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Arthritis und Rheuma 2022; 42(05): 330-336
DOI: 10.1055/a-1893-4920
Schwerpunkt

Die interstitielle Lungenerkrankung bei systemischer Sklerose

Interstitial lung disease in the context of systemic sclerosis
Adela-Cristina Sarbu
1   Universitätsklinik für Rheumatologie und Immunologie, Inselspital Bern, Bern, Schweiz
,
Britta Maurer
1   Universitätsklinik für Rheumatologie und Immunologie, Inselspital Bern, Bern, Schweiz
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ZUSAMMENFASSUNG

Die systemische Sklerose (SSc) ist eine seltene autoimmune Multiorganerkrankung, bei der eine immunvermittelte Vaskulopathie, Inflammation und Fibrose betroffener Organe zu deren Funktionsverlust führen können. Ein häufig betroffenes Organ ist die Lunge, deren Beteiligung, insbesondere wenn nicht früh erkannt, mit einer schlechten Prognose einhergeht. Die interstitielle Lungenerkrankung (ILD) ist eine der häufigsten Organmanifestationen, die bereits früh und nicht selten initial asymptomatisch im Krankheitsverlauf auftreten kann. Daher kommt dem Screening mittels HRCT (High-Resolution Computed Tomography) und Lungenfunktionstest eine große Rolle zu. Bei der Früherkennung ist das HRCT dem Lungenfunktionstest überlegen. Nach Diagnosestellung einer ILD wird in Abhängigkeit von Schweregrad und Progressionsrisiko entweder eine Therapie begonnen oder eine abwartende Haltung gewählt. Dabei gilt es zu berücksichtigen, dass ca. 30–40 % der SSc-ILD-Patienten eine Progression erleben werden. Zum regelmäßigen Monitoring eignen sich insbesondere Lungenfunktionsparameter und eventuell auch das HRCT, sofern strahlenreduzierte Protokolle zum Einsatz kommen. Das therapeutische Armamentarium umfasst neben pharmakologischen immunmodulierenden und antifibrotischen Substanzen bei ausgewählten Patienten auch die Option der autologen Stammzelltransplantation oder der Lungentransplantation. Mit dem Wissenszuwachs in der molekularen Pathophysiologie der Erkrankung erwarten wir in der Zukunft Trends für eine personalisierte Medizin basierend auf spezifischen Bio- oder Bildgebungsmarkern und individualisierten Therapieansätzen.

ABSTRACT

Systemic sclerosis is a rare autoimmune, multi-organ disease. Immune-mediated vasculopathy, inflammation and fibrosis of affected organs may lead to compromised organ function or even failure. One organ frequently affected is the lung, whose involvement is associated with a poor prognosis, especially if not detected early. Interstitial lung disease (ILD) is the most common organ manifestation, which can occur early in the disease course in a still asymptomatic stage. Thus, screening with high-resolution computed tomography (HRCT) and pulmonary function tests is of utmost importance. HRCT is superior in early detection of ILD compared with pulmonary function tests. Upon the diagnosis of ILD it depends on severity and risk of progression whether a therapy is initiated or whether a watch-and-wait strategy is chosen. Of note, approximately 30–40 % of SSc-ILD patients will develop a progressive disease. For regular monitoring, pulmonary function tests are ideal and may be combined with dose-reduced HRCT scans. Therapeutic options comprise pharmacological immune modulating and anti-fibrotic drugs and in selected patients, autologous hematopoietic stem cell transplantation or lung transplantation may be considered. With the gained insights into the molecular disease pathophysiology we can expect trends toward personalized medicine approaches based on specific bio- or imaging markers and individualized treatment strategies.

Schlüsselwörter

Systemische Sklerose - interstitielle Lungenerkrankung - Diagnose - Management

Keywords

Systemic sclerosis - interstitial lung disease - diagnosis - management


Publication History

Article published online:
05 November 2022

© 2022. Thieme. All rights reserved.

