Major lung complications of systemic sclerosis

Abstract

Systemic sclerosis (SSc) is associated with high mortality owing to internal organ complications, and lung disease is the leading cause of SSc-associated death. The most notable lung complications in SSc are fibrosis and pulmonary arterial hypertension (PAH). A major challenge for the management of lung disease in SSc is detecting those patients with severe pathology and those patients who are likely to benefit from available treatments. In the past few years, strategies for managing lung fibrosis and pulmonary hypertension, including PAH, have greatly progressed. For lung fibrosis, the tools to assess risk of progression and severity of the disease have been refined. Clinical trial results support the use of immunosuppression, including high-intensity regimens with autologous stem cell transplantation. New trials are underway to test other potential therapies including treatments that are approved for use in idiopathic lung fibrosis. For PAH, identifying individuals at high risk of disease development is critical. In addition, individuals who have borderline elevation of pulmonary arterial pressure need to be appropriately managed and followed up. Many approved drugs targeting PAH are now available, and results from large-scale clinical trials provide robust evidence that various treatments for SSc-associated PAH are associated with good long-term outcomes.

Key points

  • Lung complications are frequent in systemic sclerosis (SSc) and include lung fibrosis and pulmonary hypertension, which have a substantial effect on disease outcomes and are major causes of SSc-related death.

  • Systematic evaluation of patients ensures that diagnosis of lung fibrosis and pulmonary hypertension is timely and permits treatment at the earliest possible stage.

  • Multiple licensed therapies exist for pulmonary arterial hypertension, and use of these agents alone and in combination has improved outcomes and survival in event-driven trials.

  • There are no approved therapies for lung fibrosis, but treatment with immunosuppression seems beneficial in clinical trials and is recommended for appropriate patients with severe or progressive lung fibrosis.

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Fig. 1: Pathogenesis of major lung complications in systemic sclerosis.
Fig. 2: Screening for pulmonary hypertension in systemic sclerosis.
Fig. 3: Histological and CT appearances of major lung complications in systemic sclerosis.

Change history

  • 13 October 2018

    Corrections: Table 2: the text ‘Also licensed for CTEPH; cannot be combined with a PDE5 inhibitor’ has been moved to a different row; reference for this moved statement updated.

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All authors researched data for the article, provided substantial contributions to discussions of the content, wrote the article and reviewed and/or edited the article before submission.

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Correspondence to Christopher P. Denton.

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C.P.D. has received honoraria from Actelion, Bayer, Boehringer Ingelheim, GlaxoSmithKline and Roche/Genentech and consultancy fees from Actelion, Bayer, Boehringer Ingelheim, CSL Behring, GlaxoSmithKline, Inventiva, Merck-Serono, Roche/Genentech and Sanofi-Aventis. A.U.W. and J.G.C. declare no competing interests.

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Glossary

Fibroblasts

Cells that produce extracellular matrix and that are activated inappropriately or excessively in fibrotic disease.

Myofibroblasts

Activated fibroblastic cells that have a contractile cytoskeleton that includes microfibrils containing α-smooth muscle actin.

Lung function testing

A collective term for the physiological measurement of lung volume, airways resistance and gas exchange in the lungs.

Exertional dyspnoea

Subjective breathlessness that occurs on exertion and is a cardinal feature of substantial lung complications including lung fibrosis and pulmonary hypertension.

Dyspnoea

Breathlessness that is a major symptom of lung complications in systemic sclerosis but that also has other potential causes including cardiac disease, anaemia and deconditioning.

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Denton, C.P., Wells, A.U. & Coghlan, J.G. Major lung complications of systemic sclerosis. Nat Rev Rheumatol 14, 511–527 (2018). https://doi.org/10.1038/s41584-018-0062-0

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