Skip to main content

Advertisement

SpringerLink
Log in

Rheumatoid arthritis–associated interstitial lung disease: an overview of epidemiology, pathogenesis and management

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

Abstract

Interstitial lung disease (ILD) accounts for the major cause of morbidity and mortality in rheumatoid arthritis (RA). However, little is known of the pathogenesis, diagnosis and treatment of RA-associated ILD. In this review, we describe our present understanding and ongoing research in RA-ILD. Its aetiology does appear to associate with anti-cyclic citrullinated peptide antibodies, MUC5B mutation and smoking. Another focus of this article is on recent diagnostic methods in RA-ILD. Compared with other methods, high-resolution computed tomography (HRCT) imaging is a main method for the evaluation of ILD in RA patients. Pulmonary function is better suited for assessing progression. An important topic relates to therapeutic intervention. Disease-modifying anti-rheumatic drugs (DMARDs) in RA lack strong evidence in the onset or worsening of ILD. The available literature support that methotrexate, leflunomide, abatacept and rituximab play beneficial roles in the prevention and treatment of RA-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
Fig. 2

Similar content being viewed by others

Data availability

Not applicable.

References

  1. Turesson C (2013) Extra-articular rheumatoid arthritis. Curr Opin Rheumatol 25:360–366

    Article  CAS  PubMed  Google Scholar 

  2. Lee HK, Kim DS, Yoo B, Seo JB, Rho JY, Colby TV, Kitaichi M (2005) Histopathologic pattern and clinical features of rheumatoid arthritis-associated interstitial lung disease. Chest 127:2019–2027

    Article  PubMed  Google Scholar 

  3. Suda T (2016) Up-to-date information on rheumatoid arthritis-associated interstitial lung disease. Clin Med Insights Circ Respir Pulm Med 9:155–162

    PubMed  PubMed Central  Google Scholar 

  4. Bongartz T, Nannini C, Medina-Velasquez YF, Achenbach SJ, Crowson CS, Ryu JH, Vassallo R, Gabriel SE, Matteson EL (2010) Incidence and mortality of interstitial lung disease in rheumatoid arthritis: a population-based study. Arthritis Rheum 62:1583–1591

    Article  PubMed  PubMed Central  Google Scholar 

  5. Turesson C, O'Fallon WM, Crowson CS, Gabriel SE, Matteson EL (2002) Occurrence of extraarticular disease manifestations is associated with excess mortality in a community based cohort of patients with rheumatoid arthritis. J Rheumatol 29:62–67

    PubMed  Google Scholar 

  6. Bilgici A, Ulusoy H, Kuru O, Çelenk Ç, Ünsal M, Danacı M (2005) Pulmonary involvement in rheumatoid arthritis. Rheumatol Int 25:429–435

    Article  PubMed  Google Scholar 

  7. Mori S, Cho I, Koga Y, Sugimoto M (2008) Comparison of pulmonary abnormalities on high-resolution computed tomography in patients with early versus longstanding rheumatoid arthritis. J Rheumatol 35:1513–1521

    PubMed  Google Scholar 

  8. Dawson JK, Fewins HE, Desmond J, Lynch MP, Graham DR (2001) Fibrosing alveolitis in patients with rheumatoid arthritis as assessed by high resolution computed tomography, chest radiography, and pulmonary function tests. Thorax 56:622–627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Habib HM, Eisa AA, Arafat WR, Marie MA (2011) Pulmonary involvement in early rheumatoid arthritis patients. Clin Rheumatol 30:217–221

    Article  PubMed  Google Scholar 

  10. Gabbay E, Tarala R, Will R et al (1997) Interstitial lung disease in recent onset rheumatoid arthritis. Am J Respir Crit Care Med 156:528–535

    Article  CAS  PubMed  Google Scholar 

  11. Roos Ljungberg K, Joshua V, Skogh T et al. (2019) Secretory anti-citrullinated protein antibodies in serum associate with lung involvement in early rheumatoid arthritis. Rheumatology (Oxford)

