Validity of European Scleroderma Study Group (EScSG) activity indexes currently used to assess disease activity in systemic sclerosis (SSc) has been criticised.
Three investigators assigned an ...activity score on a 0-10 scale for 97 clinical charts. The median score served as gold standard. Two other investigators labelled the disease as inactive/moderately active or active/very active. Univariate-multivariate linear regression analyses were used to define variables predicting the 'gold standard', their weight and derive an activity index. The cut-off point of the index best separating active/very active from inactive/moderately active disease was identified by a receiver-operating curve analysis. The index was validated on a second set of 60 charts assessed by three different investigators on a 0-10 scale and defined as inactive/moderately active or active/very active by other two investigators. One hundred and twenty-three were investigated for changes over time in the index and their relationships with those in the summed Medsger severity score (MSS).
A weighted 10-point activity index was identified and validated: Δ-skin=1.5 (Δ=patient assessed worsening during the previous month), modified Rodnan skin score (mRss) >18=1.5, digital ulcers=1.5, tendon friction rubs=2.25, C-reactive protein >1 mg/dL=2.25 and diffusing capacity of the lung for CO (DLCO) % predicted <70%=1.0. A cut-off ≥2.5 was found to identify patients with active disease. Changes in the index paralleled those of MSS (p=0.0001).
A preliminarily revised SSc activity index has been developed and validated, providing a valuable tool for clinical practice and observational studies.
Objectives Bronchoalveolar lavage (BAL) has been used for clinical and research purposes in scleroderma interstitial lung disease (SSc-ILD). However, inconsistencies regarding technical aspects of ...BAL are obstacles in the reproducibility and interpretation of BAL results. This review summarizes clinical correlations and methodological issues of using BAL in the assessment of patients with SSc-ILD. In addition, we review the investigational use of BAL in SSc-ILD. Methods The PubMed database from inception through May 2008 was searched using the following keywords: “systemic sclerosis, scleroderma, interstitial lung disease, and bronchoalveolar lavage.” The search was limited to English-language studies that included at least 15 SSc patients that had BAL. Results An increased percentage of neutrophils, eosinophils, and/or lymphocytes, often referred to as “alveolitis,” was reported in a significant percentage of SSc patients (range, 38 to 100%) irrespective of patient selection criteria, cytological cutoff values, or technical aspects of BAL processing. Alveolitis is associated with more severe lung impairment as defined by lung function tests and overall lung high-resolution computed tomography scores, but there is insufficient evidence at this time to recommend BAL cytology as an independent predictor of outcome in SSc-ILD patients. Myofibroblasts have been cultured from BAL fluid, and inflammatory and fibrogenic mediators can be measured in the supernatant of BAL fluid from patients with SSc-ILD. Conclusions Further studies using standardized BAL protocols are required to establish the role of BAL fluid in the clinical evaluation of SSc-ILD. When performed for research purposes, BAL has provided valuable insight into the pathogenesis of SSc-ILD.
Limited cutaneous systemic sclerosis (LcSSc) is the most common subset of SSc but it has been overlooked in the past years. At a time at which clinical trials focus on diffuse cutaneous SSc (DcSSc) ...we aimed at clarifying the outcomes of LcSSc and at evaluating whether potential drug positioned in DcSSc may also be used in LcSSc.
The EUSTAR database was used to investigate skin, lung and peripheral vasculopathy outcomes in LcSSc. Worsening of skin fibrosis, ILD and peripheral vasculopathy were defined by an increase in modified Rodnan skin score (mRSS) > 3.5 points, a decrease of FVC > 10% in patients with ILD at baseline, and by the development of new digital ulcers (DU) in patients without DU at baseline.
8013 LcSSc and 4786 DcSSc patients were included. In contrast to DcSSc, skin disease was remarkably stable in the majority of LcSSc patients with >80% having a change lower than ±4 units of mRSS at 12, 24 and 36 months follow-up. Conversely, FVC changes over time were very similar between LcSSc and DcSSc. Regarding DU, numbers of patients with new DU over time seemed to be almost similar between the two subsets.
LcSSc patients have a low mRSS at baseline with marginal changes with time. Conversely, SSc-ILD can be as progressive as in DcSSc supporting the inclusion of LcSSc patients in SSc-ILD trials and suggesting potential benefit of any anti-ILD drugs. Similarly, although slightly less common, DU should receive the same attention in the two subsets.
•LcSSc patients have a low mRSS at baseline with marginal changes with time.•Similar rates of ILD progression were observed between LcSSc and DcSSc.•Rates of patients with new DU over time were almost similar between the two subsets.
Objective
Classification criteria for systemic sclerosis (SSc; scleroderma) are being updated. Our objective was to select a set of items potentially useful for the classification of SSc using ...consensus procedures, including the Delphi and nominal group techniques (NGT).
Methods
Items were identified through 2 independent consensus exercises performed by the Scleroderma Clinical Trials Consortium and the European League Against Rheumatism Scleroderma Trials and Research Group. The first‐round items from both exercises were collated and redundancies were removed, leaving 168 items. A 3‐round Delphi exercise was performed using a 1–9 scale (where 1 = completely inappropriate and 9 = completely appropriate) and a consensus meeting using NGT was conducted. During the last Delphi round, the items were ranked on a 1–10 scale.
