SpringerLink
Log in

Connective Tissue Related Interstitial Lung Disease

  • Interstitial Lung Disease (A. Hajari Case, Section Editor)
  • Published:
Current Pulmonology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Interstitial lung disease (ILD) is a common complication of the connective tissue diseases (CTD) and results in significant morbidity and mortality. This review will focus on recent literature pertaining to the epidemiology, clinical presentation, diagnosis, and treatment of CTD-ILD.

Recent Findings

Subclinical ILD can be found in the majority of patients with CTD. Clinically significant ILD is most commonly seen in scleroderma followed by polymyositis/dermatomyositis and rheumatoid arthritis, although it can occur in all of the CTDs. Nonspecific interstitial pneumonia is the most common radiographic and histologic pattern, although usual interstitial pneumonia occurs more frequently in rheumatoid arthritis. Pathogenesis is likely related to a combination of autoimmunity/inflammation, disordered fibrogenesis, and vascular injury. Treatment strategies are evolving to target all three of these pathways.

Summary

Although further research into treatment strategies is needed, the clinician should be aware of the risk factors and clinical presentation of ILD in the various CTDs in order to identify patients who should be screened and/or have modifications in treatment strategies in order to mitigate the morbidity and mortality associated with CTD-ILD.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

6MWT:

Six-minute walk test

AIP:

Acute interstitial pneumonia

ALP:

Acute lupus pneumonitis

ANA:

Antinuclear antibody

AZA:

Azathioprine

BAL:

Bronchoalveolar lavage

CCP:

Cyclic citrullinated peptide

CRP:

C-Reactive protein

CTD:

Connective tissue disease

CYC:

Cyclophosphamide

DLCO:

Diffusion limitation of carbon monoxide

DM:

Dermatomyositis

ESR:

Erythrocyte sedimentation rate

FVC:

Forced vital capacity

HRCT:

High resolution computed tomography of the chest

HSCT:

Hematopoietic stem cell transplantation

IIM:

Idiopathic inflammatory myopathies

ILD:

Interstitial lung disease

IPAF:

Interstitial pneumonia with autoimmune features

IPF:

Idiopathic pulmonary fibrosis

JVD:

Jugular venous distension

LIP:

Lymphocytic interstitial pneumonia

MCTD:

Mixed connective tissue disease

MMF:

Mycophenolate mofetil

NSIP:

Nonspecific interstitial pneumonia

OP:

Organizing pneumonia

PAH:

Pulmonary arterial hypertension

PFT:

Pulmonary function test

PH:

Pulmonary hypertension

PM:

Polymyositis

RA:

Rheumatoid arthritis

SLE:

Systemic lupus erythematosus

SS:

Sjögren’s syndrome

TLC:

Total lung capacity

TPMT:

Thiopurine methyltransferase levels

TR:

Tricuspid regurgitation murmur

ab:

Antibody

UCTD:

Undifferentiated connective tissue disease

UIP:

Usual interstitial pneumonia

References

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

  1. Woodhead F, Wells AU, Desai SR. Pulmonary complications of connective tissue diseases. Clin Chest Med. 2008;29:149–64, vii. https://doi.org/10.1016/j.ccm.2007.11.009.

    Article  PubMed  Google Scholar 

  2. Wells AU, Denton CP. Interstitial lung disease in connective tissue disease—mechanisms and management. Nat Rev Rheumatol. 2014;10:728–39. https://doi.org/10.1038/nrrheum.2014.149.

    Article  CAS  PubMed  Google Scholar 

  3. Koo SM, Uh ST. Treatment of connective tissue disease-associated interstitial lung disease: the pulmonologist’s point of view. Korean J Intern Med. 2017;32:600–10. https://doi.org/10.3904/kjim.2016.212.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Antoniou KM, Margaritopoulos G, Economidou F, Siafakas NM. Pivotal clinical dilemmas in collagen vascular diseases associated with interstitial lung involvement. Eur Respir J. 2009;33:882–96. https://doi.org/10.1183/09031936.00152607.

    Article  CAS  PubMed  Google Scholar 

  5. Vij R, Strek ME. Diagnosis and treatment of connective tissue disease-associated interstitial lung disease. Chest. 2013;143:814–24. https://doi.org/10.1378/chest.12-0741.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kim HC, Ji W, Kim MY, Colby TV, Jang SJ, Lee CK, et al. Interstitial pneumonia related to undifferentiated connective tissue disease: pathologic pattern and prognosis. Chest. 2015;147:165–72. https://doi.org/10.1378/chest.14-0272.

    Article  PubMed  Google Scholar 

  7. •• Fischer A, Antoniou KM, Brown KK, Cadranel J, Corte TJ, du Bois RM, et al. An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. Eur Respir J. 2015;46:976–87. https://doi.org/10.1183/13993003.00150-2015 This article reviews the new criteria for idiopathic pneumonia with autoimmune features, which defines a cohort of patients with interstitial lung disease and autoimmune features, who do not meet criteria for a well-defined connective tissue disease.

    Article  CAS  PubMed  Google Scholar 

  8. Fujita J, Ohtsuki Y, Yoshinouchi T, Yamadori I, Bandoh S, Tokuda M, et al. Idiopathic non-specific interstitial pneumonia: as an “autoimmune interstitial pneumonia”. Respir Med. 2005;99:234–40.

    Article  PubMed  Google Scholar 

  9. Raghu G, Brown KK. Interstitial lung disease: clinical evaluation and keys to an accurate diagnosis. Clin Chest Med. 2004;25:409–19, v. https://doi.org/10.1016/j.ccm.2004.05.007.

    Article  PubMed  Google Scholar 

  10. Kinder BW, Collard HR, Koth L, Daikh DI, Wolters PJ, Elicker B, et al. Idiopathic nonspecific interstitial pneumonia: lung manifestation of undifferentiated connective tissue disease? Am J Respir Crit Care Med. 2007;176:691–7. https://doi.org/10.1164/rccm.200702-220OC.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Martinez FJ. Idiopathic interstitial pneumonias: usual interstitial pneumonia versus nonspecific interstitial pneumonia. Proc Am Thorac Soc. 2006;3:81–95. https://doi.org/10.1513/PATS.200511-123JH.

    Article  CAS  PubMed  Google Scholar 

  12. Kinder BW, Shariat C, Collard HR, Koth LL, Wolters PJ, Golden JA, et al. Undifferentiated connective tissue disease-associated interstitial lung disease: changes in lung function. Lung. 2010;188:143–9. https://doi.org/10.1007/s00408-009-9226-7.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Vij R, Noth I, Strek ME. Autoimmune-featured interstitial lung disease: a distinct entity. Chest. 2011;140:1292–9. https://doi.org/10.1378/chest.10-2662.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Corte TJ, Copley SJ, Desai SR, Zappala CJ, Hansell DM, Nicholson AG, et al. Significance of connective tissue disease features in idiopathic interstitial pneumonia. Eur Respir J. 2012;39:661–8. https://doi.org/10.1183/09031936.00174910.

