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Background The main clinical associations of anti-PM/Scl in Systemic Sclerosis (SSc) include calcinosis, joint and muscle involvement, interstitial lung disease (ILD), and, possibly, scleroderma renal crisis (1,2). A possible association of anti-PM/Scl with cancer was reported in single-centre SSc series (2,3), but was never analysed in large multicentre studies. Moreover, the characteristics of malignancies, in particular their temporal association with the onset of SSc, were not explored. Objectives To evaluate the association of anti-PM/Scl with malignancies in a large, international, multicentre cohort. Methods 16 EUSTAR centres provided data on anti-PM/Scl+ SSc patients in their cohorts (cases), and on anti-PM/Scl-negative controls, matched for sex, age at onset (±5 years), cutaneous subset, and disease duration (±24 months). Only SSc patients with age >16 years at disease onset were included in this analysis. Anti-RNA Polymerase3+ patients were not included in controls, given the known association with synchronous cancer. Malignancies diagnosed between 2 years before and after the onset of SSc were defined as “synchronous to the onset of SSc”. Results 123 anti-PM/Scl+ SSc patients and 160 matched anti-PM-Scl- controls (28% anti-Topoisomerase I, 40% anti-centromere, 32% others) were compared (Table 1): anti-Pm/Scl+ patients had a higher prevalence of myositis (p Conclusion: in this EUSTAR multicentre case control-study, the association of anti-Pm/Scl with malignancies in SSc patients could not be confirmed. Patients with older age at SSc onset seems to be at higher risk for synchronous malignancies, regardless the autoantibody status. References [1] Lazzaroni MG, et al. Ann Rheum Dis2018; 77:(Suppl 2),421-422. [2] Bruni C, et al. Rheumatology (Oxford). 2017;56:317-8. [3] Bernal-Bello D, et al. Autoimmun Rev2017;16:461-8. Acknowledgement Authors would like to thank GILS (Gruppo Italiano Lotta Sclerodermia) for the grant to support this project Disclosure of Interests Maria Grazia Lazzaroni: None declared, Stefania Zingarelli: None declared, Jeska de Vries-Bouwstra: None declared, Eric Hachulla Consultant for: Received consulting fees or other remuneration from Actelion, GSK, Pfizer, and Bayer, Elisabetta Zanatta: None declared, Simone Barsotti: None declared, Marie-Elise Truchetet: None declared, Giacomo De Luca Speakers bureau: Pfeizer, Sobi, Vanessa Smith: None declared, Ellen De Langhe: None declared, Roger Hesselstrand: None declared, Francesca Ingegnoli: None declared, Cristian Caimmi: None declared, Silvia Bellando Randone: None declared, Enrico Colombo: None declared, Angela Ceribelli: None declared, Franco Franceschini: None declared, Yannick Allanore Grant/research support from: Inventiva, F Hoffman La-Roche, Sanofi, BMS, Pfizer, Consultant for: Actelion, Bayer, BMS, Boehringer, Roche, Sanofi, Paolo Airo: None declared

