scholarly journals Skin score as a predictor of prolonged QTc in systemic sclerosis.

2021 ◽  
Author(s):  
◽  
Nafiseh Abdolahi ◽  
Mehrdad Aghaei ◽  
Ahmad Mohammadi ◽  
Keyword(s):  
Systemic Sclerosis ◽  
Significant Relationship ◽  
Rna Polymerase Iii ◽  
Cardiac Conduction ◽  
Control Group ◽  
Qtc Interval ◽  
Skin Score ◽  
Duration Of Disease ◽  
Pulmonary Arterial ◽  
American Society

Abstract Background Systemic sclerosis is an autoimmune disease characterized by endothelial dysfunction and fibrosis of the skin and internal organs. Cardiac involvement during systemic sclerosis can be primary or secondary to pulmonary arterial hypertension and renal pathology. Among the disorders in systemic sclerosis, prolongation of QTc time is also associated with more anti-RNA polymerase III antibodies, longer duration and severity of disease. Methods This case-control study was performed on 35 patients with systemic scleroderma who filled in the American Society of Rheumatism (ACR / EULAR criteria) and 35 healthy subjects prior to entering the study. Then, the QTc distance was extracted from the electrocardiogram and calculated using the formula. The measured QTc distance in the electrocardiogram, QTc> 440ms in men and QTc> 460ms in women, was defined as QTc long. Then the patients and the control group underwent echocardiography and changes in QTc interval and its relation with echocardiographic findings was evaluated. Results The results of this study indicated a significant relationship between QTc distance in patients with scleroderma compared with healthy controls. There was also a significant relationship between QTc and Skin Score of patients. However, there was no significant correlation between QTc distance and age, gender, duration of disease, Anti-Centromere, Anti-Scl70, and pulmonary artery pressure. Conclusion This study concludes that patients with scleroderma are at high risk for cardiac conduction impairment. The only factor that significantly correlated with QTc was the Skin Score of the patients.

Systemic sclerosis

2013 ◽  
pp. 971-988 ◽  
Author(s):  
Christopher P. Denton ◽  
Pia Moinzadeh
Keyword(s):  
Systemic Sclerosis ◽  
Cell Injury ◽  
Rna Polymerase Iii ◽  
Systematic Investigation ◽  
Clinical Markers ◽  
Topoisomerase 1 ◽  
Skin Sclerosis ◽  
Female Predominance ◽  
Organ Manifestations ◽  
Pulmonary Arterial

The term ’scleroderma’ describes a group of conditions in which the development of thickened, fibrotic skin is a cardinal feature. This includes localized forms of scleroderma (e.g. morphoea) and also systemic forms of the disease that are more correctly termed systemic sclerosis. Systemic sclerosis (SSc) is a multiorgan, autoimmune disease that has a high clinical burden and mortality, due to affecting the skin as well as internal organs. As with other related diseases there is a female predominance and marked clinical diversity. The pathogenesis of SSc is not fully elucidated; it includes endothelial cell injury fibroblast activation and autoimmunity that lead to skin and internal organ manifestations. The majority of cases exhibit characteristic serum autoantibodies. Some of these antibodies are scleroderma-specific reactivities including anti-centromere (ACA), anti-topoisomerase-1 (ATA or Scl 70) or anti-RNA polymerase III antibodies. These anti-nuclear antibody (ANA) patterns are generally mutually exclusive and serve as useful clinical markers of disease subgroups. Additional subsetting of scleroderma cases, based on the extent of skin sclerosis, permits classification into limited and diffuse subsets. Because of the heterogeneity of the disease patients may suffer from different organ manifestations, such as lung fibrosis, hypertensive renal crisis, severe cardiac disease, gastrointestinal involvement, and pulmonary arterial hypertension. Although outcomes have improved recently, systemic sclerosis still has the highest case-specific mortality of any of the autoimmune rheumatic diseases and requires careful and systematic investigation, management and follow-up. Treatment includes symptomatic strategies with attention to each involved organ system; it is still an area where therapeutic progress and better understanding of pathogenesis is increasingly anticipated.

