Skip to main content

Advertisement

SpringerLink
Log in

Long-term pulmonary outcomes and mortality in idiopathic inflammatory myopathies associated with interstitial lung disease

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Objective

To study prognostic factors in different types of idiopathic inflammatory myopathies (IIM) associated with interstitial lung disease (ILD).

Patients and methods

Multicenter retrospective study of a Spanish cohort of patients diagnosed with IIM. Patients were classified into four categories: polymyositis (PM), dermatomyositis (DM), antisynthetase syndrome (ASS), and overlap myositis (OM). Sociodemographic data, clinical characteristics, antibodies, and treatments were collected. Cox regression models were calculated to identify factors associated with mortality, the necessity for long-term oxygen therapy (LTOT), and deterioration in respiratory function tests (RFT).

Results

The number of patients included was 478, of whom 112 (23.4%) suffered from ILD: 17% PM, 16% DM, 45% ASS, and 22% OM. Factors associated with mortality in the multivariate analysis were clinically meaningful progression of ILD after 3 months (CMP 3m) (hazard ratio (HR) 9.48, p = 0.005), severe infections (HR 6.41, p = 0.016), heliotrope erythema (HR 31.1, p = 0.002), delay in diagnosis (HR 1.29; p = 0.011), and Raynaud’s phenomenon (HR 11.9, p = 0.007). However, being female (HR 0.19, p = 0.044) and positivity solely for ANAs (HR 0.08, p = 0.008) presented a protective effect. CMP 3m (HR 22.7, p = 0.027) was associated with the need for LTOT, while basal aldolase (HR 0.90; p = 0.049) had a protective effect. Likewise, joint manifestations (HR 0.04, p = 0.034) were shown to reduce risk of deterioration in RFT.

Conclusions

CMP 3m, severe infections, delay in diagnosis, heliotrope erythema, and Raynaud’s phenomenon were identified as factors of poor prognosis in different IIM associated with ILD.

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

Fig. 1

Similar content being viewed by others

References

  1. Hallowell RW, Ascherman DP, Danoff SK (2014) Pulmonary manifestations of polymyositis/dermatomyositis. Seminars in respiratory and critical care medicine 35(2):239–248

    Article  PubMed  Google Scholar 

  2. Nuno-Nuno L, Joven BE, Carreira PE et al (2017) Mortality and prognostic factors in idiopathic inflammatory myositis: a retrospective analysis of a large multicenter cohort of Spain. Rheumatol Int 37(11):1853–1861

    Article  PubMed  Google Scholar 

  3. Yamasaki Y, Yamada H, Ohkubo M et al (2011) Longterm survival and associated risk factors in patients with adult-onset idiopathic inflammatory myopathies and amyopathic dermatomyositis: experience in a single institute in Japan. J Rheumatol 38(8):1636–1643

    Article  PubMed  CAS  Google Scholar 

  4. Dobloug GC, Svensson J, Lundberg IE, Holmqvist M (2018) Mortality in idiopathic inflammatory myopathy: results from a Swedish nationwide population-based cohort study. Ann Rheum Dis 77(1):40–47

    Article  PubMed  Google Scholar 

  5. Tanizawa K, Handa T, Nakashima R, Kubo T, Hosono Y, Aihara K, Ikezoe K, Watanabe K, Taguchi Y, Hatta K, Oga T, Chin K, Nagai S, Mimori T, Mishima M (2013) The prognostic value of HRCT in myositis-associated interstitial lung disease. Respir Med 107(5):745–752

    Article  PubMed  Google Scholar 

  6. Moghadam-Kia S, Oddis CV, Sato S, Kuwana M, Aggarwal R (2016) Anti-melanoma differentiation-associated gene 5 is associated with rapidly progressive lung disease and poor survival in US patients with amyopathic and myopathic dermatomyositis. Arthritis care & research 68(5):689–694

    Article  CAS  Google Scholar 

  7. Fujisawa T, Hozumi H, Kono M, Enomoto N, Hashimoto D, Nakamura Y, Inui N, Yokomura K, Koshimizu N, Toyoshima M, Shirai T, Yasuda K, Hayakawa H, Suda T (2014) Prognostic factors for myositis-associated interstitial lung disease. PLoS One 9(6):e98824

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Kurita T, Yasuda S, Amengual O, Atsumi T (2015) The efficacy of calcineurin inhibitors for the treatment of interstitial lung disease associated with polymyositis/dermatomyositis. Lupus 24(1):3–9

