Skip to main content

Advertisement

SpringerLink
Log in

Management of Interstitial Lung Disease in Patients With Myositis Specific Autoantibodies

  • Inflammatory Muscle Disease (I Lundberg, Section Editor)
  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

To review advances in the management of idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-associated ILD) in the past 5 years, with highlights in myositis-specific antibody (MSA) groups.

Recent Findings

With the recent advent of widespread MSA testing, the study of specific homogeneous autoantibody-based subgroups of IIM-associated ILD is now possible. The prevalence, severity, prognosis, and response to treatment are under study for these individual MSAs. Early evidence suggests that PL-7- and PL-12-positive patients are more likely to have ILD and worse severity, compared to Jo-1 patients. Many medications have been efficacious for the treatment of IIM-associated ILD, including calcineurin inhibitors, rituximab, and cyclophosphamide. We suggest vigilant screening and monitoring of ILD in IIM patients with focus on the potential side effects associated with therapy and thus advocate appropriate vaccination, PCP prophylaxis, and bone health protection.

Summary

Many different agents are used to manage patients with ILD with no comparative effectiveness studies to guide the clinician. The possibility of using MSAs to help guide treatment decisions is an appealing, although unproven, focus of research. Unfortunately, the rarity of non-Jo-1 myositis-specific antibodies has precluded robust study of response to treatment and overall management. Ongoing clinical trials and working groups are coordinating efforts to provide evidence-based management.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Mathai SC, Danoff SK. Management of interstitial lung disease associated with connective tissue disease. BMJ. 2016;352:h6819.

    Article  PubMed  Google Scholar 

  2. Hamaguchi Y, Fujimoto M, Matsushita T, Kaji K, Komura K, Hasegawa M, et al. Common and distinct clinical features in adult patients with anti-aminoacyl-tRNA synthetase antibodies: heterogeneity within the syndrome. PLoS One. 2013;8:e60442.

  3. Johnson C, Connors GR, Oaks J, Han S, Truong A, Richardson B, et al. Clinical and pathologic differences in interstitial lung disease based on antisynthetase antibody type. Respir Med. 2014;108:1542–8.

  4. Tomonaga M, Sakamoto N, Ishimatsu Y, Kakugawa T, Harada T, Nakashima S, et al. Comparison of pulmonary involvement between patients expressing anti-PL-7 and anti-Jo-1 antibodies. Lung. 2015;193:79–83.

  5. Marie I, et al. Interstitial lung disease in anti-Jo-1 patients with antisynthetase syndrome. Arthritis Care Res. (Hoboken). 2013;65:800–8.

  6. Hervier B, Devilliers H, Stanciu R, Meyer A, Uzunhan Y, Masseau A, et al. Hierarchical cluster and survival analyses of antisynthetase syndrome: phenotype and outcome are correlated with anti-tRNA synthetase antibody specificity. Autoimmun Rev. 2012;12:210–7.

  7. Pinal-Fernandez I, Casal-Dominguez M, Huapaya JA, Albayda J, Paik JJ, Johnson C, et al. A longitudinal cohort study of the anti-synthetase syndrome: increased severity of interstitial lung disease in black patients and patients with anti-PL7 and anti-PL12 autoantibodies. Rheumatology. 2017;56:999–1007.

  8. Debray M-P, Borie R, Revel MP, Naccache JM, Khalil A, Toper C, et al. Interstitial lung disease in anti-synthetase syndrome: initial and follow-up CT findings. Eur J Radiol. 2015;84:516–23.

  9. Takada K, Kishi J, Miyasaka N. Step-up versus primary intensive approach to the treatment of interstitial pneumonia associated with dermatomyositis/polymyositis: a retrospective study. Mod Rheumatol. 2007;17:123–30.

  10. Yokoyama Y, Furuta S, Ikeda K, Hirose K, Nakajima H. Corticosteroid-sparing effect of tacrolimus in the initial treatment of dermatomyositis and polymyositis. Mod Rheumatol. 2015;25:888–92.

