Subgroups of capillaroscopic scleroderma landscape have been correlated with stages of SSc: two groups for Maricq's classification (slow and active), and three for Cutolo's classification (early, ...active and late). We report inter- and intra-observer agreement for these classifications as a preliminary step in the multicentre prospective SCLEROCAP study, which aims to assess the classification and single capillaroscopic items as prognostic tools for SSc.
SCLEROCAP included 385 patients. Agreement was studied in the first 100 patients, who were independently rated twice by two observers, blind to patients' characteristics; 30 of the patients were rated once by six observers. After consensus meetings, these ratings were held again. Kappa and intraclass correlation coefficients were used to assess agreement.
Interobserver agreement on 100 patients was moderate for Maricq and Cutolo classifications κ 0.47 (0.28, 0.66) and 0.49 (0.33, 0.65), respectively, and became substantial after consensus meetings 0.64 (0.50, 0.77) and 0.69 (0.56, 0.81). Intra-observer agreement between two observers was moderate to substantial: κ 0.54 (0.33, 0.75) and 0.70 (0.57, 0.83) for Maricq's classification; 0.57 (0.38, 0.77) and 0.76 (0.65, 0.87) for Cutolo's. Thirty patients were rated once by each of six observers, and agreement was moderate to substantial: κ 0.57 ± 0.10 (Maricq) and 0.61 ± 0.12 (Cutolo). Agreement was substantial for bushy, giant capillaries and microhaemorrhages, moderate for capillary density and low for oedema, disorganization and avascular areas.
The moderate reproducibility of Maricq and Cutolo classifications might hamper their prognostic value in SSc patients. Consensus meetings improve reliability, a prerequisite for better prognostic performances. A focus on giant capillaries, haemorrhages and capillary density might be more reliable.
Introduction
Severe Raynaud's syndrome and DUs are the most prevalent manifestations of SSc peripheral microvascular disease. We tested whether treprostinil iontophoresis on the finger pad of ...patients with SSc would improve digital blood flow during hand cooling.
Methods
Eleven patients with limited cutaneous SSc underwent a double‐blinded iontophoresis of treprostinil (2.56 × 10−4 M during two hours) and placebo (NaCl 0.9%) on two finger pads. Then, the hand was inserted for 30 minutes in a fenestrated cooling box at 8°C, and skin blood flow was recorded continuously using LSCI.
Results
During the local cooling, CVC was significantly higher at the treprostinil site than at the placebo site and remained higher 30 minutes after the test.
Conclusions
In patients with SSc, digital treprostinil iontophoresis shifts skin blood flow upward during local cooling of the hand and during the initial rewarming phase. Digital treprostinil iontophoresis should now be tested in larger scale studies.
The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the ...previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc.
Direct oral anticoagulants (DOACs) are an alternative to low-molecular-weight heparin for treating cancer-associated VTE.
Is rivaroxaban as efficient and safe as dalteparin to treat patients with ...cancer-associated VTE?
In a randomized open-label noninferiority trial, patients with active cancer who had proximal DVT, pulmonary embolism (PE), or both were assigned randomly to therapeutic doses of rivaroxaban or dalteparin for 3 months. The primary outcome was the cumulative incidence of recurrent VTE, a composite of symptomatic or incidental DVT or PE, and worsening of pulmonary vascular or venous obstruction at 3 months.
Of 158 randomized patients, 74 and 84 patients were assigned to receive rivaroxaban and dalteparin, respectively. Mean age was 69.4 years, and 115 patients (76.2%) had metastatic disease. The primary outcome occurred in 4 and 6 patients in the rivaroxaban and dalteparin groups, respectively (both the intention-to-treat and per-protocol populations: cumulative incidence, 6.4% vs 10.1%; subdistribution hazard ratio SHR, 0.75; 95% CI, 0.21-2.66). Major bleeding occurred in 1 and 3 patients in the rivaroxaban and dalteparin groups, respectively (cumulative incidence, 1.4% vs 3.7%; SHR, 0.36; 95% CI, 0.04-3.43). Major or clinically relevant nonmajor bleeding occurred in 9 and 8 patients in the rivaroxaban and dalteparin groups, respectively (cumulative incidence, 12.2% vs 9.8%; SHR, 1.27; 95% CI, 0.49-3.26). Overall, 19 patients (25.7%) and 20 patients (23.8%) died in the rivaroxaban and dalteparin groups, respectively (hazard ratio, 1.05; 95% CI, 0.56-1.97).