  12. Robles-Perez A, Luburich P, Rodriguez-Sanchon B, Dorca J, Nolla JM, Molina-Molina M, Narvaez-Garcia J (2016) Preclinical lung disease in early rheumatoid arthritis. Chron Respir Dis 13:75–81

    Article  PubMed  PubMed Central  Google Scholar 

  13. Hyldgaard C, Hilberg O, Pedersen AB, Ulrichsen SP, Løkke A, Bendstrup E, Ellingsen T (2017) A population-based cohort study of rheumatoid arthritis-associated interstitial lung disease: comorbidity and mortality. Ann Rheum Dis 76:1700–1706

    Article  PubMed  Google Scholar 

  14. McInnes IB, Schett G (2011) The pathogenesis of Rheumatois arthritis. NEJM 365:2205–2219

    Article  CAS  PubMed  Google Scholar 

  15. Bongartz T, Cantaert T, Atkins SR, Harle P, Myers JL, Turesson C, Ryu JH, Baeten D, Matteson EL (2007) Citrullination in extra-articular manifestations of rheumatoid arthritis. Rheumatology 46:70–75

    Article  CAS  PubMed  Google Scholar 

  16. Paulin F, Doyle TJ, Fletcher EA, Ascherman DP, Rosas IO (2015) Rheumatoid arthritis-associated interstitial lung disease and idiopathic pulmonary fibrosis:shared mechanistic and phenotypic traits suggest overlapping disease mechanisms. Rev Investig Clin 67:280–286

    CAS  Google Scholar 

  17. Ytterberg AJ, Joshua V, Reynisdottir G et al (2014) Shared immunological targets in the lungs and joints of patients with rheumatoid arthritis: identification and validation. Ann Rheum Dis 74:1772–1777

    Article  PubMed  CAS  Google Scholar 

  18. Correia CS, Briones MR, Guo R, Ostrowski RA (2019) Elevated anti-cyclic citrullinated peptide antibody titer is associated with increased risk for interstitial lung disease. Clin Rheumatol 38:1201–1206

    Article  PubMed  PubMed Central  Google Scholar 

  19. Jearn LH, Kim TY (2012) Level of anticitrullinated peptide/protein antibody is not associated with lung diseases in rheumatoid arthritis. J Rheumatol 39:1493–1494

    Article  PubMed  Google Scholar 

  20. Korkmaz C, Us T, Kasifoglu T et al (2006) Anti-cyclic citrullinated peptide [CCP] antibodies in patients with long-standing rheumatoid arthritis and their relationship with extra-articular manifestations. Clin Biochem 39:961–965

    Article  CAS  PubMed  Google Scholar 

  21. Inui N, Enomoto N, Suda T, Kageyama Y, Watanabe H, Chida K (2008) Anti-cyclic citrullinated peptide antibodies in lung diseases associated with rheumatoid arthritis. Clin Biochem 41:1074–1077

    Article  CAS  PubMed  Google Scholar 

  22. Zhu J, Zhou Y, Chen X, Li J (2014) A metaanalysis of the increased risk of rheumatoid arthritis-related pulmonary disease as a result of serum anticitrullinated protein antibody positivity. J Rheumatol 41:1282–1289

