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Comparative analysis of connective tissue disease–associated interstitial lung disease and interstitial pneumonia with autoimmune features

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Abstract

Objective

This retrospective clinical study aimed to examine the similarities and differences between connective tissue disease–associated interstitial lung disease (CTD-ILD) and interstitial pneumonia with autoimmune features (IPAF) and to identify the influencing factors of CTD-ILD, with a goal of early detection and active treatment of the disease.

Methods

We conducted a retrospective study of 480 patients: 412 with CTD-ILD and 68 with IPAF. Demographic features, clinical characteristics, laboratory indicators, and chest high-resolution computed tomography (HRCT) imaging data were analyzed.

Results

Compared with the IPAF group, the CTD-ILD group contained more women, and the incidences of joint pain, dry mouth/dry eyes, and Raynaud’s phenomenon were higher; erythrocyte sedimentation rate (ESR) and D-dimer levels were higher; red blood cell (RBC) and hemoglobin (Hb) levels were lower; a high rheumatoid factor (RF) titer (> 2 times the normal upper limit) was observed, and anti-cyclic citrullinated peptide antibody (anti-CCP), anti-keratin antibody (AKA), antinuclear antibody (ANA), and anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5) levels were higher. Compared with CTD-ILD patients, IPAF patients were more likely to present initially with respiratory symptoms, with higher rates of fever, cough and expectoration, dyspnea, and Velcro crackles; anti-Ro52 titers were higher; incidences of honeycombing opacity, reticulate opacity, patchy opacity, and pleural thickening were greater. Female sex, a high RF titer (> 2 times the normal upper limit), anti-CCP positivity, ANA positivity, and anti-MDA5 positivity were risk factors for CTD-ILD when the odds ratios were adjusted.

Conclusion

CTD-ILD and IPAF patients differed in demographic features, clinical characteristics, laboratory indicators, and chest HRCT imaging data. Female sex, a high RF titer (> 2 times the normal upper limit), anti-CCP positivity, ANA positivity, and anti-MDA5 positivity were risk factors for CTD-ILD.

Key Points

• This retrospective clinical study comprehensively compared the demographic features, clinical characteristics, laboratory indicators, and chest HRCT imaging data of CTD-ILD and IPAF patients.

• The evidence suggested that female sex, a high RF titer, anti-CCP positivity, ANA positivity, and anti-MDA5 positivity were risk factors for CTD-ILD.

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References

  1. Antoniou KM, Margaritopoulos G, Economidou F, Siafakas NM (2009) Pivotal clinical dilemmas in collagen vascular diseases associated with interstitial lung involvement. Eur Respir J 33:882–896

    CAS  PubMed  Google Scholar 

  2. Tsuchiya Y, Fischer A, Solomon JJ, Lynch DA (2015) Connective tissue disease-related thoracic disease. Clin Chest Med 36(283-297):ix

    Google Scholar 

  3. Vij R, Strek ME (2013) Diagnosis and treatment of connective tissue disease-associated interstitial lung disease. Chest 143:814–824

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Koo SM, Uh ST (2017) Treatment of connective tissue disease-associated interstitial lung disease: the pulmonologist’s point of view. Korean J Intern Med 32:600–610

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Swigris JJ, Yorke J, Sprunger DB, Swearingen C, Pincus T, du Bois RM, Brown KK, Fischer A (2010) Assessing dyspnea and its impact on patients with connective tissue disease-related interstitial lung disease. Respir Med 104:1350–1355

    PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Demoruelle MK, Mittoo S, Solomon JJ (2016) Connective tissue disease-related interstitial lung disease. Best Pract Res Clin Rheumatol 30:39–52

    PubMed  Google Scholar 

  8. Nascimento ECTD, Baldi BG, Sawamura MVY, Dolhnikoff M (2018) Morphologic aspects of interstitial pneumonia with autoimmune features. Arch Pathol Lab Med 142:1080–1089