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  • Literatur

  • 1 Varga J, Trojanowska M, Kuwana M. Pathogenesis of systemic sclerosis: recent insights of molecular and cellular mechanisms and therapeutic opportunities. J Scleroderma Relat Disord 2017; 02 (03) 137-152
    CrossrefGoogle Scholar
  • 2 Hoffmann-Vold AM. et al Tracking Impact of Interstitial Lung Disease in Systemic Sclerosis in a Complete Nationwide Cohort. Am J Respir Crit Care Med 2019; 200 (10) 1258-1266
    CrossrefPubMedGoogle Scholar
  • 3 Steen VD, Medsger TA. Changes in causes of death in systemic sclerosis, 1972–2002. Ann Rheum Dis 2007; 66 (07) 940-944
    CrossrefPubMedGoogle Scholar
  • 4 Jaeger VK. et al Incidences and Risk Factors of Organ Manifestations in the Early Course of Systemic Sclerosis: A Longitudinal EUSTAR Study. PLoS One 2016; 11 (10) e0163894
    CrossrefPubMedGoogle Scholar
  • 5 Rubio-Riva M. et al First clinical symptom as a prognostic factor in systemic sclerosis: results of a retrospective nationwide cohort study. Clin Rheumatol 2018; 37 (04) 999-1009
    CrossrefPubMedGoogle Scholar
  • 6 Kowal-Bielecka O. et al Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis 2017; 76 (08) 1327-1339
    CrossrefPubMedGoogle Scholar
  • 7 Kennedy B. et al Biomarkers to identify ILD and predict lung function decline in scleroderma lung disease or idiopathic pulmonary fibrosis. Sarcoidosis Vasc Diffuse Lung Dis 2015; 32 (03) 228-236
    PubMedGoogle Scholar
  • 8 Hoffmann-Vold A-M. et al Circulating biomarkers of systemic sclerosis – interstitial lung disease. Journal of Scleroderma and Related Disorders 2020: 2397198319894851
    Google Scholar
  • 9 Akter T, Silver RM, Bogatkevich GS. Recent advances in understanding the pathogenesis of scleroderma-interstitial lung disease. Curr Rheumatol Rep 2014; 16 (04) 411
    CrossrefPubMedGoogle Scholar
  • 10 Trombetta AC. et al A circulating cell population showing both M1 and M2 monocyte/macrophage surface markers characterizes systemic sclerosis patients with lung involvement. Respir Res 2018; 19 (01) 186
    CrossrefPubMedGoogle Scholar
  • 11 Schiller HB. et al Deep Proteome Profiling Reveals Common Prevalence of MZB1-Positive Plasma B Cells in Human Lung and Skin Fibrosis. Am J Respir Crit Care Med 2017; 196 (10) 1298-1310
    CrossrefPubMedGoogle Scholar
  • 12 Wilfong EM. et al CD19 + CD21(lo/neg) cells are increased in systemic sclerosis-associated interstitial lung disease. Clin Exp Med 2022; 22 (02) 209-220
    CrossrefPubMedGoogle Scholar
  • 13 D‘Angelo WA. et al Pathologic observations in systemic sclerosis (scleroderma). A study of fifty-eight autopsy cases and fifty-eight matched controls. Am J Med 1969; 46 (03) 428-440
    CrossrefPubMedGoogle Scholar
  • 14 Peoples C. et al Gender differences in systemic sclerosis: relationship to clinical features, serologic status and outcomes. J Scleroderma Relat Disord 2016; 01 (02) 177-240
    Google Scholar
  • 15 Hussein H. et al The effect of male sex on survival in systemic sclerosis. J Rheumatol 2014; 41 (11) 2193-2200
    CrossrefPubMedGoogle Scholar
  • 16 Al-Sheikh H, Ahmad Z, Johnson SR. Ethnic Variations in Systemic Sclerosis Disease Manifestations, Internal Organ Involvement, and Mortality. J Rheumatol 2019; 46 (09) 1103-1108
    CrossrefPubMedGoogle Scholar
  • 17 Silver RM. et al Racial differences between blacks and whites with systemic sclerosis. Curr Opin Rheumatol 2012; 24 (06) 642-648
    CrossrefPubMedGoogle Scholar
  • 18 Steen V. et al A clinical and serologic comparison of African American and Caucasian patients with systemic sclerosis. Arthritis Rheum 2012; 64 (09) 2986-2994
    CrossrefPubMedGoogle Scholar
  • 19 Nihtyanova SI. et al Prediction of pulmonary complications and long-term survival in systemic sclerosis. Arthritis Rheumatol 2014; 66 (06) 1625-1635
    CrossrefPubMedGoogle Scholar
  • 20 Iniesta Arandia N. et al Influence of antibody profile in clinical features and prognosis in a cohort of Spanish patients with systemic sclerosis. Clin Exp Rheumatol 2017; 35 Suppl 106[4] 98-105
