Rheumatoid arthritis-associated interstitial lung disease – an underestimated, complex and interdisciplinary problem in everyday clinical practice Review article
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Published:
Dec 31, 2020
Keywords:
rheumatoid arthritis, interstitial lung disease, diagnosis, monitoring, treatment
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Abstract
Rheumatoid arthritis (RA) is a chronic, systemic inflammatory connective tissue disease affecting 0.5–1% of the general population. Interstitial lung disease (ILD) is a serious complication of RA, leads to a deterioration in the quality of life, increases the risk of hospitalization and premature death. The clinical course of RA-associated ILD (RA-ILD) varies from interstitial lesions involving little areas of the lung which do not lead to clinical symptoms, to progressive interstitial lesions that may lead to acute respiratory exacerbation, development of respiratory failure, and death. The main risk factor for the development of ILD in the course of RA, apart from older age and male sex, is the high activity of the underlying disease. Effective treatment of RA, aimed at the goal of remission, may therefore be a preventive method for the development of RA-ILD. Due to non-specific symptoms, the diagnosis of RA-ILD is often overlooked. Despite significant morbidity and increased risk of death due to RA-ILD, currently, we do not have any guidelines on the management of this clinical situation. Moreover, the problem is even more complicated due to the possibility of potential pneumotoxicity of many disease-modifying drugs and their unclear effectiveness regarding lung involvement in RA. Taken together, optimal management of a patient with RA-ILD is a clinical challenge. There is an urgent need to clarify several clinical aspects concerning the early diagnosis, monitoring, establishing indications for treatment, and choice of appropriate therapeutic management. In this work, we performed a scientific review of the current state of knowledge on RA-ILD and indicated the directions of future research needed aiming at improving patients’ care.
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Majewski, S., & Makowska , J. (2020). Rheumatoid arthritis-associated interstitial lung disease – an underestimated, complex and interdisciplinary problem in everyday clinical practice. Medycyna Faktow (J EBM), 13(4(49), 431-441. https://doi.org/10.24292/01.MF.0420.7
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References
1. Lederer DJ, Martinez FJ. Idiopathic Pulmonary Fibrosis. N Engl J Med. 2018; 378(19): 1811-23.
2. Wallace B, Vummidi D, Khanna D. Management of connective tissue diseases associated interstitial lung disease: a review of the published literature. Curr Opin Rheumatol. 2016; 28(3): 236-45.
3. Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. The Lancet. 2016; 388(10055): 2023-38.
4. Nannini C, Ryu JH, Matteson EL. Lung disease in rheumatoid arthritis. Curr Opin Rheumatol. 2008; 20(3): 340-6.
5. Marigliano B, Soriano A, Margiotta D et al. Lung involvement in connective tissue diseases: a comprehensive review and a focus on rheumatoid arthritis. Autoimmun Rev. 2013; 12(11): 1076-84.
6. Bongartz T, Nannini C, Medina-Velasquez YF et al. Incidence and Mortality of Interstitial Lung Disease in Rheumatoid Arthritis: A Population Based Study. Arthritis Rheum. 2010; 62(6): 1583-91.
7. Raimundo K, Solomon JJ, Olson AL et al. Rheumatoid Arthritis-Interstitial Lung Disease in the United States: Prevalence, Incidence, and Healthcare Costs and Mortality. J Rheumatol. 2019; 46(4): 360-9.
8. Shaw M, Collins BF, Ho LA et al. Rheumatoid arthritis-associated lung disease. Eur Respir Rev. 2015; 24(135): 1-16.
9. Olson AL, Swigris JJ, Sprunger DB et al. Rheumatoid arthritis-interstitial lung disease-associated mortality. Am J Respir Crit Care Med. 2011; 183(3): 372-8.
10. Myasoedova E, Crowson CS, Turesson C et al. Incidence of extraarticular rheumatoid arthritis in Olmsted County, Minnesota, in 1995-2007 versus 1985-1994: a population-based study. J Rheumatol. 2011; 38(6): 983-9.