    Article  CAS  PubMed  Google Scholar 

  15. 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. https://doi.org/10.3899/rheum.121043.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Keir GJ, Maher TM, Ming D, Abdullah R, de Lauretis A, Wickremasinghe M, et al. Rituximab in severe, treatment-refractory interstitial lung disease. Respirology. 2014;19:353–9. https://doi.org/10.1111/resp.12214.

    Article  PubMed  Google Scholar 

  17. •• Ferri C, Manfredi A, Sebastiani M, Colaci M, Giuggioli D, Vacchi C, et al. Interstitial pneumonia with autoimmune features and undifferentiated connective tissue disease: our interdisciplinary rheumatology-pneumology experience, and review of the literature. Autoimmun Rev. 2016;15:61–70. https://doi.org/10.1016/j.autrev.2015.09.003 This article emphasizes the importance of a rheumatolgost in multidisciplinary discussions of interstitial lung disease.

    Article  CAS  PubMed  Google Scholar 

  18. Fischer A, Richeldi L. Cross-disciplinary collaboration in connective tissue disease-related lung disease. Semin Respir Crit Care Med. 2014;35:159–65. https://doi.org/10.1055/s-0034-1371530.

    Article  PubMed  Google Scholar 

  19. Levi Y, Israeli-Shani L, Kuchuk M, Shochet GE, Koslow M, Shitrit D. Rheumatologic assessment is important for interstitial lung disease diagnosis. J Rheumatol 2018; [Epub ahead of print] doi: 10.3899/jrheum.171314.

    Article  PubMed  Google Scholar 

  20. 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. 1980;23:581–90.

  21. van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis. 2013;72:1747–55. https://doi.org/10.1136/annrheumdis-2013-204424.

    Article  PubMed  Google Scholar 

  22. Fischer A, Swigris JJ, Groshong SD, Cool CD, Sahin H, Lynch DA, et al. Clinically significant interstitial lung disease in limited scleroderma: histopathology, clinical features, and survival. Chest. 2008;134:601–5. https://doi.org/10.1378/chest.08-0053.

    Article  PubMed  Google Scholar 

  23. Steen VD. Clinical manifestations of systemic sclerosis. Semin Cutan Med Surg. 1998;17:48–54.

    Article  CAS  PubMed  Google Scholar 

  24. Woodhead F, Wells AU, Desai SR. Pulmonary complications of connective tissue diseases. Clin Chest Med. 2008;29(1):149–64, vii. https://doi.org/10.1016/j.ccm.2007.11.009.

    Article  PubMed  Google Scholar 

  25. Gelber AC, Manno RL, Shah AA, Woods A, Le EN, Boin F, et al. Race and association with disease manifestations and mortality in scleroderma: a 20-year experience at the Johns Hopkins Scleroderma Center and review of the literature. Medicine (Baltimore). 2013;92:191–205. doi: 10.097/MD.0b013e31829be125.

  26. Steen V, Domsic RT, Lucas M, Fertig N, Medsger TA Jr. A clinical and serologic comparison of African American and Caucasian patients with systemic sclerosis. Arthritis Rheum. 2012;64:2986–94. https://doi.org/10.1002/art.34482.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Bouros D, Wells AU, Nicholson AG, Colby TV, Polychronopoulos V, Pantelidis P, et al. 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. https://doi.org/10.1164/rccm.2106012.

    Article  PubMed  Google Scholar 

  28. Strange C, Bolster MB, Roth MD, Silver RM, Theodore A, Goldin J, et al. Bronchoalveolar lavage and response to cyclophosphamide in scleroderma interstitial lung disease. Am J Respir Crit Care Med. 2008;177:91–8. https://doi.org/10.1164/rccm.200705-655OC.

    Article  CAS  PubMed  Google Scholar 

  29. • Durheim MT, Kim S, Gulack BC, Burfeind WR, Gaissert HA, Kosinski AS, et al. Mortality and respiratory failure after thoracoscopic lung biopsy for interstitial lung disease. Ann Thorac Surg. 2017; 104:465-70. doi: 10.1016/j.athoracsur.2017.02.013. This is the nice review of the risk factors for surgical lung biopsy in patients with interstitial lung disease.

    Article  PubMed  Google Scholar 

  30. Goh NS, Desai SR, Veeraraghavan S, Hansell DM, Copley SJ, Maher TM, et al. Interstitial lung disease in systemic sclerosis: a simple staging system. Am J Respir Crit Care Med. 2008;177(11):1248–54. https://doi.org/10.1164/rccm.200706-877OC.

    Article  PubMed  Google Scholar 

  31. 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. https://doi.org/10.1007/s1192-009-0016-2.

    Article  CAS  PubMed  Google Scholar 

  32. Teixeira L, Mouthon L, Mahr A, Berezne A, Agard C, Mehrenberger M, et al. Mortality and risk factors of scleroderma renal crisis: a French retrospective study of 50 patients. Ann Rheum Dis. 2008;67:110–6. https://doi.org/10.1136/ard.2006.066985.

    Article  CAS  PubMed  Google Scholar 

  33. Wanchu A, Suryanaryana BS, Sharma S, Sharma A, Bambery P. High-dose prednisolone and bolus cyclophosphamide in interstitial lung disease associated with systemic sclerosis: a prospective open study. Int J Rheum Dis. 2009;12:239–42. https://doi.org/10.1111/j.1756-185X.2009.01417.

    Article  PubMed  Google Scholar 

  34. Vanthuyne M, Blockmans D, Westhovens R, Roufosse F, Coga E, Coche E, et al. A pilot study of mycophenolate mofetil combined to intravenous methylprednisolone pulses and oral low-dose glucocorticoids in severe early systemic sclerosis. Clin Exp Rheumatol. 2007;25:287–92.

    CAS  PubMed  Google Scholar 

  35. •• Kowal-Bielecka O, Fransen J, Avouac J, Becker M, Kulak A, Allonore Y, et al. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis. 2017;76:1327–39. https://doi.org/10.1136/annrheumdis-2016-209909 This article reviews evidence behind current treatment guidelines for systemic sclerosis.

    Article  PubMed  Google Scholar 

  36. Tashkin DP, Elashoff R, Clements PJ, Goldin J, Roth MD, Furst DE, et al. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med. 2006;365:2655–66. https://doi.org/10.1056/NEJMoa055120.

    Article  Google Scholar 

  37. Tashkin DP, Elashoff R, Clements PJ, Rokth MD, Furst DE, Silver RM, et al. 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. https://doi.org/10.1164/rccm.200702-326OC.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Hoyles RK, Ellis RW, Wellsbury J, Lees B, Newlands P, Goh NS, et al. 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. https://doi.org/10.1002/art.22204.