Background:Anti-PM/Scl antibodies positivity has been associated with frequent skeletal muscle involvement in patients with Systemic Sclerosis (SSc) in different studies, including the EUSTAR cohort (1). Moreover, although myositis has been previously associated with heart involvement in SSc patients (2), this issue has never been explored among anti-PM/Scl+ patients.Objectives:To evaluate the cardiac involvement in anti-PM/Scl patients with SSc in the large multicentre EUSTAR database, with focus on the subgroup of patients with muscle involvement.Methods:Patients from the EUSTAR database were included when the item anti-PM/Scl was fulfilled in at least one visit.Results:Anti-PM/Scl status was available in 7,353 SSc patients from EUSTAR database: 295 were anti-PM/Scl+. After exclusion of 151 patients with multiple autoantibody positivity, 144 anti-PM/Scl + patients were compared with 7,058 anti-PM/Scl- patients. Among them, 3,120 (44.2%) were positive for ACA, 2,361 (33.5%) for anti-Topo I and 274 (3.88%) for anti-RNAP3.Regarding the specific cardiac outcomes, in the anti-PM/Scl+ as compared to the anti-PM/Scl- group, a decreased rate of elevated sPAP at ECHO was recorded (12.8% vs 25.0%, p:0.001), while no differences were observed in the frequency of conduction blocks (26.2% vs 23.7%, p:0.526), abnormal diastolic function (33.9% vs 36.4%, p:0.582), pericardial effusion (10.2% vs 10.9%, p:1.000) and LVEF ≤50% (4.76% vs 6.11%, p:0.818). In multivariate analysis, adjusted for age at disease onset, sex, and disease duration, the negative association of anti-PM/Scl with elevated sPAP was not confirmed (p:0.061).When comparing anti-PM/Scl+ patients with (n=47) and without (n=87) CK elevation, the former group had a higher frequency of conduction blocks (43.2% vs 17.5%, p:0.005; OR 95% CI 3.47, 1.51-7.97) and left ventricular dysfunction, both diastolic (45.6% vs 27.2%, p:0.050; OR 95% CI 2.25, 1.05-4.81) and systolic (LVEF ≤50% 13.3% vs 0%, p:0.018; OR 95% CI 16.8, 0.87-324). Moreover, anti-PM/Scl+ patients with CK elevation had significantly increased rate of lung fibrosis on HRCT (p:0.045), intestinal symptoms (p:0.017), joint contractures (p:0.045) and tendon friction rubs (p:0.034).Conclusion:In the largest series of anti-PM/Scl positive SSc patients so far reported, muscle involvement in anti-PM/Scl+ patients (defined as increased serum CK) seems to represent a marker of a more severe disease phenotype, including a higher frequency of cardio-pulmonary involvement.References:[1]Lazzaroni MG, et al. Ann Rheum Dis 2018. 77 (2), 421-2.[2]Follansbee WP, et al. Am Heart J 1993. 125: 194-203.Acknowledgments:Authors would like to thank the patients’ association GILS (Gruppo Italiano Lotta Sclerodermia) for the grant that supported the project.Disclosure of Interests:Maria Grazia Lazzaroni: None declared, Stefania Zingarelli: None declared, Paolo Airò: None declared, Yannick Allanore Grant/research support from: BMS, Inventiva, Roche, Sanofi, Consultant of: Actelion, Bayer AG, BMS, BI, Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche

Background Not much information is available on the variations in the incidence and prevalence of Systemic Sclerosis (SSc) over time. Objectives To investigate the epidemiology of SSc in Valcamonica, an Alpine valley in northern Italy (Brescia Province, Lombardy region), during a 18-year-long period. Methods All patients with diagnosis of SSc living in Valcamonica between 1999 and 2016 were identified by capture/recapture method using: 1) clinical databases of the only secondary Rheumatology Unit present in the valley (Esine Hospital), and of the only tertiary referral centre for this area (Spedali Civili, Brescia); 2) administrative data (ASST Valcamonica, Esine), extracting all records with the ICD-10 code for SSc (710.1). Clinical charts were reviewed and patients included in the analysis when either the 1980 ARA or the 2013 ACR/EULAR classification criteria for SSc were satisfied. Incidence was calculated using the number of new cases observed as the numerator, and the Valcamonica population as the denominator for each year; to study temporal changes, mean yearly incidence during 3 different 6 year intervals was calculated (table 1). Prevalence rates were estimated at 4 different time points dividing the number of living patients by the number of individuals in the population (table 2).Survival, incidence and prevalence rates were expressed with 95% confidence intervals. Incidence and prevalence rates observed in different periods were compared using ANOVA test. Demographic data were expressed as the medians (IQR). Results General population with age over 14 years living in Valcamonica varied during the evaluated period between 85 168 (1999) and 91 245 inhabitants (2011). Fifty-six patients with SSc fulfilling the 2013 ACR/EULAR criteria, and in 68% of them also the 1980 ARA criteria were identified (Female 85.7%, Male: 14.3%; Caucasian: 96.4%, African 3.6%; age at diagnosis: 58;47–80 deaths: 13 (8 because of SSc); survival: at 5 years: 89.4% (76.2–95.5), at 10 years: 84.4% (69.9–92.3); diffuse SSc: 17.9%, limited SSc: 82.1%; anticentromere: 62.3%, anti-topoisomerase I (topo I): 20.8%, anti-RNA polymerase III (RNAP3): 5.4%; anti-topo I and RNAP3: 1.9%; Anti-Th/To: 1.9%; interstitial lung disease: 23.1%; group 1 pulmonary arterial hypertension 19.6%; renal crisis 5.4%). No significant variation of incidence was observed during the period of time evaluated in the study (table 1). Analysis of prevalence revealed a continuous increase of the disease using both the 1980 ARA criteria or 2013 ACR/EULAR criteria (p 14 years, one of the highest ever recorded by SSc epidemiology studies. However, notably, the prevalence in Valcamonica during the first years of the 21 st century was similar to that reported by previous other studies performed in Italy in the same years.1–2 Conclusions Although the incidence of SSc did not change significantly over time in this area, the disease prevalence constantly increased, with recruitment of new cases exceeding the number of deaths. References [1] Airo P, et al. Clin Exp Rheumatol2007;25:878–80. [2] Lo Monaco A, et al. Clin Exp Rheumatol2011;29:S10–4. Disclosure of Interest None declared