    PubMed  Google Scholar 

  9. Hu Y, Wang LS, Wei YR, Du SS, Du YK, He X, Li N, Zhou Y, Li QH, Su YL, Zhang F, Shen L, Weng D, Brown KK, Li HP (2016) Clinical characteristics of connective tissue disease-associated interstitial lung disease in 1,044 Chinese patients. Chest 149:201–208

    PubMed  Google Scholar 

  10. Kocheril SV, Appleton BE, Somers EC, Kazerooni EA, Flaherty KR, Martinez FJ, Gross BH, Crofford LJ (2005) Comparison of disease progression and mortality of connective tissue disease-related interstitial lung disease and idiopathic interstitial pneumonia. Arthritis Rheum 53:549–557

    CAS  PubMed  Google Scholar 

  11. Suzuki A, Kondoh Y, Fischer A (2017) Recent advances in connective tissue disease related interstitial lung disease. Expert Rev Respir Med 11:591–603

    CAS  PubMed  Google Scholar 

  12. Fischer A, du Bois R (2012) Interstitial lung disease in connective tissue disorders. Lancet 380:689–698

    PubMed  Google Scholar 

  13. Mira-Avendano I, Abril A, Burger CD, Dellaripa PF, Fischer A, Gotway MB, Lee AS, Lee JS, Matteson EL, Yi ES, Ryu JH (2019) Interstitial lung disease and other pulmonary manifestations in connective tissue diseases. Mayo Clin Proc 94:309–325

    PubMed  Google Scholar 

  14. De Langhe E, Lenaerts J, Bossuyt X, Westhovens R, Wuyts WA (2015) Mechanic’s hands in a woman with undifferentiated connective tissue disease and interstitial lung disease--anti-PL7 positive antisynthetase syndrome: a case report. J Med Case Rep 9:82

    PubMed  PubMed Central  Google Scholar 

  15. Strange C, Highland KB (2004) Interstitial lung disease in the patient who has connective tissue disease. Clin Chest Med 25:549–559 vii

    PubMed  Google Scholar 

  16. Jee AS, Adelstein S, Bleasel J, Keir GJ, Nguyen M, Sahhar J, Youssef P, Corte TJ (2017) Role of autoantibodies in the diagnosis of connective-tissue disease ILD (CTD-ILD) and interstitial pneumonia with autoimmune features (IPAF). J Clin Med 6:51

    PubMed Central  Google Scholar 

  17. Chartrand S, Swigris JJ, Stanchev L, Lee JS, Brown KK, Fischer A (2016) Clinical features and natural history of interstitial pneumonia with autoimmune features: a single center experience. Respir Med 119:150–154

    PubMed  Google Scholar 

  18. Fischer A, Antoniou KM, Brown KK, Cadranel J, Corte TJ, du Bois RM, Lee JS, Leslie KO, Lynch DA, Matteson EL, Mosca M, Noth I, Richeldi L, Strek ME, Swigris JJ, Wells AU, West SG, Collard HR, Cottin V (2015) An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. Eur Respir J 46:976–987

    CAS  PubMed  Google Scholar 

  19. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Ménard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovský J, Wolfe F, Hawker G (2010) 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 62:2569–2581

    Google Scholar 

  20. Shiboski CH, Shiboski SC, Seror R, Criswell LA, Labetoulle M, Lietman TM, Rasmussen A, Scofield H, Vitali C, Bowman SJ, Mariette X, International Sjögren’s Syndrome Criteria Working Group (2017) 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren’s syndrome: a consensus and data-driven methodology involving three international patient cohorts. Ann Rheum Dis 76:9–16

    Google Scholar 

  21. Aggarwal R, Rider LG, Ruperto N, Bayat N, Erman B, Feldman BM, Oddis CV, Amato AA, Chinoy H, Cooper RG, Dastmalchi M, Fiorentino D, Isenberg D, Katz JD, Mammen A, de Visser M, Ytterberg SR, Lundberg IE, Chung L, Danko K, García-De la Torre I, Song YW, Villa L, Rinaldi M, Rockette H, Lachenbruch PA, Miller FW, Vencovsky J, International Myositis Assessment and Clinical Studies Group and the Paediatric Rheumatology International Trials Organisation (2017) 2016 American College of Rheumatology/European League Against Rheumatism criteria for minimal, moderate, and major clinical response in adult dermatomyositis and polymyositis: an International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative. Ann Rheum Dis 76:792–801

