Skip to main content
SpringerLink
Log in

Management Considerations: Interstitial Lung Disease

  • Chapter
  • First Online:
Managing Myositis

  • 918 Accesses

Abstract

Interstitial lung disease (ILD) is one of the leading causes of morbidity and mortality in idiopathic inflammatory myopathy (IIM) and is unique compared to ILD in other autoimmune diseases such as rheumatoid arthritis and systemic sclerosis. Physiologic, radiographic, and demographic features, as well as emerging biomarkers, can be used to help identify those patients at highest risk for ILD and to assess response to therapy. Clinical trials assessing the efficacy of treatments in IIM-associated ILD (IIM-ILD) are lacking and have not been the primary outcome of prospective myositis trials. As such, decisions regarding treatment choices have been largely based on agents typically used to treat muscle inflammation without specific consideration for pulmonary manifestations or agents used to treat ILD in other autoimmune conditions. In this chapter, we review the agents that have been shown to have benefit in IIM-ILD and provide more focused recommendations for specific groups of patients based on severity of disease, autoantibody profile, or predominant histologic pattern. In addition, we will discuss emerging, novel therapies that may target inflammatory or fibrotic lung disease in this group of patients.

Interstitial lung disease (ILD) is a common complication in patients with idiopathic inflammatory myopathy (IIM) and contributes to significant morbidity and mortality. ILD is especially prominent in the anti-synthetase syndrome and anti-melanoma differentiation-associated gene 5 (MDA5) antibody-associated myositis. It can present with many pathologic patterns including most frequently nonspecific interstitial pneumonia (NSIP), organizing pneumonia (OP), and usual interstitial pneumonia (UIP) and, rarely and with poor prognosis, acute interstitial pneumonitis (AIP). Determining which patients are at risk for ILD is important and includes considering such factors as older age, symptoms of fever or arthritis, elevated inflammatory markers, and the presence of anti-Jo-1 or anti-MDA5 antibodies (Zhang et al., PLoS One 11:e0155381, 2016). Possible predictors of who will have more severe disease include those with polyarthritis, elevated markers of inflammation, lower diffusing capacity, and AIP or UIP pattern on high-resolution chest CT (HRCT) or pathology (Marie et al., Arthritis Rheum 47:614–622, 2002).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Zhang L, Wu G, Gao D, Liu G, Pan L, Ni L, et al. Factors associated with interstitial lung disease in patients with polymyositis and dermatomyositis: a systematic review and meta-analysis. PLoS One. 2016;11:e0155381.

    Article  Google Scholar 

  2. Marie I, Hachulla E, Cherin P, Dominique S, Hatron PY, Hellot MF, et al. Interstitial lung disease in polymyositis and dermatomyositis. Arthritis Rheum. 2002;47:614–22.

    Article  CAS  Google Scholar 

  3. Miyasaka N, Hara M, Koike T, Saito E, Yamada M, Tanaka Y, et al. Effects of intravenous immunoglobulin therapy in japanese patients with polymyositis and dermatomyositis resistant to corticosteroids: a randomized double-blind placebo-controlled trial. Mod Rheumatol. 2012;22:382–93.

    Article  CAS  Google Scholar 

  4. Suzuki Y, Hayakawa H, Miwa S, Shirai M, Fujii M, Gemma H, et al. Intravenous immunoglobulin therapy for refractory interstitial lung disease associated with polymyositis/dermatomyositis. Lung. 2009;187:201–6.

    Article  CAS  Google Scholar 

  5. Moghadam-Kia S, Oddis CV, Aggarwal R. Modern therapies for idiopathic inflammatory myopathies (iims): role of biologics. Clin Rev Allergy Immunol. 2017;52:81–7.

    Article  CAS  Google Scholar 

  6. Schwarz MI, Matthay RA, Sahn SA, Stanford RE, Marmorstein BL. DJ. S. Interstitial lung disease in polymyositis and dermatomyositis: analysis of six cases and review of the literature. Medicine (Baltimore). 1976;55:89–104.

    Article  CAS  Google Scholar 

  7. Joffe MM, Love LA, Leff RL, Fraser DD, Targoff IN, Hicks JE, et al. Drug therapy of the idiopathic inflammatory myopathies: predictors of response to prednisone, azathioprine, and methotrexate and a comparison of their efficacy. Am J Med. 1993;94:379–87.

    Article  CAS  Google Scholar 

  8. Bolosiu HD, Man L, Rednic S. The effect of methylprednisolone pulse therapy in polymyositis/dermatomyositis. Adv Exp Med Biol. 1999;455:349–57.

    Article  CAS  Google Scholar 

  9. Connors GR, Christopher-Stine L, Oddis CV, Danoff SK. Interstitial lung disease associated with the idiopathic inflammatory myopathies: what progress has been made in the past 35 years? Chest. 2010;138:1464–74.