Background Antibodies to the PM/Scl complex are found in patients with Systemic Sclerosis (SSc), but also with Polymyositis, Dermatomyositis and overlap syndromes. Historically, the main clinical association of anti-PM/Scl antibodies in SSc, which include calcinosis, articular and muscle involvement, and interstitial lung diseases, were described by some large single-centre studies, or by multicenter studies which recruited a relatively small number of positive patients. Therefore, some unresolved issue deserves further research. In particular, scleroderma renal crisis was recently identified in a sizeable number of anti-PM/Scl+SSc patients in a large monocentric British cohort (4 out of 70; 5.7%), a somewhat unexpected finding since this antibody type is generally considered not to be associated with renal crisis. 1 Objectives To evaluate clinical associations of anti-PM/Scl in patients with SSc in the large multicenter EUSTAR database, with specific focus on scleroderma renal crisis. Methods Patients from the EUSTAR database were included when the item anti-PM/Scl was fulfilled in at least one visit; clinical data were collected from the last visit available. Results Anti-PM/Scl status was available in 8,287 SSc patients from EUSTAR database: 295 were anti-PM/Scl +. After exclusion of 145 patients with multiple autoantibody positivity, 150 anti-PM/Scl+patients were compared with 7992 anti-PM/Scl -negative patients. Among these, 2530 were positive for anticentromere, 1933 for anti-topoisomerase I, 186 for anti-RNA polymerase III, and 220 for anti-U1Rnp antibodies. Renal crisis was identified in 8 of 150 anti-PM/Scl+SSc patients (5.3%), and was significantly more frequent than in anti-PM/Scl-negative SSc patients (1.6%; p=0.0015). Positivity for anti-PM/Scl was also associated with male sex, diffuse cutaneous subsets, joint and muscle involvement, lung fibrosis at chest X-rays, heart conduction blocks, stomach and intestinal symptoms (table 1). However, in multivariate analysis, adjusted for age at disease onset, sex, and disease duration, the association of anti-PM/Scl with renal crisis was not significant, whereas the associations with joint and muscle involvement, lung fibrosis, and intestinal symptoms were confirmed (table 1). Table 1 Results of the univariable and multivariable analysis adjusted on sex, age at disease onset and disease duration (n=8142 patients). Results are presented as number/number available data (%) unless stated otherwise. Conclusions In the largest series of anti-PM-Scl positive patients so far reported, well-known clinical associations were confirmed. Moreover, scleroderma renal crisis was more frequent than in the antibody-negative patient controls (which included a majority of anticentromere-positive patients, and a relatively small number of anti-RNA polymerase III-positive patients). However, this association was probably explained by covariates, such as joint and muscle involvement, or lung fibrosis. A possible role of corticosteroid therapy might therefore be suspected. Reference [1] Bruni C, et al. Rheumatology (Oxford). 2017;56:317–8. Acknowledgements Authors would like to thank the non-profit organisation ‘Gruppo Italiano Lotta alla Sclerodermia’ (GILS) for its substantial grant for this research project. Disclosure of Interest None declared

Objective.To evaluate the development of hepatitis B virus (HBV) infection in patients receiving tumor necrosis factor-α-blocking agents (TNFBA), and to evaluate whether lamivudine (LAM) prophylaxis can reduce the risk of viral reactivation in inactive HBsAg carriers.Methods.Local experience and published reports were reviewed. Patients with HBV infection were classified as having chronic HBV hepatitis, or being inactive HBsAg carriers or occult carriers.Results.Three patients in our series and 24 patients in the literature were identified: 2 had active HBV-associated disease, 23 were inactive HBsAg carriers, and 2 occult carriers. When exposed to TNFBA, HBsAg-inactive carriers pretreated with LAM had lower risk of having detectable HBV-DNA (p = 0.02) or viral reactivation (p = 0.046) than those without LAM prophylaxis. In 3 patients who discontinued TNFBA, LAM prophylaxis was also discontinued 10–12 months thereafter without hepatitis flares. Two cases of reactivation in occult carriers (HBsAg-negative, anti-HBs+, anti-HBc+) were described in the literature.Conclusion.TNFBA should be avoided in patients with active HBV replication and should be used with caution in inactive HBsAg carriers. In these patients, the risk of viral reactivation seems to be high, but it might be reduced by prophylactic LAM, which should probably be given for a long time when TNFBA are discontinued (e.g., 12 mo). Potential occult carriers might carry a low, but not negligible, risk of viral reactivation. They should therefore be monitored with particular care.

