Interstitial Lung Disease in Scleroderma

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Key points

  • Interstitial lung disease is a significant cause of morbidity and mortality in systemic sclerosis.

  • Diagnostic modalities to assess interstitial lung disease include pulmonary function tests, which may show decreases in the forced vital capacity and diffusion capacity of the lung for carbon monoxide, and high-resolution computed tomography, which may show patterns consistent with nonspecific interstitial pneumonia or usual interstitial pneumonia.

  • Pathogenesis revolves around an interplay of

Epidemiology

ILD is common in patients with SSc, with up to 90% of patients exhibiting evidence of interstitial changes on HRCT,1 and between 40% and 75% of patients having PFT abnormalities.2, 3 Clinically significant lung fibrosis is present in approximately 25% of all SSc patients,4 but there is significant heterogeneity with regard to the incidence of pulmonary involvement based on several factors, including the SSc subset and antibody profile. In particular, patients with diffuse cutaneous SSc (dcSSc)

Pathogenesis

The pathogenesis of SSc-ILD is multifactorial and incompletely understood. Endothelial cell injury with subsequent vascular damage and alveolar epithelial cell injury are key initial insults that precede fibrosis. At the time of injury, various mediators are released, and fibroblasts are activated. Over time, fibroblasts acquire features of smooth muscle cells and become myofibroblasts, resulting in dysregulated accumulation of collagen and extracellular matrix components and ultimately

Clinical manifestations

Patients with mild ILD may be asymptomatic during the early stages of the disease. As the extent of pulmonary fibrosis increases, patients often report fatigue and dyspnea on exertion, and physical examination may find dry “velcro” crackles at the lung bases. Of note, patients with PAH may also have exertional dyspnea and fatigue, and the clinician must keep both entities in mind when evaluating an SSc patient for dyspnea. Dry cough is often present and may correlate with DLCO and dyspnea.24 In

Imaging findings

HRCT plays an important role in determining the pattern and extent of involvement of ILD in SSc patients. The most common pattern seen on HRCT is nonspecific interstitial pneumonia (NSIP), although usual interstitial pneumonia (UIP) can also be seen in 25% to 40% of cases.25, 27 The NSIP pattern on HRCT is evident by ground glass opacities in a peripheral distribution with subpleural and basilar predominance (Fig. 2A). In more severe disease, volume loss with a reticular pattern and traction

Pulmonary function tests

PFTs are a key component in the diagnosis and long-term follow-up of SSc-ILD. The FVC and DLCO are important parameters for the assessment of lung function in SSc patients, and the FVC can help stratify patients for treatment.29 Reduced DLCO is sensitive for early ILD but can also be an indicator of pulmonary hypertension and needs to be interpreted in the context of the overall lung volumes. FVC and DLCO should be greater than 80% predicted to be considered normal. In a study of 890 SSc

6-minute walk test

The 6-minute walk test (6MWT) is an easy and noninvasive tool used for the assessment of lung function in pulmonary disease. Its utility in SSc-ILD is, however, limited primarily because of functional impairment of patients. In a study of 163 patients with SSc-ILD, the 6MWT did not correlate well with other parameters such as FVC, DLCO, or dyspnea index scores despite its reproducibility.34 It may play a more important role in SSc patients with PAH.

Histopathology

Histologically, SSc-ILD is characterized by early pulmonary infiltration of inflammatory cells and subsequent fibrosis of the lung parenchyma. The most common patterns seen on histologic examination are NSIP and UIP. NSIP is characterized by varying degrees of inflammation and fibrosis. In contrast, UIP is characterized by dense patchy fibrosis with “honeycombing,” primarily in a subpleural distribution. NSIP is the more common pattern seen in SSc-ILD and is present in 64% to 77% of cases.27, 35

Approach to Treatment

Multiple treatment modalities have been used in SSc-ILD with only some having modest benefit. Drug development for ILD has expanded dramatically and several investigational approaches are currently in early-phase clinical trials. The decision of which patients to treat must be considered carefully given the potential toxicities of many of the medications. An algorithm for determining the severity of disease has been proposed by Goh and colleagues,29 and use of this algorithm may aid in

Prognosis

The overall prognosis of SSc-ILD is poor, but there is variability between the different pathologic subsets. Patients with NSIP tend to have better outcomes, with a median survival of 15 years compared with 3 years in patients with UIP.27 Factors such as older age, lower FVC, and lower DLCO are predictive of mortality in SSc-ILD, and extent of disease on HRCT often predicts mortality and ILD progression.6 Particular attention should be paid to these parameters when evaluating patients with

Summary

ILD is one of the most serious complications among patients with SSc, and despite advances in the understanding of the pathogenesis and treatment of the disease there is still significant morbidity and mortality. PFTs and HRCT play a central role in the diagnosis of ILD and should be monitored routinely. Although certain subgroups of SSc patients seem to be at higher risk for ILD development, we do not have clear biomarkers for which patients will get the disease or have disease progression.

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    Disclosures: None.

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