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Treatment of Interstitial Lung Disease

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Scleroderma

Abstract

Pulmonary disease is the leading cause of hospitalizations and mortality in patients with systemic sclerosis (SSc) (Steen VD, Medsger Jr TA. Changes in causes of death in systemic sclerosis. Ann Rheum Dis. 2007;66:940–4). This chapter will discuss the management of ILD in SSc with a focus on whom to treat, how long to treat, and what pharmacological therapies to use. Previous chapters in this textbook have discussed the pathogenesis of SSc-ILD in detail.

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References

  1. Steen VD, Medsger Jr TA. Changes in causes of death in systemic sclerosis. Ann Rheum Dis. 2007;66:940–4.

    Article  PubMed  Google Scholar 

  2. Goh NS, Desai SR, Veeraraghavan S, Hansell DM, Copley SJ, Maher TM, Corte TJ, Sander CR, Ratoff J, Devaraj A, Bozovic G, Denton CP, Black CM, du Bois RM, Wells AU. Interstitial lung disease in systemic sclerosis: a simple staging system. Am J Respir Crit Care Med. 2008;177:1248–54.

    Article  PubMed  Google Scholar 

  3. Steen VD, Conte C, Owens GR, Medsger Jr TA. Severe restrictive lung disease in systemic sclerosis. Arthritis Rheum. 1994;37:1283–9.

    Article  PubMed  CAS  Google Scholar 

  4. Plastiras SC, Karadimitrakis SP, Ziakas PD, Vlachoyiannopoulos PG, Moutsopoulos HM, Tzelepis GE. Scleroderma lung: initial forced vital capacity as predictor of pulmonary function decline. Arthritis Rheum. 2006;55:598–602.

    Article  PubMed  Google Scholar 

  5. Au K, Khanna D, Clements PJ, Furst DE, Tashkin DP. Current concepts in disease-modifying therapy for systemic sclerosis-associated interstitial lung disease: lessons from clinical trials. Curr Rheumatol Rep. 2009;11:111–9.

    Article  PubMed  CAS  Google Scholar 

  6. Clements PJ, Roth MD, Elashoff R, Tashkin DP, Goldin J, Silver RM, Sterz M, Seibold JR, Schraufnagel D, Simms RW, Bolster M, Wise RA, Steen V, Mayes MD, Connelly K, Metersky M, Furst DE. Scleroderma lung study (SLS): differences in the presentation and course of patients with limited versus diffuse systemic sclerosis. Ann Rheum Dis. 2007;66:1641–7.

    Article  PubMed  Google Scholar 

  7. Walker UA, Tyndall A, Czirjak L, Denton C, Farge-Bancel D, Kowal-Bielecka O, Muller-Ladner U, Bocelli-Tyndall C, Matucci-Cerinic M. Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR Scleroderma trials and research group database. Ann Rheum Dis. 2007;66:754–63.

    Article  PubMed  CAS  Google Scholar 

  8. Khanna D, Denton CP. Evidence-based management of rapidly progressing systemic sclerosis. Best Pract Res Clin Rheumatol. 2010;24:387–400.

    Article  PubMed  Google Scholar 

  9. Bouros D, Wells AU, Nicholson AG, Colby TV, Polychronopoulos V, Pantelidis P, Haslam PL, Vassilakis DA, Black CM, du Bois RM. Histopathologic subsets of fibrosing alveolitis in patients with systemic sclerosis and their relationship to outcome. Am J Respir Crit Care Med. 2002;165:1581–6.

    Article  PubMed  Google Scholar 

  10. Latsi PI, du Bois RM, Nicholson AG, Colby TV, Bisirtzoglou D, Nikolakopoulou A, Veeraraghavan S, Hansell DM, Wells AU. Fibrotic idiopathic interstitial pneumonia: the prognostic value of longitudinal functional trends. Am J Respir Crit Care Med. 2003;168:531–7.

    Article  PubMed  Google Scholar 

  11. Goldin JG, Lynch DA, Strollo DC, Suh RD, Schraufnagel DE, Clements PJ, Elashoff RM, Furst DE, Vasunilashorn S, Nitt-Gray MF, Brown MS, Roth MD, Tashkin DP. High-resolution CT scan findings in patients with symptomatic scleroderma-related interstitial lung disease. Chest. 2008;134:358–67.