  11. •• Morisset J, Johnson C, Rich E, Collard HR, Lee JS. Management of myositis-related interstitial lung disease. Chest. 2016;150:1118–28. This study provides a thorough review of management of IIM-associated ILD including proposed algorithms.

    Article  PubMed  Google Scholar 

  12. Aggarwal R, et al. Myositis-associated usual interstitial pneumonia has a better survival than idiopathic pulmonary fibrosis. Rheumatology. 2017;56:kew426.

    Article  Google Scholar 

  13. Mira-Avendano IC, Parambil JG, Yadav R, Arrossi V, Xu M, Chapman JT, et al. A retrospective review of clinical features and treatment outcomes in steroid-resistant interstitial lung disease from polymyositis/dermatomyositis. Respir Med. 2013;107(6):890–6.

  14. 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.

  15. Labirua-Iturburu A, et al. Calcineurin inhibitors in a cohort of patients with antisynthetase-associated interstitial lung disease. Clin Exp Rheumatol. 31:436–9.

  16. Cavagna L, Caporali R, Abdi-Ali L, Dore R, Meloni F, Montecucco C. Cyclosporine in anti-Jo1-positive patients with corticosteroid-refractory interstitial lung disease. J Rheumatol. 2013;40:484–92.

    Article  CAS  PubMed  Google Scholar 

  17. 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.

  18. Keir GJ, Maher TM, Hansell DM, Denton CP, Ong VH, Singh S, et al. Severe interstitial lung disease in connective tissue disease: rituximab as rescue therapy. Eur Respir J. 2012;40:641–8.

  19. Sem M, Molberg Ø, Lund MB, Gran JT. Rituximab treatment of the anti-synthetase syndrome—a retrospective case series. Rheumatology. 2009;48:968–71.

    Article  CAS  PubMed  Google Scholar 

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

  21. 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  PubMed  PubMed Central  Google Scholar 

  22. 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  PubMed  Google Scholar 

  23. Ingegnoli F, Lubatti C, Ingegnoli A, Boracchi P, Zeni S, Meroni PL. Interstitial lung disease outcomes by high-resolution computed tomography (HRCT) in anti-Jo1 antibody-positive polymyositis patients: a single centre study and review of the literature. Autoimmun Rev. 2012;11:335–40.

    Article  PubMed  Google Scholar 

  24. La Corte R, Lo Mo Naco A, Locaputo A, Dolzani F, Trotta F. In patients with antisynthetase syndrome the occurrence of anti-Ro/SSA antibodies causes a more severe interstitial lung disease. Autoimmunity. 2006;39:249–53.

    Article  PubMed  Google Scholar 

  25. Váncsa A, Csípő I, Németh J, Dévényi K, Gergely L, Dankó K. Characteristics of interstitial lung disease in SS-A positive/Jo-1 positive inflammatory myopathy patients. Rheumatol Int. 2009;29:989–94.

    Article  PubMed  Google Scholar 

  26. Bauhammer J, Blank N, Max R, Lorenz HM, Wagner U, Krause D, et al. Rituximab in the treatment of Jo1 antibody-associated antisynthetase syndrome: anti-Ro52 positivity as a marker for severity and treatment response. J Rheumatol. 2016;43:1566–74.

  27. Tillie-Leblond I, Wislez M, Valeyre D, Crestani B, Rabbat A, Israel-Biet D, et al. Interstitial lung disease and anti-Jo-1 antibodies: difference between acute and gradual onset. Thorax. 2008;63:53–9.

  28. Hirakata M, Suwa A, Takada T, Sato S, Nagai S, Genth E, et al. Clinical and immunogenetic features of patients with autoantibodies to asparaginyl–transfer RNA synthetase. Arthritis Rheum. 2007;56:1295–303.

  29. Kunimasa K, Arita M, Nakazawa T, Tanaka M, Tsubouchi K, Konishi S, et al. The clinical characteristics of two anti-OJ (anti-isoleucyl-tRNA synthetase) autoantibody-positive interstitial lung disease patients with polymyositis/dermatomyositis. Intern Med. 2012;51:3405–10.