Results
In round 1, 106 experts rated the 168 items. Those with a median score of <4 were removed, resulting in a list of 102 items. In round 2, the items were again rated for appropriateness and subjected to a consensus meeting using NGT by European and North American SSc experts (n = 16), resulting in 23 items. In round 3, SSc experts (n = 26) then individually scored each of the 23 items in a last Delphi round using an appropriateness score (1–9) and ranking their 10 most appropriate items for the classification of SSc. Presence of skin thickening, SSc‐specific autoantibodies, abnormal nailfold capillary pattern, and Raynaud's phenomenon ranked highest in the final list that also included items indicating internal organ involvement.
Conclusion
The Delphi exercise and NGT resulted in a set of 23 items for the classification of SSc that will be assessed for their discriminative properties in a prospective study.
Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by widespread vascular injury and progressive fibrosis of the skin and internal organs. The involvement of internal organs ...results in significant morbidity and mortality of SSc patients with cardiopulmonary involvement being the leading cause of SSc‑related deaths. The management of SSc patients remains a challenge because therapeutic options are rather limited and no therapy has definitively shown a disease‑modifying effect. A significant progress that has recently been made in the understanding of the SSc pathogenesis contributed to the introduction of new therapeutic options. Preliminary clinical studies have yielded promising results for mycophenolate mofetil, anti‑CD20 antibodies, and stem‑cell in the treatment of SSc. Multicenter cohort studies help understand the natural history of SSc, which leads to improvement in the care of SSc patients. The major objective of those studies is to establish the screening strategies for early diagnosis and, subsequently, to introduce appropriate management concerning specific organ involvement in SSc as well as to formulate specific treatment recommendations.
Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of ...connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities.
The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology-a non-profit international organisation dedicated to consensus methodology in identification of outcome measures-conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF).
A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed.
Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field.
Background: The purpose of our study was to assess the diagnostic power of galectin-3 and compare its between rheumatic diseases and with routinely used tests such as CRP and ESR. Methods: Eighty-two ...patients with rheumatoid arthritis (RA), 49 patients with systemic sclerosis (SSc), and 18 patients with systemic lupus erythematosus (SLE) were enrolled in this study. The control group comprised 30 healthy controls. Serum galectin-3 concentration was measured using immunochemical method. Results: The galectin-3 concentration were significantly elevated in the RA, SSc, and SLE in comparison to the controls (p = 0.000, p = 0.000, p < 0.001; respectively). However, there were no significant differences in the serum galectin-3 levels between rheumatic diseases (H = 0.395, p = 0.821). In RA and SSc patients, galectin-3 positively correlated with erythrocyte sedimentation rate (R = 0.332, p = 0.004; R = 0.384, p = 0.009; respectively). ROC analysis revealed that galectin-3 had an excellent diagnostic power in RA (AUC = 0.911) and SSc (AUC = 0.903) and very good for SLE (AUC = 0.859). Conclusion: We concluded that diagnostic power of serum galectin-3 is as great as CRP and ESR in rheumatic diseases and it can be a very good laboratory marker in RA and SSc patients and a useful tool in the diagnosis of SLE.
Introduction
Patients with systemic sclerosis (SSc) present an increased risk of developing glaucomatous optic neuropathy (GON). We investigated peripapillary choroidal parameters and peripapillary ...retinal nerve fiber layer (RNFL) thickness using spectral domain optical coherence tomography (SD-OCT) to determine the relationships of these factors with clinical variables.
Methods
A total of 33 patients with SSc were enrolled and compared to 40 controls. After obtaining circular scans around the optic disc, the global and quadrant peripapillary choroidal thickness (pCT) and RNFL thickness were measured. Additionally, the peripapillary choroidal vascularity index (pCVI), which allows for a quantitative analysis of the choroidal vasculature, was determined.
Results
No significant differences were found in pCT and RNFL thickness between patients with SSc and controls, or within SSc subtypes (diffuse cutaneous systemic sclerosis (dcSSc) compared to limited cutaneous systemic sclerosis (lcSSc)) (
p
> 0.05). The pCVI was significantly lower in patients with SSc than in control subjects (64.25 ± 1.94 vs.65.73 ± 2.12,
p
< 0.001).
Conclusion
Our results suggest that the statistically significant decrease in pCVI in patients with SSc compared to the control group is probably due to a decrease in the vascular layer, which would partially explain an increased risk of GON in patients with SSc.
Purtscher-like retinopathy (PLR) is an uncommon occlusive microangiopathy associated with various systemic conditions. We report a case of PLR related to severe progressive systemic sclerosis (SSc), ...an autoimmune disease characterized by widespread angiopathy and fibrosis, in a 44-year-old Caucasian male diagnosed with early diffuse cutaneous systemic sclerosis (dSSc). Upon ophthalmological examination, pathognomonic fundoscopy abnormalities were found. Spectral domain optical coherence tomography (SD-OCT), angio-OCT, and visual field results are documented at initial diagnosis and follow-up visits. The detailed ophthalmological assessment is juxtaposed with rheumatological evaluation and treatment. Current literature on probable pathophysiological mechanisms is reviewed in accordance with the described case. The PLR seems to be connected to severe SSc-related angiopathy initiated by capillary endothelial damage, with ultimate arteriolar precapillary occlusion in the inner retinal layer. Although this is not routinely recommended, we suggest that ophthalmological examinations may be advantageous in patients with SSc, as serious eye pathology may be present despite the lack of symptoms reported by the patient. Patients with PLR require a differential diagnosis and regular follow-up. Proper treatment of the underlying disease may have beneficial effects on the natural course of PLR.
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