Background/Purpose: Extensive skin disease and renal crisis are hallmarks of anti-RNA polymerase III (RNAP) positive systemic sclerosis (SSc), while data on lung and heart involvement are conflicting. Here, the aims were to perform time-course analyses of interstitial lung disease (ILD) and pulmonary hypertension (PH) in the RNAP subset in a prospective unselected SSc cohort with longitudinal follow up data and use the other auto-antibody subsets as comparators.   <>

Methods: The study cohort included 276 SSc patients from the observational Oslo University Hospital cohort with complete data on (A) SSc-related auto-antibodies, (B) paired, serial analyses of lung function and extent of fibrosis by lung HRCT at baseline and follow-up, and (C) PH verified by right heart catheterization. All patients in the SSc cohort met the 2013 ACR/EULAR classification criteria.  

Results: RNAP was positive in 33/276 patients (12%), of which 79% had diffuse cutaneous SSc. Patients with RNAP had higher modified Rodnan Skin Score, developed more frequently scleroderma renal crisis and gastric antral vascular ectasia than anti-Topoisomerase 1 (ATA) and anti-centromere antibody (ACA) positive patients. Pulmonary findings in the RNAP subset were heterogeneous; 49% had no signs of ILD, while 33.3%  had moderate fibrosis (1-20% fibrosis) and 18.2% had severe fibrosis at follow up (>20% fibrosis); (Figure 1 and 2). The annual fibrosis progression rate was higher in RNAP (1.2% SD 2.0) compared to ATA (0.5%, SD 5.0) and ACA (0.7%, SD 1.4) but did not reach statistical significance. Forced Vital Capacity at follow up was <80% in 39% of the RNAP subset; comparable to the anti-topoisomerase subset (ATA: 47%), but higher than anti-centromere (ACA: 13%). The accumulated frequency of PH in the RNAP subset (12 %) was lower than in ACA (18 %). The 5- and 10 year survival rates in RNAP cases were 93% and 78%, respectively. The survival of RNAP positive patients was comparable to the ATA and ACA subsets, but significantly higher than in the ANA negative patient subset.

Conclusion: In this cohort, the RNAP subset was marked by cardiopulmonary heterogeneity with progression to extensive ILD in 18 %, and PH development in 12 %. These data indicate that cardiopulmonary risk stratification early in the disease course is particularly important in RNAP positive SSc.