    Article  CAS  PubMed  Google Scholar 

  39. Nannini C, West CP, Erwin PJ, Matteson EL. Effects of cyclophosphamide on pulmonary function in patients with scleroderma and interstitial lung disease: a systematic review and meta-analysis of randomized controlled trials and observational prospective cohort studies. Arthritis Res Ther. 2008;10(5):R124. https://doi.org/10.1186/ar2534.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. •• Tashkin DP, Roth MD, Clements PJ, Furst DE, Khanna D, Kleerup EC, et al. Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial. Lancet Respir Med. 2016;4:708–19. doi: 10.1016/S2213-2600(16)30152-7. This randomized trial in scleroderma interstitial lung disease compares mycophenolate to cyclophosphamide. Mycophenolate has similar efficacy, but is less toxic.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Berezne A, Ranque B, Valeyre D, Brauner M, Allanore Y, Launay D, et al. Therapeutic strategy combining intravenous cyclophosphamide followed by oral azathioprine to treat worsening interstitial lung disease associated with systemic sclerosis: a retrospective multicenter open-label study. J Rheumatol. 2008;35:1064–72.

    CAS  PubMed  Google Scholar 

  42. Poormoghim H, Rezaei N, Sheidaie Z, Almasi AR, Moradi-Lakeh M, Almasi S, et al. Systemic sclerosis: comparison of efficacy of oral cyclophosphamide and azathioprine on skin score and pulmonary involvement—a retrospective study. Rheumatol Int. 2014;34:1691–9. https://doi.org/10.1007/s00296-014-3026-7.

    Article  CAS  PubMed  Google Scholar 

  43. Daoussis D, Liossis SN, Tsamandas AC, Kalogeropoulou C, Kazantzi A, Sirinian C, et al. Experience with rituximab in scleroderma: results from a 1-year, proof-of-principle study. Rheumatology (Oxford). 2010;49:271–80. https://doi.org/10.1093//rheumatology/kep093.

    Article  CAS  Google Scholar 

  44. Daoussis D, Liossis SN, Tsamandas AC, Kalogeropoulou C, Paliogianni F, Sirinian C, et al. Effect of long-term treatment with rituximab on pulmonary function and skin fibrosis in patients with diffuse systemic sclerosis. Clin Exp Rheumatol. 2012;30:S17–22.

    PubMed  Google Scholar 

  45. Daoussis D, Melissaropoulos K, Sakellaropoulos G, Antonopoulos I, Markatseli TE, Simopoulou T, et al. A multicenter, open-label, comparative study of B-cell depletion therapy with rituximab for systemic sclerosis-associated interstitial lung disease. Semin Arthritis Rheum. 2017;46:625–31. https://doi.org/10.1016/j.semarthrit.2016.10.003.

    Article  CAS  PubMed  Google Scholar 

  46. Daoussis D, Melissaropoulos K, Sakellaropoulos G, Antonopoulos I, Markatseli TE, Simopoulou T, et al. A multicenter, open-label, comparative study of B-cell depletion therapy with rituximab for systemic sclerosis-associated interstitial lung disease. Semin Arthritis Rheum. 2017;46(5):625–31. https://doi.org/10.1016/j.semarthrit.2016.10.003.

    Article  CAS  PubMed  Google Scholar 

  47. van Laar JM, Farge D, Sont JK, Naraghi K, Marjanovic Z, Larghero J, et al. Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial. JAMA. 2014 25;311:2490–8. doi: https://doi.org/10.1001/jama.2014.6368.

    Article  CAS  PubMed  Google Scholar 

  48. • Sullivan KM, Goldmuntz EA, Keyes-Elstein L, McSweeney PA, Pinckney A, Welch B, et al. Myeloablative autologous stem-cell transplantation for severe scleroderma. N Engl J Med. 2018;378:35–47. https://doi.org/10.1056/NEJMoa1703327 Clinical trial revealing significant long-term benefit from autologous stem cell transplantation in patients with scleroderma, including a benefit in pulmonary function.

    Article  PubMed  PubMed Central  Google Scholar 

  49. • Khanna D, Denton CP, Lin CJF, van Laar JM, Frech TM, Anderson ME, et al. Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial (faSScinate). Ann Rheum Dis. 2018;77:212–20. https://doi.org/10.1136/annrheumdis-2017-211682 An interesting phase II trial, which suggests a benefit from tocilizumab in scleroderma associated interstitial lung disease.

    Article  PubMed  Google Scholar 

  50. King TE Jr, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2083–92. https://doi.org/10.1056/NEJMoa1402582.

    Article  CAS  PubMed  Google Scholar 

  51. Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2071–82. https://doi.org/10.1056/NEJMoa1402584.

    Article  CAS  PubMed  Google Scholar 

  52. Huang J, Maier C, Zhang Y, Soare A, Dees C, Beyer C, et al. Nintedanib inhibits macrophage activation and ameliorates vascular and fibrotic manifestations in the Fra2 mouse model of systemic sclerosis. Ann Rheum Dis. 2017;76:1941–8. https://doi.org/10.1136/annrheumdis-2016-210823.

    Article  CAS  PubMed  Google Scholar 

  53. Distler O, Brown KK, Distler JHW, Assassi S, Maher TM, Cottin V, et al. Design of a randomised, placebo-controlled clinical trial of nintedanib in patients with systemic sclerosis-associated interstitial lung disease (SENSCIS). Clin Exp Rheumatol. 2017 Suppl 106(4):75–81.

  54. Khanna D, Albera C, Fischer A, Khalidi N, Raghu G, Chung L, et al. An open-label, phase II study of the safety and tolerability of pirfenidone in patients with scleroderma-associated interstitial lung disease: the LOTUSS trial. J Rheumatol. 2016;43:1672–9. https://doi.org/10.3899/jrheum.151322.

    Article  PubMed  Google Scholar 

  55. Bogatlkevich GS, Ludwicka-Bradley A, Silver RM. Dabigatran, a direct thrombin inhibitor, blocks differentiation of normal fibroblasts to a myofibroblast phenotype and demonstrates anti-fibrotic effects on scleroderma lung fibroblasts. Arthritis Rheum. 2009;60:3455–64. https://doi.org/10.1002/art.24935.

    Article  CAS  Google Scholar 

  56. Sharp GC, Irvin WS, Tan EM, Gould RG, Holman HR. Mixed connective tissue disease-an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA). Am J Med. 1972;52:148–59.

    Article  CAS  PubMed  Google Scholar 

  57. Zimmerman C, Steiner G, Skriner K, Hassfeld W, Petera P, Smolen. The concurrence of rheumatoid arthritis and limited systemic sclerosis: clinical and serological characteristics of an overlap syndrome. Arthritis Rheum 1998; 41:1938–45. doi: 10.1002/1529-0131(199811)41:11<1938::AID-ART7>3.0.CO;2-X.

  58. Ortega-Hernandez O-D, Shoenfeld Y. Mixed connective tissue disease: an overview of clinical manifestations, diagnosis and treatment. Best Pract Res Clin Rheumatol. 2012;26:61–72. https://doi.org/10.1016/j.berh.2012.01.009.

    Article  CAS  PubMed  Google Scholar 

  59. Kahn MF, Appelboom T. Syndrome de Sharp. In: Kahn MF, Peltier AP, Meyer O, Piette JC, editors. Les maladies systemiques. 3rd ed. Paris: Flammarion; 1991. p. 454–6.

