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Semin Respir Crit Care Med 2019; 40(02): 271-277
DOI: 10.1055/s-0039-1684007
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Interstitial Pneumonia with Autoimmune Features and Undifferentiated Connective Tissue Disease

Andrea K. Chernau
1   Rocky Vista University College of Osteopathic Medicine, Parker, Colorado
,
Paolo M. Leone
2   Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
3   Università Cattolica del Sacro Cuore, Roma, Italy
4   Interstitial Lung Disease Program, National Jewish Health, Denver, Colorado
,
Jeffrey J. Swigris
4   Interstitial Lung Disease Program, National Jewish Health, Denver, Colorado
› Author Affiliations
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Publication History

Publication Date:
28 May 2019 (online)

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Abstract

In 2015, a multidisciplinary task force comprising pulmonologists, rheumatologists, pathologists, and radiologists representing the European Respiratory Society and American Thoracic Society published a diagnostic classification schema for individuals with interstitial lung disease and autoimmune features who did not meet criteria for a defined connective tissue disease. The term interstitial pneumonia with autoimmune features (IPAF) was applied. Classification criteria are often nonspecific, but up to 90% of subjects with IPAF have serological evidence for autoimmunity (particularly (+) antinuclear antibodies). Distinguishing patients with IPAF from idiopathic pulmonary disorders may be difficult. The natural history and appropriate management of IPAF have not been clarified, as data are largely limited to retrospective studies. In this review, we discuss the salient clinical, serologic, histologic, and radiographic features of IPAF and discuss an approach to management.

Keywords

interstitial lung disease - autoimmune disease - connective tissue disease - interstitial pneumonia with autoimmune features (IPAF) - antinuclear antibody
 

