Characterization of Incident Interstitial Lung Disease in Late Systemic Sclerosis

Interstitial lung disease (ILD) is a common and potentially lethal complication of systemic sclerosis (SSc). Screening by high-resolution computed tomography (HRCT) is recommended in all patients with risk factors, including early disease. Little is known on late presentations of ILD. This study aimed to characterize the incidence, risk factors, and outcomes of late-onset SSc-ILD.

Study participants enrolled in the Canadian Scleroderma Research Group cohort from 2004 to 2020 without prevalent ILD were included. Incidence and risk factors for ILD (on HRCT) were compared according to disease duration above (late) and below (earlier) seven years from the first non-Raynaud manifestation. Risk of ILD progression was compared using Kaplan-Meier and multivariable Cox models.

Overall, 199 (21%) of 969 patients developed incident ILD over a median of 2.4 (interquartile range 1.2-4.3) years. The incidence rate in late SSc (3.7/100 person-years) was lower than in earlier SSc (relative risk 0.68, 95% confidence interval [CI] 0.51-0.92). Risk factors for incident ILD included male sex, diffuse subtype, myositis, antitopoisomerase I autoantibodies, and higher C-reactive protein levels. Patients with late-onset ILD were also less frequently White and more frequently had arthritis and anti-RNA-polymerase III autoantibodies. Lung disease severity was similar between late- and earlier-onset SSc-ILD (forced vital capacity 88% and 87%, diffusion capacity of the lungs for carbon monoxide 64% and 62%, respectively). Progression rates were also similar between late- and earlier-onset SSc-ILD (log rank P = 0.8, hazard ratio 1.11, 95% CI 0.58-2.10).

ILD can present in late SSc. Risk factors and progression rates overlapped with earlier-onset SSc-ILD. Surveillance for ILD should continue in longstanding SSc. Frequency and modality of monitoring remain to be defined.