Objective: to analyse efficacy and safety of anti-TNFa treatment in 17 patients with rheumatoid arthritis (AR) and anti- Ro antibodies, in order to detect difference in clinical and immunological response. Methods: 322 patients, affected by RA and treated with anti-TNFa drugs, were considered, searching every 6-12 months ANA, anti-dsDNA and anti-ENA antibodies. Seventeen were anti-Ro positive and 305 anti-Ro negative before starting treatment. Results: anti-Ro positive subjects showed active arthritis at baseline (mean DAS: 5), with frequent extra-articular features, such as ocular and oral sicca symptoms. They showed rapid and stable improvement during the treatment, without significant difference compared to anti-Ro negative group. A good clinical Eular response was shown in 46% of anti-Ro negative subjects, steady stable during time. On the contrary, fewer anti-Ro positive patients seem to be “good” responders. RA remission (DAS

Objective.To evaluate the frequency of malignancies in Italian patients with systemic sclerosis (SSc) and anti-RNA polymerase III (RNAP III), antitopoisomerase I (topo I), or anticentromere antibodies (ACA); and to characterize the temporal relationship between the 2 diseases, in order to confirm data suggesting a close temporal relationship between the onset of SSc and malignancy in American patients with anti-RNAP III antibodies.Methods.From a cohort of 466 consecutive SSc patients, 360 Italians with isolated positivity for anti-RNAP III (n = 16), anti-topo I (n = 101), or ACA (n = 243) were identified. Malignancy cases were divided according to their relationship with SSc onset into 3 categories: preceding, synchronous with, or metachronous to the onset of SSc (diagnosed more than 6 months before; 6 months before to 12 months after; and more than 12 months after onset of SSc, respectively).Results.Malignancies were more frequent in the anti-RNAP III group (7/16 patients), than in the anti-topo I (11/101) and ACA groups (21/243) (p < 0.001). This difference was accounted for by the number of patients with cancer synchronous to the onset of SSc (3/16 in the anti-RNAP III group vs 0/101 in the anti-topo I and 1/243 in the ACA group; p < 0.001), whereas neither the number of malignancies preceding nor those metachronous to the onset of SSc was significantly different between the groups.Conclusion.In a cohort of Italian patients with SSc we observed a significant association between malignancies synchronous to SSc onset and positivity for anti-RNAP III antibodies, similar to that described in American patients with SSc.

Objectives: To investigate whether the aggressive use of DMARDs can control the clinical disease in the early arthritis, to define new parameters of the disease aggressivity and to study the effectiveness of RMN in comparison with RX focusing on the articular erosions. Methods: 45 patients having a case of early arthritis (less 6 months) with 3 or more swollen joints were recruited and treated with 80 mg of steroids in order to distinguish persistent arthritis from non persistent ones. Afterward we began to use DMARDs with persistent arthritis and, if it wasn’t helpful, we shifted to anti-TNFα therapy. The clinical response was valued by SDAI. Results: After 1 year our therapeutic approach showed a remission in 60% of the patients. The 82% of remaining obtained a significant SDAI improvement and only in 3 cases we used anti-TNFα due to a persistent high disease activity. Anti-CCp were positive in 46% of patients in remission and in 53% of the rest. The bone erosions were present in 4 patients only and they were detected by RMN, only 2 by RX. Conclusions: We observed a clinical remission in the 60% of patients treated with aggressive DMARDs. During our trial, anti-CCp weren’t predictive about the therapy response. We observed that RMN is more effective than RX in detecting erosions and it’s necessary for diagnosis and follow-up of early arthritis.