In this trial comparing rivaroxaban and dalteparin in the treatment of cancer-associated VTE, the number of patients was insufficient to reach the predefined criteria for noninferiority, but efficacy and safety results were consistent with those previously reported with DOACs. An updated meta-analysis of randomized trials comparing DOACs with low-molecular-weight heparin in patients with cancer-associated VTE is provided.
ClinicalTrials.gov; No.: NCT02746185; URL: www.
gov.
•US was more sensitive than clinical examination to detect synovitis and tenosynovitis in SSc.•US foot involvement is less frequent than hand involvement but affects a quarter of the patients and is ...mostly located at MTP joints.•US hand synovitis seems associated with hand disability and DcSSc.•This is the first and largest US study investigating specifically foot's synovitis and tenosynovitis in SSc classified with ACR/EULAR 2013 criteria.
In systemic sclerosis, few studies have shown that hand and wrist ultrasound is more sensitive than clinical examination in the detection of synovitis and tenosynovitis. Even fewer studies have investigated ankle and foot involvement with ultrasound. Our objectives were to investigate ultrasound prevalence of wrist, hand, ankle and foot synovitis and tenosynovitis in patients with systemic sclerosis classified with ACR/EULAR 2013 criteria, and to study their relationship with disease features and hand disability.
Consecutive patients with systemic sclerosis, classified with ACR/EULAR 2013 criteria, were included in a monocentric cross-sectional study. They underwent standardized musculoskeletal clinical examination and hand, wrist, ankle and foot ultrasound. Clinical, biological and imaging data were also collected.
Fifty-five patients were included. Ultrasound was more sensitive than clinical examination to detect at least one synovitis (respectively 52% versus 25%, P=0.025) and at least one tenosynovitis (respectively 16% versus 4%, P=0.009); 18% of patients had ankle tenosynovitis and 29% had ankle and/or foot synovitis, mostly located at metatarsophalangeal joints (25.5%). Having at least one ultrasound hand synovitis was associated with higher Cochin hand functional disability scale (mean 25±3 versus 12±2, P=0.003) and diffuse cutaneous subset (P=0.038).
Our study shows that ultrasound is more sensitive than clinical examination to detect synovitis and tenosynovitis in systemic sclerosis. The foot involvement is less frequent than hand involvement, mainly localized at metatarsophalangeal joint. Finally, having at least one synovitis of the hand is associated with diffuse cutaneous subset and higher hand disability.
Objective
To evaluate the prevalence and clinical correlates of peripheral arterial disease of the upper limbs in patients with systemic sclerosis (SSc), as detected with finger brachial pressure ...index (FBPI) measurements.
Methods
This work is based on the baseline data of the SCLEROCAP multicenter cohort of SSc patients. Finger systolic blood pressure was measured with laser Doppler flowmetry, and the FBPI was obtained as its ratio over the ipsilateral brachial systolic blood pressure. An FBPI of <0.70 was used as the diagnostic criterion for occlusive arterial disease of the upper limbs. Thus, the prevalence of defined arterial disease as well as its clinical, biologic, and capillaroscopic correlates were evaluated.
Results
Among 326 enrolled patients, 177 (54.3%) met the criterion for arterial disease (FBPI <0.70). No association was found with the type of SSc nor with the type of associated antinuclear antibodies, but a significant association was found with the duration of the disease (P < 0.001), the capillaroscopic pattern (P < 0.001), and most strikingly with the presence of digital ulcers (42.9% versus 13.4%; P < 0.001). A quantitative relationship was found between the FBPI and the prevalence of digital ulcers and was shown to be independent from the capillaroscopic pattern.
Conclusion
This cross‐sectional study shows a high prevalence of arterial disease of the upper limbs in patients with SSc. FBPI appears to be a strong and independent predictor of digital ulcers. This study suggests that both macro‐ and microangiopathy are contributing to the ischemic damage of the fingertips.