    PubMedGoogle Scholar
  • 21 Liaskos C. et al Disease-related autoantibody profile in patients with systemic sclerosis. Autoimmunity 2017; 50 (07) 414-421
    CrossrefPubMedGoogle Scholar
  • 22 Walker UA. et al 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 (06) 754-763
    CrossrefPubMedGoogle Scholar
  • 23 Liu X. et al Does C-reactive protein predict the long-term progression of interstitial lung disease and survival in patients with early systemic sclerosis?. Arthritis Care Res (Hoboken) 2013; 65 (08) 1375-1380
    CrossrefPubMedGoogle Scholar
  • 24 Le Gouellec N. et al Predictors of lung function test severity and outcome in systemic sclerosis-associated interstitial lung disease. PLoS One 2017; 12 (08) e0181692
    CrossrefPubMedGoogle Scholar
  • 25 Christmann RB. et al Gastroesophageal reflux incites interstitial lung disease in systemic sclerosis: clinical, radiologic, histopathologic, and treatment evidence. Semin Arthritis Rheum 2010; 40 (03) 241-249
    CrossrefPubMedGoogle Scholar
  • 26 Suliman YA. et al Brief Report: Pulmonary Function Tests: High Rate of False-Negative Results in the Early Detection and Screening of Scleroderma-Related Interstitial Lung Disease. Arthritis Rheumatol 2015; 67 (12) 3256-3261
    CrossrefPubMedGoogle Scholar
  • 27 Distler O. et al Factors influencing early referral, early diagnosis and management in patients with diffuse cutaneous systemic sclerosis. Rheumatology (Oxford) 2018; 57 (05) 813-817
    CrossrefPubMedGoogle Scholar
  • 28 Showalter K. et al Performance of Forced Vital Capacity and Lung Diffusion Cutpoints for Associated Radiographic Interstitial Lung Disease in Systemic Sclerosis. J Rheumatol 2018; 45 (11) 1572-1576
    CrossrefPubMedGoogle Scholar
  • 29 Wangkaew S. et al Correlation of delta high-resolution computed tomography (HRCT) score with delta clinical variables in early systemic sclerosis (SSc) patients. Quant Imaging Med Surg 2016; 06 (04) 381-390
    CrossrefPubMedGoogle Scholar
  • 30 Tashkin DP. et al Relationship between quantitative radiographic assessments of interstitial lung disease and physiological and clinical features of systemic sclerosis. Ann Rheum Dis 2016; 75 (02) 374-381
    CrossrefPubMedGoogle Scholar
  • 31 Hansell DM. et al CT staging and monitoring of fibrotic interstitial lung diseases in clinical practice and treatment trials: a position paper from the Fleischner Society. Lancet Respir Med 2015; 03 (06) 483-496
    CrossrefPubMedGoogle Scholar
  • 32 Nguyen-Kim TDL. et al The impact of slice-reduced computed tomography on histogram-based densitometry assessment of lung fibrosis in patients with systemic sclerosis. J Thorac Dis 2018; 10 (04) 2142-2152
    CrossrefPubMedGoogle Scholar
  • 33 Frauenfelder T. et al Screening for interstitial lung disease in systemic sclerosis: performance of high-resolution CT with limited number of slices: a prospective study. Ann Rheum Dis 2014; 73 (12) 2069-2073
    CrossrefPubMedGoogle Scholar
  • 34 Bruni C, Tofani L, Fretheim H. et al Developing a screening tool for the detection of interstitial lung disease in systemic sclerosis: the ILD-RISC RISK SCORE. Annals of Rheumatic Diseases (congress abstract), 2022; 81: 449
    CrossrefGoogle Scholar
  • 35 Gigante A. et al Lung ultrasound in systemic sclerosis: correlation with high-resolution computed tomography, pulmonary function tests and clinical variables of disease. Intern Emerg Med 2016; 11 (02) 213-217
    CrossrefPubMedGoogle Scholar
  • 36 Song G, Bae SC, Lee YH. Diagnostic accuracy of lung ultrasound for interstitial lung disease in patients with connective tissue diseases: a meta-analysis. Clin Exp Rheumatol 2016; 34 (01) 11-16
    PubMedGoogle Scholar
  • 37 Hoffmann-Vold AM. et al Progressive interstitial lung disease in patients with systemic sclerosis-associated interstitial lung disease in the EUSTAR database. Ann Rheum Dis 2021; 80 (02) 219-227