Systemic sclerosis

2013 ◽  
Author(s):  
Christopher P. Denton ◽  
Pia Moinzadeh
Keyword(s):  
Systemic Sclerosis ◽  
Cell Injury ◽  
Rna Polymerase Iii ◽  
Systematic Investigation ◽  
Clinical Markers ◽  
Topoisomerase 1 ◽  
Skin Sclerosis ◽  
Female Predominance ◽  
Organ Manifestations ◽  
Pulmonary Arterial

The term 'scleroderma' describes a group of conditions in which the development of thickened, fibrotic skin is a cardinal feature. This includes localized forms of scleroderma (e.g. morphoea) and also systemic forms of the disease that are more correctly termed systemic sclerosis. Systemic sclerosis (SSc) is a multiorgan, autoimmune disease that has a high clinical burden and mortality, due to affecting the skin as well as internal organs. As with other related diseases there is a female predominance and marked clinical diversity. The pathogenesis of SSc is not fully elucidated; it includes endothelial cell injury fibroblast activation and autoimmunity that lead to skin and internal organ manifestations. The majority of cases exhibit characteristic serum autoantibodies. Some of these antibodies are scleroderma-specific reactivities including anti-centromere (ACA), anti-topoisomerase-1 (ATA or Scl 70) or anti-RNA polymerase III antibodies. These anti-nuclear antibody (ANA) patterns are generally mutually exclusive and serve as useful clinical markers of disease subgroups. Additional subsetting of scleroderma cases, based on the extent of skin sclerosis, permits classification into limited and diffuse subsets. Because of the heterogeneity of the disease patients may suffer from different organ manifestations, such as lung fibrosis, hypertensive renal crisis, severe cardiac disease, gastrointestinal involvement, and pulmonary arterial hypertension. Although outcomes have improved recently, systemic sclerosis still has the highest case-specific mortality of any of the autoimmune rheumatic diseases and requires careful and systematic investigation, management and follow-up. Treatment includes symptomatic strategies with attention to each involved organ system; it is still an area where therapeutic progress and better understanding of pathogenesis is increasingly anticipated.

scholarly journals Proactive Prophylaxis With Azithromycin and HydroxyChloroquine in Hospitalised Patients With COVID-19 (ProPAC-COVID): A structured summary of a study protocol for a randomised controlled trial

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Pradeesh Sivapalan ◽  
Charlotte Suppli Ulrik ◽  
Rasmus Dahlin Bojesen ◽  
Therese Sophie Lapperre ◽  
Josefin Viktoria Eklöf ◽  
...  
Keyword(s):  
Study Protocol ◽  
Standard Treatment ◽  
Controlled Trial ◽  
Intervention Group ◽  
Cardiac Conduction ◽  
Control Group ◽  
Qtc Interval ◽  
Patient Will ◽  
Full Protocol ◽  
Fertile Women