    Article  Google Scholar 

  10. Douglas WW, Tazelaar HD, Hartman TE, Hartman RP, Decker PA, Schroeder DR, et al. Polymyositis-dermatomyositis-associated interstitial lung disease. Am J Respir Crit Care Med. 2001;164:1182–5.

    Article  CAS  Google Scholar 

  11. Oldham JM, Lee C, Valenzi E, Witt LJ, Adegunsoye A, Hsu S, et al. Azathioprine response in patients with fibrotic connective tissue disease-associated interstitial lung disease. Respir Med. 2016;121:117–22.

    Article  Google Scholar 

  12. Tashkin DP, Roth MD, Clements PJ, Furst DE, Khanna D, Kleerup EC, et al. Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (sls ii): a randomised controlled, double-blind, parallel group trial. Lancet Respir Med. 2016;4:708–19.

    Article  CAS  Google Scholar 

  13. Fischer A, Brown KK, Du Bois RM, Frankel SK, Cosgrove GP, Fernandez-Perez ER, et al. Mycophenolate mofetil improves lung function in connective tissue disease-associated interstitial lung disease. J Rheumatol. 2013;40:640–6.

    Article  CAS  Google Scholar 

  14. Ge Y, Zhou H, Shi J, Ye B, Peng Q, Lu X, et al. The efficacy of tacrolimus in patients with refractory dermatomyositis/polymyositis: a systematic review. Clin Rheumatol. 2015;34:2097–103.

    Article  Google Scholar 

  15. Wilkes MR, Sereika SM, Fertig N, Lucas MR, Oddis CV. Treatment of antisynthetase-associated interstitial lung disease with tacrolimus. Arthritis Rheum. 2005;52:2439–46.

    Article  CAS  Google Scholar 

  16. Kurita T, Yasuda S, Oba K, Odani T, Kono M, Otomo K, et al. The efficacy of tacrolimus in patients with interstitial lung diseases complicated with polymyositis or dermatomyositis. Rheumatology (Oxford). 2015;54:39–44.

    Article  CAS  Google Scholar 

  17. Yamasaki Y, Yamada H, Yamasaki M, Ohkubo M, Azuma K, Matsuoka S, et al. Intravenous cyclophosphamide therapy for progressive interstitial pneumonia in patients with polymyositis/dermatomyositis. Rheumatology (Oxford). 2007;46:124–30.

    Article  CAS  Google Scholar 

  18. Kameda H, Nagasawa H, Ogawa H, Sekiguchi N, Takei H, Tokuhira M, et al. Combination therapy with corticosteroids, cyclosporin a, and intravenous pulse cyclophosphamide for acute/subacute interstitial pneumonia in patients with dermatomyositis. J Rheumatol. 2005;32:1719–26.

    CAS  PubMed  Google Scholar 

  19. Ge Y, Peng Q, Zhang S, Zhou H, Lu X, Wang G. Cyclophosphamide treatment for idiopathic inflammatory myopathies and related interstitial lung disease: a systematic review. Clin Rheumatol. 2015;34:99–105.

    Article  Google Scholar 

  20. Sharp C, McCabe M, Dodds N, Edey A, Mayers L, Adamali H, et al. Rituximab in autoimmune connective tissue disease-associated interstitial lung disease. Rheumatology (Oxford). 2016;55:1318–24.

    Article  CAS  Google Scholar 

  21. Oddis CV, Reed AM, Aggarwal R, Rider LG, Ascherman DP, Levesque MC, et al. Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. Arthritis Rheum. 2013;65:314–24.

    Article  CAS  Google Scholar 

  22. Allenbach Y, Guiguet M, Rigolet A, Marie I, Hachulla E, Drouot L, et al. Efficacy of rituximab in refractory inflammatory myopathies associated with anti- synthetase auto-antibodies: an open-label, phase ii trial. PLoS One. 2015;10:e0133702.

    Article  Google Scholar 

  23. Andersson H, Sem M, Lund MB, Aalokken TM, Gunther A, Walle-Hansen R, et al. Long-term experience with rituximab in anti-synthetase syndrome-related interstitial lung disease. Rheumatology (Oxford). 2015;54:1420–8.

    Article  CAS  Google Scholar 

  24. Marie I, Dominique S, Janvresse A, Levesque H, Menard JF. Rituximab therapy for refractory interstitial lung disease related to antisynthetase syndrome. Respir Med. 2012;106:581–7.

    Article  CAS  Google Scholar 

  25. Doyle TJ, Dhillon N, Madan R, Cabra F, Fletcher EA, Koontz DC, et al. Rituximab in the treatment of interstitial lung disease associated with antisynthetase syndrome: a multi-center retrospective case review. J Rheumatol. 2017:In Press.

    Google Scholar 

  26. Zou J, Li T, Huang X, Chen S, Guo Q, Bao C. Basiliximab may improve the survival rate of rapidly progressive interstitial pneumonia in patients with clinically amyopathic dermatomyositis with anti-mda5 antibody. Ann Rheum Dis. 2014;73:1591–3.