    CrossrefPubMedGoogle Scholar
  • 38 Benan M, Hande I, Gul O. The natural course of progressive systemic sclerosis patients with interstitial lung involvement. Clin Rheumatol 2007; 26 (03) 349-354
    CrossrefPubMedGoogle Scholar
  • 39 Markusse IM. et al Predicting cardiopulmonary involvement in patients with systemic sclerosis: complementary value of nailfold videocapillaroscopy patterns and disease-specific autoantibodies. Rheumatology (Oxford) 2017; 56 (07) 1081-1088
    PubMedGoogle Scholar
  • 40 Assassi S. et al Predictors of interstitial lung disease in early systemic sclerosis: a prospective longitudinal study of the GENISOS cohort. Arthritis Research & Therapy 2010; 12 (05) R166
    CrossrefPubMedGoogle Scholar
  • 41 Ahmed SS. et al Lung function and survival in systemic sclerosis interstitial lung disease. J Rheumatol 2014; 41 (11) 2326-2328
    CrossrefPubMedGoogle Scholar
  • 42 Skaug B, Assassi S. Biomarkers in systemic sclerosis. Curr Opin Rheumatol 2019; 31 (06) 595-602
    CrossrefPubMedGoogle Scholar
  • 43 Goh NS. et al Short-Term Pulmonary Function Trends Are Predictive of Mortality in Interstitial Lung Disease Associated With Systemic Sclerosis. Arthritis Rheumatol 2017; 69 (08) 1670-1678
    CrossrefPubMedGoogle Scholar
  • 44 Volkmann ER. et al Short-term progression of interstitial lung disease in systemic sclerosis predicts long-term survival in two independent clinical trial cohorts. Ann Rheum Dis 2019; 78 (01) 122-130
    CrossrefPubMedGoogle Scholar
  • 45 Goh NS. et al Interstitial lung disease in systemic sclerosis: a simple staging system. Am J Respir Crit Care Med 2008; 177 (11) 1248-1254
    CrossrefPubMedGoogle Scholar
  • 46 Khanna D. et al Clinical course of lung physiology in patients with scleroderma and interstitial lung disease: analysis of the Scleroderma Lung Study Placebo Group. Arthritis Rheum 2011; 63 (10) 3078-3085
    CrossrefPubMedGoogle Scholar
  • 47 Moore OA. et al Extent of disease on high-resolution computed tomography lung is a predictor of decline and mortality in systemic sclerosis-related interstitial lung disease. Rheumatology (Oxford) 2013; 52 (01) 155-160
    CrossrefPubMedGoogle Scholar
  • 48 Ariani A. et al Quantitative chest computed tomography is associated with two prediction models of mortality in interstitial lung disease related to systemic sclerosis. Rheumatology (Oxford) 2017; 56 (06) 922-927
    CrossrefPubMedGoogle Scholar
  • 49 Bergmann C, Distler J, Treutlein C. et al 68Ga-FAPI-04 PET-CT for molecular assessment of fibroblast activation and risk evaluation in systemic sclerosis-associated interstitial lung disease: a single-centre, pilot study. Lancet Rheumatol 2021; 03: e185-e194
    CrossrefGoogle Scholar
  • 50 Ledoult E. et al (18)F-FDG positron emission tomography scanning in systemic sclerosis-associated interstitial lung disease: a pilot study. Arthritis Res Ther 2021; 23 (01) 76
    CrossrefPubMedGoogle Scholar
  • 51 Wu W. et al Prediction of progression of interstitial lung disease in patients with systemic sclerosis: the SPAR model. Ann Rheum Dis 2018; 77 (09) 1326-1332
    CrossrefPubMedGoogle Scholar
  • 52 Schniering J. et al Computed tomography-based radiomics decodes prognostic and molecular differences in interstitial lung disease related to systemic sclerosis. Eur Respir J 2022; 59 (05) 2004503
    CrossrefPubMedGoogle Scholar
  • 53 Flaherty KR. et al Nintedanib in Progressive Fibrosing Interstitial Lung Diseases. N Engl J Med 2019; 381 (18) 1718-1727
    CrossrefPubMedGoogle Scholar
  • 54 Raghu G. et al Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med 2022; 205 (09) e18-e47
    CrossrefPubMedGoogle Scholar
  • 55 Takei R. et al Radiographic fibrosis score predicts survival in systemic sclerosis-associated interstitial lung disease. Respirology 2018; 23 (04) 385-391
    CrossrefPubMedGoogle Scholar
  • 56 Hoffmann-Vold AM, Maher MT, Philpot EE. et al The identification and management of interstitial lung disease in systemic sclerosis: evidence-based European consensus statements. Lancet Rheumatol 2020; 02 (02) E71-E83