Abstract Objectives The aim of this randomised GCP-controlled trial is to clarify whether combination therapy with the antibiotic azithromycin and hydroxychloroquine via anti-inflammation/immune modulation, antiviral efficacy and pre-emptive treatment of supra-infections can shorten hospitalisation duration for patients with COVID-19 (measured as "days alive and out of hospital" as the primary outcome), reduce the risk of non- invasive ventilation, treatment in the intensive care unit and death. Trial design This is a multi-centre, randomised, Placebo-controlled, 2-arm ratio 1:1, parallel group double-blind study. Participants 226 participants are recruited at the trial sites/hospitals, where the study will take place in Denmark: Aalborg, Bispebjerg, Gentofte, Herlev, Hillerød, Hvidovre, Odense and Slagelse hospitals. Inclusion criteria: • Patient admitted to Danish emergency departments, respiratory medicine departments or internal medicine departments • Age≥ 18 years • Hospitalized ≤48 hours • Positive COVID-19 test / diagnosis during the hospitalization (confirmed). • Men or non-fertile women. Fertile women* must not be pregnant, i.e. negative pregnancy test must be available at inclusion • Informed consent signed by the patient *Defined as after menarche and until postmenopausal (no menstruation for 12 months) Exclusion criteria: • At the time of recruitment, the patient uses >5 LO2/min (equivalent to 40% FiO2 if measured) • Known intolerance/allergy to azithromycin or hydroxychloroquine or hypersensitivity to quinine or 4-aminoquinoline derivatives • Neurogenic hearing loss • Psoriasis • Retinopathy • Maculopathy • Visual field changes • Breastfeeding • Severe liver diseases other than amoebiasis (INR> 1.5 spontaneously) • Severe gastrointestinal, neurological and hematological disorders (investigator-assessed) • eGFR <45 ml/min/1.73 m2 • Clinically significant cardiac conduction disorders/arrhythmias or prolonged QTc interval (QTc (f) of> 480/470 ms). • Myasthenia gravis • Treatment with digoxin* • Glucose-6-phosphate dehydrogenase deficiency • Porphyria • Hypoglycaemia (Blood glucose at any time since hospitalization of <3.0 mmol/L) • Severe mental illness which significantly impedes cooperation • Severe linguistic problems that significantly hinder cooperation • Treatment with ergot alkaloids *The patient must not be treated with digoxin for the duration of the intervention. For atrial fibrillation/flutter, select according to the Cardiovascular National Treatment Guide (NBV): Calcium antagonist, Beta blocker, direct current (DC) conversion or amiodarone. In case of urgent need for digoxin treatment (contraindication for the aforementioned equal alternatives), the test drug should be paused, and ECG should be taken daily. Intervention and comparator Control group: The control group will receive the standard treatment + placebo for both types of intervention medication at all times. If part or all the intervention therapy being investigated becomes standard treatment during the study, this may also be offered to the control group. Intervention group: The patients in the intervention group will also receive standard care. Immediately after randomisation to the intervention group, the patient will begin treatment with: Azithromycin: Day 1-3: 500 mg x 1 Day 4-15: 250 mg x 1 If the patient is unable to take the medication orally by themselves, the medication will, if possible, be administered by either stomach-feeding tube, or alternatively, temporary be changed to clarithromycin 500 mg x 2 (this only in agreement with either study coordinator Pradeesh Sivapalan or principal investigator Jens-Ulrik Stæhr Jensen). This will also be done in the control group if necessary. The patient will switch back to azithromycin when possible. Hydroxychloroquine: Furthermore, the patient will be treated with hydroxychloroquine as follows: Day 1-15: 200 mg x 2 Main outcomes • Number of days alive and discharged from hospital within 14 days (summarises both whether the patient is alive and discharged from hospital) ("Days alive and out of hospital") Randomisation The sponsor (Chronic Obstructive Pulmonary Disease Trial Network, COP:TRIN) generates a randomisation sequence. Randomisation will be in blocks of unknown size and the final allocation will be via an encrypted website (REDCap). There will be stratification for age (>70 years vs. <=70 years), site of recruitment and whether the patient has any of the following chronic lung diseases: COPD, asthma, bronchiectasis, interstitial lung disease (Yes vs. No). Blinding (masking) Participants and study personnel will both be blinded, i.e. neither will know which group the participant is allocated to. Numbers to be randomised (sample size) This study requires 226 patients randomised 1:1 with 113 in each group. Trial Status Protocol version 1.8, from April 16, 2020. Recruitment is ongoing (first patient recruited April 6, 2020; final patient expected to be recruited October 31, 2020). Trial registration ClinicalTrials.gov Identifier: NCT04322396 (registered March 26, 2020) Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

scholarly journals Exhaled Nitric Oxide in Pulmonary Arterial Hypertension Associated with Systemic Sclerosis

