Daniele Santilli

Autosplenectomy and antiphospholipid antibodies in systemic lupus erythematosus: a pathogenetic relationship?

OBJECTIVES To describe a systemic lupus erythematosus (SLE) patient with functional asplenia and antiphospholipid syndrome (APS) and to review the literature to better define its pathogenesis and diagnosis, emphasizing a possible relationship with antiphospholipid antibodies (aPL). METHODS Descriptive report of 1 case and review of the literature by means of a MEDLINE search from 1966 to 2002. RESULTS A SLE patient presented with cutaneous vasculitis and an unexpected thrombocytosis which resulted from autosplenectomy. Subsequently, she developed full-blown APS. In the literature, autosplenectomy has been described only in 1 other case of APS secondary to SLE. However, clinical or laboratory features linked to aPL occurred in several other cases among the 17 cases reported with functional asplenia. CONCLUSIONS Autosplenectomy in SLE may be pathogenetically related to aPL. Thrombocytosis, unusual in SLE, may be a diagnostic clue of this condition. Pneumococcal vaccination is warranted to prevent life-threatening infections that frequently complicate this asplenia.

Echocardiography may help detect pulmonary vasculopathy in the early stages of pulmonary artery hypertension associated with systemic sclerosis.

BackgroundPulmonary arterial hypertension (PAH) in patients with systemic sclerosis is associated with a poor prognosis, but this can be improved by early disease detection. Abnormal pulmonary and cardiac function can be detected early by means of echocardiography, whereas right heart catheterization is usually performed later.ObjectivesThe purpose of this prospective study was to detect early the presence of pulmonary artery vasculopathy in patients with verified systemic sclerosis without significant pulmonary fibrosis, normal lung volumes and a mildly reduced lung diffusion capacity of carbon monoxide (DLCO).MethodsNineteen consecutive female NYHA class I-II patients with scleroderma and a PAPs of < 35 mm/Hg measured by echocardiography, were enrolled between September 2007 and September 2009. They had a mean age of 51 ± 13 years, body mass index of 25 ± 5 kg/m2). They all underwent complete Doppler echocardiography, CPET, a pulmonary ventilation test (carbon monoxide lung diffusion, DLCO), HRCT. To investigate PAH by means of complete resting Doppler echocardiography estimates of systolic pulmonary artery pressure (PAPs) derived from tr icuspid regurgitation, mean PAP derived from pulmonary regurgitation, pulmonary vessel resistance (PVR) derived from the acceleration time of the pulmonary outflow tract (ACTpo), and right ventricular function derived from tricuspid annular plane systolic excursion (TAPSE). Right heart catheterisation was conducted only, if pulmonary hypertension was suggested by echocardiography and an abnormal ventilator test.The data are given as mean values ± SD, unless otherwise stated. The correlations between the variables were analysed using Pearsons r coefficient, and the predictive value of the variables was calculated using linear regression analysis. A p value of > 0.05 was considered significant.ResultsRight heart catheterization detected PAH in 15/19 patients; mean PAP was 30.5 mm/Hg and RVP 3.6 UW. Coronary angiography of the patients aged more than 55 years showed some evidence of significant coronary artery disease. Echocardiography showed high systolic PAP values (46 ± 8 mmHg), whereas right ventricular function was normal (TAPSE 23 ± 3 mm), and in line with the NYHA class. ACTpo was reduced in the patients with a systolic PAP of < 46 mm/Hg (p > 0.001) and positively correlated with DLCO (p > 0.001) and the hemodynamic data.There was a good correlation between ACTpo and PVR (hemodynamic data) (r = -0615; p > 0.01).ConclusionsAlthough they need to be confirmed by studies of larger series of patients, our findings suggest that, in comparison with hemodynamic data, non-invasive echocardiographic measurements are an excellent means of identifying early-stage PAH.

Eight‐year retention rate of first‐line tumor necrosis factor inhibitors in spondyloarthritis: A multi‐center retrospective analysis

To evaluate the 8‐year survival of the first tumor necrosis factor inhibitor (TNFi) in patients with axial spondyloarthritis (SpA) or psoriatic arthritis (PsA), identify the predictive factors for withdrawal, and compare the discontinuation rates for infliximab, etanercept, and adalimumab.