    Article  PubMed  Google Scholar 

  12. Goldin J, Elashoff R, Kim HJ, Yan X, Lynch D, Strollo D, Roth MD, Clements P, Furst DE, Khanna D, Vasunilashorn S, Li G, Tashkin DP. Treatment of scleroderma-interstitial lung disease with cyclophosphamide is associated with less progressive fibrosis on serial thoracic high-resolution CT scan than placebo: findings from the scleroderma lung study. Chest. 2009;136:1333–40.

    Article  PubMed  CAS  Google Scholar 

  13. Tashkin DP, Elashoff R, Clements PJ, Goldin J, Roth MD, Furst DE, Arriola E, Silver R, Strange C, Bolster M, Seibold JR, Riley DJ, Hsu VM, Varga J, Schraufnagel DE, Theodore A, Simms R, Wise R, Wigley F, White B, Steen V, Read C, Mayes M, Parsley E, Mubarak K, Connolly MK, Golden J, Olman M, Fessler B, Rothfield N, Metersky M. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med. 2006;354:2655–66.

    Article  PubMed  CAS  Google Scholar 

  14. Strange C, Bolster MB, Roth MD, Silver RM, Theodore A, Goldin J, Clements P, Chung J, Elashoff RM, Suh R, Smith EA, Furst DE, Tashkin DP. Bronchoalveolar lavage and response to cyclophosphamide in scleroderma interstitial lung disease. Am J Respir Crit Care Med. 2008;177:91–8.

    Article  PubMed  CAS  Google Scholar 

  15. Goh NS, Veeraraghavan S, Desai SR, Cramer D, Hansell DM, Denton CP, Black CM, du Bois RM, Wells AU. Bronchoalveolar lavage cellular profiles in patients with systemic sclerosis-associated interstitial lung disease are not predictive of disease progression. Arthritis Rheum. 2007;56:2005–12.

    Article  PubMed  Google Scholar 

  16. Steen VD. Autoantibodies in systemic sclerosis. Semin Arthritis Rheum. 2005;35:35–42.

    Article  PubMed  CAS  Google Scholar 

  17. McGoon M, Gutterman D, Steen V, Barst R, McCrory DC, Fortin TA, Loyd JE. Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest. 2004;126:14S–34.

    Article  PubMed  Google Scholar 

  18. American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med. 2000;161:646–64.

    Google Scholar 

  19. Hoyles RK, Ellis RW, Wellsbury J, Lees B, Newlands P, Goh NS, Roberts C, Desai S, Herrick AL, McHugh NJ, Foley NM, Pearson SB, Emery P, Veale DJ, Denton CP, Wells AU, Black CM, du Bois RM. A multicenter, prospective, randomized, double-blind, placebo-controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma. Arthritis Rheum. 2006;54:3962–70.

    Article  PubMed  CAS  Google Scholar 

  20. Beretta L, Caronni M, Raimondi M, Ponti A, Viscuso T, Origgi L, Scorza R. Oral cyclophosphamide improves pulmonary function in scleroderma patients with fibrosing alveolitis: experience in one centre. Clin Rheumatol. 2007;26:168–72.

    Article  PubMed  Google Scholar 

  21. White B, Moore WC, Wigley FM, **ao HQ, Wise RA. Cyclophosphamide is associated with pulmonary function and survival benefit in patients with scleroderma and alveolitis. Ann Intern Med. 2000;132:947–54.

    PubMed  CAS  Google Scholar 

  22. Silver RM, Warrick JH, Kinsella MB, Staudt LS, Baumann MH, Strange C. Cyclophosphamide and low-dose prednisone therapy in patients with systemic sclerosis (scleroderma) with interstitial lung disease. J Rheumatol. 1993;20:838–44.

    PubMed  CAS  Google Scholar 

  23. Khanna D, Yan X, Tashkin DP, Furst DE, Elashoff R, Roth MD, Silver R, Strange C, Bolster M, Seibold JR, Riley DJ, Hsu VM, Varga J, Schraufnagel DE, Theodore A, Simms R, Wise R, Wigley F, White B, Steen V, Read C, Mayes M, Parsley E, Mubarak K, Connolly MK, Golden J, Olman M, Fessler B, Rothfield N, Metersky M, Clements PJ. Impact of oral cyclophosphamide on health-related quality of life in patients with active scleroderma lung disease: results from the scleroderma lung study. Arthritis Rheum. 2007;56:1676–84.

    Article  PubMed  CAS  Google Scholar 

  24. Goldin JG, Lynch DA, Strollo DC, et al. Follow-Up HRCT after Treatment of scleroderma-interstitial lung disease with cyclophosphamide demonstrates evidence for treatment effect. Am J Respir Crit Care Med. 2008;177(A768):91, Ref Type: Abstract.

