M. Rucco

Long-term efficacy of B cell depletion therapy on lung and skin involvement in diffuse systemic sclerosis.

OBJECTIVES To assess the long-term efficacy and safety of single and multiple courses of rituximab therapy in systemic sclerosis (SSc) patients with and without lung disease. METHODS A total of 20 SSc patients with a diffuse disease were treated with rituximab. At baseline and during follow-up the lung involvement was evaluated with pulmonary function tests (FVC and DLCO) and with lung high-resolution computed tomography (HRCT). RESULTS The skin score, activity, and severity indices improved significantly after 12 months and at final follow-up compared to baseline. After 12 months, there was a significant increase of FVC and TLC compared to baseline (p = 0.024 and p = 0.005, respectively), while the mean DLCO value remained stable. Considering the last available follow-up in six patients with restrictive lung disease at baseline, two patients (33.3%) experienced an increase of more than 10% of FVC, one patient had a decrease of FVC >10%, while in three patients FVC remained stable (50%). After the mean follow-up of 48.5 ± 20.4 months, among the patients with normal lung parameters at baseline, FVC remained stable in 12 (85.7%) and in one patient (14.3%) it increased by more than 10%. At the final follow-up, the alveolar and interstitial HRCT scores remained stable in more than 80% of patients, both in patients with and without restrictive lung disease at baseline. CONCLUSIONS Anti-CD20 B cell depletion therapy is effective on skin involvement but seems also to preserve the pulmonary function, as supported by a stable or improved FVC and stable interstitial score, suggesting a possible role of rituximab as a modifying therapy overall in early diffuse SSc.

Prognostic Role of Ventricular Ectopic Beats in Systemic Sclerosis: A Prospective Cohort Study Shows ECG Indexes Predicting the Worse Outcome

Background Arrhythmias are frequent in Systemic Sclerosis (SSc) and portend a bad prognosis, accounting alone for 6% of total deaths. Many of these patients die suddenly, thus prevention and intensified risk-stratification represent unmet medical needs. The major goal of this study was the definition of ECG indexes of poor prognosis. Methods We performed a prospective cohort study to define the role of 24h-ECG-Holter as an additional risk-stratification technique in the identification of SSc-patients at high risk of life-threatening arrhythmias and sudden cardiac death (SCD). One-hundred SSc-patients with symptoms and/or signs suggestive of cardiac involvement underwent 24h-ECG-Holter. The primary end-point was a composite of SCD or need for implantable cardioverter defibrillator (ICD). Results Fifty-six patients (56%) had 24h-ECG-Holter abnormalities and 24(24%) presented frequent ventricular ectopic beats (VEBs). The number of VEBs correlated with high-sensitive cardiac troponin T (hs-cTnT) levels and inversely correlated with left-ventricular ejection fraction (LV-EF) on echocardiography. During a mean follow-up of 23.1±16.0 months, 5 patients died suddenly and two required ICD-implantation. The 7 patients who met the composite end-point had a higher number of VEBs, higher levels of hs-cTnT and NT-proBNP and lower LV-EF (p = 0.001 for all correlations). All these 7 patients had frequent VEBs, while LV-EF was not reduced in all and its range was wide. At ROC curve, VEBs>1190/24h showed 100% of sensitivity and 83% of specificity to predict the primary end-point (AUROC = 0.92,p<0.0001). Patients with VEBS>1190/24h had lower LV-EF and higher hs-cTnT levels and, at multivariate analysis, the presence of increased hs-cTnT and of right bundle branch block on ECG emerged as independent predictors of VEBs>1190/24h. None of demographic or disease-related characteristics emerged as predictors of poor outcome. Conclusions VEBS>1190/24h identify patients at high risk of life-threatening arrhythmic complications. Thus, 24h-ECG-Holter should be considered a useful additional risk-stratification test to select SSc-patients at high-risk of SCD, in whom an ICD-implantation could represent a potential life-saving intervention.