Operator-independent quantitative chest computed tomography versus standard assessment of interstitial lung disease related to systemic sclerosis: A multi-centric study

Abstract Purpose. Interstitial lung disease (ILD) related to systemic sclerosis (SSc) is assessed with pulmonary functional tests (PFTs) and semi-quantitative scores based on extent of ILD detectable on chest computed tomography (CT). CT quantitative indexes (QCTIs) are promising tools to assess extent of ILD. This studys aim is to evaluate the validity of QCTI compared with that of chest CT standard evaluation and PFTs. Moreover, QCTI differences between patients’ subgroups according to prognostic stratifications were investigated. Methods. ILD-SSc of patients from six rheumatological clinics was routinely assessed with chest CT and PFTs. Patients were clustered according to prognosis based on functional and/or radiological examinations. Finally, chest CTs were processed with OsiriX in order to obtain QCTI. Results. Two hundred fifty-seven SSc patients were enrolled. QCTI correlation between extent of ILD and PFTs range from − 0.60 to 0.58 and from − 0.54 to 0.52, respectively. The majority of QCTI have a different distribution in patients’ subgroups based on prognosis. Most of QCTI discriminate patients with an ILD severity leading to a poor prognosis. Conclusions. QCTI assessment of ILD-SSc is comparable to the evaluation based on chest CT and/or PFTs. QCTI values corresponding to severe ILD were identified. QCTIs are excellent candidates for a new and more reliable SSc-ILD assessment.

OP0095 Comparison of Interstitial Lung Disease CT Indexes and Pulmonary Function Values in Sistemic Sclerosis Patients: A Multicenter Study

Background Currently, interstitial lung disease (ILD) related to systemic sclerosis (SSc) is assessed with pulmonary function tests (PFTs) and chest Computed Tomography (CT). FVC <70% and DLco <70% were proposed as parameters to define remarkable ILD [1]. Recently, quantitative assessment of ILD extention on chest CT was suggested as reliable parameter for disease assessment [2]. Quantitative score is based on voxel-wise analysis of lung density, summarized in the following quantiatative CT (QCT) parameters: kurtosis (Kurt), skewness (Skew), mean lung attenuation (MLA), standard deviation (Sdev) and fibrosis ratio (FR). Objectives To test the correlation between QCT parameter and PFTs and report the most accurate QCT for ILD assessment. Furthermore, to descibe QCT parameters in patients with FVC and DLco above or below the suggested threshold. Methods 226 SSc patients fullfilling ACR/EULAR diagnosis criteria undewent chest CT and PFTs in six different hospitals. All CTs were processed with an open-source DICOM-viewer (OsiriX) [3] that provided FR and the other QCT parameters (i.e. Kurt, Skew, MLA, Sdev) both related to normal lung parenchyma (nQCT) and to total lung (tQCT). Spearman rank test was used to verify the correlations between QCT parameters and PFTs data. The Mann-Whitney test was used to assess differences between patients with FVC and DLco above or below the suggested threshold. QCT parameters discriminative performances were verified using ROC analysis. A p-value <0.05 was considered significant. Results Among QCT parameters, nKurt showed the best correlation with FVC (r =0,535; p<0,0001) and DLco (r =0,394; p<0,0001). Notably, nKurt was significantly lower in patients with FVC and DLco <70% (p<0.00001). ROC analysis showed that nKurt =1,69 can discriminate very well patients with FVC <70% (sensibility 67,0%, specificity 81,0%). Similarly nKurt =5,25 distiguishes subjects with DLco <70% (sensibility 80,8%, specificity 53,6%). Conclusions QCT parameters correlate with PFTs as reported in literature. In particular, nKurt showed the strongest correlation with FVC and DLco. Furthermore, the proposed thresholds of nKurt could be very useful in clinical practice allowing furhter characterization of ILD associated with SSc. References Khanna D, et al. Arthritis Rheum 2005;52(2):592–600. Ariani A, et al. Rheumatol Int 2013. Rosset A, et al. J Digit Imaging 2004;17(3):205–216. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3048

