Giovanni Delsante

Central nervous system effects of natural and synthetic glucocorticoids.

Natural glucocorticoids (NGC) physiologically modulate body homeostasis and coordinate adaptive responses to stress, involving almost all organs and tissues, including brain. Since their therapeutic availability, synthetic GC (SGC) have been successfully prescribed for a variety of diseases. Mounting evidence, however, demonstrated pleiotropic adverse effects (AE), including central nervous system (CNS) disturbances, which are often misdiagnosed or underestimated. The aim of the present study was therefore to review and discuss the CNS effects of both NGC and SGC. A detailed search was carried out of the available literature using the PubMed (US National Library of Medicine) database. Cortisolemia plays a crucial role in control of behavior, cognition, mood, and early life programming of stress reactivity. Hypercortisolemia or SGC treatments may induce behavioral, psychic and cognitive disturbances, due to functional and, over time, structural alterations in specific brain target areas. These AE are generally dose and time dependent (infrequent at prednisone‐equivalent doses <20 mg/day) and usually reversible. Pediatric patients are particularly susceptible. Behavioral changes, including feeding and sleeping modifications, are common. Psychic AE are unpredictable and heterogeneous, usually mild/moderate, severe in 5–10% of cases. Manic symptoms have been mostly associated with short SGC courses, and depressive disorder with long‐term treatments. Suicidality has been reported. Cognitive AE peculiarly affect declarative memory performance. Physiologic levels of NGC are essential for efficient brain functions. Otherwise, hypercortisolemia and SGC treatments may cause dose‐/time‐dependent neuropsychic AE and, over time, structural alterations in brain target areas. Clinicians should carefully monitor patients, especially children and/or when administering high doses SGC.

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.

Quantitative CT indexes are significantly associated with exercise oxygen desaturation in interstitial lung disease related to systemic sclerosis.

Interstitial Lung Disease (ILD) is the first cause of death related to Systemic Sclerosis (SSc). The ILD severity can be assessed with clinical, functional and radiological outcome. Nevertheless none of them is completely validated in clinical practice. Recently a new radiological evaluation based on Quantitative Computed Tomography Indexes (QCTI) was proposed on the basis of voxel‐wise quantitative analysis of chest CT.

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

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

AB0966 Correlations between Quantitative Nailfold Videocapillaroscopy and Radiological Assessment of Interstitial Lung Disease Extent in Sistemic Sclerosis: A Pilot Study

Background Naifold videocapillaroscopy (NVC) is an useful diagnostic test for the early diagnosis and monitoring of Systemic sclerosis (SSc). The NVC semiquantitative evaluation (scleroderma pattern early, active and late) is widely used for its prognostic value of the organ involvement, particularly of the lung. Some authors have proposed quantitative measurements of the following capillaroscopic parameters (also called QNVC parameters): number of giant capillaries (M), number of capillaries in the distal row (N), maximum diameter of giant capillaries (D) and M:N ratio. Recently two scores were developed to assess the nailfold microvascular damage and the digital ulcers risk [1-2]. Interstitial lung disease related to SSc (ILD-SSc) can be assessed by pulmunary function test (PFTs) and by semiquantitative scores based on the extent of radiological lesions presented on pulmonary CT. Goh et al. [3] have proposed a semiquantitative grading system of ILD-SSc that provides discriminatory prognostic information. Objectives To verify the correlation between QNVC parameters and ILD-SSc extent evaluated by pulmunary function tests and by Goh et al. semiquantitative grading system. Furthermore to compare the distribution of ILD-SSc extent and QNVC parameters in the groups of patients with different capillaroscopic pattern. Methods 24 patients with SSc (all met the ACR/EULAR classification criteria for SSC) were examined in a period of three months with the following test: NVC, chest CT e PFTs. NVC was performed according to Sulli et al. [2]. Two experienced rheumatologist in NVC (7 and 6 years) evaluate the images of each patient providing the following QNVC parameters: M, N, D, M:N. Chest CTs were evaluated by two radiologists with 15 and 6 years experience in ILD-SSc evaluation. Spearman rank test was used to verify the correlations between QNVC parameters, PFTs data and CT radiological assessment. Kruskal-Wallis test was used to assess QNVC parameters and CT radiological assessment differences between patients clustered according to capillaroscopic pattern. A p-value <0.05 was considered significant. Results The following QNVC parameters correlate with CT radiological assessment: number of megacapillaries (r = -0,488; p=0,399), density of giant capillaries (p = -0,501; p=0,0343), maximum diameter of megacapillaries (r = -0,685; p=0,0017), M:N ratio (r = -0,502; p=0,0338). The only QNVC correlating with FVC is maximum diameter of megacapillaries (r =0,488; p=0,0212). All NVC parameters had a statistically different distribution between patients with early, late and active scleroderma pattern (p<0.05). Pulmonary fibrosis extent among the three groups, although different, has not reached statistical significance. Conclusions In our study the ILD-SSc extent correlates with maximum diameter and number of giant capillaries. These findings suggest that the loss and dimensional change of giant capillaries could be indicative of a pulmonary evolution towards ILD. Hopefully with more numerous cohorts it might be developed a NVC score to predict ILD presence and/or extent. References Sulli A, et al. J Rheumatol. 2013 May;40(5):634-9. Sebastiani M, et al. Arthritis Rheum. 2009 May 15;61(5):688-94 Goh NS et al, Am J Respir Crit Care Med. 2008 Jun 1;177(11):1248-54 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5457