11. Bartels CM, Bell CL, Shinki K et al. Changing trends in serious extra-articular manifestations of rheumatoid arthritis among United State veterans over 20 years. Rheumatol Oxf Engl. 2010; 49(9): 1670-5.
12. Cavagna L, Monti S, Grosso V et al. The multifaceted aspects of interstitial lung disease in rheumatoid arthritis. BioMed Res Int. 2013; 2013: 759760.
13. Assayag D, Lubin M, Lee JS et al. Predictors of mortality in rheumatoid arthritis-related interstitial lung disease. Respirol Carlton Vic. 2014; 19(4): 493-500.
14. Saag K, Cerhan J, Kolluri S et al. Cigarette smoking and rheumatoid arthritis severity. Ann Rheum Dis. 1997; 56(8): 463-9.
15. Kronzer VL, Huang W, Dellaripa PF et al. Lifestyle and clinical risk factors for incident rheumatoid arthritis-associated interstitial lung disease. J Rheumatol. 2020 [online ahead of print]. https://doi.org/10.3899/jrheum.200863.
16. Sparks JA, He X, Huang J et al. Rheumatoid Arthritis Disease Activity Predicting Incident Clinically Apparent Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Prospective Cohort Study. Arthritis Rheumatol Hoboken NJ. 2019; 71(9): 1472-82.
17. Turesson C. Extra-articular rheumatoid arthritis. Curr Opin Rheumatol. 2013; 25(3): 360-6.
18. Yang JA, Lee JS, Park JK et al. Clinical characteristics associated with occurrence and poor prognosis of interstitial lung disease in rheumatoid arthritis. Korean J Intern Med. 2019; 34(2): 434-41.
19. Hyldgaard C, Hilberg O, Pedersen AB et al. A population-based cohort study of rheumatoid arthritis-associated interstitial lung disease: comorbidity and mortality. Ann Rheum Dis. 2017; 76(10): 1700-6.
20. Habib HM, Eisa AA, Arafat WR et al. Pulmonary involvement in early rheumatoid arthritis patients. Clin Rheumatol. 2011; 30(2): 217-21.
21. Koduri G, Norton S, Young A et al. Interstitial lung disease has a poor prognosis in rheumatoid arthritis: results from an inception cohort. Rheumatology. 2010; 49(8): 1483-9.
22. Assayag D, Elicker BM, Urbania TH et al. Rheumatoid arthritis-associated interstitial lung disease: radiologic identification of usual interstitial pneumonia pattern. Radiology. 2014; 270(2): 583-8.
23. Kim EJ, Elicker BM, Maldonado F et al. Usual interstitial pneumonia in rheumatoid arthritis-associated interstitial lung disease. Eur Respir J. 2010; 35(6): 1322-8.
24. Solomon JJ, Ryu JH, Tazelaar HD et al. Fibrosing interstitial pneumonia predicts survival in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Respir Med. 2013; 107(8): 1247-52.
25. Zamora-Legoff JA, Krause ML, Crowson CS et al. Progressive Decline of Lung Function in Rheumatoid Arthritis-Associated Interstitial Lung Disease. Arthritis Rheumatol Hoboken NJ. 2017; 69(3): 542-9.
26. Sperandeo M, Varriale A, Sperandeo G et al. Transthoracic ultrasound in the evaluation of pulmonary fibrosis: our experience. Ultrasound Med Biol. 2009; 35(5): 723-9.
27. Manfredi A, Cassone G, Cerri S et al. 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. 2019; 19(1): 111.
28. Avouac J, Cauvet A, Steelandt A et al. Improving risk-stratification of rheumatoid arthritis patients for interstitial lung disease. PLoS One. 2020; 15(5): e0232978.
29. Kawano-Dourado L, Doyle TJ, Bonfiglioli K et al. Baseline Characteristics and Progression of a Spectrum of Interstitial Lung Abnormalities and Disease in Rheumatoid Arthritis. Chest. 2020; 158(4): 1546-54.
