Phenotype of limited cutaneous systemic sclerosis patients with positive anti-topoisomerase I antibodies: data from EUSTAR cohort

Objectives: To characterize patients with positive anti-topoisomerase I (ATA) in the limited cutaneous Systemic Sclerosis (lcSSc). Methods: SSc patients enrolled in the EUSTAR cohort with disease duration ≤3 yrs at database entry were considered. We assessed the risk of major organ involvement in the following groups: 1) ATA-lcSSc vs anticentromere (ACA)-lcSSc and vs antinuclear antibodies without specificity (ANA)-lcSSc; 2) ATA-lcSSc vs ATA-diffuse cutaneous (dc)SSc. 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 ± 3.5 yrs 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. 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, lower than in ACA-lcSSc; no difference in PH and mortality risk was observed among lcSSc subsets. Risk of any organ involvement, PMI, 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 a careful screening for ILD in this subgroup.