2016 ◽  
Vol 6 (4) ◽  
pp. 545-550 ◽  
Author(s):  
Zeling Cao ◽  
Stephen C. Mathai ◽  
Laura K. Hummers ◽  
Ami A. Shah ◽  
Fredrick M. Wigley ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Systemic Sclerosis ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Pulmonary Involvement ◽  
Control Group ◽  
Significant Difference ◽  
Pulmonary Capillary Blood ◽  
Treatment Naïve ◽  
Pulmonary Arterial

The fractional exhaled concentration of nitric oxide (FENO) has been shown to be reduced in idiopathic pulmonary arterial hypertension (PAH) but has not been adequately studied in PAH associated with systemic sclerosis (SSc). We measured FENO at an expiratory flow rate of 50 mL/s in 21 treatment-naive patients with SSc-associated PAH (SSc-PAH), 94 subjects with SSc without pulmonary involvement, and 84 healthy volunteers. Measurements of FENO at additional flow rates of 100, 150, and 250 mL/s were obtained to derive the flow-independent nitric oxide exchange parameters of maximal airway flux (J′awNO) and steady-state alveolar concentration (CANO). FENO at 50 mL/s was similar ( P = 0.22) in the SSc-PAH group (19 ± 12 parts per billion [ppb]) compared with the SSc group (17 ± 12 ppb) and healthy control group (21 ± 11 ppb). No change was observed after 4 months of targeted PAH therapy in 14 SSc-PAH group patients ( P = 0.9). J′awNO was modestly reduced in SSc group subjects without lung disease (1.2 ± 0.5 nl/s) compared with healthy controls (1.64 ± 0.9; P < 0.05) but was similar to that in the SSc-PAH group. CANO was elevated in individuals with SSc-PAH (4.8 ± 2.6 ppb) compared with controls with SSc (3.3 ± 1.4 ppb) and healthy subjects (2.6 ± 1.5 ppb; P < 0.001 for both). However, after adjustment for the diffusing capacity of CO, there was no significant difference in CANO between individuals with SSc-PAH and controls with SSc. We conclude that FENO is not useful for the diagnosis of PAH in SSc. Increased alveolar nitric oxide in SSc-PAH likely represents impaired diffusion into pulmonary capillary blood.

scholarly journals A Unique Presentation of Anti-RNA Polymerase III Positive Systemic Sclerosis Sine Scleroderma

2016 ◽  
Vol 2016 ◽  
pp. 1-4
Author(s):  
Cody M. Lee ◽  
Diana Girnita ◽  
Arundhati Sharma ◽  
Surabhi Khanna ◽  
Jean M. Elwing
Keyword(s):  
Systemic Sclerosis ◽  
Rna Polymerase ◽  
Wide Spectrum ◽  
Rna Polymerase Iii ◽  
Clinical Manifestations ◽  
Autoimmune Disorder ◽  
Scleroderma Renal Crisis ◽  
Polymerase Iii ◽  
Digital Ischemia ◽  
Pulmonary Arterial

Systemic sclerosis is a rare autoimmune disorder with a wide spectrum of clinical manifestations and a multitude of autoantibodies that are associated with it. In the past several years, advances in serologic testing have led to research indicating important prognostic and phenotypic associations with certain subsets of autoantibodies. In particular, anti-RNA polymerase III (anti-RNAP III) has been associated with diffuse cutaneous disease, scleroderma renal crisis, a temporal relationship with malignancy, myositis, synovitis, joint contractures, and gastric antral vascular ectasia. However, anti-RNAP III has not been associated with systemic sclerosis sine scleroderma. We describe a patient with an atypical presentation of anti-RNAP III positive systemic sclerosis sine scleroderma who presented without the typical features of anti-RNAP III disease. Instead, she presented with critical digital ischemia, pulmonary arterial hypertension, gastroesophageal reflux disease, interstitial lung disease, and no clinically detectable sclerodactyly.