    PubMed  PubMed Central  Google Scholar 

  22. Bradley B, Branley HM, Egan JJ, Greaves MS, Hansell DM, Harrison NK, Hirani N, Hubbard R, Lake F, Millar AB, Wallace WA, Wells AU, Whyte MK, Wilsher ML, British Thoracic Society Interstitial Lung Disease Guideline Group, British Thoracic Society Standards of Care Committee; Thoracic Society of Australia; New Zealand Thoracic Society; Irish Thoracic Society (2008) Interstitial lung disease guideline: the British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society. Thorax 63(Suppl 5):v1–v58

    PubMed  Google Scholar 

  23. Wannamethee SG, Whincup PH, Lennon L, Papacosta O, Lowe GD (2014) Associations between fibrin D-dimer, markers of inflammation, incident self-reported mobility limitation, and all-cause mortality in older men. J Am Geriatr Soc 62:2357–2362

    PubMed  PubMed Central  Google Scholar 

  24. Hargett CW, Tapson VF (2008) Clinical probability and D-dimer testing: how should we use them in clinical practice? Semin Respir Crit Care Med 29:15–24

    PubMed  Google Scholar 

  25. Paydar-Darian N, Kimia AA, Monuteaux MC, Michelson KA, Landschaft A, Maulden AB, Chenard RL, Nigrovic LE (2018) C-reactive protein or erythrocyte sedimentation rate results reliably exclude invasive bacterial infections. Am J Emerg Med S0735-6757:30919–30917

    Google Scholar 

  26. Kelkar AH, Shah AA, Yong SL, Ahmed Z (2017) An unusual association between hemophagocytic lymphohistiocytosis, mixed connective tissue disease, and autoimmune hemolytic anemia: a case report. Medicine (Baltimore) 96:e7488

    Google Scholar 

  27. Gormezano NW, Kern D, Pereira OL, Esteves GC, Sallum AM, Aikawa NE, Pereira RM, Silva CA, Bonfá E (2017) Autoimmune hemolytic anemia in systemic lupus erythematosus at diagnosis: differences between pediatric and adult patients. Lupus 26:426–430

    CAS  PubMed  Google Scholar 

  28. Katsumata K (2006) A case of systemic sclerosis complicated by autoimmune hemolytic anemia. Mod Rheumatol 16:191–195

    PubMed  Google Scholar 

  29. van Santen S, van Dongen-Lases EC, de Vegt F, Laarakkers CM, van Riel PL, van Ede AE, Swinkels DW (2011) Hepcidin and hemoglobin content parameters in the diagnosis of iron deficiency in rheumatoid arthritis patients with anemia. Arthritis Rheum 63:3672–3680

    PubMed  Google Scholar 

  30. Wen W, Liu Y, Zhao C, Sun X, Zhang C, Li Z (2015) Clinical and serologic features of primary Sjögren’s syndrome concomitant with autoimmune hemolytic anemia: a large-scale cross-sectional study. Clin Rheumatol 34:1877–1884

    PubMed  Google Scholar 

  31. Bas S, Perneger TV, Seitz M, Tiercy JM, Roux-Lombard P, Guerne PA (2002) Diagnostic tests for rheumatoid arthritis: comparison of anti-cyclic citrullinated peptide antibodies, anti-keratin antibodies and IgM rheumatoid factors. Rheumatology (Oxford) 41:809–814

    CAS  Google Scholar 

  32. Jearn LH, Kim TY (2016) Autoantibodies are already found in connective tissue disease-associated interstitial lung disease. Chest 150:753–755

    PubMed  Google Scholar 

  33. Kelmenson LB, Demoruelle MK, Deane KD (2016) The complex role of the lung in the pathogenesis and clinical outcomes of rheumatoid arthritis. Curr Rheumatol Rep 18:69

