nach oben

Erschienen in:

06.01.2017 | Pathology Review

Interstitial lung disease in systemic sclerosis: current and future treatment

verfasst von: Roberto Giacomelli, Vasiliki Liakouli, Onorina Berardicurti, Piero Ruscitti, Paola Di Benedetto, Francesco Carubbi, Giuliana Guggino, Salvatore Di Bartolomeo, Francesco Ciccia, Giovanni Triolo, Paola Cipriani

Erschienen in: Rheumatology International | Ausgabe 6/2017

Einloggen, um Zugang zu erhalten

Abstract

Systemic sclerosis (SSc) has the highest fatality rate among connective tissue diseases and is characterized by vascular damage, inflammation and fibrosis of the skin and various internal organs. Interstitial lung disease (ILD) frequently complicates SSc and can be a debilitating disorder with a poor prognosis. ILD is the most frequent cause of death in SSc, and the management of SSc–ILD patients is a great challenge. Early detection of pulmonary involvement based on a recent decline of lung function tests and on the extent of lung involvement at high-resolution computed tomography is critical for the best management of these patients. This article summarizes classification, pathogenesis, diagnosis, prognosis, survival and finally current and future treatment options in SSc–ILD.

LeRoy EC, Black C, Fleischmajer R et al (1988) Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 15:202–205PubMed

Steen VD, Medsger TA (2007) Changes in causes of death in systemic sclerosis, 1972–2002. Ann Rheum Dis 66:940–944CrossRefPubMedPubMedCentral

Toya SP, Tzelepis GE (2009) The many faces of scleroderma sine scleroderma: a literature review focusing on cardiopulmonary complications. Rheumatol Int 29:861–868CrossRefPubMed

American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias (2002) 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 by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med 165:277–304CrossRef

MacDonald SL, Rubens MB, Hansell DM et al (2001) Nonspecific interstitial pneumonia and usual interstitial pneumonia: comparative appearances at and diagnostic accuracy of thin-section CT. Radiology 221:583–584CrossRef

Bouros D, Wells AU, Nicholson AG et al (2002) Histopathologic subsets of fibrosing alveolitis in patients with systemic sclerosis and their relationship to outcome. Am J Respir Crit Care Med 165:1581–1586CrossRefPubMed

Kim DS, Yoo B, Lee JS et al (2002) The major histopathologic pattern of pulmonary fibrosis in scleroderma is nonspecific interstitial pneumonia. Sarcoidosis Vasc Diffuse Lung Dis 19:121–127PubMed

Wynn TA (2011) Integrating mechanisms of pulmonary fibrosis. J Exp Med 208:1339–1350CrossRefPubMedPubMedCentral

Sakkas LI, Platsoucas CD (2004) Is systemic sclerosis an antigen-driven T cell disease? Arthritis Rheum 50:1721–1733CrossRefPubMed

10.

Gurujeyalakshmi G, Giri SN (1995) Molecular mechanisms of antifibrotic effect of interferon gamma in bleomycin-mouse model of lung fibrosis: downregulation of TGF-beta and procollagen I and III gene expression. Exp Lung Res 21:791–808CrossRefPubMed

11.

Willis BC, Borok Z (2007) TGF-b-induced EMT: mechanisms and implications for fibrotic lung disease. Am J Physiol Lung Cell Mol Physiol 293:525–534CrossRef

12.

Khalil N, Bereznay O, Sporn M et al (1989) Macrophage production of transforming growth factor beta and fibroblast collagen synthesis in chronic pulmonary inflammation. J Exp Med 70:727–737CrossRef

13.

Riccieri V, Rinaldi T, Spadaro A et al (2003) Interleukin-13 in systemic sclerosis: relationship to nailfold capillaroscopy abnormalities. Clin Rheumatol 22:102–106CrossRefPubMed

14.

Vettori S, Cuomo G, Iudici M et al (2014) Early systemic sclerosis: serum profiling of factors involved in endothelial, T-cell, and fibroblast interplay is marked by elevated interleukin-33 levels. J Clin Immunol 34:663–668CrossRefPubMed

15.