30. Izuka S, Yamashita H, Iba A et al. Acute exacerbation of rheumatoid arthritis-associated interstitial lung disease: clinical features and prognosis. Rheumatol Oxf Engl. 2020 [online Ahead of print]. https://doi.org/10.1093/rheumatology/keaa608.
31. Fragoulis GE, Nikiphorou E, Larsen J et al. Methotrexate-Associated Pneumonitis and Rheumatoid Arthritis-Interstitial Lung Disease: Current Concepts for the Diagnosis and Treatment. Front Med. 2019; 6: 238.
32. Imokawa S, Colby TV, Leslie KO et al. Methotrexate pneumonitis: review of the literature and histopathological findings in nine patients. Eur Respir J. 2000; 15(2): 373.
33. Conway R, Low C, Coughlan RJ et al. Methotrexate and Lung Disease in Rheumatoid Arthritis: A Meta-Analysis of Randomized Controlled Trials: Risk of Lung Disease in RA Patients Treated With MTX. Arthritis Rheumatol. 2014; 66(4): 803-12.
34. Kiely P, Busby AD, Nikiphorou E et al. 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. 2019; 9(5): e028466.
35. Lake F, Proudman S. Rheumatoid Arthritis and Lung Disease: From Mechanisms to a Practical Approach. Semin Respir Crit Care Med. 2014; 35(02): 222-38.
36. Conway R, Low C, Coughlan RJ et al. Leflunomide Use and Risk of Lung Disease in Rheumatoid Arthritis: A Systematic Literature Review and Metaanalysis of Randomized Controlled Trials. J Rheumatol. 2016; 43(5): 855-60.
37. Curtis JR, Sarsour K, Napalkov P et al. Incidence and complications of interstitial lung disease in users of tocilizumab, rituximab, abatacept and anti-tumor necrosis factor α agents, a retrospective cohort study. Arthritis Res Ther. 2015; 17(1): 319.
38. Sparks JA, He X, Huang J et al. Rheumatoid Arthritis Disease Activity Predicting Incident Clinically Apparent Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Prospective Cohort Study. Arthritis Rheumatol. 2019; 71(9): 1472-82.
39. Herrinton LJ, Harrold LR, Liu L et al. Association between anti-TNF- α therapy and interstitial lung disease: ANTI-TNF-Α AND INTERSTITIAL LUNG DISEASE. Pharmacoepidemiol Drug Saf. 2013; 22(4): 394-402.
40. Vadillo C, Nieto MA, Romero-Bueno F et al. Efficacy of rituximab in slowing down progression of rheumatoid arthritis-related interstitial lung disease: data from the NEREA Registry. Rheumatology. 2020; 59(8): 2099-108.
41. Fui A, Bergantini L, Selvi E et al. Rituximab therapy in interstitial lung disease associated with rheumatoid arthritis. Intern Med J. 2020; 50(3): 330-6.
42. Manfredi A, Cassone G, Furini F et al. Tocilizumab therapy in rheumatoid arthritis with interstitial lung disease: a multicenter retrospective study. Intern Med J. 2020; 50(9): 1085-90.
43. Fernández-Díaz C, Castañeda S, Melero-González RB et al. Abatacept in interstitial lung disease associated with rheumatoid arthritis: national multicenter study of 263 patients. Rheumatology. 2020; 59(12): 3906-16.
44. Md Yusof MY, Kabia A, Darby M et al. Effect of rituximab on the progression of rheumatoid arthritis-related interstitial lung disease: 10 years’ experience at a single centre. Rheumatology. 2017; 56(8): 1348-57.
45. England BR, Hershberger D. Management issues in rheumatoid arthritis-associated interstitial lung disease: Curr Opin Rheumatol. 2020; 32(3): 255-63.
46. Sendo S, Saegusa J, Yamada H et al. Tofacitinib facilitates the expansion of myeloid-derived suppressor cells and ameliorates interstitial lung disease in SKG mice. Arthritis Res Ther. 2019; 21(1): 184.