Tumour-associated antigens in systemic sclerosis patients with interstitial lung disease: association with lung involvement and cancer risk

OBJECTIVE To evaluate the serum levels of tumour-associated antigens (TAAs) in patients with SSc and interstitial lung disease (ILD) and to define whether their levels mirror the severity and the progression of lung damage. METHODS Data from 80 SSc patients with ILD were collected at baseline and after 2 years as well as from 40 SSc controls without ILD. The occurrence of any malignancy was recorded. RESULTS At baseline, an increase of at least one TAA was present in 35 SSc patients with ILD compared with 6 SSc patients without ILD (P < 0.0001); this was associated with lower forced vital capacity (FVC) and higher interstitial and alveolar scores. Levels of carbohydrate antigen 15-3 and carcinoembryonic antigen inversely correlated with FVC and directly correlated with alveolar and interstitial scores and their levels were higher in patients who presented a progression of lung damage after 2 years. During 4 years of follow-up, a malignancy was detected in seven patients who already had an increase of at least one TAA. Values of TAAs increased over time in patients who developed cancer, while their trend remained stable in the others. At multivariate analysis, to have three or more TAAs emerged as a strong independent predictor of the development of malignancies [relative risk 24.1 (95% CI 1.8, 315.0), P = 0.02]. CONCLUSION TAAs can be elevated in the sera of SSc patients and correlate with the degree of lung damage, suggesting a role as severity biomarkers. Close follow-up is necessary in SSc patients because of the increased cancer risk overall in patients with increased TAAs.

AB0699 Beta-Blockers Control Frequent Ventricular Ectopic Beats in Systemic Sclerosis: A Monocentric Study

Background Ventricular ectopic beats (VEBs) are associated with a substantial increase in the risk of sudden and total cardiac death, both in the general population and in Systemic Sclerosis (SSc) patients (1,2). Beta-blockers are the mainstay of medical suppression of VEBs but are not routinely used in SSc patients due to possible Raynauds phenomenon exacerbation and digital ischemic complications. Objectives To evaluate safety and effectiveness of beta-blockers in SSc patients with heart involvement and arrhythmic burden. Methods 96 patients of our cohort with signs and/or symptoms suggestive of cardiac involvement (dyspnoea, palpitations and/or rise of cardiac enzymes) underwent 24h-ECG-Holter. Among these, 14 patients with palpitations and/or frequent VEBs were treated with beta-blockers and prospectively followed. Ten patients were treated with bisoprolol (doses between 1.25-5 mg/day) and 4 with carvedilol. A complete assessment of disease characteristics and cardiac involvement was also performed and, after a mean follow-up of 14.0±9.4 months, a second 24h-ECG-Holter was performed. The effects on active ulcers were examined. Results Eighteen patients (18.9%) presented VEBs >1000/24h at baseline. Considering the 14 patients treated with beta-blockers (mean age:47.5 years; mean disease duration:6.4 years; diffuse disease:57.1%; anti-Scl70 positivity: 64.3%), all of them presented an increase of troponin T and 8 (57.1%) a right bundle branch block. An history of digital ulcers was present in the majority of patients (71.4%) and 7 of them (50%) presented active ulcers at the time of study enrolment, 3 of whom with tissue loss. All patients were on sinus rhythm and none of them presented ST/T alterations; the mean number of VEBs at baseline was strikingly higher (6917.4±9911.9/24h) and 9 patients (64.3%) had a number of VEBs>1000/24h, that were polymorphic in 6 (42.8%). In 6 patients (42.8%), moreover, an episode of non-sustained ventricular tachycardia (NS-VT), the longest of 34 beats, was recorded. After beta-blockers treatment, the number of VEBs decreased in 10 patients (71.4%). The relative mean reduction was 74.7% (range:41.7-100%), while the absolute mean reduction was 4753.4±5610 VEBs/24h, with a range of 183-14408 VEBs/24h. The number of VEBs remained stable in the only 3 patients who presented a baseline number of VEBs<30/24h, and it increased in one patient. Considering the 9 patients with VEBs>1000/24h at baseline, in 3 (33.3%) the treatment with bisoprol led the number of VEBs far below this prognostic cut-off value, while among the 6 patients with baseline NS-VT, 3 had no more episodes recorded at follow-up. Despite continuative beta-blocker therapy, none of the patients presented a worsening of digital and legs ulcers, that rather improved in 4 patients, and none developed new digital ulcers. The Raynauds phenomenon remained stable in all patients. Conclusions Despite the small number of patients in this pilot study, our data suggest the efficacy of beta-blockers in reducing VEBs without an increase of digital ulcers complication or worsensing of Raynauds phenomenon. References Kostis JB. Am J Med 1988;84:1007-14. Ataklte F. Am J Cardiol 2013;112:1263-70. Disclosure of Interest None declared