Audiological Involvement in Patients with Systemic Sclerosis

2021 ◽  
Author(s):  
Kubra Turan ◽  
Mucteba Enes Yayla ◽  
Murat Arslan ◽  
Suna Tokgoz Yilmaz ◽  
Ercan Okatan ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Systemic Sclerosis ◽  
Otoacoustic Emission ◽  
Clinical Findings ◽  
Control Group ◽  
Significant Difference ◽  
Transient Evoked Otoacoustic Emission ◽  
Antibody Positivity ◽  
Healthy Control ◽  
Duration Of Disease

Abstract Objective The aim of the present study was to evaluate hearing loss in patients diagnosed with SSc (systemic sclerosis) and to investigate the relation between hearing loss, subtypes of the disease, its duration and clinical findings, and antibody positivity. Methods The study included 47 patients with SSc and 44 healthy controls. Audiometric, tympanometric and otoacoustic emission measurements were applied to both groups. Results The evaluation of the participants medical history showed that among the patients with SSc, 19.1% experienced ear fullness, 27.7% experienced vertigo and 36.2% experienced tinnitus. Hearing loss was detected in 23.4% of the patients with SSc. The corresponding result was 4.3% in the control group with a statistically significant difference (p = 0.001). Transient evoked otoacoustic emission (TEOAE) amplitude values were significantly lower in the patients both ears with SSc than the control group (p &lt; 0.005). Duration of disease was significantly longer and DLCO (diffusing capacity of the lungs for carbon monoxide) values were significantly higher in the patients with SSc and sensorineural hearing loss. Conclusions The present study found that the incidence of hearing loss was significantly higher in the study group than healthy control group. In addition to other organ involvements, cochlear involvement occurs in these patients, and further studies are required.

scholarly journals AB0575 THE ROLE OF LONG-TERM AND INTENSIVE IV ILOPROST TREATMENT IN REDUCTION OF PULMONARY ARTERY PRESSURE AND PRO-BRAIN NATRIURETIC PEPTIDE (PBNP) IN SCLERODERMA PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1584.3-1584
Author(s):  
R. Foti ◽  
E. Visalli ◽  
G. Amato ◽  
A. Benenati ◽  
S. Bellofiore ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Cardiac Involvement ◽  
Alveolar Volume ◽  
Skin Score ◽  
Pulmonary Arterial

