Phenotype of limited cutaneous systemic sclerosis patients with positive anti-topoisomerase I antibodies: data from the EUSTAR cohort
Authors: Zanatta Elisabetta , Huscher Dörte , Ortolan Augusta , Avouac Jérôme , Airò Paolo , Balbir-Gurman Alexandra , Siegert Elise , Matucci Cerinic Marco , Cozzi Franco , Riemekasten Gabriela , Hoffmann-Vold Anna-Maria , Distler Oliver , Gabrielli Armando , Heitmann Stefan , Hunzelmann Nicolas , Montecucco Carlomaurizio , Morovic-Vergles Jadranka , Ribi Camillo , Doria Andrea , Allanore Yannick ,   EUSTAR collaborators, Cuomo Giovanna , Moroncini Gianluca , Stork Jiri , Iannone Fiorenzo , Walker Ulrich , Bertoldo Eugenia , Krasowska Dorota , Salvador Maria João , Tikly Mohammed , Hachulla Eric , Riccieri Valeria , Sha Ami , Gheorghiu Ana Maria , Sunderkötter Cord , Ingegnoli Francesca , Mouthon Luc , Smith Vanessa , Cantatore Francesco Paolo , Eyerich Kilian , Wiland Piotr , Vanthuyne Marie , Anic Branimir , Üprus Maria , Granel Brigitte , Vacca Alessandra , Tanaseanu Cristina-Mihaela , de la Peña Lefebvre Paloma García , Sibilia Jean , Litinsky Ira , Saketkoo Lesley Ann , Kerzberg Eduardo , Limonta Massimiliano , Rimar Doron , Sfikakis Petros , Cutolo Maurizio , Carreira Patricia E , Foti Rosario , Novak Srdan , Iudici Michele , Radic Mislav , Pellerito Raffaele , Rozzano Carlo Francesco Selmi , Ananieva Lidia P , Szücs Gabriela , de la Puente Carlos , Ionescu Ruxandra Maria , Distler Jörg , Pozzi Maria Rosa , Alegre-Sancho Juan Jose , Herrmann Kristine , De Langhe Ellen , Altunizade Sule Yavuz , de Souza Müller Carolina , Agachi Svetlana , Veale Douglas , Loyo Esthela , Li Mengtao , Rosato Edoardo , Maurer Britta , Castellví Ivan , Spertini François , Solanki Kamal , Del Papa Nicoletta , Espinosa Gerard , Czirják László , Coleiro Bernard , Bancel Dominique Farge , Pellerito Raffaele , Denton Christopher , Damjanov Nemanja , Henes Jörg , Granollers Vera Ortiz Santamaria , Kohm Michaela , Stamenkovic Bojana 
Published: March 2022

Abstract

Objectives
To characterize patients with positive anti-topoisomerase I (ATA) in lcSSc.

Methods
SSc patients enrolled in the EUSTAR cohort with a disease duration of ≤3 years at database entry were considered. We assessed the risk of major organ involvement in the following groups: ATA-lcSSc vs ACA-lcSSc and vs ANA without specificity (ANA)-lcSSc, and ATA-lcSSc vs ATA-dcSSc. Cox regression models with time-dependent covariates were performed with the following outcomes: new-onset interstitial lung disease (ILD), ILD progression [forced vital capacity (FVC) decline ≥10% and ≥5% vs values at ILD diagnosis), primary myocardial involvement (PMI), pulmonary hypertension (PH), any organ involvement and all-cause mortality.

Results
We included 1252 patients [194 ATA-lcSSc (15.5%)], with 7.7 years (s.d. 3.5) of follow-up. ILD risk was higher in ATA-lcSSc vs ACA- and ANA-lcSSc and similar to ATA-dcSSc, although with less frequent restrictive lung disease. The risk of FVC decline ≥10% (35% of ATA-lcSSc) was lower in ATA-lcSSc than in ATA-dcSSc, whereas FVC decline ≥5% occurs similarly between ATA-lcSSc (58% of patients) and other SSc subsets, including ATA-dcSSc. The risk of PMI was similar in ATA-lcSSc and ANA-lcSSc but lower than in ACA-lcSSc; no difference in PH and mortality risk was observed among lcSSc subsets. The risk of any organ involvement, PMI and PH was lower and the mortality tended to be lower in ATA-lcSSc vs ATA-dcSSc.

Conclusion
ATA-lcSSc patients have a high risk of ILD, albeit with a lower risk of progression compared with ATA-dcSSc, supporting careful screening for ILD in this subgroup.