Objective
Findings from the WEGENT trial and other short‐term studies have suggested that azathioprine (AZA) or methotrexate (MTX) could effectively maintain remission of granulomatosis with ...polyangiitis (Wegener's) (GPA) or microscopic polyangiitis (MPA). This study was undertaken to examine whether differences in rates of relapse or adverse events would appear after discontinuation of these 2 maintenance regimens, when assessed over a longer followup period.
Methods
Long‐term outcomes in patients enrolled in the WEGENT trial were analyzed according to their randomized treatment group (AZA or MTX). Parameters at trial entry were evaluated as potential prognostic factors for death, relapse, or damage in multivariate models.
Results
Data from 10 years of followup were available for 112 (88.8%) of the 126 original trial participants. The median followup time was 11.9 years (95% confidence interval 95% CI 11.3–12.5 years). In patients receiving AZA and those receiving MTX, the 10‐year overall survival rates were 75.1% (95% CI 64.8–86.9%) and 79.9% (95% CI 70.3–90.8%) (P = 0.56), respectively, and relapse‐free survival rates were 26.3% (95% CI 17.3–40.1%) and 33.5% (95% CI 23.5–47.7%) (P = 0.29), respectively. No between‐treatment differences were observed with regard to rates of relapse, adverse events, damage, survival without severe side effects, and survival without relapse and severe side effects. In analyses limited to the 97 patients with GPA, no between‐treatment differences in survival rates were observed. The 10‐year relapse‐free survival rate was lower in patients with GPA than in patients with MPA. However, in the multivariate analysis, anti–proteinase 3 antineutrophil cytoplasmic antibody (ANCA) positivity, and not GPA, was retained as being independently associated with the relapse rate.
Conclusion
The results of this long‐term analysis confirm that AZA and MTX are comparable treatment options for maintaining remission of GPA or MPA. Despite achieving good overall survival with these treatments, relapse rates, adverse events, and damage remain matters of concern and further studies are needed to reduce their frequency in these ANCA‐associated vasculitides.
Objectives
To propose a scale of severity for post-thrombotic venous lesions (PTVLs) after ilio-femoral deep venous thrombosis and to compare the grade with the results of endovascular treatment of ...ilio-femoral PTVLs.
Methods
In this retrospective monocentric observational study, we included 95 patients treated for ilio-femoral PTVLs. We proposed a four-grade scale evaluating the severity of PTVLS caudal to the common femoral vein based on CT phlebography and per-operative phlebography. For most patients, venous patency was assessed with color duplex ultrasonography and the clinical efficacy of the intervention using the Villalta and CIVIQ scores.
Results
Recanalization was successful in 100% of patients with a morbidity rate of 4%. After a mean follow-up of 21 months, the overall primary patency was 75%, the assisted primary patency 82%, and the secondary patency 93%. Secondary patency was 100% for grade 0–1, 90% for grade 2, and 63% for grade 3 (
p
< 0.002). There was no correlation between the extension of stenting caudally of the common femoral vein and venous patency. The mean improvements in the Villalta and CIVIQ-20 scores were, respectively, 4.6 (
p
< 0.0001) and 18 (
p
< 0.0001); scores were not correlated with the grade of PTVLs in the thigh.
Conclusion
Venous patency after endovascular treatment of ilio-femoral PTVLs was strongly linked to the severity of PTVLs caudal to the common femoral vein but not to the extent of stenting.
Abstract
Systemic sclerosis (SSc) is a generalized disease of the connective tissue, arterioles, and microvessels, characterized by the appearance of fibrosis and vascular obliteration. There are two ...main phenotypical forms of SSc: a diffuse cutaneous form that extends towards the proximal region of the limbs and/or torso, and a limited cutaneous form where the cutaneous sclerosis only affects the extremities of the limbs (without passing beyond the elbows and knees). There also exists in less than 10% of cases forms that never involve the skin. This is called SSc sine scleroderma. The prognosis depends essentially on the occurrence of visceral damage and more particularly interstitial lung disease (which is sometimes severe), pulmonary arterial hypertension, or primary cardiac damage, which represent the three commonest causes of mortality in SSc. Another type of involvement with poor prognosis, scleroderma renal crisis, is rare (less than 5% of cases). Cutaneous extension is also an important parameter, with the diffuse cutaneous forms having less favorable prognosis.
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