    Article  PubMed  Google Scholar 

  23. Young HW, Williams OW, Chandra D et al (2007) Central role of Muc5ac expression in mucous metaplasia and its regulation by conserved 5′ elements. Am J Respir Cell Mol Biol 37:273–290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Juge PA, Lee JS, Ebstein E, Furukawa H, Dobrinskikh E, Gazal S, Kannengiesser C, Ottaviani S, Oka S, Tohma S, Tsuchiya N, Rojas-Serrano J, González-Pérez MI, Mejía M, Buendía-Roldán I, Falfán-Valencia R, Ambrocio-Ortiz E, Manali E, Papiris SA, Karageorgas T, Boumpas D, Antoniou K, van Moorsel CHM, van der Vis J, de Man YA, Grutters JC, Wang Y, Borie R, Wemeau-Stervinou L, Wallaert B, Flipo RM, Nunes H, Valeyre D, Saidenberg-Kermanac’h N, Boissier MC, Marchand-Adam S, Frazier A, Richette P, Allanore Y, Sibilia J, Dromer C, Richez C, Schaeverbeke T, Lioté H, Thabut G, Nathan N, Amselem S, Soubrier M, Cottin V, Clément A, Deane K, Walts AD, Fingerlin T, Fischer A, Ryu JH, Matteson EL, Niewold TB, Assayag D, Gross A, Wolters P, Schwarz MI, Holers M, Solomon JJ, Doyle T, Rosas IO, Blauwendraat C, Nalls MA, Debray MP, Boileau C, Crestani B, Schwartz DA, Dieudé P (2018) MUC5B promoter variant and rheumatoid arthritis with interstitial lung disease. N Engl J Med 379:2209–2219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Helling BA, Gerber AN, Kadiyala V, Sasse SK, Pedersen BS, Sparks L, Nakano Y, Okamoto T, Evans CM, Yang IV, Schwartz DA (2017) Regulation of MUC5B expression in idiopathic pulmonary fibrosis. Am J Respir Cell Mol Biol 57:91–99

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Seibold MA, Wise AL, Speer MC, Steele MP, Brown KK, Loyd JE, Fingerlin TE, Zhang W, Gudmundsson G, Groshong SD, Evans CM, Garantziotis S, Adler KB, Dickey BF, du Bois RM, Yang IV, Herron A, Kervitsky D, Talbert JL, Markin C, Park J, Crews AL, Slifer SH, Auerbach S, Roy MG, Lin J, Hennessy CE, Schwarz MI, Schwartz DA (2011) A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med 364:1503–1512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zhang Y, Noth I, Garcia JG et al (2011) A variant in the promoter of MUC5B and idiopathic pulmonary fibrosis. N Engl J Med 364:1576–1577

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Juge PA, Borie R, Kannengiesser C et al (2017) Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease and familial pulmonary fibrosis. Eur Respir J 49:1602314

    Article  PubMed  Google Scholar 

  29. Peljto AL, Zhang Y, Fingerlin TE, Ma SF, Garcia JGN, Richards TJ, Silveira LJ, Lindell KO, Steele MP, Loyd JE, Gibson KF, Seibold MA, Brown KK, Talbert JL, Markin C, Kossen K, Seiwert SD, Murphy E, Noth I, Schwarz MI, Kaminski N, Schwartz DA (2013) Association between the MUC5B promoter polymorphism and survival in patients with idiopathic pulmonary fibrosis. JAMA 309:2232–2239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Adegunsoye A (2019) MUC5B promoter variant: genomic fingerprint for early identification of undiagnosed pulmonary fibrosis. Thorax 74:1111–1112

    Article  PubMed  Google Scholar 

  31. Charles PJ, Sweatman MC, Markwick JR, Maini RN (1991) HLA-B40: a marker for susceptibility to lung disease in rheumatoid arthritis. Dis Markers 9:97–101

    CAS  PubMed  Google Scholar 

  32. Scott TE, Wise RA, Hochberg MC, Wigley FM (1987) HLA-DR4 and pulmonary dysfunction in rheumatoid arthritis. Am J Med 82:765–771

    Article  CAS  PubMed  Google Scholar 

  33. Hillarby MC, McMahon MJ, Grennan DM et al (1993) HLA associations in subjects with rheumatoid arthritis and bronchiectasis but not with other pulmonary complications of rheumatoid disease. Br J Rheumatol 32:794–797

    Article  CAS  PubMed  Google Scholar 

  34. Sugiyama Y, Ohno S, Kano S et al (1994) Diffuse panbronchiolitis and rheumatoid arthritis: a possible correlation with HLA-B54. Intern Med 33:612–614

    Article  CAS  PubMed  Google Scholar 

  35. Gochuico BR, Avila NA, Chow CK, Novero LJ, Wu HP, Ren P, MacDonald S, Travis WD, Stylianou MP, Rosas IO (2008) Progressive preclinical interstitial lung disease in rheumatoid arthritis. Arch Intern Med 168:159–166