47. d’Alessandro M, Perillo F, Metella Refini R et al. Efficacy of baricitinib in treating rheumatoid arthritis: Modulatory effects on fibrotic and inflammatory biomarkers in a real-life setting. Int Immunopharmacol. 2020; 86: 106748.
48. Raghu G, Rochwerg B, Zhang Y et al. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of Idiopathic Pulmonary Fibrosis. An Update of the 2011 Clinical Practice Guideline. Am J Respir Crit Care Med. 2015; 192(2): e3-19.
49. Flaherty KR, Wells AU, Cottin V et al. Nintedanib in Progressive Fibrosing Interstitial Lung Diseases. N Engl J Med. 2019; 381(18): 1718-27.
50. Wells AU, Flaherty KR, Brown KK et al. Nintedanib in patients with progressive fibrosing interstitial lung diseases-subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: a randomised, double-blind, placebo-controlled, parallel-group trial. Lancet Respir Med. 2020; 8(5): 453-60.
2. Wallace B, Vummidi D, Khanna D. Management of connective tissue diseases associated interstitial lung disease: a review of the published literature. Curr Opin Rheumatol. 2016; 28(3): 236-45.
3. Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. The Lancet. 2016; 388(10055): 2023-38.
4. Nannini C, Ryu JH, Matteson EL. Lung disease in rheumatoid arthritis. Curr Opin Rheumatol. 2008; 20(3): 340-6.
5. Marigliano B, Soriano A, Margiotta D et al. Lung involvement in connective tissue diseases: a comprehensive review and a focus on rheumatoid arthritis. Autoimmun Rev. 2013; 12(11): 1076-84.
6. Bongartz T, Nannini C, Medina-Velasquez YF et al. Incidence and Mortality of Interstitial Lung Disease in Rheumatoid Arthritis: A Population Based Study. Arthritis Rheum. 2010; 62(6): 1583-91.
7. Raimundo K, Solomon JJ, Olson AL et al. Rheumatoid Arthritis-Interstitial Lung Disease in the United States: Prevalence, Incidence, and Healthcare Costs and Mortality. J Rheumatol. 2019; 46(4): 360-9.
8. Shaw M, Collins BF, Ho LA et al. Rheumatoid arthritis-associated lung disease. Eur Respir Rev. 2015; 24(135): 1-16.
9. Olson AL, Swigris JJ, Sprunger DB et al. Rheumatoid arthritis-interstitial lung disease-associated mortality. Am J Respir Crit Care Med. 2011; 183(3): 372-8.
10. Myasoedova E, Crowson CS, Turesson C et al. Incidence of extraarticular rheumatoid arthritis in Olmsted County, Minnesota, in 1995-2007 versus 1985-1994: a population-based study. J Rheumatol. 2011; 38(6): 983-9.
11. Bartels CM, Bell CL, Shinki K et al. Changing trends in serious extra-articular manifestations of rheumatoid arthritis among United State veterans over 20 years. Rheumatol Oxf Engl. 2010; 49(9): 1670-5.
12. Cavagna L, Monti S, Grosso V et al. The multifaceted aspects of interstitial lung disease in rheumatoid arthritis. BioMed Res Int. 2013; 2013: 759760.
13. Assayag D, Lubin M, Lee JS et al. Predictors of mortality in rheumatoid arthritis-related interstitial lung disease. Respirol Carlton Vic. 2014; 19(4): 493-500.
14. Saag K, Cerhan J, Kolluri S et al. Cigarette smoking and rheumatoid arthritis severity. Ann Rheum Dis. 1997; 56(8): 463-9.
15. Kronzer VL, Huang W, Dellaripa PF et al. Lifestyle and clinical risk factors for incident rheumatoid arthritis-associated interstitial lung disease. J Rheumatol. 2020 [online ahead of print]. https://doi.org/10.3899/jrheum.200863.