  30. Giannini M, Notarnicola A, Dastmalchi M, Lundberg IE, Lopalco G, Iannone F. Heterogeneous clinical spectrum of interstitial lung disease in patients with anti-EJ anti-synthetase syndrome: a case series. Clin Rheumatol. 2016;35:2363–7.

  31. Targoff IN, Trieu EP, Plotz PH, Miller FW. Antibodies to glycyl-transfer RNA synthetase in patients with myositis and interstitial lung disease. Arthritis Rheum. 1992;35:821–30.

    Article  CAS  PubMed  Google Scholar 

  32. Marie I, Josse S, Decaux O, Dominique S, Diot E, Landron C, et al. Comparison of long-term outcome between anti-Jo1- and anti-PL7/PL12 positive patients with antisynthetase syndrome. Autoimmun Rev. 2012;11:739–45.

  33. Sato S, Hirakata M, Kuwana M, Suwa A, Inada S, Mimori T, et al. Autoantibodies to a 140-kd polypeptide, CADM-140, in Japanese patients with clinically amyopathic dermatomyositis. Arthritis Rheum. 2005;52:1571–6.

  34. Moghadam-Kia S, Oddis CV, Sato S, Kuwana M, Aggarwal R. Antimelanoma differentiation-associated gene 5 antibody: expanding the clinical spectrum in North American patients with dermatomyositis. J Rheumatol. 2017;44:319–25.

    Article  CAS  PubMed  Google Scholar 

  35. Allenbach Y, Leroux G, Suárez-Calvet X, Preusse C, Gallardo E, Hervier B, et al. Dermatomyositis with or without anti-melanoma differentiation-associated gene 5 antibodies. Am J Pathol. 2016;186:691–700.

    Article  CAS  PubMed  Google Scholar 

  36. Koguchi-Yoshioka H, Okiyama N, Iwamoto K, Matsumura Y, Ogawa T, Inoue S, et al. Intravenous immunoglobulin contributes to control anti-melanoma differentiation-associated protein 5 (MDA5) antibody-associated dermatomyositis with palmar violaceous macules/papules. Br J Dermatol. 2017;177:1442–6. https://doi.org/10.1111/bjd.15499.

  37. Koichi Y, et al. A case of anti-MDA5-positive rapidly progressive interstitial lung disease in a patient with clinically amyopathic dermatomyositis ameliorated by rituximab, in addition to standard immunosuppressive treatment. Mod Rheumatol. 2015;27:1–5.

    Google Scholar 

  38. 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. 2012;51:1563–70.

  39. Sato S, Kuwana M, Fujita T, Suzuki Y. Anti-CADM-140/MDA5 autoantibody titer correlates with disease activity and predicts disease outcome in patients with dermatomyositis and rapidly progressive interstitial lung disease. Mod Rheumatol. 2013;23:496–502.

    Article  CAS  PubMed  Google Scholar 

  40. Muro Y, Sugiura K, Akiyama M. Limitations of a single-point evaluation of anti-MDA5 antibody, ferritin, and IL-18 in predicting the prognosis of interstitial lung disease with anti-MDA5 antibody-positive dermatomyositis. Clin Rheumatol. 2013;32:395–8.

    Article  PubMed  Google Scholar 

  41. Hall JC, et al. Anti-melanoma differentiation-associated protein 5-associated dermatomyositis: expanding the clinical spectrum. Arthritis Care Res. (Hoboken). 2013;65:1307–15.

    Article  CAS  Google Scholar 

  42. Alexanderson H, Munters LA, Dastmalchi M, Loell I, Heimburger M, Opava CH, et al. Resistive home exercise in patients with recent-onset polymyositis and dermatomyositis—a randomized controlled single-blinded study with a 2-year followup. J Rheumatol. 2014;41:1124–32.

  43. Alemo Munters L, Dastmalchi M, Katz A, Esbjörnsson M, Loell I, Hanna B, et al. Improved exercise performance and increased aerobic capacity after endurance training of patients with stable polymyositis and dermatomyositis. Arthritis Res Ther. 2013;15:R83.