    Article  CAS  PubMed  Google Scholar 

  36. Albano SA, Santana-Sahagun E, Weisman MH (2001) Cigarette smoking and rheumatoid arthritis. Semin Arthritis Rheum 31:146–159

    Article  CAS  PubMed  Google Scholar 

  37. Matsuo T, Hashimoto M, Ito I, Kubo T, Uozumi R, Furu M, Ito H, Fujii T, Tanaka M, Terao C, Kono H, Mori M, Hamaguchi M, Yamamoto W, Ohmura K, Morita S, Mimori T (2019) Interleukin-18 is associated with the presence of interstitial lung disease in rheumatoid arthritis: a cross-sectional study. Scand J Rheumatol 48:87–94

    Article  CAS  PubMed  Google Scholar 

  38. Doyle TJ, Patel AS, Hatabu H, Nishino M, Wu G, Osorio JC, Golzarri MF, Traslosheros A, Chu SG, Frits ML, Iannaccone CK, Koontz D, Fuhrman C, Weinblatt ME, el-Chemaly SY, Washko GR, Hunninghake GM, Choi AMK, Dellaripa PF, Oddis CV, Shadick NA, Ascherman DP, Rosas IO (2015) Detection of rheumatoid arthritis-interstitial lung disease is enhanced by serum biomarkers. Am J Respir Crit Care Med 191:1403–1412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Wang T, Zheng XJ, Liang BM, Liang ZA (2015) Clinical features of rheumatoid arthritis-associated interstitial lung disease. Sci Rep 5:14897

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zhang Y, Li H, Wu N, Dong X, Zheng Y (2017) Retrospective study of the clinical characteristics and risk factors of rheumatoid arthritis-associated interstitial lung disease. Clin Rheumatol 36:817–823

    Article  PubMed  Google Scholar 

  41. Assayag D, Elicker BM, Urbania TH, Colby TV, Kang BH, Ryu JH, King TE, Collard HR, Kim DS, Lee JS (2014) Rheumatoid arthritis-associated interstitial lung disease: radiologic identification of usual interstitial pneumonia pattern. Radiology 270:583–588

    Article  PubMed  PubMed Central  Google Scholar 

  42. Solomon JJ, Ryu JH, Tazelaar HD, Myers JL, Tuder R, Cool CD, Curran-Everett D, Fischer A, Swigris JJ, Brown KK (2013) Fibrosing interstitial pneumonia predicts survival in patients with rheumatoid arthritis-associated interstitial lung disease [RA-ILD]. Respir Med 107:1247–1252

    Article  PubMed  Google Scholar 

  43. Ascherman DP (2010) Interstitial lung disease in rheumatoid arthritis. Curr Rheumatol Rep 12:363–369

    Article  PubMed  Google Scholar 

  44. Kim EJ, Elicker BM, Maldonado F, Webb WR, Ryu JH, van Uden JH, Lee JS, King TE, Collard HR (2010) Usual interstitial pneumonia in rheumatoid arthritis-associated interstitial lung disease. Eur Respir J 35:1322–1132

    Article  CAS  PubMed  Google Scholar 

  45. Rajasekaran BA, Shovlin D, Lord P, Kelly CA (2001) Interstitial lung disease in patients with rheumatoid arthritis: a comparison with cryptogenic fibrosing alveolitis. Rheumatology (Oxford) 40:1022–1025

    Article  CAS  Google Scholar 

  46. Travis WD, Costabel U, Hansell DM, King te Jr, Lynch DA, Nicholson AG, Ryerson CJ, Ryu JH, Selman M, Wells AU, Behr J, Bouros D, Brown KK, Colby TV, Collard HR, Cordeiro CR, Cottin V, Crestani B, Drent M, Dudden RF, Egan J, Flaherty K, Hogaboam C, Inoue Y, Johkoh T, Kim DS, Kitaichi M, Loyd J, Martinez FJ, Myers J, Protzko S, Raghu G, Richeldi L, Sverzellati N, Swigris J, Valeyre D, ATS/ERS Committee on Idiopathic Interstitial Pneumonias (2013) An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 188:733–748