Abraham DJ, Varga J (2005) Scleroderma: from cell and molecular mechanisms to disease models. Trends Immunol 26:587–595CrossRefPubMed

16.

Liu T, Jin H, Ullenbruch M et al (2004) Regulation of found in inflammatory zone 1 expression in bleomycin-induced lung fibrosis: role of IL-4/IL-13 and mediation via STAT-6. J Immunol 173:3425–3431CrossRefPubMed

17.

Jakubzick C, Choi ES, Joshi BH et al (2003) Therapeutic attenuation of pulmonary fibrosis via targeting of IL-4- and IL-13-responsive cells. J Immunol 171:2684–2693CrossRefPubMed

18.

Tiev KP, Abriol J, Burland MC, Antonelli D et al (2005) T cell repertoire in patients with stable scleroderma. Clin Exp Immunol 139:348–354CrossRefPubMedPubMedCentral

19.

Fuschiotti P, Larregina AT, Ho J et al (2013) Interleukin-13-producing CD8+ T cells mediate dermal fibrosis in patients with systemic sclerosis. Arthritis Rheum 65:236–246CrossRefPubMedPubMedCentral

20.

Luzina IG, Atamas SP, Wise R, Wigley FM et al (2003) Occurrence of an activated, profibrotic pattern of gene expression in lung CD8+ T cells from scleroderma patients. Arthritis Rheum 48:2262–2274CrossRefPubMed

21.

Gustafsson R, Tötterman TH, Klareskog L et al (1990) Increase in activated T cells and reduction in suppressor inducer T cells in systemic sclerosis. Ann Rheum Dis 49:40–45CrossRefPubMedPubMedCentral

22.

Radstake TRDJ, van Bon L, Broen J et al (2009) Increased frequency and compromised function of T regulatory cells in systemic sclerosis (SSc) is related to a diminished CD69 and TGFb expression. PLoS ONE 6:e5981–e5992CrossRef

23.

Sato S, Hasegawa M, Fujimoto M et al (2000) Quantitative genetic variation in CD19 expression correlates with autoimmunity. J Immunol 165:6635–6643CrossRefPubMed

24.

Sato S, Fujimoto M, Hasegawa M et al (2004) Altered blood B lymphocyte homeostasis in systemic sclerosis: expanded naive B cells and diminished but activated memory B cells. Arthritis Rheum 50:1918–1927CrossRefPubMed

25.

Saito E, Fujimoto M, Hasegawa M et al (2002) CD19-dependent B lymphocyte signaling thresholds influence skin fibrosis and autoimmunity in the tight-skin mouse. J Clin Invest 109:1453–1462CrossRefPubMedPubMedCentral

26.

Yamamoto T, Takagawa S, Katayama I et al (1999) Animal model of sclerotic skin. I: local injections of bleomycin induce sclerotic skin mimicking scleroderma. J Invest Dermatol 112:456–462CrossRefPubMed

27.

Yamamoto T (2006) The bleomycin-induced scleroderma model: what have we learned for scleroderma pathogenesis? Arch Dermatol Res 297:333–344CrossRefPubMed

28.

Yoshizaki A, Iwata Y, Komura K et al (2008) CD19 regulates skin and lung fibrosis via Toll-like receptor signaling in a model of bleomycin induced scleroderma. Am J Pathol 172:1650–1663CrossRefPubMedPubMedCentral

29.

Wynn TA (2004) Fibrotic disease and the T(H)1/T(H)2 paradigm. Nat Rev Immunol 4:583–594CrossRefPubMedPubMedCentral

30.

Khan K, Xu S, Nihtyanova S et al (2012) Clinical and pathological significance of interleukin 6 overexpression in systemic sclerosis. Ann Rheum Dis 71:1235–1242CrossRefPubMed

31.

Saito F, Tasaka S, Inoue K et al (2008) Role of interleukin-6 in bleomycin-induced lung inflammatory changes in mice. Am J Respir Cell Mol Biol 38:566–571CrossRefPubMed

32.