    Google Scholar 

  60. Kasukawa R, Tojo T, Miyawaki S. Preliminary diagnostic criteria for classification of mixed connective tissue disease. In: Kasukawa R, Sharp G, editors. Mixed connective tissue disease and antinuclear antibodies. Amsterdam: Elsevier; 1987. p. 41–7.

    Google Scholar 

  61. Sharp GC. Diagnostic criteria for classification of MCTD. In: Kasukawa R, Sharp GC, editors. Mixed connective tissue diseases and antinuclear antibodies. Amsterdam: Elsevier; 1987. p. 23–32.

    Google Scholar 

  62. Alarcón-Segovia D, Villareal M. Classification and diagnostic criteria for mixed connective tissue disease. In: Kasukawa R, Sharp GC, editors. Mixed connective tissue disease and antinuclear antibodies. Amsterdam: Elsevier; 1987. p. 33–40.

    Google Scholar 

  63. Sullivan WD, Hurst DJ, Harmon CE, Esther JH, Agia GA, Maltby JD, et al. A prospective evaluation emphasizing pulmonary involvement in patients with mixed connective tissue disease. Medicine (Baltimore). 1984;63:92–107.

    Article  CAS  Google Scholar 

  64. O’Connell DJ, Bennett RM. Mixed connective tissue disease: clinical and radiological aspects of 20 cases. Br J Radiol. 1977;50:620–5. https://doi.org/10.1259/0007-1285-50-597-620.

    Article  PubMed  Google Scholar 

  65. Wiener-Kronish JP, Solinger AM, Warnock ML, Churg A, Ordonez N, Golden JA. Severe pulmonary involvement in mixed connective tissue disease. Am Rev Respir Dis. 1981;124:499–503. https://doi.org/10.1164/arrd.1981.124.4.499.

    Article  CAS  PubMed  Google Scholar 

  66. Derderian SS, Tellis CJ, Abbbrecht PH, Welton RC, Rajagopal KR. Pulmonary involvement in mixed connective tissue disease. Chest. 1985;88:45–8.

    Article  CAS  PubMed  Google Scholar 

  67. Bennett RM, O’Connell DJ. Mixed connective tissue disease: a clinicopathologic study of 20 cases. Semin Arthritis Rheum. 1980;10:25–51.

    Article  CAS  PubMed  Google Scholar 

  68. Burdt MA, Hoffman RW, Deutscher SL, Wang GS, Johnson JC, Sharp GC. Long-term outcome in mixed connective tissue disease: longitudinal clinical and serologic findings. Arthritis Rheum. 1999;42:899–909. https://doi.org/10.1002/1529-0131(199905)42:5,899::AID-ANR8>3.0.CO;2-L.

    Article  CAS  PubMed  Google Scholar 

  69. Alpert MA, Goldberg SH, Singsen BH, Durham JB, Sharp GC, Ahmad M, et al. Cardiovascular manifestations of mixed connective tissue disease in adults. Circulation. 1983;68:1182–93.

    Article  CAS  PubMed  Google Scholar 

  70. Saito Y, Terada M, Takada T, Ishida T, Moriyama H, Ooi H, et al. Pulmonary involvement in mixed connective tissue disease: comparison with other collagen vascular disease using high resolution CT. J Comput Assit Tomogr. 2002;36:349–57.

    Article  Google Scholar 

  71. Bodolay E, Szekanecz Z, Dévényl K, Galuska L, Csípő I, Veègh J, et al. Evaluation of interstitial lung disease in mixed connective tissue disease (DMTC). Rheumatology. 2005;44:656–81. https://doi.org/10.1093/rheumatology/keh575.

    Article  CAS  PubMed  Google Scholar 

  72. Kozuka T, Johkoh T, Honda O, Mihara N, Koyama M, Tomiyama N, et al. Pulmonary involvement in mixed connective tissue disease: high resolution CT findings in 41 patients. J Thorac Imag. 2001;16:94–8.

    Article  CAS  Google Scholar 

  73. American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This Joint Statement of the American Thoracic Society (ATS) and the European Respiratory Society (ERS) was adopted by the ATS Board of Directors, June 2001, and The ERS Executive Committee, June 2001. Am J Respir Crit Care Med. 2002;165:277–304. https://doi.org/10.1164/ajrccm.165.2.ats01.

  74. Bull TM, Fagan KA, Badesch DB. Pulmonary vascular manifestations of mixed connective tissue disease. Rheum Dis Clin N Am. 2005;31:451–64. https://doi.org/10.1016/jrdc.2005.04.010.

    Article  Google Scholar 

  75. Kim EA, Lee KS, Johkoh T, Kim TS, Suh GY, Kwon OJ, et al. Interstitial lung diseases associated with collagen vascular diseases: radiologic and histopathologic findings. Radiographics. 2002;22:15S–65S. https://doi.org/10.1148/radiogrpahics.22.suppl_1.g020c04s151.

    Article  Google Scholar 

  76. Fagundes MN, Caleiro MTC, Navarro-Rodriguez T, Baldi BG, Kavakama J, Salge JM, et al. Esophageal involvement and interstitial lung disease in mixed connective tissue disease. Respir Med. 2009;103:854–60. https://doi.org/10.1016/j.rmed.2008.12.018.

    Article  CAS  PubMed  Google Scholar 

  77. Gunnarsson R, Aaløkken TM, Molberg Ø, Lund MB, Mynarek GK, Lexberg ÅS, et al. Prevalence and severity of interstitial lung disease in mixed connective tissue disease: a nationwide, cross-sectional study. Ann Rheum Dis. 2012;71:1966–72. https://doi.org/10.1136/annrheumdis-2011-201253.

    Article  PubMed  Google Scholar 

  78. •• Brito Y, Glassberg M, Asherman DP. Rheumatoid arthritis-associated interstitial lung disease: current concepts. Curr Rheumatol Rep. 2017;19:79. https://doi.org/10.1007/s11926-017-0701-5 A nice detailed review of rheumatoid arthritis associated interstitial lung disease.

    Article  CAS  PubMed  Google Scholar 

  79. Olson AL, Swigris JJ, Sprunger DB, Fischer A, Fernanez-Perez ER, Solomon J, et al. Rheumatoid arthritis-interstitial lung disease-associated mortality. Am J Respir Crit Care Med. 2011;183:372–8. https://doi.org/10.1164/rccm.201004-0622OC.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Hyldgaard C, Hilbert O, Pedersen AB, Ulrichsen SP, Lokke A, Bedstraw E, et al. A population-based cohort study of rheumatoid arthritis-associated interstitial lung disease: comorbidity and mortality. Ann Rheum Dis 2017; 76:1700–6. 10.1136/annrheumdis-2017-211138.

    Article  PubMed  Google Scholar 

  81. Kim DS. Interstitial lung disease in rheumatoid arthritis: recent advances. Curr Opin Pulm Med. 2006;12:346–53. https://doi.org/10.1097/01.mcp.0000239552.55326.ee.