FRI0487 Cardiac Magnetic Resonance in the Evaluation of Symptomatic Patients with Systemic Sclerosis: Correlation with Clinical Characteristics and Arrhythmic Burden

Background Cardiovascular magnetic resonance imaging (CMRI) has been proposed as a useful tool for early assessment of sub-clinical cardiac involvement in Systemic Sclerosis (SSc). Objectives To evaluate the role of CMRI in the detection of cardiac involvement in selected SSc patients. Methods Fifty SSc-patients with symptoms of cardiac involvement (dyspnea, palpitations) and/or elevation of cardiac troponin T underwent CMRI. Twenty sex and aged matched healthy controls were also enrolled. Clinical and cardiac (echocardiography and 24h-ECG-Holter) characteristics were available for all scleroderma patients. Results SSc patients and healthy controls presented comparable end-diastolic volume (EDV) and end-systolic volume (ESV) of right and left ventricles. Despite SSc patients presented lower left ventricle ejection fraction (EF)(61.2±10.8%) and lower right ventricle EF (57.5±12.2%) compared to healthy controls (LVEF:64.3±4.9% and RVEF:61.2±3.6%), the differences were not statistically significant. Nineteen SSc patients (38%) presented abnormalities on CMRI study, with respect to none of the healthy controls. CMRI demonstrated T2 hyperintensity in 5 SSc patients (10%), while none of the patients presented early gadolinium enhancement and 17 (34%) patients presented late gadolinium enhancement (LGE). We identified 3 different patterns of distribution of LGE: subepicardial, midwall and subendocardial. Fourteen patients (82.3%) presented a single pattern of distribution, while 3 patients (17.7%) presented more than one: 58.8% of patients presented a midwall distribution of LGE, 29.4% of patients presented a subepicardial LGE with a linear distribution pattern and 35.3% presented a subendocardial LGE distribution. Twelve SSc patients (38%) showed hypokinetic area and only one patient an akinetic area. Twenty-two SSc patients (44.0%) presented a pericardial effusion on CMRI. Patients with CMRI abnormalities presented a longer disease duration (10.1±5.6 years) when compared with SSc patients without CMRI abnormalities (4.3±7.6 years, p=0.003). Furthermore, LVEF and RVEF were lower in patients with CMRI abnormalities, while ESV of both ventricles was higher in these SSc patients when compared to SSc patients with normal CMRI. Finally, in SSc patients LVEF inversely correlated with disease duration (R=-0.3, p=0.035) and number of ventricular ectopic beats (VEBs) on 24h-ECG Holter (R=-0.3, p=0.04). Interestingly, considering the right ventricle, the number of VEBs inversely correlated also with EF (R=-0.4, p=0.04) and directly correlated with EDV (R=0.4, p=0.01) and ESV (R=0.5, p=0.002). Conclusions CMRI could be a useful tool to detect abnormal ventricular function and volumes and allows to identify cardiac abnormalities (T2 hyperintensity and LGE) in a subgroup of scleroderma patients. Even though the correlations between EF, end-systolic and diastolic volumes of both ventricles and some clinical characteristics (disease duration and number of VEBs) suggest a possible clinical significance of CMRI abnormalities, their real clinical value need to be further investigated. Disclosure of Interest None declared