    Article  PubMed  CAS  Google Scholar 

  9. Isoda K, Takeuchi T, Kotani T et al (2014) Pre-treatment ferritin level and alveolar-arterial oxygen gradient can predict mortality rate due to acute/subacute interstitial pneumonia in dermatomyositis treated by cyclosporine a/glucocorticosteroid combination therapy: a case control study [corrected]. PLoS One 9(2):e89610

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Shi J, Li S, Yang H, Zhang Y, Peng Q, Lu X, Wang G (2017) Clinical profiles and prognosis of patients with distinct antisynthetase autoantibodies. J Rheumatol 44(7):1051–1057

    Article  PubMed  CAS  Google Scholar 

  11. Zamora AC, Hoskote SS, Abascal-Bolado B, White D, Cox CW, Ryu JH, Moua T (2016) Clinical features and outcomes of interstitial lung disease in anti-Jo-1 positive antisynthetase syndrome. Respir Med 118:39–45

    Article  PubMed  Google Scholar 

  12. Bohan A, Peter JB (1975) Polymyositis and dermatomyositis (first of two parts). N Engl J Med 292(7):344–347

    Article  PubMed  CAS  Google Scholar 

  13. Bohan A, Peter JB (1975) Polymyositis and dermatomyositis (second of two parts). N Engl J Med 292(8):403–407

    Article  PubMed  CAS  Google Scholar 

  14. Tanimoto K, Nakano K, Kano S et al (1995) Classification criteria for polymyositis and dermatomyositis. J Rheumatol 22(4):668–674

    PubMed  CAS  Google Scholar 

  15. Arnett FC, Edworthy SM, Bloch DA et al (1998) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31(3):315–324

    Article  Google Scholar 

  16. (1980) Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Arthritis Rheum 23(5):581–590

  17. Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40(9):1725

    Article  PubMed  CAS  Google Scholar 

  18. Alarcon-Segovia D, Cardiel MH (1989) Comparison between 3 diagnostic criteria for mixed connective tissue disease. Study of 593 patients. The Journal of rheumatology 16(3):328–334

    PubMed  CAS  Google Scholar 

  19. Fox RI, Robinson CA, Curd JG, Kozin F, Howell FV (1986) Sjogren's syndrome. Proposed criteria for classification. Arthritis Rheum 29(5):577–585

    Article  PubMed  CAS  Google Scholar 

  20. Nuno L, Joven B, Carreira P et al (2017) Multicenter registry on inflammatory myositis from the Rheumatology Society in Madrid, Spain: descriptive analysis. Reumatologia clinica 13(6):331–337

    Article  PubMed  Google Scholar 

  21. Khanna D, Mittoo S, Aggarwal R, Proudman SM, Dalbeth N, Matteson EL, Brown K, Flaherty K, Wells AU, Seibold JR, Strand V (2015) Connective tissue disease-associated interstitial lung diseases (CTD-ILD) - report from OMERACT CTD-ILD working group. J Rheumatol 42(11):2168–2171

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Zhang L, Wu G, Gao D, Liu G, Pan L, Ni L, Li Z, Wang Q (2016) Factors associated with interstitial lung disease in patients with polymyositis and dermatomyositis: a systematic review and meta-analysis. PLoS One 11(5):e0155381

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Fujisawa T, Hozumi H, Kono M, Enomoto N, Nakamura Y, Inui N, Nakashima R, Imura Y, Mimori T, Suda T (2017) Predictive factors for long-term outcome in polymyositis/dermatomyositis-associated interstitial lung diseases. Respir Investig 55(2):130–137

    Article  PubMed  Google Scholar 

  24. Tada Y, Suematsu E, Ueda A et al (2012) Clinical factors to predict a poor prognosis and refractory disease in patients with polymyositis and dermatomyositis associated with interstitial lung disease. Clin Exp Rheumatol 30(3):450

    PubMed  CAS  Google Scholar 

  25. Sugiyama Y, Yoshimi R, Tamura M, Takeno M, Kunishita Y, Kishimoto D, Yoshioka Y, Kobayashi K, Takase-Minegishi K, Watanabe T, Hamada N, Nagai H, Tsuchida N, Soejima Y, Nakano H, Kamiyama R, Uehara T, Kirino Y, Sekiguchi A, Ihata A, Ohno S, Nagaoka S, Nakajima H (2018) The predictive prognostic factors for polymyositis/dermatomyositis-associated interstitial lung disease. Arthritis research & therapy 20(1):7