    Article  PubMed  PubMed Central  Google Scholar 

  47. Katzenstein AL, Mukhopadhyay S, Myers JL (2008) Diagnosis of usual interstitial pneumonia and distinction from other fibrosing interstitial lung diseases. Hum Pathol 39:1562–1581

    Article  PubMed  Google Scholar 

  48. Doyle TJ, Dellaripa PF (2017) Lung manifestations in the rheumatic diseases. Chest 152:1283–1295

    Article  PubMed  PubMed Central  Google Scholar 

  49. Jacob J, Hirani N, van Moorsel CHM et al. (2019) Predicting outcomes in rheumatoid arthritis related interstitial lung disease. Eur Respir J 53(1)

  50. Caiulo VA, Gargani L, Caiulo S, Fisicaro A, Moramarco F, Latini G, Picano E (2011) Lung ultrasound in bronchiolitis: comparison with chest X-ray. Eur J Pediatr 170:1427–1433

    Article  PubMed  Google Scholar 

  51. Doveri M, Frassi F, Consensi A, Vesprini E, Gargani L, Tafuri M, Picano E, Della Rossa A, Delle Sedie A, d'Ascanio A, Giacomelli C, Bazzichi L, Bombardieri S (2008) Ultrasound lung comets: new echographic sign of lung interstitial fibrosis in systemic sclerosis. Reumatismo 60:180–184

    CAS  PubMed  Google Scholar 

  52. Mathis G, Gehmacher O (2001) Lung and pleural ultrasound. Praxis (Bern 1994) 90:681–686

    CAS  Google Scholar 

  53. Volpicelli G, Elbarbary M, Blaivas M et al (2012) International evidence-based recommendations for point-of-care lung ultrasound. Intensive Care Med 38:577–591

    Article  PubMed  Google Scholar 

  54. Wohlgenannt S, Gehmacher O, Gehmacher U, Kopf A, Mathis G (2001) Sonographic findings in interstitial lung diseases. Ultraschall Med 22:27–31

    Article  CAS  PubMed  Google Scholar 

  55. Sperandeo M, Varriale A, Sperandeo G, Filabozzi P, Piattelli ML, Carnevale V, Decuzzi M, Vendemiale G (2009) Transthoracic ultrasound in the evaluation of pulmonary fibrosis: our experience. Ultrasound Med Biol 35:723–729

    Article  PubMed  Google Scholar 

  56. Moazedi-Fuerst FC, Kielhauser SM, Scheidl S et al (2014) Ultrasound screening for interstitial lung disease in rheumatoid arthritis. Clin Exp Rheumatol 32:199–203

    CAS  PubMed  Google Scholar 

  57. Solomon JJ, Chung JH, Cosgrove GP, Demoruelle MK, Fernandez-Perez ER, Fischer A, Frankel SK, Hobbs SB, Huie TJ, Ketzer J, Mannina A, Olson AL, Russell G, Tsuchiya Y, Yunt ZX, Zelarney PT, Brown KK, Swigris JJ (2016) Predictors of mortality in rheumatoid arthritis-associated interstitial lung disease. Eur Respir J 47:588–596

    Article  PubMed  Google Scholar 

  58. Ley B, Collard HR, King TE et al (2011) Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 183:431–440

    Article  PubMed  Google Scholar 

  59. Zamora-Legoff JA, Krause ML, Crowson CS, Ryu JH, Matteson EL (2017) Progressive decline of lung function in rheumatoid arthritis-associated interstitial lung disease. Arthritis Rheumatol 69:542–549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Dawson JK, Fewins HE, Desmond J, Lynch MP, Graham DR (2002) Predictors of progression of HRCT diagnosed fibrosing alveolitis in patients with rheumatoid arthritis. Ann Rheum Dis 61:517–521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Manfredi A, Cassone G, Cerri S et al (2019) Diagnostic accuracy of a velcro sound detector [VECTOR] for interstitial lung disease in rheumatoid arthritis patients: the InSPIRAtE validation study [INterStitial pneumonia in rheumatoid arthritis with an electronic device]. BMC Pulm Med 19:111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Wu EK, Ambrosini RD, Kottmann RM et al. (2019) Reinterpreting evidence of rheumatoid arthritis-associated interstitial lung disease to understand etiology. Curr Rheumatol Rev

