Cutaneous Manifestations, Clinical Characteristics, and Prognosis of Patients With Systemic Sclerosis Sine Scleroderma
Alain Lescoat, Suiyuan Huang, Patrícia Carreira, Elise Siegert, Jeska de Vries‐Bouwstra, Jörg H. W. Distler, Vanessa Smith, Francesco Del Galdo, Branimir Anić, Nemanja Damjanov, Simona Rednic, Camillo Ribi, Dominique Farge Bancel, Anna‐Maria Hoffmann‐Vold, Armando Gabrielli, Oliver Distler, Dinesh Khanna, Yannick Allanore, EUSTAR collaborators, Marco Matucci‐Cerinic, Ulrich A. Walker, Florenzo Iannone, Radim Bečvář, Otylia Kowal Bielecka, Carmen Pizzorni, Francesco Ciccia, Elise Siegert, Simona Rednic, Panayiotis G. Vlachoyiannopoulos, Jiří Štork, Murat İnanç, Patricia E. Carreira, Srđan Novak, László Czirják, Michele Iudici, Eugene J. Kucharz, Katja Perdan Pirkmajer, Bernard Coleiro, Gianluca Moroncini, Dominique Farge Bancel, Roger Hesselstrand, Mislav Radić, Alexandra Balbir‐Gurman, Andrea Lo Monaco, Raffaele Pellerito, Alessandro Giollo, Jadranka Morović‐Vergles, Christopher P. Denton, Madelon C Vonk, Nemanja Damjanov, Jörg Henes, Vera Ortiz-Santamaría, Stefan Heitmann, Dorota Krasowska, Paul Hasler, Michaela Köhm, Ivan Foeldvari, Gianluigi Bajocchi, Maria João Salvador, Bojana Stamenković, Carlo Selmi, Mohammed Tikly, Lidia P Ananieva, Ariane L. Herrick, Ulf Müller‐Ladner, Klaus Søndergaard, Francesco Puppo, Merete Engelhart, G Szücs, Carlos de la Puente, Valeria Riccieri, Ruxandra Ionescu, Ami Sha, Ana Maria Gheorghiu, Cord Sunderkötter, Jörg H. W. Distler, Francesca Ingegnoli, Luc Mouthon, Vanessa Smith, Francesco Paolo Cantatore, Susanne Ullman, Carlos Alberto von Mühlen, Maria Rosa Pozzi, Kilian Eyerich, Piotr Wiland, Marie Vanthuyne, Juan José Alegre Sancho, Kristine Herrmann, Ellen De Langhe, Branimir Anić, Marko Barešić, Miroslav Mayer, Maria Üprus, Kati Otsa, Şule Yavuz, B. Granel, Carolina de Souza Müller, Svetlana Agachi, Simon Stebbings, Alessandro Mathieu
Abstract
Importance: Systemic sclerosis (SSc) sine scleroderma (ssSSc) is a subset of SSc defined by the absence of skin fibrosis. Little is known about the natural history and skin manifestations among patients with ssSSc. Objective: To characterize the clinical phenotype of patients with ssSSc compared with patients with limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) within the EUSTAR database. Design, Setting, and Participants: This longitudinal observational cohort study based on the international EUSTAR database included all patients fulfilling the classification criteria for SSc assessed by the modified Rodnan Skin score (mRSS) at inclusion and with at least 1 follow-up visit; ssSSc was defined by the absence of skin fibrosis (mRSS = 0 and no sclerodactyly) at all available visits. Data extraction was performed in November 2020, and data analysis was performed from April 2021 to April 2023. Main Outcomes and Measures: Main outcomes were survival and skin manifestations (onset of skin fibrosis, digital ulcers, telangiectasias, puffy fingers). Results: Among the 4263 patients fulfilling the inclusion criteria, 376 (8.8%) were classified as having ssSSc (mean [SD] age, 55.3 [13.9] years; 345 [91.8%] were female). At last available visit, in comparison with 708 patients with lcSSc and 708 patients with dcSSc with the same disease duration, patients with ssSSc had a lower prevalence of previous or current digital ulcers (28.2% vs 53.1% in lcSSc; P < .001; and 68.3% in dcSSc; P < .001) and puffy fingers (63.8% vs 82.4% in lcSSc; P < .001; and 87.6% in dcSSc; P < .001). By contrast, the prevalence of interstitial lung disease was similar in ssSSc and lcSSc (49.8% and 57.1%; P = .03) but significantly higher in dcSSc (75.0%; P < .001). Skin telangiectasias were associated with diastolic dysfunction in patients with ssSSc (odds ratio, 4.778; 95% CI, 2.060-11.081; P < .001). The only independent factor for the onset of skin fibrosis in ssSSc was the positivity for anti-Scl-70 antibodies (odds ratio, 3.078; 95% CI, 1.227-7.725; P = .02). Survival rate was higher in patients with ssSSc (92.4%) compared with lcSSc (69.4%; P = .06) and dcSSc (55.5%; P < .001) after up to 15 years of follow-up. Conclusions and Relevance: Systemic sclerosis sine scleroderma should not be neglected considering the high prevalence of interstitial lung disease (>40%) and SSc renal crisis (almost 3%). Patients with ssSSc had a higher survival than other subsets. Dermatologists should be aware that cutaneous findings in this subgroup may be associated with internal organ dysfunction. In particular, skin telangiectasias in ssSSc were associated with diastolic heart dysfunction.