SAT0312 Efficacy and Safety of High Dose Steroid Pulse Therapy in Early Progressive Systemic Sclerosis: the Risk of Renal Crisis is with Older Age

Background Therapeutic options for progressive systemic sclerosis (SSc) are extremely restricted. Up to date, high doses of glucocorticoids have a limited role in SSc skin and lung disease severity treatment because of their possible implication in precipitating renal crisis. Objectives To evaluate the efficacy and safety of high doses of glucocorticoid pulse therapy combined with cyclophosphamide, in the treatment of skin and lung involvement in early progressive SSc. Methods Among the 200 SSc patients referred to our center between 2008 and 2013, 27 patients with early diffuse skin disease were treated with high dose steroid pulse therapy and cyclophosphamide for a progressive cutaneous involvement. The mean age was 46.4±14.1. Three out of 27 patients (11%) were male, two (7.4%) had a limited cutaneous involvement, 24 (88.8%) were anti-topoisomerase I positive, 3 (11%) were ANA positive. All patients were treated with six consecutive steroid pulses (250 mg of 6-Methylprednisolone for three days, then tapered to 125 mg for other three days), in association with oral cyclophosphamide (6 or 9 gr of cumulative dose). Clinical features of disease, modified Rodnan skin score (mRSS), FVC and DLCO were evaluated at baseline and after treatment. A further follow-up of at least one year was available for each patient. A decrease of more than 25% of mRSS, of more than 10% for FVC and of more than 15% of DLCO was considered clinically significant. Results Skin score significantly decreased after treatment (15.1±8.6) compared to baseline (20.4±7.7), (p=0.003). In 14 patients (51.9%) mRSS improved more than 25%, with a median improvement of 47.0% (range: 25.0 to 86.0%). In 4 (14.8%) mRSS remained stable and in 9 (33.3%) worsened. During further follow-up, in 11 (78,6%) of 14 responder patients the mRSS remained stable without any additional therapy. Considering the 15 patients with lung involvement and available PFTs after steroids and cyclophosphamide therapy, the FVC values significantly increased after treatment (97.0±12.1%) compared with baseline (91.0±12.0%, p=0.02), while DLCO remained stable. In particular 5 patients (33.3%) presented a FVC increase higher than 10%. In the remaining 10 (66.7%) patients the FVC values remained stable. Neither demographic nor clinical parameters demonstrated correlation with a good response. Five adverse events were observed: 1 patient presented an increase of liver function tests, 2 patients developed a transient cytopenia, 1 an haemorragic cystitis and 2 patients a renal crisis. In our cohort 2 patients were older than 70 years and both developed a renal crisis, while none of the patients younger than 70 years presented kidney complications (p=0,003). Conclusions in the early inflammatory phase of cutaneous scleroderma disease steroid pulse therapy and cyclophosphamide can represent a chance to control persistently the progression of the disease in a subgroup of patients. Steroids seem to precipitate the renal crisis overall in patients with older age. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4900

OP0092 The Arrhythmic Burden in Systemic Sclerosis: Ventricular Ectopic Beat Rate Correlates with Cardiac Damage and Bad Prognosis

