SAT0232 Anti-Centromere Antibody Positive Diffuse Scleroderma Is Uncommon but Has A Distinct Clinical Phenotype
Authors: J. Caetano, S. Nihtyanova, J. Harvey, V. Ong, C. Denton
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Anti-centromere antibodies (ACA) typically associate with limited cutaneous disease subset (lcSSc) in scleroderma, and are protective for renal crisis (RC) and interstitial lung disease (ILD). Only 5–7% of ACA positive patients have the diffuse subset (dcSSc). Both antibody specificity and disease subset may influence disease phenotypic expression and organ manifestations. <h3>Objectives</h3> To describe demographic and clinical manifestations of ACA positive patients with dcSSc (ACA+diffuse), comparing with two other subsets: ACA positive with lcSSc (ACA+limited) and ACA negative with dcSSc (non-ACA diffuse). <h3>Methods</h3> Retrospective study of consecutive patients ACA+diffuse from a single large referral center between 2001–2015. Comparative analysis was made with 160 consecutive patients ACA+limited and 260 consecutive patients non-ACA diffuse. Data were obtained by medical records review. <h3>Results</h3> 1313 patients ACA+ were identified, 36 (2.7%) had dcSSc. The peak modified Rodnan skin score was lower in ACA+diffuse compared with non-ACA diffuse (24.0±9.9 vs 27.4±10.4, p=0.031), but occurred later in disease course (88.8±77.2 vs 30.7±33.1 months, p&lt;0.001). Survival in ACA+ was similar for both subsets with 5, 10 and 15 years survival rates of 96%, 84% and 73% in ACA+limited and 94%, 80% and 72% in ACA+diffuse. Non-ACA diffuse had lower survival of 85%, 72% and 55% at 5, 10 and 15 years respectively, although the difference from ACA+diffuse was not significant. ACA+diffuse had higher incidence of ILD than ACA+limited (p=0.018), but significantly lower than non-ACA diffuse (p=0.003). During follow-up at 5 years, 15% of ACA+diffuse developed ILD (3% - ACA+limited; 36% - non-ACA diffuse). At 15 years, cumulative incidence of ILD was 26% in ACA+diffuse (5% - ACA+limited; 49% - non-ACA diffuse). More patients developed pulmonary hypertension (PH) in ACA+diffuse group (27.8%), than in the other groups (12.5% - ACA+limited; 11.9% - non-ACA diffuse), though this was mainly due to longer follow-up of ACA+diffuse. Cumulative incidence of PH in ACA+diffuse was not different from the other groups. At 5 years, 8% of ACA+diffuse had PH (6% - ACA+limited, 6% - non-ACA diffuse), while at 15 years cumulative incidence was 24%, 20% and 18% respectively. Similarly, cardiac involvement was more frequent in ACA+diffuse (8.3%) vs 1.9% in ACA+limited and 6.5% in non-ACA diffuse, but differences were not significant adjusting for time of follow-up. In contrast, incidence of RC was higher in non-ACA diffuse (13.9%), affecting only 2 patients in ACA+diffuse (5.6%) and none in ACA+limited. <h3>Conclusions</h3> This study confirms that ACA diffuse subset is infrequent, but has a distinct clinical phenotype. Despite the dcSSc, these patients have a more insidious onset of skin and major organ involvement, which may represent a therapeutic window for early intervention. We confirm that ACA+ has a protective role and is associated with lower incidence of ILD and RC and better survival than expected in dcSSc. The role of ACA in patients with dcSSc as a possible phenotype modifier needs to be explored further in larger prospective studies. <h3>Disclosure of Interest</h3> None declared