    Article  PubMed  Google Scholar 

  82. Lee HK, Kim DS, Yoo B, Seo JB, Rho JY, Colby TV, et al. Histopathologic pattern and clinical features of rheumatoid arthritis-associated interstitial lung disease. Chest. 2005;127:2019–27. https://doi.org/10.1378/chest.127.6.2019.

    Article  PubMed  Google Scholar 

  83. Sato T, Fujita J, Yamadori I, Ohtsuki Y, Yoshinouchi T, Bandoh S, et al. Non-specific interstitial pneumonia; as the first clinical presentation of various collagen vascular disorders. Rheumatol Int. 2006;26:551–5. https://doi.org/10.1007/s00296-005-0028-9.

    Article  PubMed  Google Scholar 

  84. Brannan HM, Good CA, Divertie MB, Baggenstoss AH. Pulmonary disease associated with rheumatoid arthritis. JAMA. 1964;189:914–8.

    Article  CAS  PubMed  Google Scholar 

  85. Antin-Ozerkis D, Evans J, Rubinowitz A, Homer RJ, Matthay RA. Pulmonary manifestations of rheumatoid arthritis. Clin Chest Med. 2010;31(3):451–78. https://doi.org/10.1016/j.ccm.2010.04.003.

    Article  PubMed  Google Scholar 

  86. Cervantes-Perez P, Toro-Perez AH, Rodriguez-Jurado P. Pulmonary involvement in rheumatoid arthritis. JAMA. 1980;243:1715–9.

    Article  CAS  PubMed  Google Scholar 

  87. Cortet B, Perez T, Roux N, Flipo RM, Duquesnoy B, Delcambre B, et al. Pulmonary function tests and high resolution computed tomography of the lungs in patients with rheumatoid arthritis. Ann Rheum Dis. 1997;56:596–600.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Dawson JK, Fewins HE, Desmond J, Lymch MP, Graham DR. Fibrosing alveolitis in patients with rheumatoid arthritis as assessed by high resolution computed tomography, chest radiography, and pulmonary function tests. Thorax. 2001;56:622–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Gochuico BR, Avila NA, Chow CK, Novero LJ, Wu HP, Ren P, et al. Progressive preclinical interstitial lung disease in rheumatoid arthritis. Arch Intern Med. 2008;168:159–66. https://doi.org/10.1001/archinternmed.2007.59.

    Article  CAS  PubMed  Google Scholar 

  90. Lamblin C, Bergoin C, Saelens T, Wallaert B. Interstitial lung diseases in collagen vascular diseases. Eur Respir J Suppl. 32:69s–80s.

  91. Cordier JF. Cryptogenic organising pneumonia. Eur Respir J. 2006;28(2):422–46. https://doi.org/10.1183/09031936.06.00013505.

    Article  PubMed  Google Scholar 

  92. Hilliquin P, Renoux M, Perrot S, Puechal X, Menkes CJ. Occurrence of pulmonary complications during methotrexate therapy in rheumatoid arthritis. Br J Rheumatol. 1996;35(5):441–5.

    Article  CAS  PubMed  Google Scholar 

  93. Cooper JA Jr, White DA, Matthay RA. Drug-induced pulmonary disease. Part 1: cytotoxic drugs. Am Rev Respir Dis. 1986;133(2):321–40. https://doi.org/10.1164/arrd.1986.133.2.321.

    Article  CAS  PubMed  Google Scholar 

  94. Solomon JJ, Chung JH, Cosgrove GP, Demoruelle MK, Fernandez-Perez ER, Fischer A, et al. Predictors of mortality in rheumatoid arthritis-associated interstitial lung disease. Eur Respir J. 2016;47:588–96. https://doi.org/10.1183/13993003.00357-2015.

    Article  PubMed  Google Scholar 

  95. Zamora-Legoff JA, Krause ML, Crowson CS, Ryu JH, Matteson EL. Patterns of interstitial lung disease and mortality in rheumatoid arthritis. Rheumatology (Oxford). 2017;56(3):344–50. https://doi.org/10.1093/rheumatology/kew391.

    Article  CAS  Google Scholar 

  96. van Vollenhoven RF. Treatment of rheumatoid arthritis: state of the art 2009. Nat Rev Rheumatol. 2009;5:531–41. https://doi.org/10.1038/nrrheum.2009.182.

    Article  CAS  PubMed  Google Scholar 

  97. Kelly C, Saravanan V. Treatment strategies for a rheumatoid arthritis patient with interstitial lung disease. Expert Opin Pharmacother. 2008;9(18):3221–30. https://doi.org/10.1517/14656560802591430.

    Article  CAS  PubMed  Google Scholar 

  98. Antoniou KM, Margaritopoulos G, Economidou F, Siafakas NM. Pivotal clinical dilemmas in collagen vascular diseases associated with interstitial lung involvement. Eur Respir J. 2009;33:882–96. https://doi.org/10.1183/09031936.00152607.

    Article  CAS  PubMed  Google Scholar 

  99. Chang HK, Park W, Ryu DS. Successful treatment of progressive rheumatoid interstitial lung disease with cyclosporine: a case report. J Korean Med Sci. 2002;17(2):270–3. https://doi.org/10.3346/jkms.2002.17.2.270.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Antoniou KM, Mamoulaki M, Malagari K, Kritikos HD, Bouros D, Siafakas NM, et al. Infliximab therapy in pulmonary fibrosis associated with collagen vascular disease. Clin Exp Rheumatol. 2007;25:23–8.

    CAS  PubMed  Google Scholar 

  101. Mohr M, Jacobi AM. Interstitial lung disease in rheumatoid arthritis: response to IL-6R blockade. Scand J Rheumatol. 2011;40(5):400–1. https://doi.org/10.3109/03009742.2011.599072.

    Article  CAS  PubMed  Google Scholar 

  102. •• Dixon WG, Hyrich KL, Watson KD, Lunt M, Symmons DPM, BSRBR Control Center Consortium. Influence of anti-TNF therapy on mortality in patients with rheumatoid arthritis-associated interstitial lung disease: results from the British Society for Rheumatology. Ann Rheum Dis 2010; 69:1086-1091. doi: 10.1136/ard.2009.120626. A nice study of a large database of patients on anti-TNF therapy and its influence on interstitial lung disease.

    Article  CAS  PubMed  Google Scholar 

  103. • Yusof MY MD, Kabia A, Darby M, Lettieri G, Beirne P, Vital EM. Effect of rituximab on the progression of rheumatoid arthritis-related interstitial lung disease: 10 years’ experience at a single centre. Rheumatol. 2017;56:1348–57. https://doi.org/10.1093/rheumatology/kex072 A case series of patients receiving rituximab that are followed for 10 years suggesting that rituximab may be beneficial in patients with ILD and may decrease incidence of ILD.

    Article  CAS  Google Scholar 

  104. Mimori T, Nakashima R, Hosono Y. Interstitial lung disease in myositis: clinical subsets, biomarkers, and treatment. Curr Rheumatol Rep. 2012;14:264–74. https://doi.org/10.1007/s11926-012-0246-6.

