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  • Review Article
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Interstitial lung disease in connective tissue disease—mechanisms and management

Nature Reviews Rheumatology volume 10, pages 728–739 (2014)Cite this article

Subjects

Key Points

  • Extra-articular features, particularly pulmonary complications, are a major cause of mortality in autoimmune rheumatic disease

  • Interstitial lung disease (ILD) is an important pulmonary complication in a variety of connective tissues diseases, particularly systemic sclerosis

  • Despite advances in understanding of disease mechanisms, more work needs to be done to identify cardinal pathogenetic pathways in order to develop more efficacious therapies

  • The most difficult clinical decision in ILD associated with connective tissue disease is to determine when treatment should be initiated and when meticulous observation without intervention is appropriate

  • The initiation of treatment is warranted when disease progression is probable, based on pulmonary disease severity, evidence of ongoing progression and short duration of systemic disease

  • Current treatment is essentially based on immunosuppression: it is imperative that novel immunomodulatory and antifibrotic agents be evaluated in multicentre treatment trials

Abstract

Pulmonary complications are an important extra-articular feature of autoimmune rheumatic diseases and a major cause of mortality. The underlying pathogenesis probably involves multiple cellular compartments, including the epithelium, lung fibroblasts, and the innate and adaptive immune system. Heterogeneity in the extent and progression of lung fibrosis probably reflects differences in underlying pathogenic mechanisms. Growing understanding of the key pathogenic drivers of lung fibrosis might lead to the development of more effective targeted therapies to replicate the treatment advances in other aspects of these diseases. Interstitial lung disease (ILD) in connective tissue disease (CTD) is characterized using the classification of the idiopathic interstitial pneumonias. Systemic sclerosis is most frequently associated with ILD and, in most of these patients, ILD manifests as a histological pattern of nonspecific interstitial pneumonia. Conversely, in rheumatoid arthritis, the pattern of ILD is most often usual interstitial pneumonia. The key goals of clinical assessment of patients with both ILD and CTD are the detection of ILD and prognostic evaluation to determine which patients should be treated. Data from treatment trials in systemic sclerosis support the use of immunosuppressive therapy, with the treatment benefit largely relating to the prevention of progression of lung disease.

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Figure 1: Cellular pathogenesis of fibrotic lung injury.
Figure 2: Generation of profibrotic myofibroblasts after lung injury.

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Acknowledgements

The authors of this Review are supported by the NIHR Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London.

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  1. Interstitial lung disease unit, Royal Brompton Hospital, Fulham Road, Chelsea, London, SW3 6NP, UK

    Athol U. Wells

  2. Division of Medicine, Centre for Rheumatology and Connective Tissue Disease, Royal Free Campus, University College London, London, NW3 2QG, UK

    Christopher P. Denton

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Correspondence to Athol U. Wells.

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A.U.W. declares the following competing interests: consultancy fees from Boehringer Ingelheim, Genentech, Gilead, Intermune, MedImmune, Takeda; and honoraria from Actelion Pharmaceuticals, Beohringer Ingelheim and Intermune. C.P.D. declares that he has received consultancy fees, honoraria and research funding from Actelion Pharmaceuticals, and consultancy fees and honoraria from GlaxoSmithKline, Merck-Serono, Novartis, Pfizer and Sanofi-Aventis.

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Wells, A., Denton, C. Interstitial lung disease in connective tissue disease—mechanisms and management. Nat Rev Rheumatol 10, 728–739 (2014). https://doi.org/10.1038/nrrheum.2014.149

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