Ihn H, Yamane K, Kubo M et al (2001) Blockade of endogenous transforming growth factor beta signaling prevents up-regulated collagen synthesis in scleroderma fibroblasts: association with increased expression of transforming growth factor beta receptors. Arthritis Rheum 44:474–480CrossRefPubMed

33.

Famularo G, Giacomelli R, Alesse E et al (1989) Polyclonal B lymphocyte activation in progressive systemic sclerosis. J Clin Lab Immunol 29:59–63PubMed

34.

Maddur MS, Sharma M, Hegde P et al (2014) Human B cells induce dendritic cell maturation and favour Th2 polarization by inducing OX-40 ligand. Nat Commun 5:4092CrossRefPubMedPubMedCentral

35.

Hocher B, Schwarz A, Fagan KA et al (2000) Pulmonary fibrosis and chronic lung inflammation in ET-1 transgenic mice. Am J Respir Cell Mol Biol 23:19–26CrossRefPubMed

36.

Mutsaers SE, Foster LM, Chambers RC et al (1998) Increased endothelin-1 and its localization during the development of bleomycin-induced pulmonary fibrosis in rats. Am J Respir Cell Mol Biol 18:611–619CrossRefPubMed

37.

Abraham DJ, Vancheeswaran R, Dashwood MR et al (1997) Increased levels of endothelin 1 and differential endothelin type A and B receptor expression in scleroderma-associated fibrotic lung disease. Am J Pathol 151:831–841PubMedPubMedCentral

38.

Bauer M, Wilkens H, Langer F et al (2002) Selective upregulation of endothelin B receptor gene expression in severe pulmonary hypertension. Circulation 105:1034–1036CrossRefPubMed

39.

Shi-Wen X, Kennedy L, Renzoni EA et al (2007) Endothelin is a downstream mediator of profibrotic responses to transforming growth factor β in human lung fibroblasts. Arthritis Rheum 56:4189–4194CrossRefPubMed

40.

Jain R, Shaul PW, Borok Z et al (2007) Endothelin-1 induces alveolar epithelial mesenchymal transition through endothelin type A receptor-mediated production of TGF-β1. Am J Respir Cell Mol Biol 37:38–47CrossRefPubMedPubMedCentral

41.

Steen VD, Conte C, Owens GR et al (1994) Severe restrictive lung disease in systemic sclerosis. Arthritis Rheum 37:1283–1289CrossRefPubMed

42.

Behr J, Furst DE (2008) Pulmonary function tests. Rheumatology (Oxford) 47(Suppl 5):v65–v67CrossRef

43.

Morgan C, Knight C, Lunt M et al (2003) Predictors of end stage lung disease in a cohort of patients with scleroderma. Ann Rheum Dis 62:146–150CrossRefPubMedPubMedCentral

44.

Hudson M, Lo E, Lu Y et al (2011) Canadian Scleroderma Research Group. Cigarette smoking in patients with systemic sclerosis. Arthritis Rheum 63:230–238CrossRefPubMed

45.

Steen VD, Graham G, Conte C et al (1992) Isolated diffusing capacity reduction in systemic sclerosis. Arthritis Rheum 35:765–770CrossRefPubMed

46.

Moore OA, Proudman SM, Goh N et al (2015) Quantifying change in pulmonary function as a prognostic marker in systemic sclerosis-related interstitial lung disease. Clin Exp Rheumatol 33:S111–S116PubMed

47.

Moore OA, Goh N, Corte T et al (2013) 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) 52:155–160CrossRef

48.

Goh NS, Desai SR, Veeraraghavan S et al (2008) Interstitial lung disease in systemic sclerosis: a simple staging system. Am J Respir Crit Care Med 177(11):1248–1254CrossRefPubMed

49.

Winstone TA, Assayag D, Wilcox PG et al (2014) Predictors of mortality and progression in scleroderma-associated interstitial lung disease: a systematic review. Chest 146:422–436CrossRefPubMed

50.

Behr J, Vogelmeier C, Beinert T et al (1996) Bronchoalveolar lavage for evaluation and management of scleroderma disease of the lung. Am J Respir Crit Care Med 154:400–406CrossRefPubMed

51.