Background:Systemic sclerosis (SSc) is a chronic immune-mediated connective tissue disease with heterogeneous organ involvement that reduces the life expectancy of this patients. In particular cardiopulmonary manifestations, such as pulmonary arterial hypertension (PAH), are currently the primary cause of death and stabilizing this condiction may represent an important therapeutic goal (1,2). An increased NT-proBNP is predictors of PAH in SSc and use this markers should result in improved PAH risk stratification (3)Some studies have suggested the role of intravenous iloprost in preventing the incidence of most severe vascular complications in long term treated patients (4).Objectives:The aim of our study is to evaluate the evolution of the disease, with particular focus on cardiopulmonary function, in a group of consecutive patients chronically treated with iloprost at the Rheumatology Unit of Catania Hospital, Italy, from 2006 to 2019.Methods:68 SSc patients (58F, 52.88 ± 12.6 years). At baseline, 67.6%, 25% and 5.9% had a limited, diffuse and early scleroderma type respectively and 20,6% had interstitial lung disease. The follow-up period of the study was of 9.9 ± 2.9 years. Iloprost was administered with a regimen of 6 infusions per month (6 hours/day, 0.5-2.0 ng/kg/min) to treat secondary Raynaud’s phenomenon (RP), diagnosed at an average age of 46.6 ± 13.7 years. We evaluated: skin score (SS), systolic pulmonary arterial pressure (PAPs), plane tricuspid annular systolic excursion (TAPSE), lung diffusing capacity of carbon monoxide (DLCO), forced vital capacity (FVC), alveolar volume (VA), DLCO/VA, pro-brain natriuretic peptide (pBNP), and NYHA class.We analyzed the patients as a whole group (68 subjects), as a group who continued the treatment (57 subjects) and as a group who stopped the treatment during the follow-up (11 patients).Results:After the long follow up period in the study (almost 10 years) in the whole group of patients, PAPs and pBNP showed statistically significant improvement from baseline (30.91 ± 6.4 vs 27.36 ± 7.1 and 97.20 ± 69.3 vs 66.65 ± 44.3 respectively, p < 0.0001 for both) while the other parameters showed no significant changes: SS (4.70 ± 5.3 vs 3.86 ± 4.2 mm), TAPSE (22.07 ± 2.4 vs 22.06 ± 3.8 mm), DLCO (83.68 ± 13.5 vs 77.70 ± 14.6 mmol/kPa.min), FVC (107.09 ± 14.5 vs 107.72 ± 18.7 liters), VA (91.12 ± 13 vs 90.30 ± 14.4 liters), DLCO/VA (88.48 ± 13.5 vs 89.5 ± 16.3) and NYHA class (1.0 ± 0.0 vs 1.0 ± 0.0). A subgroup analysis indicated a significant improvement in addition to PAPs and pBNP also for skin score for 57 patients who continued the treatment (5.09 ± 5.7 vs 3.30± 4.2, p < 0.0001) and a significant worsening of this parameter as early as the first year of suspension (p <0.05 year 1, p<0.01 year 2 and 3) in 11 patients who stopped the treatment.Conclusion:Cardiac involvement is recognised as a poor prognostic factor among systemic sclerosis (SSc) patients, significantly to mortality and N-TproBNP peptide may represent a surrogate marker for cardiac involvement in SSc, selectively identifying patients with severe impairment of cardiac function. Our intensive (6 infusions/month) and chronic regimen of iv iloprost administration seems improve the long-term evolution of disease in SSc patients, as suggested by the improvement of cardiopulmonary parameters and the significant improvement of SS.References:[1]Rheumatology 51, 1027-36 2) Best Pract Res Clin Rheumatol.32, 223-240 3) Arthritis Rheum. 2008 58, 284-9 4) Rheumatol Int 2012;32:1933-8.Disclosure of Interests:Rosario Foti Consultant of: lilly, sanofi, MSD, Janssen, Abbvie, BMS, celgene, roche, Speakers bureau: lilly, sanofi, MSD, Janssen, Abbvie, BMS, celgene, roche, elisa visalli Consultant of: lilly, sanofi, MSD, Janssen, Abbvie, BMS, celgene, roche, Speakers bureau: lilly, sanofi, MSD, Janssen, Abbvie, BMS, celgene, roche, Giorgio Amato: None declared, Alessia Benenati: None declared, Salvatore Bellofiore: None declared, Massimiliano Mule’: None declared, Marcella Di Gangi: None declared

scholarly journals AB0557 CO-EXISTENCE OF SYSTEMIC SCLEROSIS HALLMARK AUTOANTIBODIES ASSOCIATES WITH DISTINCT CLINICAL PHENOTYPE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1575.2-1575
Author(s):  
C. Campochiaro ◽  
K. Clark ◽  
L. Host ◽  
A. Sari ◽  
S. Nihtyanova ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Clinical Features ◽  
Topoisomerase I ◽  
Clinical Phenotype ◽  
Rna Polymerase Iii ◽  
Scleroderma Renal Crisis ◽  
Fisher Exact Test ◽  
Pulmonary Arterial