Quantitative chest computed tomography is associated with two prediction models of mortality in interstitial lung disease related to systemic sclerosis

Objective In this multicentre study, we aimed to evaluate the capacity of a computer-assisted automated QCT method to identify patients with SSc-associated interstitial lung disease (SSc-ILD) with high mortality risk according to validated composite clinical indexes (ILD-Gender, Age, Physiology index and du Bois index). Methods Chest CT, anamnestic data and pulmonary function tests of 146 patients with SSc were retrospectively collected, and the ILD-Gender, Age, Physiology score and DuBois index were calculated. Each chest CT underwent an operator-independent quantitative assessment performed with a free medical image viewer (Horos). The correlation between clinical prediction models and QCT parameters was tested. A value of P < 0.05 was considered statistically significant. Results Most QCT parameters had a statistically different distribution in patients with diverging mortality risk according to both clinical prediction models (P < 0.01). The cut-offs of QCT parameters were calculated by receiver operating characteristic curve analysis, and most of them could discriminate patients with different mortality risk according to clinical prediction models. Conclusion QCT assessment of SSc-ILD can discriminate between well-defined different mortality risk categories, supporting its prognostic value. These findings, together with the operator independence, strengthen the validity and clinical usefulness of QCT for assessment of SSc-ILD.

AB0930 Quantitative Chest Ct in Ild-Ssc Patients with Divergent Risks of Mortality

Background Quantitative analysis of chest CT (QCT) is increasingly applied to characterization of Interstitial Lung Disease (ILD) associated to Systemic Sclerosis (SSc). However, there is no prognostic evidence for QCT in predicting lung detrimental evolution or death. Many Authors proposed composite clinical indexes to predict 1-year mortality. Recently the ILD-GAP index and du Bois index were proven to stratify ILD-SSc patients in outcome-related subgroups. Objectives The main aim of this study was to compare QCT assessment of SSc-ILD and composite clinical indexes in the selection of patients with high risk of mortality. Methods Chest CT, anamnestic data and pulmonary function test of 146 patients with SSc were retrospectively collected and ILD-GAP and DuBois score were calculated. Each chest CT underwent a quantitative assessment. Correlation between clinical prediction models and QCT parameters was tested. p<0,05 was considered statistically significant. Results All QCT parameters had a statistically different distribution in patients with diverging mortality risk according to both clinical prediction models. The cut-off of QCT parameters were calculated by ROC curve analysis, with statistically significant value as compared to clinical prediction models (AUC >0.7, p<0.0001). Conclusions QCT assessment of SSc-ILD can distinguish between different mortality risk categories, therefore it yields prognostic value. These findings, together with the operator-independence, strengthen the accuracy of QCT for assessment of SSc-ILD. Disclosure of Interest None declared

SAT0391 The 8-Year Retention Rate of The First TNF-Inhibitor in The Treatment of Spondyloarthropathies: Real-Life Data from A Multicentric Local Registries