    CrossrefGoogle Scholar
  • 57 Hoyles RK. 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 (12) 3962-3970
    CrossrefPubMedGoogle Scholar
  • 58 Tashkin DP. 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 (10) 1026-1034
    CrossrefPubMedGoogle Scholar
  • 59 Barnes H. et al Cyclophosphamide for connective tissue disease-associated interstitial lung disease. Cochrane Database Syst Rev 2018; 01: CD010908
    Google Scholar
  • 60 Tashkin DP. 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; 04 (09) 708-719
    CrossrefPubMedGoogle Scholar
  • 61 Tzouvelekis A. et al Effect and safety of mycophenolate mofetil or sodium in systemic sclerosis-associated interstitial lung disease: a meta-analysis. Pulm Med 2012; 2012: 143637
    CrossrefPubMedGoogle Scholar
  • 62 Daoussis D. 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 (05) 625-631
    CrossrefPubMedGoogle Scholar
  • 63 Jordan S. et al Effects and safety of rituximab in systemic sclerosis: an analysis from the European Scleroderma Trial and Research (EUSTAR) group. Ann Rheum Dis 2015; 74 (06) 1188-1194
    CrossrefPubMedGoogle Scholar
  • 64 Lepri G. et al Effects of rituximab in connective tissue disorders related interstitial lung disease. Clin Exp Rheumatol 2016; 34 Suppl 100(5): 181–185
    Google Scholar
  • 65 Ebata S, Yoshizaki A, Oba K. et al Safety and efficacy of rituximab in systemic sclerosis (DESIRES): a double-blind, investigator-initiated, randomised, placebo-controlled trial. Lancet Rheumatol 2021; 07: e489-e497
    CrossrefGoogle Scholar
  • 66 Distler O. et al Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease. N Engl J Med 2019; 380 (26) 2518-2528
    CrossrefPubMedGoogle Scholar
  • 67 Highland KB. et al Efficacy and safety of nintedanib in patients with systemic sclerosis-associated interstitial lung disease treated with mycophenolate: a subgroup analysis of the SENSCIS trial. Lancet Respir Med 2021; 09 (01) 96-106
    CrossrefPubMedGoogle Scholar
  • 68 Burt RK. et al Autologous non-myeloablative haemopoietic stem-cell transplantation compared with pulse cyclophosphamide once per month for systemic sclerosis (ASSIST): an open-label, randomised phase 2 trial. Lancet 2011; 378 9790 498-506
    CrossrefPubMedGoogle Scholar
  • 69 van Laar JM. et al Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial. JAMA 2014; 311 (24) 2490-2498
    CrossrefPubMedGoogle Scholar
  • 70 Fernandez-Codina A. et al Lung transplantation in systemic sclerosis: A single center cohort study. Joint Bone Spine 2018; 85 (01) 79-84
    CrossrefPubMedGoogle Scholar
  • 71 Khan IY. et al Survival after lung transplantation in systemic sclerosis. A systematic review. Respir Med 2013; 107 (12) 2081-2087
    CrossrefPubMedGoogle Scholar
  • 72 Khanna D. et al Tocilizumab in systemic sclerosis: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med 2020; 08 (10) 963-974
    CrossrefPubMedGoogle Scholar
  • 73 Hoffmann-Vold AM. et al Recent advances in the management of systemic sclerosis-associated interstitial lung disease. Curr Opin Pulm Med 2022; 28 (05) 441-447
    CrossrefPubMedGoogle Scholar
  • 74 Cottin V, Brown KK. Interstitial lung disease associated with systemic sclerosis (SSc-ILD). Respir Res 2019; 20 (01) 13
    CrossrefPubMedGoogle Scholar
  • 75 Bruni C. et al Patient preferences for the treatment of systemic sclerosis-associated interstitial lung disease: a discrete choice experiment. Rheumatology (Oxford). 2022: keac126
    Google Scholar
  • 76 Assassi S. et al Peripheral blood gene expression profiling shows predictive significance for response to mycophenolate in systemic sclerosis-related interstitial lung disease. Ann Rheum Dis 2022; 81 (06) 854-860
    CrossrefPubMedGoogle Scholar
  • 77 de Oliveira NC. et al Aerobic and resistance exercise in systemic sclerosis: State of the art. Musculoskeletal Care 2017; 15 (04) 316-323
    CrossrefPubMedGoogle Scholar