thirty sex- and age-matched healthy subjects (HS) served as controls. RESULTS: At baseline, 67 patients showed capillaroscopic normal pattern (CNP) and 15 patients, of which 11 were very early SSc, had capillaroscopic scleroderma pattern (CSP). Plasma levels of t-PA, vWF and IL-6 were higher in patients with CNP (p=0.0001) than in HS and even much higher in patients with CSP (p=0.0001). In patients with CNP and RP of recent onset (<18months), vWF plasma levels were higher when autoantibodies were present (p=0.020). After 36months, among 48 RP patients with CNP who remained in follow-up, 24 were diagnosed as primary and 24 as secondary RP. In secondary RP, basal levels of t-PA, IL-6 and particularly vWF were higher than in primary RP (p=0.005, p=0.004, p=0.0001 respectively) and HS (p=0.0001 for all). CONCLUSIONS: Our findings indicate that markers of endothelial damage are elevated in RP patients who subsequently develop SSc or other CTDs, even in the absence of capillaroscopic abnormalities.

An international SUrvey on non-iNvaSive tecHniques to assess the mIcrocirculation in patients with RayNaud's phEnomenon (SUNSHINE survey).

To canvas opinion concerning the role of non-invasive techniques in the assessment of patients with Raynaud's phenomenon (Rp) in clinical and research settings: four nailfold capillaroscopy methods [videocapillaroscopy (NVC), dermoscopy, stereomicroscopy, digital USB microscopy], four laser Doppler methods (laser Doppler flowmetry, imaging, anemometry/velocimetry, laser speckle contrast analysis), thermographic imaging, and upper limb arterial Doppler ultrasound. Emails with a link to the survey were sent to physicians from the European Scleroderma Trials and Research group (EUSTAR), the EULAR Study Group on Microcirculation in Rheumatic Diseases (SG_MC/RD) and members of the pediatric rheumatology Email board. The main descriptive analysis related to physicians looking after adult patients, with some analysis also of opinions from paediatric rheumatologists. 106 'adult physicians' responded (a response rate of 25.8%), of whom 68.9% were European, and 81.1% practising for more than 10 years. Nineteen paediatricians responded. The most widely available technique was NVC (72.7%). Nailfold capillaroscopy was most frequently performed by the physician him/herself, using different types of equipment relating to availability. Most rheumatologists reported high levels of appropriateness for NVC in both clinical and research settings for global assessment and differential diagnosis of Rp. Other techniques were less used. Of all the different techniques, nailfold capillaroscopy was the one most used in both clinical and research settings by adult physicians, the majority of whom use NVC in their everyday practice. The low proportion of clinicians using other techniques suggests that these are currently mainly research tools, available only in specialist centres.