Natural History of Systemic Sclerosis-Related Interstitial Lung Disease: How to Identify a Progressive Fibrosing Phenotype

Abstract

The natural history of interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) is highly variable. Historical observational studies have demonstrated that the greatest decline in lung function in SSc occurs early in the course of the disease; however, not all patients experience a decline in lung function even in the absence of treatment. Furthermore, among patients who do experience a decline in lung function, the rate of decline can be either rapid or slow. The most common clinical phenotypes of SSc-ILD therefore: (i) Rapid Progressors, (ii) Gradual Progressors, (iii) Stabilizers and (iv) Improvers. This review summarizes the features of SSc-ILD patients who are more likely to experience rapid progression of ILD, as well as those who are more likely not to experience ILD progression. Understanding the clinical, biological and radiographic factors that consistently predict ILD-related outcomes in SSc is central to our ability to recognize those patients who are at heightened risk for ILD progression. With new options available for treating patients with SSc-ILD, it is more important than ever to accurately identify patients who may derive the most benefit from aggressive SSc-ILD therapy. Early therapeutic intervention in patients with this progressive fibrosing phenotype may ultimately improve morbidity and mortality outcomes in patients with SSc-ILD.

Figure 1.

The course of %-predicted FVC from 3 through 24 months by treatment arm in SLS II based on the joint model (N = 126). The horizontal dotted line represents the average baseline FVC% predicted for both treatment arms based on the joint model. The vertical lines (dashed CYC; solid MMF) represent 95% confidence intervals. The * represents a significant change from baseline within treatment groups (p < 0.05). Source: Reproduced with permission from Lancet Respiratory Medicine.

Figure 2.

Increased long-term mortality among SSc-ILD patients who met the criteria for a compositive categorical decline (CCD) in lung function at 12 months (N = 162). The CCD was defined as either a decline in the forced vital capacity (FVC) of ⩾10% or a decline in the FVC of 5%–9% in combination with a decline in the diffusing capacity for carbon monoxide of ⩾15%. Source: Reproduced with permission from Arthritis and Rheumatology.