16. Sparks JA, He X, Huang J et al. Rheumatoid Arthritis Disease Activity Predicting Incident Clinically Apparent Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Prospective Cohort Study. Arthritis Rheumatol Hoboken NJ. 2019; 71(9): 1472-82.
17. Turesson C. Extra-articular rheumatoid arthritis. Curr Opin Rheumatol. 2013; 25(3): 360-6.
18. Yang JA, Lee JS, Park JK et al. Clinical characteristics associated with occurrence and poor prognosis of interstitial lung disease in rheumatoid arthritis. Korean J Intern Med. 2019; 34(2): 434-41.
19. Hyldgaard C, Hilberg O, Pedersen AB et al. A population-based cohort study of rheumatoid arthritis-associated interstitial lung disease: comorbidity and mortality. Ann Rheum Dis. 2017; 76(10): 1700-6.
20. Habib HM, Eisa AA, Arafat WR et al. Pulmonary involvement in early rheumatoid arthritis patients. Clin Rheumatol. 2011; 30(2): 217-21.
21. Koduri G, Norton S, Young A et al. Interstitial lung disease has a poor prognosis in rheumatoid arthritis: results from an inception cohort. Rheumatology. 2010; 49(8): 1483-9.
22. Assayag D, Elicker BM, Urbania TH et al. Rheumatoid arthritis-associated interstitial lung disease: radiologic identification of usual interstitial pneumonia pattern. Radiology. 2014; 270(2): 583-8.
23. Kim EJ, Elicker BM, Maldonado F et al. Usual interstitial pneumonia in rheumatoid arthritis-associated interstitial lung disease. Eur Respir J. 2010; 35(6): 1322-8.
24. Solomon JJ, Ryu JH, Tazelaar HD et al. Fibrosing interstitial pneumonia predicts survival in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Respir Med. 2013; 107(8): 1247-52.
25. Zamora-Legoff JA, Krause ML, Crowson CS et al. Progressive Decline of Lung Function in Rheumatoid Arthritis-Associated Interstitial Lung Disease. Arthritis Rheumatol Hoboken NJ. 2017; 69(3): 542-9.
26. Sperandeo M, Varriale A, Sperandeo G et al. Transthoracic ultrasound in the evaluation of pulmonary fibrosis: our experience. Ultrasound Med Biol. 2009; 35(5): 723-9.
27. Manfredi A, Cassone G, Cerri S et al. 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. 2019; 19(1): 111.
28. Avouac J, Cauvet A, Steelandt A et al. Improving risk-stratification of rheumatoid arthritis patients for interstitial lung disease. PLoS One. 2020; 15(5): e0232978.
29. Kawano-Dourado L, Doyle TJ, Bonfiglioli K et al. Baseline Characteristics and Progression of a Spectrum of Interstitial Lung Abnormalities and Disease in Rheumatoid Arthritis. Chest. 2020; 158(4): 1546-54.
30. Izuka S, Yamashita H, Iba A et al. Acute exacerbation of rheumatoid arthritis-associated interstitial lung disease: clinical features and prognosis. Rheumatol Oxf Engl. 2020 [online Ahead of print]. https://doi.org/10.1093/rheumatology/keaa608.
31. Fragoulis GE, Nikiphorou E, Larsen J et al. Methotrexate-Associated Pneumonitis and Rheumatoid Arthritis-Interstitial Lung Disease: Current Concepts for the Diagnosis and Treatment. Front Med. 2019; 6: 238.
32. Imokawa S, Colby TV, Leslie KO et al. Methotrexate pneumonitis: review of the literature and histopathological findings in nine patients. Eur Respir J. 2000; 15(2): 373.
33. Conway R, Low C, Coughlan RJ et al. Methotrexate and Lung Disease in Rheumatoid Arthritis: A Meta-Analysis of Randomized Controlled Trials: Risk of Lung Disease in RA Patients Treated With MTX. Arthritis Rheumatol. 2014; 66(4): 803-12.