    Article  CAS  Google Scholar 

  26. Cavagna L, Nuno L, Scire CA et al (2015) Clinical spectrum time course in anti Jo-1 positive antisynthetase syndrome: results from an international retrospective multicenter study. Medicine 94(32):e1144

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Obert J, Freynet O, Nunes H, Brillet PY, Miyara M, Dhote R, Valeyre D, Naccache JM (2016) Outcome and prognostic factors in a French cohort of patients with myositis-associated interstitial lung disease. Rheumatol Int 36(12):1727–1735

    Article  PubMed  Google Scholar 

  28. Trallero-Araguas E, Grau-Junyent JM, Labirua-Iturburu A et al (2016) Clinical manifestations and long-term outcome of anti-Jo1 antisynthetase patients in a large cohort of Spanish patients from the GEAS-IIM group. Semin Arthritis Rheum 46(2):225–231

    Article  PubMed  CAS  Google Scholar 

  29. Chen F, Wang D, Shu X, Nakashima R, Wang G (2012) Anti-MDA5 antibody is associated with a/SIP and decreased T cells in peripheral blood and predicts poor prognosis of ILD in Chinese patients with dermatomyositis. Rheumatol Int 32(12):3909–3915

    Article  PubMed  CAS  Google Scholar 

  30. Hoshino K, Muro Y, Sugiura K, Tomita Y, Nakashima R, Mimori T (2010) Anti-MDA5 and anti-TIF1-gamma antibodies have clinical significance for patients with dermatomyositis. Rheumatology (Oxford, England) 49(9):1726–1733

    Article  CAS  Google Scholar 

  31. Fujikawa K, Kawakami A, Kaji K et al (2009) Association of distinct clinical subsets with myositis-specific autoantibodies towards anti-155/140-kDa polypeptides, anti-140-kDa polypeptides, and anti-aminoacyl tRNA synthetases in Japanese patients with dermatomyositis: a single-centre, cross-sectional study. Scand J Rheumatol 38(4):263–267

    Article  PubMed  CAS  Google Scholar 

  32. Labrador-Horrillo M, Martinez MA, Selva-O’Callaghan A et al (2014) Anti-MDA5 antibodies in a large Mediterranean population of adults with dermatomyositis. J Immunol Res 2014:290797

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Mejia M, Herrera-Bringas D, Perez-Roman DI et al (2017) Interstitial lung disease and myositis-specific and associated autoantibodies: clinical manifestations, survival and the performance of the new ATS/ERS criteria for interstitial pneumonia with autoimmune features (IPAF). Respir Med 123:79–86

    Article  PubMed  Google Scholar 

  34. Ha YJ, Hur J, Go DJ, Kang EH, Park JK, Lee EY, Shin K, Lee EB, Song YW, Lee YJ (2018) Baseline peripheral blood neutrophil-to-lymphocyte ratio could predict survival in patients with adult polymyositis and dermatomyositis: a retrospective observational study. PLoS One 13(1):e0190411

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Pinal-Fernandez I, Casal-Dominguez M, Huapaya JA, Albayda J, Paik JJ, Johnson C, Silhan L, Christopher-Stine L, Mammen AL, Danoff SK (2017) 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 (Oxford, England) 56(6):999–1007

    Article  CAS  Google Scholar 

  36. Marie I, Hatron PY, Dominique S, Cherin P, Mouthon L, Menard JF, Levesque H, Jouen F (2012) Short-term and long-term outcome of anti-Jo1-positive patients with anti-Ro52 antibody. Semin Arthritis Rheum 41(6):890–899

    Article  PubMed  CAS  Google Scholar 

  37. Amaral Silva M, Cogollo E, Isenberg DA (2016) Why do patients with myositis die? A retrospective analysis of a single-centre cohort. Clin Exp Rheumatol 34(5):820–826

    PubMed  Google Scholar 

  38. Airio A, Kautiainen H, Hakala M (2006) Prognosis and mortality of polymyositis and dermatomyositis patients. Clin Rheumatol 25(2):234–239

    Article  PubMed  CAS  Google Scholar 

  39. Huber AM, Mamyrova G, Lachenbruch PA, Lee JA, Katz JD, Targoff IN, Miller FW, Rider LG, for the Childhood Myositis Heterogeneity Collaborative Study Group (2014) Early illness features associated with mortality in the juvenile idiopathic inflammatory myopathies. Arthritis care & research 66(5):732–740