Wells AU, Hansell DM, Haslam PL et al (1998) Bronchoalveolar lavage cellularity: lone cryptogenic fibrosingalveolitis compared with the fibrosing alveolitis of systemic sclerosis. Am J Respir Crit Care Med 157:1474–1482CrossRefPubMed

52.

Tashkin DP, Elashoff R, Clements PJ et al (2006) Scleroderma Lung Study Research Group. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med 354:2655–2666CrossRefPubMed

53.

Silver RM, Bogatkevich G, Tourkina E et al (2012) Racial differences between blacks and whites with systemic sclerosis. Curr Opin Rheumatol 24:642–648CrossRefPubMedPubMedCentral

54.

Walker UA, Tyndall A, Czirják L et al (2007) Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials and Research Group database. Ann Rheum Dis 66:754–763CrossRefPubMedPubMedCentral

55.

De Lauretis A, Sestini P, Pantelidis P et al (2013) Serum interleukin 6 is predictive of early functional decline and mortality in interstitial lung disease associated with systemic sclerosis. J Rheumatol 40:435–446CrossRefPubMed

56.

Lee CG, Herzog EL, Ahangari F et al (2012) Chitinase 1 is a biomarker for and therapeutic target in scleroderma-associated interstitial lung disease that augments TGF-β1 signaling. J Immunol 189:2635–2644CrossRefPubMedPubMedCentral

57.

Rubio-Rivas M, Royo C, Simeón CP et al (2014) Mortality and survival in systemic sclerosis: systematic review and meta-analysis. Semin Arthritis Rheum 44:208–219CrossRefPubMed

58.

Steen VD, Medsger TA Jr (2000) Severe organ involvement in systemic sclerosis with diffuse scleroderma. Arthritis Rheum 43:2437–2444CrossRefPubMed

59.

Wells AU, Hansell DM, Rubens MB et al (1997) Fibrosing alveolitis in systemic sclerosis: indices of lung function in relation to extent of disease on computed tomography. Arthritis Rheum 40:1229–1236PubMed

60.

Au K, Khanna D, Clements PJ et al (2009) Current concepts in disease-modifying therapy for systemic sclerosis-associated interstitial lung disease: lessons from clinical trials. Curr Rheumatol Rep 11:111–119CrossRefPubMed

61.

American Thoracic Society (2000) Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med 161(2 Pt 1):646–664

62.

Hoyles RK, Ellis RW, Wellsbury J et al (2006) 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 54:3962–3970CrossRefPubMed

63.

Nannini C, West CP, Erwin PJ et al (2008) 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 10:R124CrossRefPubMedPubMedCentral

64.

Poormoghim H, Moradi Lakeh M et al (2012) Cyclophosphamide for scleroderma lung disease: a systematic review and meta-analysis. Rheumatol Int 32:2431–2444CrossRefPubMed

65.

Panopoulos ST, Bournia VK, Trakada G et al (2013) Mycophenolate versus cyclophosphamide for progressive interstitial lung disease associated with systemic sclerosis: a 2-year case control study. Lung 191:483–489CrossRefPubMed

66.

Yilmaz N, Can M, Kocakaya D et al (2014) Two-year experience with mycophenolate mofetil in patients with scleroderma lung disease: a case series. Int J Rheum Dis 17:923–928CrossRefPubMed

67.

Tzouvelekis A, Galanopoulos N, Bouros E et al (2012) Effect and safety of mycophenolate mofetil or sodium in systemic sclerosis-associated interstitial lung disease: a meta-analysis. Pulm Med 2012:143637CrossRefPubMedPubMedCentral

68.

Omair MA, Alahmadi A, Johnson SR (2015) Safety and effectiveness of mycophenolate in systemic sclerosis. A systematic review. PLoS ONE 10:e0124205CrossRefPubMedPubMedCentral

69.

Tashkin DP, Roth MD, Clements PJ et al (2016) Sclerodema Lung Study II Investigators. Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial. Lancet Respir Med 4:708–719CrossRefPubMed

70.