Objective: To evaluate the efficacy and the safety of anti-TNF-alfa treatment in elderly patients (≥65 years old) with active rheumatoid arthritis (RA), in comparison with younger (17-65 years old). Methods: We considered retrospectively 295 patients, affected by RA and treated with anti-TNF-alfa drugs. They were divided in two groups, according to their age, and followed up for two years: over-65-years old patients (190) and under-65-years old patients (105). Effectiveness of drugs was assessed analyzing RA disease activity (DAS28, DAS44, SDAI), functional status (HAQ) and serological parameters (CRP) before and after anti-TNF-alfa therapy. Safety was studied considering discontinuation rate of biological disease-modifying antirheumatic drugs, and collateral events rate. Results: At baseline, elderly patients showed higher disease activity’s score (DAS 28, DAS44, SDAI, HAQ) with important loss of articular function (worse quality of life, HAQ) than younger patients (p0.05). Conclusions: Anti-TNF-alfa treatment was efficacious and safe in both groups of patients. These drugs induced improvement in disease activity, apart from the age. No functional improvement was observed in HAQ, showing the irreversible loss of articular function and the incomplete recovery in elderly patients. Age doesn’t interfere with the possibility to treat elderly patients with anti-TNF-alfa drugs.

The antiphospholipid syndrome (APS) in pregnancy is associated with repeated miscarriages and fetal loss. Other complications of pregnancy such as preeclampsia and placental insufficiency are also frequently reported during pregnancy in APS. The pathogenesis of pregnancy failures in APS is related to both the thrombophilic effect of antiphospholipid antibodies and also to different mechanisms including a direct effect of antibodies on trophoblast differentiation and invasion. Although optimal pharmacologic treatment is essential to achieve a successful outcome in APS pregnancy, the standard APS pharmacologic treatment alone may not be sufficient. A good obstetric outcome is the result of careful obstetric monitoring, proper delivery timing, and skillful neonatal care. A multidisciplinary team (obstetricians, rheumatologists, and neonatologists) and the progress in neonatal intensive care are as important as drugs in achieving a good obstetric outcome and to reduce the possible consequences of premature delivery.

To evaluate the safety and tolerability of lamivudine in patients with HBV infection needing immunosuppressive treatment for rheumatic diseases.Twenty patients with rheumatic diseases planned to receive immunosuppressive DMARDs or biological agents were screened for HBV markers. In all active carriers antiviral treatment was recommended. Inactive carriers (HBsAg positive, aminotrasferase and viremia persistently normal) were divided into two risk categories according to the type and the degree of immunosuppression, and antiviral prophylaxis was started only in patients of the high risk category. Antiviral treatment was recommended also in potential occult carriers (HBsAg negative, HBcAb positive) treated with rituximab. In twenty patients antiviral treatment was started: 1 was a potential occult carrier planned to receive rituximab; 9 were inactive carriers, in which prophylactic therapy was needed for a high risk of HBV reactivation (in 3, for the use of TNF blocking agents); 10 were treated for active viral replication. Prophylaxis and therapy were performed with lamivudine. In three patients adefovir was associated.Antiviral drugs were well tolerated. In all cases, immunosuppressive treatment was given for the planned duration of therapy, with good results on the rheumatic diseases. Median duration of antiviral treatment was 19 months (for a total of 386 month/person). No cases of viral reactivation were observed.Our experience demonstrates the feasibility of a prophylaxis and therapy of HBV infection in patients with rheumatic diseases. This approach reduces the risk of viral reactivation and allows the choice of the optimal immunosuppressive treatment in rheumatic patients.