    PubMed  Google Scholar 

  25. Martinez FJ, McCune WJ. Cyclophosphamide for scleroderma lung disease. N Engl J Med. 2006;354:2707–9.

    Article  PubMed  CAS  Google Scholar 

  26. Tashkin DP, Elashoff R, Clements PJ, Roth MD, Furst DE, Silver RM, Goldin J, Arriola E, Strange C, Bolster MB, Seibold JR, Riley DJ, Hsu VM, Varga J, Schraufnagel D, Theodore A, Simms R, Wise R, Wigley F, White B, Steen V, Read C, Mayes M, Parsley E, Mubarak K, Connolly MK, Golden J, Olman M, Fessler B, Rothfield N, Metersky M, Khanna D, Li N, Li G. Effects of 1-year treatment with cyclophosphamide on outcomes at 2 years in scleroderma lung disease. Am J Respir Crit Care Med. 2007;176:1026–34.

    Article  PubMed  CAS  Google Scholar 

  27. Kowal-Bielecka O, Landewe R, Avouac J, Chwiesko S, Miniati I, Czirjak L, Clements P, Denton C, Farge D, Fligelstone K, Foldvari I, Furst DE, Muller-Ladner U, Seibold J, Silver RM, Takehara K, Garay TB, Tyndall A, Valentini G, van den Hoogen F, Wigley F, Zulian F, Matucci-Cerinic M. EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR). Ann Rheum Dis. 2009;60:620–8.

    Article  Google Scholar 

  28. Takebe N, Cheng X, Fandy TE, Srivastava RK, Wu S, Shankar S, Bauer K, Shaughnessy J, Tricot G. IMP dehydrogenase inhibitor mycophenolate mofetil induces caspase-dependent apoptosis and cell cycle inhibition in multiple myeloma cells. Mol Cancer Ther. 2006;5:457–66.

    Article  PubMed  CAS  Google Scholar 

  29. Colic M, Stojic-Vukanic Z, Pavlovic B, Jandric D, Stefanoska I. Mycophenolate mofetil inhibits differentiation, maturation and allostimulatory function of human monocyte-derived dendritic cells. Clin Exp Immunol. 2003;134:63–9.

    Article  PubMed  CAS  Google Scholar 

  30. Andrikos E, Yavuz A, Bordoni V, Ratanarat R, De CM, Bonello M, Salvatori G, Levin N, Yakupoglu G, Pappas M, Ronco C. Effect of cyclosporine, mycophenolate mofetil, and their combination with steroids on apoptosis in a human cultured monocytic U937 cell line. Transplant Proc. 2005;37:3226–9.

    Article  PubMed  CAS  Google Scholar 

  31. Nihtyanova SI, Brough GM, Black CM, Denton CP. Mycophenolate mofetil in diffuse cutaneous systemic sclerosis – a retrospective analysis. Rheumatology (Oxford). 2007;46:442–5.

    Article  CAS  Google Scholar 

  32. Kaminska D, Tyran B, Mazanowska O, Letachowicz W, Kochman A, Rabczynski J, Szyber P, Patrzalek D, Chudoba P, Klinger M. Mycophenolate mofetil but not the type of calcineurin inhibitor (cyclosporine vs tacrolimus) influences the intragraft mRNA expression of cytokines in human kidney allograft biopsies by in situ RT-PCR analysis. Transplant Proc. 2005;37:770–2.

    Article  PubMed  CAS  Google Scholar 

  33. Liossis SN, Bounas A, Andonopoulos AP. Mycophenolate mofetil as first-line treatment improves clinically evident early scleroderma lung disease. Rheumatology (Oxford). 2006;45:1005–8.

    Article  CAS  Google Scholar 

  34. Zamora AC, Wolters PJ, Collard HR, Connolly MK, Elicker BM, Webb WR, King Jr TE, Golden JA. Use of mycophenolate mofetil to treat scleroderma-associated interstitial lung disease. Respir Med. 2008;102:150–5.

    Article  PubMed  Google Scholar 

  35. Gerbino AJ, Goss CH, Molitor JA. Effect of mycophenolate mofetil on pulmonary function in scleroderma-associated interstitial lung disease. Chest. 2008;133:455–60.