  44. Spruit, M. A., Singh S.J., Garvey C., ZuWallack R., Nici L., Rochester C., Hill K., Holland A.E., Lareau S.C., Man W.D., Pitta F., Sewell L., Raskin J., Bourbeau J., Crouch R., Franssen F.M., Casaburi R., Vercoulen J.H., Vogiatzis I., Gosselink R., Clini E.M., Effing T.W., Maltais F., van der Palen J., Troosters T., Janssen D.J., Collins E., Garcia-Aymerich J., Brooks D., Fahy B.F., Puhan M.A., Hoogendoorn M., Garrod R., Schols A.M., Carlin B., Benzo R., Meek P., Morgan M., Rutten-van Mölken M., Ries A.L., Make B., Goldstein R.S., Dowson C.A., Brozek J.L., Donner C.F., Wouters E.F., ATS/ERS Task Force on Pulmonary Rehabilitation. An official American Thoracic Society/European Respiratory Society statement: key concepts and advances in pulmonary rehabilitation. Am J Respir Crit Care Med 188, e13–e64 (2013).

  45. Dowman L, Hill CJ, Holland AE. In Cochrane Database of Systematic Reviews (ed. Holland, A. E.) CD006322 (John Wiley & Sons, Ltd, 2014). https://doi.org/10.1002/14651858.CD006322.pub3.

  46. Mecoli CA, Saylor D, Gelber AC, Christopher-Stine L. Pneumocystis jiroveci pneumonia in rheumatic disease: a 20-year single-centre experience. Clin Exp Rheumatol. 35:671–3.

  47. Buckley L, et al. American College of Rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res (Hoboken). 2017;69(2017):1095–110.

    Article  Google Scholar 

  48. Mittoo S, Frankel S, LeSage D, Strand V, Shah AA, Christopher-Stine L, et al. Patient perspectives in OMERACT provide an anchor for future metric development and improved approaches to healthcare delivery in connective tissue disease related interstitial lung disease (CTD-ILD). Curr Respir Med Rev. 2015;11(2):175–83.

    Article  PubMed  PubMed Central  Google Scholar 

  49. 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(11):2168–71.

  50. Chen F, Lu X, Shu X, Peng Q, Tian X, Wang G. Predictive value of serum markers for the development of interstitial lung disease in patients with polymyositis and dermatomyositis: a comparative and prospective study. Intern Med J. 2015;45:641–7.

    Article  CAS  PubMed  Google Scholar 

  51. 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  PubMed  Google Scholar 

  52. Obert J, Freynet O, Nunes H, Brillet PY, Miyara M, Dhote R, et al. Outcome and prognostic factors in a French cohort of patients with myositis-associated interstitial lung disease. Rheumatol Int. 2016;36:1727–35.

  53. Ameye H, Ruttens D, Benveniste O, Verleden GM, Wuyts WA. Is lung transplantation a valuable therapeutic option for patients with pulmonary polymyositis? Experiences from the Leuven Transplant Cohort. Transplant Proc. 2014;46:3147–53.

  54. Takada T, et al. Clinical features of polymyositis/dermatomyositis with steroid-resistant interstitial lung disease. Intern Med. 1998;37:669–73.

    Article  CAS  PubMed  Google Scholar 

  55. 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  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Rheumatology, Johns Hopkins University School of Medicine, 5200 Eastern Ave, Mason F. Lord, Center Tower; Suite 4100, Baltimore, MD, 21224, USA

    Christopher A. Mecoli & Lisa Christopher-Stine

Authors
  1. Christopher A. Mecoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lisa Christopher-Stine
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lisa Christopher-Stine.

Ethics declarations

Conflict of Interest

Dr. Christopher-Stine reports personal fees from Mallinckrodt, personal fees from Medimmune, and personal fees from OptionCare, during the conduct of the study. In addition, Dr. Christopher-Stine has a patent to Inova Diagnostics with royalties paid.

Dr. Mecoli has nothing to disclose.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Inflammatory Muscle Disease

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mecoli, C.A., Christopher-Stine, L. Management of Interstitial Lung Disease in Patients With Myositis Specific Autoantibodies. Curr Rheumatol Rep 20, 27 (2018). https://doi.org/10.1007/s11926-018-0731-7

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11926-018-0731-7

Keywords

Search

Navigation