Background Pulmonary arterial hypertension (PAH) is one of the leading causes of death in Systemic Sclerosis (SSc). World Health Organization (WHO) functional class at diagnosis is one of the most reliable outcome predictors of PAH. Moreover, patients starting in a poor functional class (eg. class III-IV) have a favorable long-term course if they achieve a better class (eg. class II) after initiation of PAH-targeted therapy. Therefore, current guidelines suggest a goal-oriented treatment aimed at obtaining a good functional class. Objectives To evaluate the proportions of patients with SSc-associated PAH in WHO functional class II at time of diagnosis and during follow-up. Methods In this retrospective single-center study all patients affected by SSc-associated pre-capillary PAH diagnosed between 2001 and 2014 were included, excluding those with clinically significant interstitial lung disease (ILD; Forced Vital Capacity Results PAH was diagnosed in 41 patients with SSc. Six of them (15%) were excluded because of associated ILD. Among 35 patients included, 11 (35%) were in WHO functional class II at the time of diagnosis, and 24 in class III-IV. Other main demographical and clinical characteristics of these patients were: limited cutaneous SSc: 35 (100%); female: 34 (97%); median age (IQR) 71.5 (64-75) years; time since Raynaud9s phenomenon (RP) onset: 21 (13-31) years; time since first non-RP symptom: 10 (2-15) years; ANA+ 34 (97%); anticentromere+: 27 (77%); anti-Topo I+: 0; anti-RNA polymerase III+: 1 (3%); sPAP estimated by echocardiography: 74 mmHg (58-88); TAPSE: 14 mm (12-19); FVC 115% (104-130); DLCO: 40% (36-52); 6 minutes walking test distance: 242 m (168-311); mean PAP on right heart catheterization: 38 mmHg (33-49); Cardiac Index: 2.9 l/min/m2 (2.1-3.5); PVR: 5.4 UW (3.5-6.4). Patients were divided in two groups according the time of diagnosis: 13 were diagnosed after 2010 and 22 before 2010. In patients with more recent diagnosis WHO functional class II was more frequent than in the others (7/13 (53%) vs. 4/22 (18%); p:0.03). There were trends toward better haemodynamic parameters in the first group, but these did not reach statistical significance. Twenty-one patients died; median survival from diagnosis of PAH was 49.5 months. Survival was better in patients diagnosed after 2010, as compared with those diagnosed before (log-rank test: p: 0.048; figure 1). At January, 2015, 14 patients were alive: in 8 of them the diagnosis was done in WHO functional class II, and all were still in this functional class; in 6 patients the diagnosis was done in WHO class III, and 3 of them were in WHO class II at the last evaluation. Therefore, the majority of patients in follow-up (11/14; 76%) had a good functional class at the moment of the last evaluation. Conclusions This retrospective evaluation of a real-life setting shows that diagnosis of SSc- associated PAH in a good functional class was rare before 2010, but it became more frequent in the last years. Moreover, the majority of patients can obtain a good functional class with PAH-targeted therapy. These data reflects better awareness of the problem and better strategies of diagnosis and of treatment, and may be linked to a better survival. Disclosure of Interest None declared

Autoimmunity Reviews 12 (2013) 457DOI of original article: http://dx.doi.org/10.1016/j.autrev.2009.02.002.⁎ Corresponding author at: Reumatologia e Immunologia Clinica, Spedali Civili, Piazzale Spedali Civili 1, 25100 Brescia, Italy. Tel.: +39 0303995487; fax: +39 0303995085.E-mail address: ilariacava@virgilio.it (I. Cavazzana).

The endocellular incorporation of asbestos fibres seems to be capable to induce on Chinese hamster cell cultures numerical and structural chromosome aberrations. In the present study asbestos fibres have been added at different concentrations to human cultured lymphocytes which have been harvested at 48 and 72 h, respectively. The results do not show significant difference in the distribution of chromatid and chromosome-type aberrations between the control cultures and the cultures treated with asbestos.

Objective To evaluate clinical associations of anti-PM/Scl antibodies in patients with SSc in a multicentre international cohort, with particular focus on unresolved issues, including scleroderma renal crisis (RC), malignancies, and functional outcome of interstitial lung disease (ILD). Methods (1) Analysis of SSc patients from the EUSTAR database: 144 anti-PM/Scl+ without SSc-specific autoantibodies were compared with 7202 anti-PM/Scl−, and then to 155 anti-Pm/Scl+ with SSc-specific antibodies. (2) Case–control study: additional data were collected for 165 anti-PM/Scl+ SSc patients (85 from the EUSTAR registry) and compared with 257 anti-PM/Scl− SSc controls, matched for sex, cutaneous subset, disease duration and age at SSc onset. Results Patients with isolated anti-PM/Scl+, as compared with anti-Pm/Scl−, had higher frequency of muscle involvement, ILD, calcinosis and cutaneous signs of DM, but similar frequency of SRC and malignancies (either synchronous with SSc onset or not). The presence of muscle involvement was associated with a more severe disease phenotype. Although very frequent, ILD had a better functional outcome in cases than in controls. In patients with both anti-PM/Scl and SSc-specific antibodies, a higher frequency of typical SSc features than in those with isolated anti-PM/Scl was observed. Conclusion The analysis of the largest series of anti-PM/Scl+ SSc patients so far reported helps to delineate a specific clinical subset with muscle involvement, cutaneous DM, calcinosis and ILD characterized by a good functional outcome. SRC and malignancies do not seem to be part of this syndrome.