Background Primary heart involvement is a relevant prognostic determinant in Systemic Sclerosis (SSc) and, together with pulmonary disease, is the leading cause of death in these patients. Arrhytmhias are a frequent event and portend a bad prognosis, accounting alone for the 6% of total deaths. Objectives The aim of our study was to define the role of EKG-Holter in the characterization of arrhythmic burden in SSc-patients and in the identification of patients with poor prognosis. Methods Seventy-two consecutive SSc-patients (median age:55.0 years, range 23-81 years; median disease duration: 6.0years, range:0.3-32; diffuse disease: 55.6%; anti-Scl70 positivity: 41.7%), with signs and or symptoms suggestive of cardiac involvement (i.e. dyspnoea, palpitations and/or rise of cardiac enzymes) underwent 24h EKG-Holter from 2008 to 2013. A complete assessment of disease characteristics and organ involvement was also performed. During the same period the occurrence of any cardiac complication and death was recorded. Results Major EKG-holter modifications (presence of ventricular or supraventricular ectopic beats, ventricular and/or supraventricular tachycardia, rhythm alterations) were present in 55.6% of patients. The majority of patients (94.4%) were on sinus rhythm, while atrial fibrillation or idioventricular rhythm were identifiable only in 2 patients. The mean cardiac frequency was 78.0±11.4 bpm, with a maximum frequency of 131.0±28.7 bpm and a minimum of 54.9±11.3 bpm. Right bundle brunch block was present in 20.8% and ventricular ectopic beats (VEBs) >1000/24h in 19 patients (26.4%); VEBs were classified as polymorphic in 7 patients (9.7%). The mean number of VEBs was strikingly higher (1611.9±4678.3). Supraventricular ectopic beats (SVEBs) >1000/24h were also frequent (16.7%).Twelve patients (16.7%) presented during 24-h evalutation a supraventricular tachycardia and 7 patients (9.7%) a non-sustained ventricular tachycardia (NSVT). The number of VEBs and SVEBs correlated with troponin T levels (R=0.26, R=0.36 respectively, p<0.04 for both correlations). Furthermore, the number of VEBs directly correlated with modified Rodnan skin score (R=0.24, p=0.04) and inversely correlated with ejection fraction (R=-0.39, p=0.001). During the observational period of 5 years, 6 deaths related to the sclerodermic disease progression occurred; five patients (6.9%) died for sudden cardiac death and all of them had VEBs >1000/24h. Dead patients presented higher number of VEBs and SVEBs (p<0.001 for both comparisons), higher levels of troponin T, CPK-MB and NT-proBNP (p<0.001 for all comparisons), and higher disease activity index (p<0.008). On ROC curve, VEBs >1125 showed a sensitivity of 83.3% and a specificity of 92.5% to predict SSc-cardiac related death (AUROC=0.85, CI=0.70-0.98). Patients with VEBS>1125 more frequently presented an increase of cardiac enzymes, right bundle brunch block and episodes of NSVT (p<0.001 for all comparisons) and had higher severity index score. Conclusions Our data reveal that arrhythmyas are frequent in the course of scleroderma disease and the presence of VEBS>1125/24h correlates with cardiac damage and poor prognosis. The presence of EKG-Holter modifications need to be routinely investigated in SSc patients in order to identify those with a bad prognosis. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4462

AB0208 FMD, VEGF, and IL-6 in VEDOSS Patients: the Precocity of Endothelial Dysfunction