    Article  Google Scholar 

  40. Tanizawa K, Handa T, Nakashima R, Kubo T, Hosono Y, Watanabe K, Aihara K, Ikezoe K, Sokai A, Nakatsuka Y, Taguchi Y, Hatta K, Noma S, Kobashi Y, Yoshizawa A, Oga T, Hirai T, Chin K, Nagai S, Izumi T, Mimori T, Mishima M (2017) The long-term outcome of interstitial lung disease with anti-aminoacyl-tRNA synthetase antibodies. Respir Med 127:57–64

    Article  PubMed  Google Scholar 

Download references

Funding

This study was partially funded with a grant from MSD (MSD-SORCOM). The SORCOM and MSD had no role in the extraction and interpretation of data or in the draft of the manuscript. All authors had full access to all the data included in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Author information

Authors and Affiliations

  1. Rheumatology Department, Hospital Universitario Infanta Sofía, Universidad Europea, Paseo de Europa 34, 28702, Madrid, San Sebastián de los Reyes, Spain

    Tatiana Cobo-Ibáñez & Santiago Muñoz-Fernández

  2. Rheumatology Department, Hospital General Universitario Gregorio Marañón, Dr. Esquerdo 46, 28007, Madrid, Spain

    Francisco-Javier López-Longo

  3. Rheumatology Department, Hospital Universitario 12 de Octubre, Avda. Córdoba s/n, 28041, Madrid, Spain

    Beatriz Joven & Patricia E. Carreira

  4. Rheumatology Department, Hospital Universitario Ramón y Cajal, Ctra. de Colmenar Viejo Km. 9,100, 28034, Madrid, Spain

    Valentina Maldonado-Romero & Carmen Larena-Grijalba

  5. Rheumatology Department, Hospital Universitario de la Princesa, Diego de León 62, 28006, Madrid, Spain

    Irene Llorente Cubas & Eva Tomero Muriel

  6. Rheumatology Department, Hospital Universitario Puerta de Hierro Majadahonda, Manuel de Falla 1, 28220, Madrid, Majadahonda, Spain

    Carmen Barbadillo Mateos

  7. Rheumatology Department, Hospital Universitario HM Sanchinarro, Oña 10, 28050, Madrid, Spain

    Paloma García de la Peña Lefebvre & Alejandro Gomez-Gomez

  8. Rheumatology Department, Hospital Universitario Príncipe de Asturias, Alcalá-Meco s/n, 28805, Madrid, Alcalá de Henares, Spain

    Laura Barrio Nogal & Ana Pérez

  9. Rheumatology Department, Hospital Universitario Fundación Alcorcon, Budapest s/n, 28922, Madrid, Spain

    Raquel Almodovar

  10. Rheumatology Department, Hospital Universitario Infanta Leonor, Gran Vía del Este 80, 28031, Madrid, Spain

    Leticia Lojo

  11. Rheumatology Department, Hospital Infantil Universitario Niño Jesús, Avenida Menéndez Pelayo 65, 28009, Madrid, Spain

    Lucía Ruiz-Gutiérrez & Juan Carlos López-Robledillo

  12. Instituto de Salud Musculoesquelética (InMusc), Conde de la Cimera 6, Oficina C, 28040, Madrid, Spain

    María Jesús García de Yébenes

  13. Rheumatology Department, Hospital Universitario La Paz, Paseo de la Castellana 261, 28046, Madrid, Spain

    Laura Nuño-Nuño

Authors
  1. Tatiana Cobo-Ibáñez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Francisco-Javier López-Longo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Beatriz Joven
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Patricia E. Carreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Santiago Muñoz-Fernández
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Valentina Maldonado-Romero
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Carmen Larena-Grijalba
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Irene Llorente Cubas
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Eva Tomero Muriel
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Carmen Barbadillo Mateos
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Paloma García de la Peña Lefebvre
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Alejandro Gomez-Gomez
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Laura Barrio Nogal
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Ana Pérez
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Raquel Almodovar
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Leticia Lojo
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Lucía Ruiz-Gutiérrez
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Juan Carlos López-Robledillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. María Jesús García de Yébenes
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Laura Nuño-Nuño
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tatiana Cobo-Ibáñez.

Ethics declarations

Disclosures

None

Ethical approval

This study was approved by the ethics committees of the participant hospitals and carried out in compliance with the Helsinki Declaration.

Electronic supplementary material

ESM 1

(DOCX 32 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cobo-Ibáñez, T., López-Longo, FJ., Joven, B. et al. Long-term pulmonary outcomes and mortality in idiopathic inflammatory myopathies associated with interstitial lung disease. Clin Rheumatol 38, 803–815 (2019). https://doi.org/10.1007/s10067-018-4353-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-018-4353-2

Keywords

Search

Navigation