Background Long-term data on drug survival of TNF inhibitors (TNFi) in the treatment of spondyloarthropathies are still lacking. Objectives The aim of the study is to analyze in a setting of real-life the 8-year retention rate of the first TNFi for the treatment of psoriatic arthritis (PsA) and axial spondyloarthritis (ax-SpA) and to compare the between-group discontinuation rates for each TNFi (infliximab [IFX], etanercept [ETN], and adalimumab [ADA]). Methods Data were retrospectively extracted from four local registries including all patients affected by PsA and ax-SpA treated with a biologic drug between January 2005 and May 2015. The analysis was limited to patients treated with IFX, ETN, or ADA as first-line biologic agent, with at least 1-year follow-up period. The 8-year drug survival was evaluated by Kaplan-Meier method and the risk for discontinuation among the 3 treatment groups was compared by a stratified log-rank test. Results The study population (614 patients) included 316 ax-SpA (69.9% male, mean age [±SD] 42.8 [±12.1] years, mean disease duration 7.2 [±7.9] years), treated with ADA (n=95), ETN (n=42), or IFX (n=179); and 298 PsA (51.7% male, mean age 47.8 [±12.1] years, mean disease duration 8.8 [±7.7] years), treated with ADA (n=108), ETN (n=89), or IFX (n=101). The overall median survival on treatment of the whole study population was 117.17 months (102.84 and >117.17 months for axSpA and PsA, respectively; p=NS). The overall retention rate was 66.2% (69.5% versus 62.8% in axSpA and PsA, respectively) at 5 years and 55.5% (57.2% versus 53.4% in axSpA and PsA, respectively) at 8 years. No significant differences emerged in the comparison among ADA, ETN, and IFX in both ax-SpA group (p=0.1065) and PsA group (p=0.06). IFX and ETN showed similar survival rates in PsA and axSpA (HR 1.252, 95% CI 0.600–2.608, and HR 1.224, 95% CI 0.8441–1.774, respectively), whereas ADA showed a significantly higher survival in axSpA compared to PsA (HR 1.775, 95% CI 1.045–3.013). Overall, 265 (43.1%) patients (129 [43.2%] PsA and 133 [42.1%] axSpA), stopped the first course TNFi. Inefficacy led to discontinuation in 115 (18.7%) patients (65 [21.8%] PsA and 50 [15.8%] axSpA), without significant differences between the two disease groups (p=0.1076). Adverse events led to discontinuation in 88 (14.3%) patients, (43 [14.4%] PsA and 45 [14.2%] axSpA), without significant differences between PsA and axSpA (p=0.9049). Conclusions In a real-life setting, the 8-year retention rate of the first TNFi in the treatment of spondyloarthropathies was about 50%, with no significant difference between ax-SpA and PsA. The risk of stopping IFX and ETN treatment was similar in both ax-SpA and PsA group, whereas ADA showed a higher survival in axSpA group. Disclosure of Interest None declared

FRI0443 Can Quantitative Chest CT Predict Interstitial Lung Disease Worsening in Systemic Sclerosis? Results from a Multi-Centre Prospective Cohort Study

Background Interstitial Lung Disease (ILD) is the leading cause of morbidity and mortality in Systemic Sclerosis (SSc). Forced Vital Capacity (FVC) and chest Computed Tomography (CT) are the main exams to assess ILD severity. In particular, FVC <70% is associated with a high risk of death. A visual score (VS), based on extension of fibrosis detectable at chest CT>20%, has an unfavourable prognostic value [Goh et al., 2008]. Preliminary evidence supports the usefulness of an automated quantitative CT (QCT) assessment performed with a medical software, OsiriX, in identifying patients with more severe SSc-ILD [Ariani et al. 2014] Objectives The aim of this work is to investigate whether QCT can predict ILD-SSc radiological and functional worsening over time. Methods One hundred forty-nine patients with SSc according to EULAR/ACR criteria underwent chest CTs and pulmonary functional tests at baseline (t0) and after 1 year (t1). A VS was evaluated for each chest CT; the quantitative assessment, in order to obtain QCT indexes (QCTI), was performed only in chest CT done in t0. Patients were clustered in 3 groups: 1) VS <20% both at t0 and t1; 2) radiological worsening (defined as the increase of the visual score, between t0 and t1, from <20% to >20% values); 3)VS>20% both at t0 and t1. A similar subdivision in other three groups was performed on the basis of FVC values (with 70% as cutoff).The Kolmogorov-Smirnov test was used to investigate QCTI distribution in the above mentioned groups. A p-value <0.05 was considered significant. Results In group 1 (clustered according to VS variation) QCTI were different from the ones of the other two groups (p<0.001). Group 2 and 3 QCTI were not statistically different. Similar results were observed when patients were clustered according to FVC values: group1 was different from group 2 and 3 (p<0.05) but the last ones were not statistically different. Figure A shows kurtosis (one of the QCTI) distribution in the groups. Conclusions In spite of the limitations of this study (short follow up compared with the slow ILD-SSc progression) our results support the predictivity of a QCTI in terms of future radiological and functional ILD worsening. Given its reliability and easy access, quantitative CT assessment of ILD is a promising candidate in the assessment and prognostic stratification of SSc-ILD, even in clinical practice. Disclosure of Interest None declared