Background Endothelial dysfunction is a key feature of systemic sclerosis (SSc) and the involvement of the microvasculature is one of the earliest features of the disease. Recent new criteria for very early diagnosis of systemic sclerosis (VEDOSS) have been proposed. Objectives The aim of this study was to investigate brachial artery endothelial-dependent flow-mediated dilation (FMD), IL-6 and VEGF levels in patients with primary Raynauds phenomenon (RP) and SSc. Methods In this study we enrolled 59 patients: 10 VEDOSS patients fulfilling the proposed VEDOSS criteria, 28 SSc patients fulfilling the 1987 ACR criteria, 11 gender and age matched healthy individuals as first control group and 10 gender and age matched primary RP patients with normal capillaroscopic findings as the second control group. Demographic, clinical and immunological parameters have been collected at the beginning of the study. Ultrasound assessment of FMD was performed in all RP subjects and in healthy subjects to evaluate endothelial dysfunction. VEGF, VEGF-RII, IL-6 and IL-6R plasma were determined by ELISA. Results Scleroderma patients showed a reduced FMD (5.8±4.7%) compared to healthy controls (18.9±6.7%) (p<0.0001), and to subjects with RP (1.6±5.6%),(p=0.001). FMD of scleroderma patients and VEDOSS patients was comparable (6.6±3.8%). VEDOSS patients showed values of FMD significantly compromised compared to those of RP (p=0.05) and healthy controls (p<0.001). Finally, patients with primitive RP showed reduced FMD values compared to healthy controls (p=0.008). The values of FMD correlated inversely with disease duration (r=-0.46, p=0.004) and directly with the levels of KCO (r=0.47, p=0.007). The plasma levels of VEGF in patients with SSc (29.8±40.7 pg/ml) were significantly higher than in healthy controls (13.0±24.8 pg/ml,(p=0.03) while they were similar to those of patients with VEDOSS (22.6±21.7 pg/ml). Plasma levels of IL-6 were higher in SSc patients (5.7±11.1 pg/ml) compared to VEDOSS (1.5±1.2 pg/ml) (p=0.04),RP (1.1±0.5 pg/ml), (p<0.0001) and healthy controls (1.9±3.1 pg/ml) (p<0.001). Levels of VEGF-R2 and sIL-6R were comparable in all groups. IL-6 levels were higher in dcSSc patients than in lcSSc patients (7.9±13.0 pg/ml vs 1,9±0,6 pg/ml) (p=0,0027). Finally in patients with SSc the capillaroscopic density inversely correlated with the levels of IL-6, the Activity and Severity Indices, the Skin Score and the duration of the disease. Conclusions An impairment of FMD was present in patients with RP, in particular in SSc and VEDOSS patients, suggesting a contemporary impairment of microvascular and macrovascular compartments. The deeper FMD impairment that characterize either SSc and VEDOSS patients, suggests that the endothelial dysfunction is already established since the early phases of the disease and it worses during the disease. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4446

SAT0311 Tumor Associated Antigens in Systemic Sclerosis Patients with Lung Involvement: Association with Lung Function and Cancer Risk

Background An increase of some tumor associated antigens (TAAs) has been reported in Systemic Sclerosis (SSc) and interstitial lung diseases (ILD), and SSc patients had higher risk of cancer compared to general population. Objectives The aim of our study was to evaluate the serum levels of TAAs in patients with SSc and ILD and to correlate these levels to the severity and the progression of lung disease and their role during follow-up. Methods Data from 80 consecutive SSc-patients with evidence of ILD on high resolution computed tomography (HRCT) and/or restrictive lung disease on pulmonary function test (PFTs), were retrospectively collected. TAAs including CEA, CA19.9, Ca15.3, CA125, Cyfra21.1 and enolase were determined. PFTs values and HRCT scores performed after 2 years were available from database.A period of 4 years follow-up for each patient was available in order to investigate the occurrence of any malignancy. Results 43.7% patients presented an increase of at least one TAA. Among the different TAAs, 28.7% had an increase of CA15-3, 17.5% of CA19.9, 15% of Cyfra21.1, 12.5% of TPA, while CEA, enolase and CA125 were above the cut-off value in 8 patients. The increase of at least one TAA was associated with the diffuse skin involvement and with anti-Scl70 positivity. SSc patients with an increase of any TAA presented lower FVC values, higher interstitial score and higher alveolar score at baseline compared with SSc patients without TAAs increase (p<0.01 for all comparisons).The levels of CA15-3 and CEA inversely correlated with FVC (R=-0.2,p≤0.04 for both correlations) and directly correlated with the alveolar score (R=0.43, p<0.0001; R=0.24, p=0.04; respectively) and interstitial score at baseline (R=0.47, p<0.0001; R=0.31, p=0.007, respectively). After two years, 20 patients (25%) presented a decrease of FVC>10% and 18 patients (22.5%) a worsening of HRCT scores. Patients with worsening of interstitial score presented at baseline higher levels of CA15-3 and of CA125 with respect to patients with a stable interstitial score (p=0.01 and p=0.002, respectively). During the follow-up, 7 patients developed a cancer and all of them had already an increase of at least one TAA at baseline (despite the negative baseline screening for neoplasia), while none of the patients without increasing of TAAs at baseline developed malignancies during the follow-up (p=0.003). Considering the 60 patients in which at least another determination of TAAs was available during follow-up, values of specific TAA (CA15.3, CA19.9 and CEA) increased over time in patients who developed cancer, while TAAs levels tended to remain stable in others. At multivariate analysis, CEA upper the cut-off value emerged as an independent predictor of development of malignancies [RR 25.2 (CI: 29.0-220.0), p=0.004]. Conclusions TAAs can be elevated in the sera of SSc patients. CA15.3 and CEA correlate with the functional and radiological lung damage suggesting a possible role as “severitiy biomarkers”, while their prognostic significance in ILD is not clear. A close follow-up is necessary in SSc patients because of the increased risk of cancer, overall in patients with increased TAAs. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4487