    Article  CAS  PubMed  Google Scholar 

  105. Chen IH, Jan Wu YJ, Lin C, Kwa F, Luo SF, Ho HH, et al. Interstitial lung disease in polymyositis and dermatomyositis. Clin Rheumatol. 2009;28:639–46. https://doi.org/10.1007/s10067-009-111-6.

    Article  PubMed  Google Scholar 

  106. Miller SA, Glassberg MK, Ascherman DP. Pulmonary complications of inflammatory myopathy. Rheum Dis Clin N Am. 2015;41:249–62. https://doi.org/10.1016/j.rdc.2014.12.006.

    Article  Google Scholar 

  107. Won Huh J, Soon Kim D, Keun Lee C, Yoo B, Bum Seo J, Kitaichi M, et al. Two distinct clinical types of interstitial lung disease associated with polymyositis-dermatomyositis. Respir Med. 2007;101:1761–9. https://doi.org/10.1016/j.rmed.2007.02.017.

    Article  PubMed  Google Scholar 

  108. Koreeda Y, Higashimoto I, Yamamoto M, Takahashi M, Kaji K, Fujimoto M, et al. Clinical and pathological findings of interstitial lung disease patients with anti-aminoacyl-tRNA synthetase autoantibodies. Intern Med. 2010;49:361–9. https://doi.org/10.2169/internalmedicine,.49.2889.

    Article  PubMed  Google Scholar 

  109. Marie I, Josse S, Hatron PY, Dominique S, Hachulla E, Janvresse A, et al. Interstitial lung disease in anti-Jo-1 patients with antisynthetase syndrome. Arthritis Care Res (Hoboken). 2013;65:800–8. https://doi.org/10.1002/acr.21895.

    Article  CAS  Google Scholar 

  110. 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. https://doi.org/10.1371/journal.pone.0060442.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Hervier B, Benveniste O. Clinical heterogeneity and outcomes of antisynthetase syndrome. Curr Rheumatol Rep. 2013;15:349. https://doi.org/10.1007/s11926-013-0349-8.

    Article  CAS  PubMed  Google Scholar 

  112. Cao H, Pan M, Kang Y, Kang Y, **a Q, Li X, et al. Clinical manifestations of dermatomyositis and clinically amyopathic dermatomyositis patients with positive expression of antimelanoma differentiation-associated gene 5 antibody. Arthritis Care Res (Hoboken). 2012;64:1602–10. https://doi.org/10.1002/acr.21728.

    Article  Google Scholar 

  113. Hallowell RW, Ascherman DP, Danoff SK. Pulmonary manifestations of polymyositis/ dermatomyositis. Semin Respir Crit Care Med. 2014;35:239–48. https://doi.org/10.1055/s-0034-1371528.

    Article  PubMed  Google Scholar 

  114. Tazelaar H, Viggiano R, Pickersgill J, Colby TV. Interstitial lung disease in polymyositis and dermatomyositis, clinical features and prognosis as correlated with histologic findings. Am Rev Respir Dis. 1990;141:727–33. https://doi.org/10.1164/ajrccm/141.3.727.

    Article  CAS  PubMed  Google Scholar 

  115. Olsson KM, Palazzini M. Challenges in pulmonary hypertension: managing the unexpected. Eur Respir Rev. 2015;24(138):674–81. https://doi.org/10.1183/16000617.0060-2015.

    Article  PubMed  Google Scholar 

  116. Parambil JG, Myers JL, Lindell RM, Matteson EL, Ryu JH. Interstitial lung disease in primary Sjogren syndrome. Chest. 2006;130(5):1489–95. https://doi.org/10.1378/chest.130.5.1489.

    Article  PubMed  Google Scholar 

  117. Palm O, Garen T, Berge Enger T, Jensen JL, Lund MB, Aalokken TM, et al. Clinical pulmonary involvement in primary Sjogren’s syndrome: prevalence, quality of life and mortality—a retrospective study based on registry data. Rheumatology (Oxford). 2013;52(1):173–9. https://doi.org/10.1093/rheumatology/kes311.

    Article  Google Scholar 

  118. Matsuyama N, Ashizawa K, Okimoto T, Kadota J, Amano H, Hayashi K. Pulmonary lesions associated with Sjogren’s syndrome: radiographic and CT findings. Br J Radiol. 2003;76(912):880–4. https://doi.org/10.1259/bjr/18937619.

    Article  CAS  PubMed  Google Scholar 

  119. Roca F, Dominique S, Schmidt J, Smail A, Duhaut P, Lévesque H, et al. Interstitial lung disease in primary Sjögren’s syndrome. Autoimmun Rev. 2017;16(1):48–54. https://doi.org/10.1016/j.autrev.2016.09.01.

    Article  CAS  PubMed  Google Scholar 

  120. •• Flament T, Bigot A, Chaigne B, Henique H, Diot E, Marchand-Adam S. Pulmonary manifestations of Sjögren’s syndrome. Eur Respir Rev. 2016;25(140):110–23. https://doi.org/10.1183/16000617.0011-2016 An excellent review on the epidemiology, presentations, diagnosis, and treatment of the multiple pulmonary manifestations of Sjögren syndrome patients.

    Article  PubMed  Google Scholar 

  121. Reina D, Roig Vilaseca D, Torrente-Segarra V, Cerdà D, Castellví I, Díaz Torné C, et al. Sjögren’s syndrome-associated interstitial lung disease: a multicenter study. Reumatol Clin. 2015;12(xx):3–7. https://doi.org/10.1016/j.reuma.2015.09.003.

    Article  Google Scholar 

  122. Sebastian A, Misterska-Skóra M, Silicki J, Sebastian M, Wiland P. Chest HRCT findings in patients with primary Sjögren’s syndrome. Adv Clin Exp Med. 2017;26(7):1101–6. https://doi.org/10.17219/acem/68978.

    Article  PubMed  Google Scholar 

  123. Mira-Avendano IC, Abril A. Pulmonary manifestations of Sjögren syndrome, systemic lupus erythematosus, and mixed connective tissue disease. Rheum Dis Clin N Am. 2015;41(2):263–77. https://doi.org/10.1016/j.rdc.2015.01.001.

    Article  Google Scholar 

  124. Vivero M, Padera RF. Histopathology of lung disease in the connective tissue diseases. Rheum Dis Clin N Am. 2015;41(2):197–211. https://doi.org/10.1016/j.rdc.2014.12.002.

    Article  Google Scholar 

  125. M. K, E.C. R. Pulmonary involvement in Sjogren syndrome. Clin Chest Med. 2014;31(3):489–500. doi:10.1016/j.ccm.2010.05.007

    Article  PubMed  Google Scholar 

  126. Kokosi M, Riemer EC, Highland KB. Pulmonary involvement in Sjögren syndrome. Clin Chest Med. 2010;31(3):489–500. https://doi.org/10.1016/j.ccm.2010.05.007.