    PubMed  Google Scholar 

  34. 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

    CAS  PubMed  Google Scholar 

  35. Reynisdottir G, Karimi R, Joshua V, Olsen H, Hensvold AH, Harju A, Engström M, Grunewald J, Nyren S, Eklund A, Klareskog L, Sköld CM, Catrina AI (2014) Structural changes and antibody enrichment in the lungs are early features of anti-citrullinated protein antibody-positive rheumatoid arthritis. Arthritis Rheum 66:31–39

    CAS  Google Scholar 

  36. Tzelepis GE, Toya SP, Moutsopoulos HM (2008) Occult connective tissue diseases mimicking idiopathic interstitial pneumonias. Eur Respir J 31:11–20

    CAS  PubMed  Google Scholar 

  37. Tipu HN, Bashir MM (2018) Determination of specificity and pattern of antinuclear antibodies (ANA) in systemic rheumatic disease patients positive for ANA testing. J Coll Physicians Surg Pak 28:40–43

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  39. La Corte R, Lo Mo Naco A, Locaputo A, Dolzani F, Trotta F (2006) In patients with antisynthetase syndrome the occurrence of anti-Ro/SSA antibodies causes a more severe interstitial lung disease. Autoimmunity 39:249–253

    PubMed  Google Scholar 

  40. Huang W, Ren F, Wang Q, Luo L, Zhou J, Huang D, Pan Z, Tang L (2019) Clinical features of thirty-two patients with anti-melanoma differentiation-associated gene 5 antibodies. Clin Exp Rheumatol 2019 published on 11 Feb 2019

  41. Palawisuth S, Kantikosum K, Patiyasikunt M, Sriprasart T, Asawanonda P, Rerknimitr P (2019) A bad sign: dermatomyositis with interstitial lung disease. Am J Med 132:182–186

    PubMed  Google Scholar 

  42. Moghadam-Kia S, Oddis CV, Sato S, Kuwana M, Aggarwal R (2017) Antimelanoma differentiation-associated gene 5 antibody: expanding the clinical spectrum in North American patients with dermatomyositis. J Rheumatol 44:319–325

    CAS  PubMed  Google Scholar 

  43. Hall JC, Casciola-Rosen L, Samedy LA, Werner J, Owoyemi K, Danoff SK, Christopher-Stine L (2013) Anti-melanoma differentiation-associated protein 5-associated dermatomyositis: expanding the clinical spectrum. Arthritis Care Res 65:1307–1315

    CAS  Google Scholar 

  44. Chung JH, Chawla A, Peljto AL, Cool CD, Groshong SD, Talbert JL, McKean DF, Brown KK, Fingerlin TE, Schwarz MI, Schwartz DA, Lynch DA (2015) CT scan findings of probable usual interstitial pneumonitis have a high predictive value for histologic usual interstitial pneumonitis. Chest 147:450–459

    PubMed  Google Scholar 

  45. Oldham JM, Adegunsoye A, Valenzi E, Lee C, Witt L, Chen L, Husain AN, Montner S, Chung JH, Cottin V, Fischer A, Noth I, Vij R, Strek ME (2016) Characterisation of patients with interstitial pneumonia with autoimmune features. Eur Respir J 47:1767–1775

    CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This work was supported by the National Natural Science Foundation of China (grant No. 81771738).

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Authors and Affiliations

  1. Department of Rheumatology and Immunology, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Chongqing, 400010, China

    Mengxue Tian, Wenhan Huang, Feifeng Ren, Lei Luo, Jun Zhou, Dongmei Huang & Lin Tang

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  1. Mengxue Tian
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  2. Wenhan Huang
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Tian, M., Huang, W., Ren, F. et al. Comparative analysis of connective tissue disease–associated interstitial lung disease and interstitial pneumonia with autoimmune features. Clin Rheumatol 39, 575–583 (2020). https://doi.org/10.1007/s10067-019-04836-3

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