AB0151 Environmental pollution and systemic sclerosis: a pilot study on benzene and particulate exposure as risk factors for the systemic manifestations.

Background The association of systemic sclerosis (SSc) with the exposure to environmental agents is supported by a number of case reports and some case-control studies. No conclusive results have been reported, but there are some evidences that exposure to vinyl-chloride-polymers (PVC), silica dust or organic solvents such as benzene (B) and xylene (X) may be implicated. Furthermore a higher prevalence of scleroderma in boroughs in close proximity to a major airport, has been reported, but few data on air pollution exposure and risk of systemic sclerosis are available. Recently, particulate air pollution has been consistently linked to increased risk of arterial cardiovascular disease. Objectives We studied relationships between outdoor concentration of B and particulate with clinical manifestations of SSc based, for the exposure, on the urban residence of patients. Methods Before patient administration, the questionnaire was validated by Delphi technique (4 rheumatologists, 4 statisticians and 2 common people). A cohort study of 88 SSc patients, filled the validated self administered questionnaire (analyzing drug, work and environmental exposure) to investigate potential risk exposure before and after the onset of the disease. The average mean concentrations of B (11 monitoring sites) and environmental particulate matter with aerodynamic diameter ≤ 10 μm(PM10) (14 sites) were computed using data from monitors located throughout the Lazio region, in Italy. In a sample of 33 patients we performed correlations between the concentrations of PM10 and B with the demographic and clinical characteristics, going back to a prior exposure of 2 years before the onset of Raynaud’s phenomenon (RP). Results The questionnaire resulted in an agreement of the overall experts of about 94% (according to11/190 disagreement for comprehension, only few lexical modifications were done to improve the questionnaire after the consensus between the experts), with an Inter-observer agreement (measured throughout K Cohen test) of 0.8019(p<0.01) showing a very good concordance. The mean disease duration from the RP onset was 13.0±9.4 years and the mean age was 55.0±12.9 years. 92.5% of patients were female. No correlations were found between different clinical disease characteristics and drug assumption and work exposure. Considering patients that lived in Lazio, SSc patients with diffuse skin disease were exposed 2 years, before the onset of RP, to a higher concentrations of benzene (8.5±1.5µg/m3) with respect to patients with limited skin disease (4.97±2.7µg/m3), which was statistically significant of p=0.02. Furthermore the concentrations of benzene correlated directly with the skin score (R=0.3, p≤0.05) and inversely with DLCO (R=-0.36, p≤0.05). SSc patients with ulcers were exposed 2 years before the onset of RP to higher concentrations of B (6.4±3.2 µg/m3), than the patients without ulcers (4.9±2.3µg/m3), but the difference did not reach statistical significance. Conclusions This study, on the role of environmental agents in the manifestations of SSc, suggests an increased exposure to benzene in the development of a diffuse skin disease and a possible predisposing effect on the occurrence of ulcers. Disclosure of Interest None Declared