TSystemic sclerosis is an inflammatory rheumatic disease affecting small arteries, microvessels and connective tissue. Pathological findings include fibrosis, vasculopathy and production of ...autoantibodies. Clinically, two distinct subgroups can be identified. Limited cutaneous systemic sclerosis is associated with anticentromere antibodies and the skin lesion never extends proximally to the elbows and knees. Diffuse cutaneous systemic sclerosis exhibits production of anti topoisomerase I antibodies (anti Scl 70)and skin lesion affects also proximal parts of the body. The annual incidence is estimated to 0.2-1.9 per 100 000 inhabitants. The prevalence is approximately 7-15 cases per 100 000 inhabitants. Mortality is significantly increased, mainly due to pulmonal arterial hypertension and interstitial lung disease. A possible increased risk of contracting lung cancer is still debated
Objective
Systemic sclerosis (SSc) is a heterogeneous connective tissue disease that is typically subdivided into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) depending on the ...extent of skin involvement. This subclassification may not capture the entire variability of clinical phenotypes. The European Scleroderma Trials and Research (EUSTAR) database includes data on a prospective cohort of SSc patients from 122 European referral centers. This study was undertaken to perform a cluster analysis of EUSTAR data to distinguish and characterize homogeneous phenotypes without any a priori assumptions, and to examine survival among the clusters obtained.
Methods
A total of 11,318 patients were registered in the EUSTAR database, and 6,927 were included in the study. Twenty‐four clinical and serologic variables were used for clustering.
Results
Clustering analyses provided a first delineation of 2 clusters showing moderate stability. In an exploratory attempt, we further characterized 6 homogeneous groups that differed with regard to their clinical features, autoantibody profile, and mortality. Some groups resembled usual dcSSc or lcSSc prototypes, but others exhibited unique features, such as a majority of lcSSc patients with a high rate of visceral damage and antitopoisomerase antibodies. Prognosis varied among groups and the presence of organ damage markedly impacted survival regardless of cutaneous involvement.
Conclusion
Our findings suggest that restricting subsets of SSc patients to only those based on cutaneous involvement may not capture the complete heterogeneity of the disease. Organ damage and antibody profile should be taken into consideration when individuating homogeneous groups of patients with a distinct prognosis.
A man in his forties with swelling in both orbits Midtvedt, Øyvind; Gran, Jan Tore; Solheim, Hanne ...
Tidsskrift for den Norske Lægeforening,
2014-Aug-19, 20140819, Letnik:
134, Številka:
15
Journal Article
Recenzirano
Erdheim-Chester disease. A multi-disiplinary challenge. The histiocytoses are a diverse, but rare group of disorders with symptoms affecting many organs, varying from self-limiting, localised lesions ...to disseminated multi-organ disease. The diagnostic challenges are illustrated and discussed in the following case.
A man in his forties was admitted to hospital due to pain in his right eye and visual disturbances. MRI imaging detected a mass in his right orbit and a minor mass in his left orbit. The histological results of the mass in his right orbit revealed an inflammatory process with lymphocytes and macrophages and no sign of vasculitis, infection or malignancy. The diagnosis pseudotumor orbita was made and treatment with corticosteroids was initiated. He did not respond to corticosteroids or radiotherapy and increasing symptoms necessitated rehospitalisation. Further tests disclosed a multisystem disease which affected the aorta, skeleton, lung, heart and kidney. The biopsy was reconsidered and the disease was classified as a histiocytosis with CD68 positive and CD1a negative cells. The diagnosis Erdheim-Chester was given, about 14 months after the initial hospitalisation. Treatment with interferon α was started.
A middle-aged woman suffered from chronic recurrent urticarial rash and fever. After 13 years of skin disease, she developed monoclonal IgM gammopathy, myalgia and joint pain. She was diagnosed with ...Schnitzler's syndrome and successfully treated with the IL-1 receptor antagonist anakinra.
Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with ...progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs).
The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV).
66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%.
Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years.
NCT02339441.
To longitudinally map the onset and identify risk factors for skin sclerosis and digital ulcers (DUs) in patients with systemic sclerosis (SSc) from an early time point after the onset of Raynaud's ...phenomenon (RP) in the European Scleroderma Trials and Research (EUSTAR) cohort.
695 patients with SSc with a baseline visit within 1 year after RP onset were followed in the prospective multinational EUSTAR database. During the 10-year observation period, cumulative probabilities of cutaneous lesions were assessed with the Kaplan-Meier method. Cox proportional hazards regression analysis was used to evaluate risk factors.
The median modified Rodnan skin score (mRSS) peaked 1 year after RP onset, and was 15 points. The 1-year probability to develop an mRSS ≥2 in at least one area of the arms and legs was 69% and 25%, respectively. Twenty-five per cent of patients developed diffuse cutaneous involvement in the first year after RP onset. This probability increased to 36% during the subsequent 2 years. Only 6% of patients developed diffuse cutaneous SSc thereafter. The probability to develop DUs increased to a maximum of 70% at the end of the 10-year observation. The main factors associated with diffuse cutaneous SSc were the presence of anti-RNA polymerase III autoantibodies, followed by antitopoisomerase autoantibodies and male sex. The main factor associated with incident DUs was the presence of antitopoisomerase autoantibodies.
Early after RP onset, cutaneous manifestations exhibit rapid kinetics in SSc. This should be accounted for in clinical trials aiming to prevent skin worsening.
Objective
The outcome of patients with COVID‐19 improved over the pandemic, including patients with systemic rheumatic diseases. However, data on patients with systemic sclerosis (SSc) are lacking. ...This study aimed to assess the outcome of patients with both SSc and COVID‐19 over several waves.
Methods
Patients with both SSc and COVID‐19 who were registered in the European Scleroderma Trials and Research group (EUSTAR) were collected between April 2020 and April 2021. Patients were assigned to waves 1, 2, or 3 depending on the date of their COVID‐19 diagnosis. Primary endpoints were death, intensive care unit stay, or ventilatory support (severe outcome). Subgroup analyses of patients who were hospitalized or died were conducted. General and SSc‐specific characteristics and treatment were compared over the waves. Descriptive statistics and multivariate logistic regression were applied.
Results
A total of 333 patients were included; 57 patients (17%) had a severe outcome, and 30 patients (9%) died. Compared to wave 1, significantly fewer patients with SSc suffered from severe COVID‐19 in waves 2 and 3 (28.2% vs 9.8% and 12.7%; P < 0.001), fewer patients required hospitalization (46.7% vs 19.6% and 25.5%; P < 0.001) or ventilatory support (24.0% vs 8.7% and 10.9%; P = 0.001), and fewer patients died (15.7% vs 5.0% and 7.5%; P = 0.011). Patients were significantly younger, more often men, had less frequent arterial hypertension, and less SSc cardiac involvement over waves 1 to 3. Patients received significantly less medium to high doses of corticosteroids as they did SSc treatment.
Conclusion
The outcome of patients with both SSc and COVID‐19 improved significantly over time because of intrinsic and extrinsic factors.
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