    Article  PubMed  Google Scholar 

  127. Kadota J, Kusano S, Kawakami K, Morikawa T, Kohno S. Usual interstitial pneumonia associated with primary Sjögren’s syndrome. Chest. 1995;108(6):1756–8.

    Article  CAS  PubMed  Google Scholar 

  128. Ramos-Casals M, Brito-Zerón P, Seror R, Bootsma H, Bowman SJ, Dörner T, et al. Characterization of systemic disease in primary Sjögren’s syndrome: EULAR-SS Task Force recommendations for articular, cutaneous, pulmonary and renal involvements. Rheumatol (United Kingdom). 2015;54(12):2230–8. https://doi.org/10.1093/rheumatology/kev200.

    Article  Google Scholar 

  129. Honda O, Johkoh T, Ichikado K, Tomiyama N, Maeda M, Mihara N, et al. Differential diagnosis of lymphocytic interstitial pneumonia and malignant lymphoma on high-resolution CT. AJR Am J Roentgenol. 1999;173(1):71–4. https://doi.org/10.2214/ajr.173.1.10397102.

    Article  CAS  PubMed  Google Scholar 

  130. Ito I, Nagai S, Kitaichi M, Nicholson AG, Johkoh T, Noma S, et al. Pulmonary manifestations of primary Sjogren’s syndrome: a clinical, radiologic, and pathologic study. Am J Respir Crit Care Med. 2005;171(6):632–8. https://doi.org/10.1164/rccm.200403-417OC.

    Article  PubMed  Google Scholar 

  131. • Panchabhai TS, Farver C, Highland KB. Lymphocytic interstitial pneumonia. Clin Chest Med. 2016;37(3):463–74. https://doi.org/10.1016/j.ccm.2016.04.009 Nicely describes de clinical presentation and pathologic findings of lymphocytic interstitial pneumonia (LIP) and characterizes some of the clues to distinguish this entity from lymphoma.

    Article  PubMed  Google Scholar 

  132. Gupta N, Wikenheiser-Brokamp KA, Fischer A, McCormack FX. Diffuse cystic lung disease as the presenting manifestation of Sjögren syndrome. Ann Am Thorac Soc. 2016;13(3):371–5. https://doi.org/10.1513/AnnalsATS.201511-759BC.

    Article  PubMed  PubMed Central  Google Scholar 

  133. Thompson G, Mclean-Tooke A, Wrobel J, Lavender M, Lucas M. Sjögren syndrome with associated lymphocytic interstitial pneumonia successfully treated with tacrolimus and abatacept as an alternative to rituximab. Chest. 2018;153(3):756–9. https://doi.org/10.1016/j.chest.2017.12.010.

    Article  Google Scholar 

  134. Ramos-Casals M, Brito-Zeron P, Siso-Almirall A, Bosch X. Primary Sjogren syndrome. BMJ. 2012;344:e3821. https://doi.org/10.1136/bmj.e3821.

    Article  CAS  PubMed  Google Scholar 

  135. Gottenberg JE, Cinquetti G, Larroche C, Combe B, Hachulla E, Meyer O, et al. Efficacy of rituximab in systemic manifestations of primary Sjogren’s syndrome: results in 78 patients of the AutoImmune and Rituximab registry. Ann Rheum Dis. 2013;72(6):1026–31. https://doi.org/10.1136/annrheumdis-2012-202293.

    Article  CAS  PubMed  Google Scholar 

  136. Stojan G, Petri M. Epidemiology of systemic lupus erythematosus. Curr Opin Rheumatol. 2017;30(2):1–150. https://doi.org/10.1097/BOR.0000000000000480.

    Article  Google Scholar 

  137. Wan SA, Teh CL, Jobli AT. Lupus pneumonitis as the initial presentation of systemic lupus erythematosus: case series from a single institution. Lupus. 2016;25:1485–90. https://doi.org/10.1177/0961203316646461.

    Article  CAS  PubMed  Google Scholar 

  138. Alamoudi OSB, Attar SM. Pulmonary manifestations in systemic lupus erythematosus: association with disease activity. Respirology. 2015;20(3):474–80. https://doi.org/10.1111/resp.12473.

    Article  PubMed  PubMed Central  Google Scholar 

  139. Mittoo S, Fell C. Pulmonary manifestations of systemic lupus erythematosus. Semin Respir Crit Care Med. 2014;35(2):249–54. https://doi.org/10.1055/s-0034-1371537.

    Article  PubMed  Google Scholar 

  140. Mira-Avendano IC, Abril A. Pulmonary manifestations of Sjögren syndrome, systemic lupus erythematosus, and mixed connective tissue disease. Rheum Dis Clin N Am. 2015;41(2):263–77. https://doi.org/10.1016/j.rdc.2015.01.001.

    Article  Google Scholar 

  141. Tselios K, Urowitz MB. Cardiovascular and pulmonary manifestations of systemic lupus erythematosus. Curr Rheumatol Rev. 2017;13(3):206–18. https://doi.org/10.2174/1573397113666170704102444.

    Article  PubMed  Google Scholar 

  142. Carmier D, Marchand-Adam S, Diot P, Diot E. Respiratory involvement in systemic lupus erythematosus. Rev Mal Respir. 2010;27(8):e66–78. https://doi.org/10.1016/j.rmr.2010.01.00.

    Article  CAS  PubMed  Google Scholar 

  143. Memet B, Ginzler EM. Pulmonary manifestations of systemic lupus erythematosus. Lung. 2007;1(212):441–50. https://doi.org/10.1055/s-2007-985665.

    Article  Google Scholar 

  144. • Mathai SC, Danoff SK. Management of interstitial lung disease associated with connective tissue disease. BMJ. 2016:h6819. https://doi.org/10.1136/bmj.h6819 A thorough work that briefly discusses the differences in ILD between the different connective tissue diseases with a focus on management.

  145. •• Atzeni F, Gerardi MC, Barilaro G, Masala IF, Benucci M, Sarzi-Puttini P. Interstitial lung disease in systemic autoimmune rheumatic diseases: a comprehensive review. Expert Rev Clin Immunol. 2018;14(1):69–82. https://doi.org/10.1080/1744666X.2018.1411190 A comprehensive review on the pathogenesis of CTD-associated ILD and its distinguishing features in different rheumatic diseases. Clinical aspects and treatment options are also discussed with attention given to emergent treatments.

    Article  CAS  PubMed  Google Scholar 

  146. Vivero M, Padera RF. Histopathology of lung disease in the connective tissue diseases. Rheum Dis Clin N Am. 2015;41(2):197–211. https://doi.org/10.1016/j.rdc.2014.12.002.

    Article  Google Scholar 

  147. Swigris JJ, Olson AL, Fischer A, Lynch DA, Cosgrove GP, Frankel SK, et al. Mycophenolate mofetil is safe, well tolerated, and preserves lung function in patients with connective tissue disease-related interstitial lung disease. Chest. 2006;130(1):30–6. https://doi.org/10.1378/chest.130.1.30.

