SSc-ILD

Course of disease

Systemic sclerosis associated interstitial lung disease (SSc-ILD) is associated with early mortality. In a study of causes of death in 1,508 patients with systemic sclerosis (SSc) from a single US center, deaths attributed to pulmonary fibrosis increased from 6% in 1972–1976 to 33% in 1997–2001, making interstitial lung disease (ILD) the most frequent cause of SSc-related death. Similarly, in an analysis of 5,850 patients in the EULAR Scleroderma Trials and Research Group (EUSTAR) database, pulmonary fibrosis was responsible for 35% of SSc-related deaths from 2004 to 2008.¹

SSc-ILD has a variable clinical course. Most patients will experience a slow decline in lung function, but some progress rapidly after disease onset, with progression defined by an increase in the extent of pulmonary fibrosis on high-resolution computed tomography (HRCT) or by a decline in pulmonary function test (PFTs). Among patients in the EUSTAR cohort, 65% of patients had diffusion capacity of the lung for carbon monoxide (DLCO) < 80% predicted and 31% had FVC < 80% predicted 1 year after the onset of Raynaud’s phenomenon.¹

Predictors of disease progression in SSc-ILD^1,2

Pulmonary function test (PFT)²

Lung physiology is the most well studied marker of disease progression. Restrictive physiology and impaired gas exchange have repeatedly been shown to be independent predictors of poor outcomes, and dynamic monitoring over a longer period is useful to more accurately predict the course of SSc-ILD. A decrease in forced vital capacity (FVC) of more than 10%, or of 5–9% with an associated 15% decrease in DLCO identifies a population at particularly high risk of death. However, short-term changes (<12 months) should be interpreted with caution because they might not be as reliable as longer trends. Moreover, when assessing a decline in spirometry, factors such as worsening myopathy or increased truncal skin thickness should also be considered. ²

Exercise capacity²

Few data exist regarding the value of the six-minute walk test in patients with SSc-ILD. Only a weak correlation exists between the six-minute walk distance and clinically significant endpoints such as the Borg Dyspnea Index, FVC, and DLCO in SSc-ILD. Nevertheless, the six-minute walk distance predicted mortality at one year and improved performance of the Composite Physiologic Index and the Gender-Age-Physiology prognostic scores in a cohort of 156 patients with SSc-ILD. ²

Finding from high-resolution computed tomography (HRCT) imaging^1,2

A cohort study has found that fibrosis in more than 20% of the parenchyma is associated with a dramatic increase in the odds of mortality. Similarly, a higher fibrosis score on HRCT has been associated with higher risk of 5-year mortality and a faster decline in FVC over 12 months. In contrast, the absence of ILD on an initial HRCT is a favorable sign, with up to 88% of individuals remaining disease free at follow-up. The usual interstitial pneumonia (UIP) pattern or honeycombing, or both, confers a worse prognosis than nonspecific interstitial pneumonia (NSIP) pattern, although this association is not evident in all cohorts. Finally, a pulmonary artery-to- aorta ratio of more than 1:1 and an increase in esophageal diameter on HRCT have also been linked to increased risk of death and faster disease progression. ²

A simple staging system, often referred to as the Goh criteria, which divides patients into those with extensive disease (> 30% disease extent on HRCT, or 10–30% disease extent on HRCT and FVC < 70% predicted) or limited disease (< 30% disease extent on HRCT, or 10–30% disease extend on HRCT and FVC ≥70% predicted) demonstrated that extensive disease was a powerful predictor of mortality (HR 3.46, 95% CI 2.19, 5.46). (Figure 1) ¹

Figure 1. A simple staging system for prediction of survival in patients with SSc-ILD.¹

Biomarkers²

Data on the prognostic value of novel biomarkers have started to accumulate. Lower levels of FeNO and IL-10 and higher levels of carbohydrate antigen 15.3, C-reactive protein, and monocyte chemoattractant protein 1 are associated with a more aggressive course of disease. ²