    Article  CAS  Google Scholar 

  27. Kerola AM, Kauppi MJ. Abatacept as a successful therapy for myositis-a case-based review. Clin Rheumatol. 2015;34:609–12.

    Article  Google Scholar 

  28. Kondo M, Murakawa Y, Matsumura T, Matsumoto O, Taira M, Moriyama M, et al. A case of overlap syndrome successfully treated with tocilizumab: a hopeful treatment strategy for refractory dermatomyositis? Rheumatology (Oxford). 2014;53:1907–8.

    Article  CAS  Google Scholar 

  29. Li T, Guo L, Chen Z, Gu L, Sun F, Tan X, et al. Pirfenidone in patients with rapidly progressive interstitial lung disease associated with clinically amyopathic dermatomyositis. Sci Rep. 2016;6:33226.

    Article  CAS  Google Scholar 

  30. Goh NS, Desai SR, Veeraraghavan S, Hansell DM, Copley SJ, Maher TM, et al. Interstitial lung disease in systemic sclerosis: a simple staging system. Am J Respir Crit Care Med. 2008;177:1248–54.

    Article  Google Scholar 

  31. Idiopathic Pulmonary Fibrosis Clinical Research N, Raghu G, Anstrom KJ, King TE Jr, Lasky JA, Martinez FJ. Prednisone, azathioprine, and n-acetylcysteine for pulmonary fibrosis. N Engl J Med. 2012;366:1968–77.

    Article  Google Scholar 

  32. Aggarwal R, McBurney C, Schneider F, Yousem SA, Gibson KF, Lindell K, et al. Myositis-associated usual interstitial pneumonia has a better survival than idiopathic pulmonary fibrosis. Rheumatology (Oxford). 2017;56:384–9.

    Article  Google Scholar 

  33. Saunders P, Tsipouri V, Keir GJ, Ashby D, Flather MD, Parfrey H, et al. Rituximab versus cyclophosphamide for the treatment of connective tissue disease-associated interstitial lung disease (recital): study protocol for a randomised controlled trial. Trials. 2017;18:275.

    Article  Google Scholar 

  34. Aggarwal R, Cassidy E, Fertig N, Koontz DC, Lucas M, Ascherman DP, et al. Patients with non-jo-1 anti-trna-synthetase autoantibodies have worse survival than jo-1 positive patients. Ann Rheum Dis. 2014;73:227–32.

    Article  Google Scholar 

  35. Khanna D, Mittoo S, Aggarwal R, Proudman SM, Dalbeth N, Matteson EL, et al. Connective tissue disease-associated interstitial lung diseases (ctd-ild) – report from omeract ctd-ild working group. J Rheumatol. 2015;42:2168–71.

    Article  CAS  Google Scholar 

  36. Ihn H, Asano Y, Kubo M, Yamane K, Jinnin M, Yazawa N, et al. Clinical significance of serum surfactant protein d (sp-d) in patients with polymyositis/dermatomyositis: correlation with interstitial lung disease. Rheumatology (Oxford). 2002;41:1268–72.

    Article  CAS  Google Scholar 

  37. Gono T, Sato S, Kawaguchi Y, Kuwana M, Hanaoka M, Katsumata Y, et al. Anti-mda5 antibody, ferritin and il-18 are useful for the evaluation of response to treatment in interstitial lung disease with anti-mda5 antibody-positive dermatomyositis. Rheumatology (Oxford). 2012;51:1563–70.

    Article  CAS  Google Scholar 

  38. Oguz EO, Kucuksahin O, Turgay M, Yildizgoren MT, Ates A, Demir N, et al. Association of serum kl-6 levels with interstitial lung disease in patients with connective tissue disease: a cross-sectional study. Clin Rheumatol. 2016;35:663–6.

    Article  Google Scholar 

  39. Fathi M, Barbasso Helmers S, Lundberg IE. Kl-6: a serological biomarker for interstitial lung disease in patients with polymyositis and dermatomyositis. J Intern Med. 2012;271:589–97.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pulmonary and Critical Care Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Tracy J. Doyle

  2. Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Boston, MA, USA

    Paul F. Dellaripa

  3. Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Paul F. Dellaripa

Authors
  1. Tracy J. Doyle
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul F. Dellaripa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paul F. Dellaripa .

Editor information

Editors and Affiliations

  1. Division of Rheumatology and Clinical Immunology, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA

    Rohit Aggarwal

  2. Division of Rheumatology and Clinical Immunology, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA

    Chester V. Oddis

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Doyle, T.J., Dellaripa, P.F. (2020). Management Considerations: Interstitial Lung Disease. In: Aggarwal, R., Oddis, C. (eds) Managing Myositis. Springer, Cham. https://doi.org/10.1007/978-3-030-15820-0_32

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-15820-0_32

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-15819-4

  • Online ISBN: 978-3-030-15820-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation