Clinical Characteristics and Prognosis of Patients with Systemic Sclerosis Sine Scleroderma: Data from the International EUSTAR Database

BackgroundLeRoy’s classification defines two main subsets of Systemic Sclerosis (SSc) based on the extent of skin fibrosis: limited cutaneous SSc (lcSSc) with skin thickening sparing the trunk and distal to the elbow and knees, and diffuse cutaneous SSc (dcSSc) with proximal and distal skin thickening. These two subsets notably differ in terms of survival and frequency of visceral involvement, dcSSc being less prevalent but having a higher mortality rate with more frequent visceral manifestations. SSc sine scleroderma (ssSSc) is a third subset initially described by Rodnan et al. and characterized by the absence of skin fibrosis but with the existence of SSc-associated visceral manifestations.ObjectivesThis study aimed to characterise the main clinical features of patients with ssSSc in comparison with the lcSSc and dcSSc subsets within the international EUSTAR database.MethodsAll patients from the EUSTAR database fulfilling the ACR2013 or 1980 classification criteria for SSc assessed by the modified Rodnan Skin score (mRSS) at inclusion and with at least one follow-up visit were eligible. Sine scleroderma (ssSSc) was defined by the absence of skin thickening (mRSS=0 and no sclerodactyly) at all available visits. The clinical characteristics of these ssSSc patients were compared to those of patients with lcSSc and dcSSc with similar disease duration at last follow-up visit. Descriptive statistics were applied.ResultsAmong the 4263 patients fulfilling the inclusion criteria, 376 (8.8%) were classified as ssSSc. Among them, 40.3% had puffy fingers, 39.4% had interstitial lung disease (ILD), 1.6% had a history of scleroderma renal crisis at inclusion visit. At last available visit, in comparison with 708 lcSSc and 708 dcSSc with the same disease duration, ssSSc patients had a lower prevalence of previous or current digital ulcers (28.2% versus 53.1% in lcSSc (P<0.001) and 68.3% in dcSSc (P<0.001)), of joint synovitis (16.9% versus 24.3% in lcSSc (P<0.01) and 30.8% in dcSSc (P<0.0001)), and of elevated sPAP on echocardiogram (15.2% versus 23.9% in lcSSc (P<0.01) and 28.7% in dcSSc (P<0.0001)). Despite similar disease duration, disease activity at follow up visit (assessed by the EScSG disease activity index 2001 and 2016) was lower in ssSSc in comparison with lcSSc and dcSSc. By contrast, the prevalence of ILD was almost similar in ssSSc and lcSSc (49.8% and 57.1% (P=0.03)) but significantly higher in dcSSc (75.0%, P<0.0001). Based on forced vital capacity, ILD was less severe in ssSSc in comparison with the other subsets (mean FVC 100% (SD=22)(%pred) versus 93% (SD=21) in lcSSc and 82% (SD=23) in dcSSc (P<0.0001 for both)). Anti-centromere antibodies were most represented in ssSSc (61.7% versus 41.9% in lcSSc (P<0.0001) and 16.3% in dcSSc (P<0.0001), whereas the opposite distribution was observed for anti-Scl70 antibodies. Survival was significantly higher in ssSSc patients compared to lcSSc (P<0.05) and dcSSc (P<0.0001).ConclusionThis study highlights that ssSSc patients account for almost 10% of SSc patients with milder disease severity compared to both lcSSc and dcSSc.AcknowledgementsThe authors thank all EUSTAR collaboratorsDisclosure of InterestsAlain LESCOAT: None declared, Suiyuan Huang: None declared, Patricia Carreira: None declared, Elise Siegert: None declared, Jeska de Vries-Bouwstra: None declared, Jörg H.W. Distler: None declared, Vanessa Smith: None declared, Francesco Del Galdo: None declared, Branimir Anic: None declared, Nemanja Damjanov: None declared, Simona Rednic: None declared, Camillo Ribi: None declared, DOMNIQUE FARGE: None declared, Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Jansen, Lilly, Medscape, Merck Sharp & Dohme, Roche, Consultant of: Actelion, ARXX, Bayer, Boehringer Ingelheim, Jansen, Lilly, Medscape, Merck Sharp & Dohme, Roche, Grant/research support from: Boehringer Ingelheim, Armando Gabrielli: None declared, Oliver Distler: None declared, Dinesh Khanna: None declared, Yannick Allanore: None declared