  63. Sparks JA, He X, Huang J, Fletcher EA, Zaccardelli A, Friedlander HM, Gill RR, Hatabu H, Nishino M, Murphy DJ, Iannaccone CK, Mahmoud TG, Frits ML, Lu B, Rosas IO, Dellaripa PF, Weinblatt ME, Karlson EW, Shadick NA, Doyle TJ (2019) Rheumatoid arthritis disease activity predicting incident clinically apparent rheumatoid arthritis-associated interstitial lung disease: a prospective cohort study. Arthritis Rheumatol 71:1472–1482

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Paulin F, Mercado JF, Fernández ME, Caro FM, Alberti ML, Fassola LA (2018) Correlation between lung and joint involvement in patients with rheumatoid arthritis and interstitial lung disease: a cross-sectional study. Rev Investig Clin 70:76–81

    CAS  Google Scholar 

  65. Travis WD, Costabel U, Hansell DM, King te Jr, Lynch DA, Nicholson AG, Ryerson CJ, Ryu JH, Selman M, Wells AU, Behr J, Bouros D, Brown KK, Colby TV, Collard HR, Cordeiro CR, Cottin V, Crestani B, Drent M, Dudden RF, Egan J, Flaherty K, Hogaboam C, Inoue Y, Johkoh T, Kim DS, Kitaichi M, Loyd J, Martinez FJ, Myers J, Protzko S, Raghu G, Richeldi L, Sverzellati N, Swigris J, Valeyre D, ATS/ERS Committee on Idiopathic Interstitial Pneumonias (2013) ATS/ERS Committee on idiopathic interstitial pneumonias. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 188:733–748

    Article  PubMed  PubMed Central  Google Scholar 

  66. Lake F, Proudman S (2014) Rheumatoid arthritis and lung disease: from mechanisms to a practical approach. Semin Respir Crit Care Med 35:222–238

    Article  PubMed  Google Scholar 

  67. Kelly C, Saravanan V (2008) Treatment strategies for a rheumatoid arthritis patient with interstitial lung disease. Expert Opin Pharmacother 9:3221–3230

    Article  CAS  PubMed  Google Scholar 

  68. Picchianti Diamanti A, Markovic M, Argento G, Giovagnoli S, Ricci A, Laganà B, D’Amelio R (2017) Therapeutic management of patients with rheumatoid arthritis and associated interstitial lung disease: case report and literature review. Ther Adv Respir Dis 11:64–72

    Article  CAS  PubMed  Google Scholar 

  69. Smolen JS, Landewe R, Breedveld FC et al (2014) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis 73:492–509

    Article  CAS  PubMed  Google Scholar 

  70. Hozumi H, Nakamura Y, Johkoh T, Sumikawa H, Colby TV, Kono M, Hashimoto D, Enomoto N, Fujisawa T, Inui N, Suda T, Chida K (2013) Acute exacerbation in rheumatoid arthritis-associated interstitial lung disease: a retrospective case control study. BMJ Open 3:e003132

    Article  PubMed  PubMed Central  Google Scholar 

  71. McKendry RJ, Dale P (1993) Adverse effects of low dose methotrexate therapy in rheumatoid arthritis. J Rheumatol 20:1850–1856

    CAS  PubMed  Google Scholar 

  72. Hendrick DJ, Spickett GP (2005) Drug-induced lung disease. In: Oxford textbook of medicine, vol 2. Oxford University Press, Oxford, pp 1507–1512

    Google Scholar 

  73. Conway R, Low C, Coughlan RJ, O'Donnell MJ, Carey JJ (2014) Methotrexate and lung disease in rheumatoid arthritis: a meta-analysis of randomized controlled trials. Arthritis Rheumatol 66:803–812