34. Kiely P, Busby AD, Nikiphorou E et al. 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. 2019; 9(5): e028466.
35. Lake F, Proudman S. Rheumatoid Arthritis and Lung Disease: From Mechanisms to a Practical Approach. Semin Respir Crit Care Med. 2014; 35(02): 222-38.
36. Conway R, Low C, Coughlan RJ et al. Leflunomide Use and Risk of Lung Disease in Rheumatoid Arthritis: A Systematic Literature Review and Metaanalysis of Randomized Controlled Trials. J Rheumatol. 2016; 43(5): 855-60.
37. Curtis JR, Sarsour K, Napalkov P et al. Incidence and complications of interstitial lung disease in users of tocilizumab, rituximab, abatacept and anti-tumor necrosis factor α agents, a retrospective cohort study. Arthritis Res Ther. 2015; 17(1): 319.
38. Sparks JA, He X, Huang J et al. Rheumatoid Arthritis Disease Activity Predicting Incident Clinically Apparent Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Prospective Cohort Study. Arthritis Rheumatol. 2019; 71(9): 1472-82.
39. Herrinton LJ, Harrold LR, Liu L et al. Association between anti-TNF- α therapy and interstitial lung disease: ANTI-TNF-Α AND INTERSTITIAL LUNG DISEASE. Pharmacoepidemiol Drug Saf. 2013; 22(4): 394-402.
40. Vadillo C, Nieto MA, Romero-Bueno F et al. Efficacy of rituximab in slowing down progression of rheumatoid arthritis-related interstitial lung disease: data from the NEREA Registry. Rheumatology. 2020; 59(8): 2099-108.
41. Fui A, Bergantini L, Selvi E et al. Rituximab therapy in interstitial lung disease associated with rheumatoid arthritis. Intern Med J. 2020; 50(3): 330-6.
42. Manfredi A, Cassone G, Furini F et al. Tocilizumab therapy in rheumatoid arthritis with interstitial lung disease: a multicenter retrospective study. Intern Med J. 2020; 50(9): 1085-90.
43. Fernández-Díaz C, Castañeda S, Melero-González RB et al. Abatacept in interstitial lung disease associated with rheumatoid arthritis: national multicenter study of 263 patients. Rheumatology. 2020; 59(12): 3906-16.
44. Md Yusof MY, Kabia A, Darby M et al. Effect of rituximab on the progression of rheumatoid arthritis-related interstitial lung disease: 10 years’ experience at a single centre. Rheumatology. 2017; 56(8): 1348-57.
45. England BR, Hershberger D. Management issues in rheumatoid arthritis-associated interstitial lung disease: Curr Opin Rheumatol. 2020; 32(3): 255-63.
46. Sendo S, Saegusa J, Yamada H et al. Tofacitinib facilitates the expansion of myeloid-derived suppressor cells and ameliorates interstitial lung disease in SKG mice. Arthritis Res Ther. 2019; 21(1): 184.
47. d’Alessandro M, Perillo F, Metella Refini R et al. Efficacy of baricitinib in treating rheumatoid arthritis: Modulatory effects on fibrotic and inflammatory biomarkers in a real-life setting. Int Immunopharmacol. 2020; 86: 106748.
48. Raghu G, Rochwerg B, Zhang Y et al. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of Idiopathic Pulmonary Fibrosis. An Update of the 2011 Clinical Practice Guideline. Am J Respir Crit Care Med. 2015; 192(2): e3-19.
49. Flaherty KR, Wells AU, Cottin V et al. Nintedanib in Progressive Fibrosing Interstitial Lung Diseases. N Engl J Med. 2019; 381(18): 1718-27.
50. Wells AU, Flaherty KR, Brown KK et al. Nintedanib in patients with progressive fibrosing interstitial lung diseases-subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: a randomised, double-blind, placebo-controlled, parallel-group trial. Lancet Respir Med. 2020; 8(5): 453-60.