  • References

  • 1 LeRoy EC, Maricq HR, Kahaleh MB. Undifferentiated connective tissue syndromes. Arthritis Rheum 1980; 23 (03) 341-343
    CrossrefPubMedSearch in Google Scholar
  • 2 LeRoy EC, Medsger Jr TA. Criteria for the classification of early systemic sclerosis. J Rheumatol 2001; 28 (07) 1573-1576
    PubMedSearch in Google Scholar
  • 3 Mosca M, Tani C, Neri C. , et al. [Analysis of the evolution to defined connective tissue diseases of patients with “early unidifferentiated connective tissue diseases (UCTD)”]. Reumatismo 2008; 60 (01) 35-40
    PubMedSearch in Google Scholar
  • 4 Mosca M, Tani C, Bombardieri S. Undifferentiated connective tissue diseases (UCTD): a new frontier for rheumatology. Best Pract Res Clin Rheumatol 2007; 21 (06) 1011-1023
    CrossrefPubMedSearch in Google Scholar
  • 5 Danieli MG, Fraticelli P, Franceschini F. , et al. Five-year follow-up of 165 Italian patients with undifferentiated connective tissue diseases. Clin Exp Rheumatol 1999; 17 (05) 585-591
    PubMedSearch in Google Scholar
  • 6 Ganczarczyk L, Urowitz MB, Gladman DD. “Latent lupus”. J Rheumatol 1989; 16 (04) 475-478
    PubMedSearch in Google Scholar
  • 7 Greer JM, Panush RS. Incomplete lupus erythematosus. Arch Intern Med 1989; 149 (11) 2473-2476
    CrossrefPubMedSearch in Google Scholar
  • 8 Swaak AJ, van de Brink H, Smeenk RJ. , et al; Study group on incomplete SLE and SLE with disease duration longer than 10 years. Incomplete lupus erythematosus: results of a multicentre study under the supervision of the EULAR Standing Committee on International Clinical Studies Including Therapeutic Trials (ESCISIT). Rheumatology (Oxford) 2001; 40 (01) 89-94
    PubMedSearch in Google Scholar
  • 9 Bodolay E, Csiki Z, Szekanecz Z. , et al. Five-year follow-up of 665 Hungarian patients with undifferentiated connective tissue disease (UCTD). Clin Exp Rheumatol 2003; 21 (03) 313-320
    PubMedSearch in Google Scholar
  • 10 Hoffman RW, Greidinger EL. Mixed connective tissue disease. Curr Opin Rheumatol 2000; 12 (05) 386-390
    CrossrefPubMedSearch in Google Scholar
  • 11 Riccardi A, Irace R, Di Stefano I. , et al. Lung involvement in “stable” undifferentiated connective tissue diseases: a rheumatology perspective. Clin Rheumatol 2017; 36 (08) 1833-1837
    CrossrefPubMedSearch in Google Scholar
  • 12 Nascimento ECTD, Baldi BG, Sawamura MVY, Dolhnikoff M. Morphologic aspects of interstitial pneumonia with autoimmune features. Arch Pathol Lab Med 2018; 142 (09) 1080-1089
    CrossrefPubMedSearch in Google Scholar
  • 13 Kinder BW, Shariat C, Collard HR. , et al. Undifferentiated connective tissue disease-associated interstitial lung disease: changes in lung function. Hai 2010; 188 (02) 143-149
    PubMedSearch in Google Scholar
  • 14 Fischer A, West SG, Swigris JJ, Brown KK, du Bois RM. Connective tissue disease-associated interstitial lung disease: a call for clarification. Chest 2010; 138 (02) 251-256
    CrossrefPubMedSearch in Google Scholar
  • 15 Fischer A, Antoniou KM, Brown KK. , et al; “ERS/ATS Task Force on Undifferentiated Forms of CTD-ILD”. An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. Eur Respir J 2015; 46 (04) 976-987
    CrossrefPubMedSearch in Google Scholar
  • 16 Oldham JM, Adegunsoye A, Valenzi E. , et al. Characterisation of patients with interstitial pneumonia with autoimmune features. Eur Respir J 2016; 47 (06) 1767-1775
    CrossrefPubMedSearch in Google Scholar
  • 17 Ahmad K, Barba T, Gamondes D. , et al. Interstitial pneumonia with autoimmune features: clinical, radiologic, and histological characteristics and outcome in a series of 57 patients. Respir Med 2017; 123: 56-62
    CrossrefPubMedSearch in Google Scholar
  • 18 Yoshimura K, Kono M, Enomoto Y. , et al. Distinctive characteristics and prognostic significance of interstitial pneumonia with autoimmune features in patients with chronic fibrosing interstitial pneumonia. Respir Med 2018; 137: 167-175
    CrossrefPubMedSearch in Google Scholar
  • 19 Adegunsoye A, Oldham JM, Valenzi E. , et al. Interstitial pneumonia with autoimmune features: value of histopathology. Arch Pathol Lab Med 2017; 141 (07) 960-969
    CrossrefPubMedSearch in Google Scholar
  • 20 Chartrand S, Swigris JJ, Stanchev L, Lee JS, Brown KK, Fischer A. Clinical features and natural history of interstitial pneumonia with autoimmune features: a single center experience. Respir Med 2016; 119: 150-154
    CrossrefPubMedSearch in Google Scholar
  • 21 Collins BF, Spiekerman CF, Shaw MA. , et al. Idiopathic interstitial pneumonia associated with autoantibodies: a large case series followed over 1 year. Chest 2017; 152 (01) 103-112
    CrossrefPubMedSearch in Google Scholar
  • 22 Ferri C, Manfredi A, Sebastiani M. , 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 (01) 61-70
    CrossrefPubMedSearch in Google Scholar
  • 23 Caspi D, Elkayam O, Eisinger M, Vardinon N, Yaron M, Burke M. Clinical significance of low titer anti-nuclear antibodies in early rheumatoid arthritis: implications on the presentation and long-term course of the disease. Rheumatol Int 2001; 20 (02) 43-47
    CrossrefPubMedSearch in Google Scholar
  • 24 Sox Jr HC, Liang MH. The erythrocyte sedimentation rate. Guidelines for rational use. Ann Intern Med 1986; 104 (04) 515-523
    PubMedSearch in Google Scholar
  • 25 Spoorenberg A, van der Heijde D, de Klerk E. , et al. Relative value of erythrocyte sedimentation rate and C-reactive protein in assessment of disease activity in ankylosing spondylitis. J Rheumatol 1999; 26 (04) 980-984