    Article  CAS  PubMed  Google Scholar 

  74. Kiely P, Busby AD, Nikiphorou E et al (2019) Is incident rheumatoid arthritis interstitial lung disease associated with methotrexate treatment? Results from a multivariate analysis in the ERAS and ERAN inception cohorts. BMJ Open 9:e028466

    Article  PubMed  PubMed Central  Google Scholar 

  75. Sawada T, Inokuma S, Sato T, Otsuka T, Saeki Y, Takeuchi T, Matsuda T, Takemura T, Sagawa A, on behalf of the Study Committee for Leflunomide-induced Lung Injury, Japan College of Rheumatology (2009) Leflunomide-induced interstitial lung disease:prevalence and risk factors in Japanese patients with rheumatoid arthritis. Rheumatology (Oxford) 48:1069–1072

    Article  CAS  Google Scholar 

  76. Conway R, Low C, Coughlan RJ, O’Donnell MJ, Carey JJ (2016) Leflunomide use and risk of lung disease in rheumatoid arthritis: a systematic literature review and metaanalysis of randomized controlled trials. J Rheumatol 43:855–860

    Article  PubMed  CAS  Google Scholar 

  77. Perez-Alvarez R, Perez-de-Lis M, Diaz-Lagares C et al (2011) Interstitial lung disease induced or exacerbated by TNF-targeted therapies: analysis of 122 cases. Semin Arthritis Rheum 41:256Y26

    Article  CAS  Google Scholar 

  78. Hadjinicolaou AV, Nisar MK, Bhagat S, Parfrey H, Chilvers ER, Ostor AJK (2011) Non-infectious pulmonary complications of newer biological agents for rheumatic diseases—a systematic literature review. Rheumatology (Oxford) 50:2297–2305

    Article  Google Scholar 

  79. Pearce F, Johnson SR, Courtney P (2012) Interstitial lung disease following certolizumab pegol. Rheumatology (Oxford) 51:578–580

    Article  CAS  Google Scholar 

  80. Koike T, Harigai M, Inokuma S, Ishiguro N, Ryu J, Takeuchi T, Takei S, Tanaka Y, Ito K, Yamanaka H (2011) Postmarketing surveillance of tocilizumab for rheumatoid arthritis in Japan: interim analysis of 3881 patients. Ann Rheum Dis 70:2148–2151

    Article  CAS  PubMed  Google Scholar 

  81. Kurata I, Tsuboi H, Terasaki M, Shimizu M, Toko H, Honda F, Ohyama A, Yagishita M, Osada A, Ebe H, Kawaguchi H, Takahashi H, Hagiwara S, Asashima H, Kondo Y, Matsumoto I, Sumida T (2019) Effect of biological disease-modifying anti-rheumatic drugs on airway and interstitial lung disease in patients with rheumatoid arthritis. Intern Med 58:1703–1712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Fernández-Díaz C, Loricera J, Castañeda S, López-Mejías R, Ojeda-García C, Olivé A, Rodríguez-Muguruza S, Carreira PE, Pérez-Sandoval T, Retuerto M, Cervantes-Pérez EC, Flores-Robles BJ, Hernández-Cruz B, Urruticoechea A, Maíz-Alonso O, Arboleya L, Bonilla G, Hernández-Rodríguez Í, Palma D, Delgado C, Expósito-Molinero R, Ruibal-Escribano A, Álvarez-Rodríguez B, Blanco-Madrigal J, Bernal JA, Vela-Casasempere P, Rodríguez-Gómez M, Fito C, Ortiz-Sanjuán F, Narváez J, Moreno M, López-Corbeto M, Mena-Vázquez N, Aguilera-Cros C, Romero-Yuste S, Ordóñez S, Villa-Blanco I, Gonzélez-Vela MC, Mora-Cuesta V, Palmou-Fontana N, Hernández JL, González-Gay MA, Blanco R (2018) Abatacept in patients with rheumatoid arthritis and interstitial lung disease: a national multicenter study of 63 patients. Semin Arthritis Rheum 48:22–27

    Article  PubMed  CAS  Google Scholar 

  83. Fui A, Bergantini L, Selvi E et al (2019) Rituximab therapy in interstitial lung disease associated with rheumatoid arthritis. Intern Med J 9

