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Systemic sclerosis interstitial lung disease: unmet needs and potential solutions

Nature Reviews Rheumatology volume 20, pages 21–32 (2024)Cite this article

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Abstract

Systemic sclerosis (SSc), or scleroderma, is a rare, complex, systemic autoimmune disease of unknown aetiology, characterized by high morbidity and mortality often resulting from cardiopulmonary complications such as interstitial lung disease and pulmonary arterial hypertension. Despite substantial progress in unravelling the pathways involved in the pathogenesis of SSc and the increasing number of therapeutic targets tested in clinical trials, there is still no cure for this disease, although several proposed treatments might limit the involvement of specific organs, thereby slowing the natural history of the disease. A specific focus of recent research has been to address the plethora of unmet needs regarding the global management of SSc-related interstitial lung disease, including its pathogenesis, early diagnosis, risk stratification of patients, appropriate treatment regimens and monitoring of treatment response, as well as the definition of progression and predictors of progression and mortality. More refined stratification of patients on the basis of clinical features, molecular signatures, identification of subpopulations with distinct clinical trajectories and implementation of outcome measures for future clinical trials could also improve therapeutic management strategies, helping to avoid poor outcomes related to lung involvement.

Key points

  • Systemic sclerosis (SSc) is a rare systemic autoimmune disease characterized by high clinical heterogeneity, in which interstitial lung disease (ILD) is one of the main causes of morbidity and mortality.

  • Despite many advances in the understanding of pathogenetic mechanisms and clinical definition, SSc–ILD management is still associated with several unmet needs.

  • Discovery of new therapeutic targets and specific diagnostic and prognostic markers will help optimize the management of SSc–ILD.

  • Stratification of patients by clinical features and molecular signatures, identification of subpopulations with distinct clinical trajectories, and implementation of outcome measures in clinical trials can also improve SSc–ILD management.

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Fig. 1: Pathogenesis of SSc interstitial lung disease.

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Authors and Affiliations

  1. Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy

    Vasiliki Liakouli, Antonio Ciancio & Francesco Ciccia

  2. Leeds Institute of Rheumatic and Musculoskeletal Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, UK

    Francesco Del Galdo

  3. Scleroderma Programme, NIHR Biomedical Research Centre, Leeds Teaching Hospital Trusts, Leeds, UK

    Francesco Del Galdo

  4. Rheumatology and Immunology Unit, Department of Medicine, University of Rome Campus Biomedico, Rome, Italy

    Roberto Giacomelli

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All authors researched data for the article. All authors contributed substantially to the discussion of content. V.L., F.D.G., R.G. and F.C. wrote the article. V.L., F.D.G., R.G. and F.C. reviewed and/or edited the manuscript before submission.

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Liakouli, V., Ciancio, A., Del Galdo, F. et al. Systemic sclerosis interstitial lung disease: unmet needs and potential solutions. Nat Rev Rheumatol 20, 21–32 (2024). https://doi.org/10.1038/s41584-023-01044-x

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