    PubMedSearch in Google Scholar
  • 26 Akçakaya MO, Yörükoğlu AG, Aydoseli A. , et al. Serum creatine phosphokinase levels as an indicator of muscle injury following lumbar disc surgery: comparison of fully endoscopic discectomy and microdiscectomy. Clin Neurol Neurosurg 2016; 145: 74-78
    CrossrefPubMedSearch in Google Scholar
  • 27 Damoiseaux J, Csernok E, Rasmussen N. , et al. Detection of antineutrophil cytoplasmic antibodies (ANCAs): a multicentre European Vasculitis Study Group (EUVAS) evaluation of the value of indirect immunofluorescence (IIF) versus antigen-specific immunoassays. Ann Rheum Dis 2017; 76 (04) 647-653
    CrossrefPubMedSearch in Google Scholar
  • 28 Radice A, Sinico RA. Antineutrophil cytoplasmic antibodies (ANCA). Autoimmunity 2005; 38 (01) 93-103
    CrossrefPubMedSearch in Google Scholar
  • 29 van den Hoogen F, Khanna D, Fransen J. , et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum 2013; 65 (11) 2737-2747
    CrossrefPubMedSearch in Google Scholar
  • 30 Steen VD. Autoantibodies in systemic sclerosis. Semin Arthritis Rheum 2005; 35 (01) 35-42
    CrossrefPubMedSearch in Google Scholar
  • 31 Chudwin DS, Ammann AJ, Cowan MJ, Wara DW. Significance of a positive antinuclear antibody test in a pediatric population. Am J Dis Child 1983; 137 (11) 1103-1106
    PubMedSearch in Google Scholar
  • 32 Dellavance A, Viana VS, Leon EP, Bonfa ES, Andrade LE, Leser PG. The clinical spectrum of antinuclear antibodies associated with the nuclear dense fine speckled immunofluorescence pattern. J Rheumatol 2005; 32 (11) 2144-2149
    PubMedSearch in Google Scholar
  • 33 Hilário MO, Len CA, Roja SC, Terreri MT, Almeida G, Andrade LE. Frequency of antinuclear antibodies in healthy children and adolescents. Clin Pediatr (Phila) 2004; 43 (07) 637-642
    CrossrefPubMedSearch in Google Scholar
  • 34 Solomon DH, Kavanaugh AJ, Schur PH. ; American College of Rheumatology Ad Hoc Committee on Immunologic Testing Guidelines. Evidence-based guidelines for the use of immunologic tests: antinuclear antibody testing. Arthritis Rheum 2002; 47 (04) 434-444
    CrossrefPubMedSearch in Google Scholar
  • 35 Sambataro G, Torrisi SE, Vancheri A. , et al. Interstitial Pneumonia with Autoimmune Features (IPAF): a single center prospective experience. Eur Respir J 2018; 52: PA2968
    PubMedSearch in Google Scholar
  • 36 Lynch DA, Travis WD, Müller NL. , et al. Idiopathic interstitial pneumonias: CT features. Radiology 2005; 236 (01) 10-21
    CrossrefPubMedSearch in Google Scholar
  • 37 Travis WD, Costabel U, Hansell DM. , et al; ATS/ERS Committee on Idiopathic Interstitial Pneumonias. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2013; 188 (06) 733-748
    CrossrefPubMedSearch in Google Scholar
  • 38 Ito Y, Arita M, Kumagai S. , et al. Serological and morphological prognostic factors in patients with interstitial pneumonia with autoimmune features. BMC Pulm Med 2017; 17 (01) 111
    CrossrefPubMedSearch in Google Scholar
  • 39 Kono M, Nakamura Y, Enomoto N. , et al. Usual interstitial pneumonia preceding collagen vascular disease: a retrospective case control study of patients initially diagnosed with idiopathic pulmonary fibrosis. PLoS One 2014; 9 (04) e94775
    CrossrefPubMedSearch in Google Scholar
  • 40 Churg A, Wright JL, Ryerson CJ. Pathologic separation of chronic hypersensitivity pneumonitis from fibrotic connective tissue disease-associated interstitial lung disease. Am J Surg Pathol 2017; 41 (10) 1403-1409
    CrossrefPubMedSearch in Google Scholar
  • 41 de Lauretis A, Veeraraghavan S, Renzoni E. Review series: aspects of interstitial lung disease: connective tissue disease-associated interstitial lung disease: how does it differ from IPF? How should the clinical approach differ?. Chron Respir Dis 2011; 8 (01) 53-82
    CrossrefPubMedSearch in Google Scholar
  • 42 Chung JH, Montner SM, Adegunsoye A. , et al. CT findings, radiologic-pathologic correlation, and imaging predictors of survival for patients with interstitial pneumonia with autoimmune features. AJR Am J Roentgenol 2017; 208 (06) 1229-1236
    CrossrefPubMedSearch in Google Scholar
  • 43 Collins B, Raghu G. Interstitial pneumonia with autoimmune features: the new consensus-based definition for this cohort of patients should be broadened. Eur Respir J 2016; 47 (04) 1293-1295
    CrossrefPubMedSearch in Google Scholar
  • 44 Strek ME, Oldham JM, Adegunsoye A, Vij R. A call for uniformity in implementing the IPAF (interstitial pneumonia with autoimmune features) criteria. Eur Respir J 2016; 48 (06) 1813-1814
    CrossrefPubMedSearch in Google Scholar
  • 45 McCoy SS, Mukadam Z, Meyer KC. , et al. Mycophenolate therapy in interstitial pneumonia with autoimmune features: a cohort study. Ther Clin Risk Manag 2018; 14: 2171-2181
    CrossrefPubMedSearch in Google Scholar
  • 46 Wilfong EM, Lentz RJ, Guttentag A. , et al. Interstitial pneumonia with autoimmune features: an emerging challenge at the intersection of rheumatology and pulmonology. Arthritis Rheumatol 2018; 70 (12) 1901-1913
    PubMedSearch in Google Scholar
  • 47 Dai J, Wang L, Yan X. , et al. Clinical features, risk factors, and outcomes of patients with interstitial pneumonia with autoimmune features: a population-based study. Clin Rheumatol 2018; 37 (08) 2125-2132
    CrossrefPubMedSearch in Google Scholar