  84. Md Yusof MY, Kabia A, Darby M, Lettieri G, Beirne P, Vital EM, Dass S, Emery P (2017) Effect of rituximab on the progression of rheumatoid arthritis-related interstitial lung disease: 10 years’ experience at a single centre. Rheumatology (Oxford) 56:1348–1357

    Article  CAS  Google Scholar 

  85. Hadjinicolaou AV, Nisar MK, Parfrey H, Chilvers ER, Ostor AJK (2012) Non-infectious pulmonary toxicity of rituximab: a systematic review. Rheumatology (Oxford) 51:653–662

    Article  CAS  Google Scholar 

  86. Tanoue LT (1998) Pulmonary manifestations of rheumatoid arthritis. Clin Chest Med 19:667–685

    Article  CAS  PubMed  Google Scholar 

  87. Chang HK, Park W, Ryu DS (2002) Successful treatment of progressive rheumatoid interstitial lung disease with cyclosporine: a case report. J Korean Med Sci 17:270–273

    Article  PubMed  PubMed Central  Google Scholar 

  88. Wallace B, Vummidi D, Khanna D (2016) Management of connective tissue diseases associated interstitial lung disease: a review of the published literature. Curr Opin Rheumatol 28:236–245

    Article  PubMed  PubMed Central  Google Scholar 

  89. Tashkin DP, Roth MD, Clements PJ, Furst DE, Khanna D, Kleerup EC, Goldin J, Arriola E, Volkmann ER, Kafaja S, Silver R, Steen V, Strange C, Wise R, Wigley F, Mayes M, Riley DJ, Hussain S, Assassi S, Hsu VM, Patel B, Phillips K, Martinez F, Golden J, Connolly MK, Varga J, Dematte J, Hinchcliff ME, Fischer A, Swigris J, Meehan R, Theodore A, Simms R, Volkov S, Schraufnagel DE, Scholand MB, Frech T, Molitor JA, Highland K, Read CA, Fritzler MJ, Kim GHJ, Tseng CH, Elashoff RM, Sclerodema Lung Study II Investigators (2016) Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease [SLS II]: a randomised controlled, double-blind, parallel group trial. Lancet Respir Med 4:708–719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Wu C, Lin H, Zhang X (2019) Inhibitory effects of pirfenidone on fibroblast to myofibroblast transition in rheumatoid arthritis-associated interstitial lung disease via the downregulation of activating transcription factor 3 [ATF3]. Int Immunopharmacol 74:105700

    Article  CAS  PubMed  Google Scholar 

  91. Solomon JJ, Danoff SK, Goldberg HJ et al (2019) Trail network. The design and rationale of the Trail1 trial: a randomized double-blind phase 2 clinical trial of Pirfenidone in rheumatoid arthritis-associated interstitial lung disease. Adv Ther 36:3279–3287

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors appreciate all researchers who contribute to the scientific research about RA-ILD. We also extremely grateful to Junwu Dong who gave a lot of suggestions when we prepared for this work.

Funding

The grants from the Wuhan health and Family Planning Commission research projects WG15A02 and WX18 Q31 supported this work.

Author information

Authors and Affiliations

  1. Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 JieFang Road, Wuhan, HuBei, China

    Yujie Dai, Yikai Yu & Shaoxian Hu

  2. Department of Nephrology and Rheumatology, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Yujie Dai

  3. Department of Respiration, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Weina Wang

Authors
  1. Yujie Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Weina Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yikai Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shaoxian Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the preparation and editing of this paper, and they all reviewed and approved the manuscript for submission.

Corresponding authors

Correspondence to Yikai Yu or Shaoxian Hu.

Ethics declarations

Disclosures

None.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

Not applicable

Code availability

Not applicable.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dai, Y., Wang, W., Yu, Y. et al. Rheumatoid arthritis–associated interstitial lung disease: an overview of epidemiology, pathogenesis and management. Clin Rheumatol 40, 1211–1220 (2021). https://doi.org/10.1007/s10067-020-05320-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-020-05320-z

Keywords

Search

Navigation