    Article  CAS  PubMed  Google Scholar 

  148. Lim SW, Gillis D, Smith W, Hissaria P, Greville H, Peh CA. Rituximab use in systemic lupus erythematosus pneumonitis and a review of current reports. Intern Med J. 2006;36(4):260–2. https://doi.org/10.1111/j.1445-5994.2006.01055.x.

    Article  CAS  PubMed  Google Scholar 

  149. Okada M, Suzuki K, Matsumoto M, Nakashima M, Nakanishi T, Takada K, et al. Intermittent intravenous cyclophosphamide pulse therapy for the treatment of active interstitial lung disease associated with collagen vascular diseases. Mod Rheumatol. 2007;17(2):131–6. https://doi.org/10.1007/s10165-007-0554-2.

    Article  CAS  PubMed  Google Scholar 

  150. • Papiris SA, Manali ED, Kolilekas L, Kagouridis K, Maniati M, Filippatos G, et al. Acute respiratory events in connective tissue disorders. Respiration. 2016;91(3):181–201. https://doi.org/10.1159/000444535 A nice review of diagnosing and managing acute exacerbations in connective tissue disease associated ILD.

    Article  PubMed  Google Scholar 

  151. Disayabutr S, Calfee CS, Collard HR, Wolters PJ. Interstitial lung diseases in the hospitalized patient. BMC Med. 2015;13:245. https://doi.org/10.1186/s12916-015-0487-0.

    Article  PubMed  PubMed Central  Google Scholar 

  152. Suda T, Kaida Y, Nakamura Y, Enomoto N, Fujisawa T, Imokawa S, et al. Acute exacerbation of interstitial pneumonia associated with collagen vascular diseases. Respir Med. 2009;103(6):846–53. https://doi.org/10.1016/j.rmed.2008.12.019.

    Article  PubMed  PubMed Central  Google Scholar 

  153. Hartwig MG, Anderson DJ, Onaitis MW, Reddy S, Snyder LD, Lin SS, et al. Fundoplication after lung transplantation prevents the allograft dysfunction associated with reflux. Ann Thorac Surg. 2011;92:462,8; discussion; 468–9–9. https://doi.org/10.1016/j.athoracsur.2011.04.035.

    Article  PubMed  PubMed Central  Google Scholar 

  154. Reid KR, McKenzie FN, Menkis AH, Novick RJ, Pflugfelder PW, Kostuk WJ, et al. Importance of chronic aspiration in recipients of heart-lung transplants. Lancet. 1990;336:206–8.

    Article  CAS  PubMed  Google Scholar 

  155. Davis CS, Shankaran V, Kovacs EJ, Gagermeier J, Dilling D, Alex CG, et al. Gastroesophageal reflux disease after lung transplantation: pathophysiology and implications for treatment. Surgery. 2010;148:737,44; discussion 744-5. https://doi.org/10.1016/j.surg2010.07.011.

    Article  Google Scholar 

  156. Young LR, Hadjiliadis D, Davis RD, Palmer SM. Lung transplantation exacerbates gastroesophageal reflux disease. Chest. 2003;124:1689–93.

    Article  PubMed  Google Scholar 

  157. Davis RD Jr, Lau CL, Eubanks S, Messier RH, Hadjiliadis D, Steele MP, et al. Improved lung allograft function after fundoplication in patients with gastroesophageal reflux disease undergoing lung transplantation. J Thorac Cardiovasc Surg. 2003;125:533–42. https://doi.org/10.1067/mtc.2003.166.

    Article  PubMed  Google Scholar 

  158. Sottile PD, Iturbe D, Katsumoto TR, Connolly MK, Collard HR, Leard LA, et al. Outcomes in systemic sclerosis-related lung disease after lung transplantation. Transplantation. 2013;95:975–80. https://doi.org/10.1097/TP.0b013e3182845f23.

    Article  PubMed  PubMed Central  Google Scholar 

  159. Miele CH, Schwab K, Saggar R, Duffy E, Elashoff D, Tseng CH, et al. Lung transplant outcomes in systemic sclerosis with significant esophageal dysfunction. A comprehensive single-center experience. Ann Am Thorac Soc. 2016;13:793–802. https://doi.org/10.1513/AnnalsATS.201512-806OC.

    Article  PubMed  PubMed Central  Google Scholar 

  160. Crespo MM, Bermudez CA, Dew MA, Johnson BA, George MP, Bhama J, et al. Lung transplant in patients with scleroderma compared with pulmonary fibrosis. Short- and long-term outcomes. Ann Am Thorac Soc. 2016;13:784–92. https://doi.org/10.1513/AmmalsATS.201503-177OC.

    Article  PubMed  Google Scholar 

  161. Pradere P, Tudorache I, Magnusson J, Savale L, Brugiere O, Douvry B, et al. Lung transplantation for scleroderma lung disease: an international, multicenter, observational cohort study. J Heart Lung Transplant. 2018;37:903–11. https://doi.org/10.1016/j.healun.2018.03.003.

    Article  PubMed  Google Scholar 

  162. Khan IY, Singer LG, de Perrot M, Granton JT, Keshavjee S, Chau C, et al. Survival after lung transplantation in systemic sclerosis. A systematic review. Respir Med. 2013;107:2081–7. https://doi.org/10.1016/j.rmed.2013.09.015.

    Article  PubMed  Google Scholar 

  163. Park JE, Kim SY, Song JH, Kim YS, Chang J, Lee JG, et al. Comparison of short-term outcomes for connective tissue disease-related interstitial lung disease and idiopathic pulmonary fibrosis after lung transplantation. J Thorac Dis. 2018;10(3):1538–47. https://doi.org/10.21037/jtd.2018.02.50.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Pulmonary and Critical Care Medicine, University of California San Diego, La Jolla, CA, USA

    Abhishek Gadre

  2. Cleveland Clinic Foundation, Respiratory Institute, 9500 Euclid Avenue, A90, Cleveland, OH, 44195, USA

    Kristin B. Highland

Authors
  1. Abhishek Gadre
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kristin B. Highland
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kristin B. Highland.

Ethics declarations

Conflict of Interest

Abhishek Gadre declares no conflict of interest. Highland receives grants/contracts, does consulting, and/or is on the Speaker’s Bureau of Actelion Pharmaceuticals, Bayer Healthcare, Boehringer Ingelheim, Eiger Pharmaceuticals, Gilead Sciences, Reata Pharmaceuticals, and United Therapeutics. Dr. Highland is the global coordinating investigator for the SENSCIS trial (nintedanib versus placebo for scleroderma associated lung disease). She is also a consultant for Boehringer Ingelheim and is on their Speaker’s Bureau. She is also a consultant for Boehringer Ingelheim and is on their Speaker’s Bureau.

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 Interstitial Lung Disease

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gadre, A., Highland, K.B. Connective Tissue Related Interstitial Lung Disease. Curr Pulmonol Rep 7, 133–148 (2018). https://doi.org/10.1007/s13665-018-0212-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13665-018-0212-5

Keywords

Search

Navigation