Cutaneous Manifestations, Clinical Characteristics, and Prognosis of Patients With Systemic Sclerosis Sine Scleroderma
Authors: Lescoat Alain , Huang Suiyuan , Carreira Patricia E. , Siegert Elise , de Vries-Bouwstra Jeska , Distler Jörg H. W. , Smith Vanessa , Del Galdo Francesco , Anic Branimir , Damjanov Nemanja , Rednic Simona , Ribi Camillo , Bancel Dominique Farge , Hoffmann-Vold Anna-Maria , Gabrielli Armando , Distler Oliver , Khanna Dinesh , Allanore Yannick ,   EUSTAR collaborators, Matucci Cerinic Marco , Walker Ulrich , Iannone Florenzo , Becvar Radim , Kowal Bielecka Otylia , Pizzorni Carmen , Ciccia Francesco , Siegert Elise , Rednic Simona , Vlachoyiannopoulos Panayiotis G. , Stork Jiri , Inanc Murat , Carreira Patricia E. , Novak Srdan , Czirják László , Iudici Michele , Kucharz Eugene J. , Perdan-Pirkmajer Katja , Coleiro Bernard , Moroncini Gianluca , Farge Bancel Dominique , Hesselstrand Roger , Radic Mislav , Balbir-Gurman Alexandra , Lo Monaco Andrea , Pellerito Raffaele , Giollo Alessandro , Morovic-Vergles Jadranka , Denton Christopher , Vonk Madelon , Damjanov Nemanja , Henes Jörg , Ortiz Santamaria Vera , Heitmann Stefan , Krasowska Dorota , Hasler Paul , Kohm Michaela , Foeldvari Ivan , Bajocchi Gianluigi , João Salvador Maria , Stamenkovic Bojana , Selmi Carlo F. , Tikly Mohammed , Ananieva Lidia P. , Herrick Ariane , Müller-Ladner Ulf , Søndergaard Klaus , Puppo Francesco , Engelhart Merete , Szücs Gabriela , de la Puente Carlos , Riccieri Valeria , Ionescu Ruxandra Maria , Sha Ami , Gheorghiu Ana Maria , Sunderkötter Cord , Distler Jörg , Ingegnoli Francesca , Mouthon Luc , Smith Vanessa , Paolo Cantatore Francesco , Ullman Susanne , von Mühlen Carlos Alberto , Pozzi Maria Rosa , Eyerich Kilian , Wiland Piotr , Vanthuyne Marie , Alegre-Sancho Juan Jose , Herrmann Kristine , De Langhe Ellen , Anic Branimir , Baresic  Marko , Mayer  Miroslav , Üprus Maria , Otsa Kati , Yavuz Sule , Granel Brigitte , de Souza Müller Carolina , Agachi Svetlana , Stebbings Simon , Mathieu Alessandro , Vacca Alessandra , Sampaio-Barros Percival D. , Stamp Lisa , Solanki Kamal , Veale Douglas , Loyo Esthela , Tineo Carmen , Toloza Sergio , Li Mengtao , Mohamed Walid Ahmed Abdel Atty , Olas Jacek , Oksel Fahrettin , Yargucu Figen , Tanaseanu Cristina-Mihaela , Foti Rosario , Ancuta Codrina , Furst Daniel E. , Maurer Britta , van Laar Jacob , Olesinska Marzena , Kayser Cristiane , Fathi Nihal , de la Peña Lefebvre Paloma García , Martin Jorge Juan Gonzalez , Carpentier Patrick , Imbert Bernard , Francès Camille , Senet Patricia , Sibilia Jean , Litinsky Ira , Senécal Jean Luc , Koenig Martial , Joval  France , Tamara Grodzicky , Del Galdo Francesco , Seskute Goda , Saketkoo Lesley Ann , Kerzberg Eduardo , Bianchi Washington , Valdetaro Bianchi Breno , Castellví Ivan , Milas-Ahic Jasminka , Visevic Roberta , Limonta Massimiliano , Rimar Doron , Couto Maura , Spertini François , Marcoccia Antonella , Kahl Sarah , Hsu Vivien M. , Martin Thierry , Moiseev Sergey , Novikov Pavel , Chung Lorinda S. , Schmeiser Tim , Majewski Dominik , Zdrojewski Zbigniew , Martínez-Barrio Julia , Khanna Dinesh , Bernardino Vera , Santo Lelita , Levy Yair , Rezus Elena , Nuri Pamuk Omer , Brito de Araujo Daniel , Sarzi Puttini Piercarlo , Brzosko Marek , Poormoghim Hadi , Maman Marta , Kötter Ina , Cuomo Giovanna , Gaches Francis , Belloli Laura , Sfikakis Petros , Markus Juliana , Furst Daniel , Ramazan Ana-Maria , Truchetet Marie-Elise , Jego Patrick , Dagna Lorenzo , van Laar Jacob M. , Voigt Lidia , Oliveira Susana , Atzeni Fabiola , Kuwana Masataka , Mekinian Arsene , Martin Mickaël , Tanaka Yoshiya , Yasuoka Hidekata , Simeón-Aznar Carmen-Pilar , Atsumi Tatsuya , Parvu Magda , Cordeiro Ines , Del Papa Nicoletta , Karonitsch Thomas , Bazela-Ostromecka Anna , Selvi Enrico , Kawaguchi Yasushi , Soukup Tomas , Rodriguez-Pinto Ignasi , Geroldinger-Simic Marija , Espinosa Gerard , Voigt Karen , Kubacki Torsten , Garmish Olena , Mosca Marta , Gerth Ulrich , Antonenko Ludmila , Mendoza Fabian A. , Airò Paolo , de Vries-Bouwstra Jeska , Riemekasten Gabriela , Hachulla Eric , Doria Andrea , Rosato Edoardo , Hunzelmann Nicolas , Montecucco Carlomaurizio , Gabrielli Armando , Hoffmann-Vold Anna-Maria , Distler Oliver , Ben Shimol Jennifer , Cutolo Maurizio , Allanore Yannick 
Published: June 2023

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 &amp;lt; .001; and 68.3% in dcSSc; P &amp;lt; .001) and puffy fingers (63.8% vs 82.4% in lcSSc; P &amp;lt; .001; and 87.6% in dcSSc; P &amp;lt; .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 &amp;lt; .001). Skin telangiectasias were associated with diastolic dysfunction in patients with ssSSc (odds ratio, 4.778; 95% CI, 2.060-11.081; P &amp;lt; .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 &amp;lt; .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 (&amp;gt;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.