Background:Systemic sclerosis (SSc) is typically manifests with distinct SSc-specific antibodies (SSc-Abs): anti-topoisomerase I (ATA), anti-centromere (ACA), anti-RNA polymerase III (ARA), anti-U3RNP (u3RNP), anti-U1RNP (U1RNP), anti-PmScl (PmScl), anti-Ku (Ku) and anti-Th/T0 (Th/T0), each being characterised by different clinical features and prognosis. The presence of >1 SSc-Abs is rare with minimum data about these patients’ clinical phenotype.Objectives:To describe and compare the clinical features of SSc patients with >1 SSc-AbMethods:The autoantibody profiles of 2799 SSc patients from February 2001 to June 2017 were retrospectively reviewed. Patients with >1 SSc-Abs were identified. Clinical features were collected and compared to historical cohorts of SSc patients with single SSc-Ab positivity. Patients were excluded if treated prior to their immunology test with rituximab, iv immunoglobulins or stem cell transplantation. Statistical analysis was performed using Fisher exact test.Results:72 patients (2.6%) with >1 SSc-Ab were identified. Full clinical data were available for 63 patients. 60 patients (2.1%) had double Ab positivity and 3 patients had triple Ab positivity (0.1%). 13 Ab combinations were present. U1RNP and ATA was the most frequent combination (35%), patients were significantly younger (51.38 years) than both U1RNP (58.64 years, p=0.050) and ATA (62.03 years, p=0.002) patients and more commonly of diffuse subset (dcSSc) (p=0.001 and p=0.041 respectively). Compared to ATA patients overlap features were more frequent (43% vs 15%, p=0.004) including inflammatory arthritis (p=0.025) and myositis (p=0.013) (Table 1). U1RNP and ACA had a significantly higher prevalence of pulmonary arterial hypertension compared to U1RNP (p=0.039) and ACA (p=0.022) patients, and compared to ACA patients they were younger (57.88 vs 68.75, p=0.015) with a higher incidence of myositis (p=0.001). U1RNP and ARA patients were more frequently dcSSc subtype compared to U1RNP patients (75% vs 21%, p=0.040). U1RNP and PmScl patients had a higher prevalence of myositis compared to U1RNP patients (p=0.006). ATA and ACA patients behaved similarly to ATA patients with a significantly higher prevalence of lung fibrosis (p=0.006) and myositis (p=0.041) compared to ACA. ACA and PmScl (7%) had higher prevalence of myositis compared to ACA patients (p=0.04).Table 1. Frequency of clinical features in some of the double antibody group combinations, compared to our cohort of patients with only one of the SSc specific antibody. Significant p values (<0.05) highlighted in bold. ILD (interstitial lung disease), PAH (pulmonary arterial hypertension), SRC (scleroderma renal crisis).Conclusion:Coexistence of hallmark autoantibodies is exceedingly rare in SSc patients. When combined, both SSc-Abs have the potential to synergistically interact and modify the clinical phenotype.Disclosure of Interests:Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Kristina Clark: None declared, Lauren Host: None declared, Alper Sari: None declared, Svetlana Nihtyanova: None declared, Christopher Denton Grant/research support from: GlaxoSmithKline, CSL Behring, and Inventiva, Consultant of: Medscape, Roche-Genentech, Actelion, GlaxoSmithKline, Sanofi Aventis, Inventiva, CSL Behring, Boehringer Ingelheim, Corbus Pharmaceuticals, Acceleron, Curzion and Bayer, Voon Ong: None declared

scholarly journals Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study

2018 ◽  
Vol 77 (4) ◽  
pp. 563-570 ◽  
Author(s):  
Ariane L Herrick ◽  
Sebastien Peytrignet ◽  
Mark Lunt ◽  
Xiaoyan Pan ◽  
Roger Hesselstrand ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Observational Study ◽  
Prediction Models ◽  
Rna Polymerase Iii ◽  
Logistic Models ◽  
Roc Curves ◽  
Skin Thickness ◽  
Skin Score ◽  
Registration Number ◽  
Randomised Controlled

ObjectivesOur 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).MethodsThe 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).Results66 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%.ConclusionsTwo 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.Trial registration numberNCT02339441.

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