    Article  PubMed  CAS  Google Scholar 

  36. Swigris JJ, Olson AL, Fischer A, Lynch DA, Cosgrove GP, Frankel SK, Meehan RT, Brown KK. Mycophenolate mofetil is safe, well tolerated, and preserves lung function in patients with connective tissue disease-related interstitial lung disease. Chest. 2006;130:30–6.

    Article  PubMed  CAS  Google Scholar 

  37. Dheda K, Lalloo UG, Cassim B, Mody GM. Experience with azathioprine in systemic sclerosis associated with interstitial lung disease. Clin Rheumatol. 2004;23:306–9.

    PubMed  CAS  Google Scholar 

  38. Nadashkevich O, Davis P, Fritzler M, Kovalenko W. A randomized unblinded trial of cyclophosphamide versus azathioprine in the treatment of systemic sclerosis. Clin Rheumatol. 2006;25:205–12.

    Article  PubMed  CAS  Google Scholar 

  39. McSweeney PA, Nash RA, Sullivan KM, Storek J, Crofford LJ, Dansey R, Mayes MD, McDonagh KT, Nelson JL, Gooley TA, Holmberg LA, Chen CS, Wener MH, Ryan K, Sunderhaus J, Russell K, Rambharose J, Storb R, Furst DE. High-dose immunosuppressive therapy for severe systemic sclerosis: initial outcomes. Blood. 2002;100:1602–10.

    PubMed  CAS  Google Scholar 

  40. Nash RA, McSweeney PA, Crofford LJ, Abidi M, Chen CS, Godwin JD, Gooley TA, Holmberg L, Henstorf G, LeMaistre CF, Mayes MD, McDonagh KT, McLaughlin B, Molitor JA, Nelson JL, Shulman H, Storb R, Viganego F, Wener MH, Seibold JR, Sullivan KM, Furst DE. High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: long-term follow-up of the US multicenter pilot study. Blood. 2007;110:1388–96.

    Article  PubMed  CAS  Google Scholar 

  41. Seibold JR, Denton CP, Furst DE, Guillevin L, Rubin LJ, Wells A, Matucci CM, Riemekasten G, Emery P, Chadha-Boreham H, Charef P, Roux S, Black CM. Randomized, prospective, placebo-controlled trial of bosentan in interstitial lung disease secondary to systemic sclerosis. Arthritis Rheum. 2010;62:2101–8.

    Article  PubMed  CAS  Google Scholar 

  42. Denton CP, Merkel PA, Furst DE, Khanna D, Emery P, Hsu VM, Silliman N, Streisand J, Powell J, Akesson A, Coppock J, Hoogen FV, Herrick A, Mayes MD, Veale D, Haas J, Ledbetter S, Korn JH, Black CM, Seibold JR. Recombinant human anti-transforming growth factor beta1 antibody therapy in systemic sclerosis: a multicenter, randomized, placebo-controlled phase I/II trial of CAT-192. Arthritis Rheum. 2006; 56:323–33.

    Article  Google Scholar 

  43. Bosello S, De SM, Lama G, Spano C, Angelucci C, Tolusso B, Sica G, Ferraccioli G. B cell depletion in diffuse progressive systemic sclerosis: safety, skin score modification and IL-6 modulation in an up to thirty-six months follow-up open-label trial. Arthritis Res Ther. 2010;12:R54.

    Article  PubMed  Google Scholar 

  44. Rao V, Khanna D. Scleroderma and fibrosing disorders: advances in management. Int J Adv Rheumatol. 2010;8:53–62.

    Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, University of Michigan, Ann Arbor, MI, USA

    Dinesh Khanna MD, MS

  2. Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Donald P. Tashkin MD

Authors
  1. Dinesh Khanna MD, MS
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  2. Donald P. Tashkin MD
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Correspondence to Dinesh Khanna MD, MS .

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Editors and Affiliations

  1. Feinberg School of Medicine, Northwestern University, E. Huron Street 240, Chicago, 60611-2909, Illinois, USA

    John Varga

  2. Royal Free and University College, Medical School, University College London, Rowland Street, London, NW3 2PF, United Kingdom

    Christopher P. Denton

  3. School of Medicine, Div. Rheumatology, Johns Hopkins University, Eastern Avenue 5200, Baltimore, 21224, Maryland, USA

    Fredrick M. Wigley

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Khanna, D., Tashkin, D.P. (2012). Treatment of Interstitial Lung Disease. In: Varga, J., Denton, C., Wigley, F. (eds) Scleroderma. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-5774-0_35

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  • DOI: https://doi.org/10.1007/978-1-4419-5774-0_35

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