Owen C, Ngian GS, Elford K et al (2016) Mycophenolate mofetil is an effective and safe option for the management of systemic sclerosis-associated interstitial lung disease: results from the Australian Scleroderma Cohort Study. Clin Exp Rheumatol 34(Suppl 100):170–176PubMed

71.

Nadashkevich O, Davis P, Fritzler M et al (2006) A randomized unblinded trial of cyclophosphamide versus azathioprine in the treatment of systemic sclerosis. Clin Rheumatol 25:205–212CrossRefPubMed

72.

Paone C, Chiarolanza I, Cuomo G et al (2007) Twelve-month azathioprine as maintenance therapy in early diffuse systemic sclerosis patients treated for 1-year with low dose cyclophosphamide pulse therapy. Clin Exp Rheumatol 25:613–616PubMed

73.

Bérezné A, Ranque B, Valeyre D et al (2008) 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 35:1064–1072PubMed

74.

Iudici M, Cuomo G, Vettori S et al (2015) Low-dose pulse cyclophosphamide in interstitial lung disease associated with systemic sclerosis (SSc–ILD): efficacy of maintenance immunosuppression in responders and non-responders. Semin Arthritis Rheum 44:437–444CrossRefPubMed

75.

Nagai S, Hamada K, Shigematsu M et al (2002) Open-label compassionate use one year-treatment with pirfenidone to patients with chronic pulmonary fibrosis. Intern Med 41:1118–1123CrossRefPubMed

76.

Udwadia ZF, Mullerpattan JB, Balakrishnan C et al (2015) Improved pulmonary function following pirfenidone treatment in a patient with progressive interstitial lung disease associated with systemic sclerosis. Lung India 32:50–52CrossRefPubMedPubMedCentral

77.

Miura Y, Saito T, Fujita K et al (2014) Clinical experience with pirfenidone in five patients with scleroderma-related interstitial lung disease. Sarcoidosis Vasc Diffuse Lung Dis 31:235–238PubMed

78.

Khanna D, Albera C, Fischer A et al (2015) Safety and tolerability of pirfenidone in patients with systemic sclerosis-associated interstitial lung disease—the LOTUSS study. Ann Rheum Dis 74:S816

79.

Seibold JR, Denton CP, Furst DE, Guillevin L, Rubin LJ, Wells A, Matucci Cerinic M, Riemekasten G, Emery P, Chadha-Boreham H, Charef P, Roux S, Black CM (2010) Randomized, prospective, placebo-controlled trial of bosentan in interstitial lung disease secondary to systemic sclerosis. Arthritis Rheum 62:2101–2108CrossRefPubMed

80.

Spiera RF, Gordon JK, Mersten JN et al (2011) Imatinib mesylate (Gleevec) in the treatment of diffuse cutaneous systemic sclerosis: results of a 1-year, phase IIa, single-arm, open-label clinical trial. Ann Rheum Dis 70:1003–1009CrossRefPubMedPubMedCentral

81.

Khanna D, Saggar R, Mayes MD et al (2011) A one-year, phase I/IIa, open-label pilot trial of imatinib mesylate in the treatment of systemic sclerosis-associated active interstitial lung disease. Arthritis Rheum 63:3540–3546CrossRefPubMedPubMedCentral

82.

Fraticelli P, Gabrielli B, Pomponio G et al (2014) Imatinib in Scleroderma Italian Study Group. Low-dose oral imatinib in the treatment of systemic sclerosis interstitial lung disease unresponsive to cyclophosphamide: a phase II pilot study. Arthritis Res Ther 16:R144CrossRefPubMedPubMedCentral

83.

Denton CP, Merkel PA, Furst DE, Khanna D, Emery P, Hsu VM, Silliman N, Streisand J, Powell J, Akesson A, Coppock J, Fv Hoogen, Herrick A, Mayes MD, Veale D, Haas J, Ledbetter S, Korn JH, Black CM, Seibold JR (2007) Cat-192 Study Group; Scleroderma Clinical Trials Consortium Recombinant human anti-transforming growth factor beta1 antibody therapy in systemic sclerosis: a multicenter, randomized, placebo-controlled phase I/II trial of CAT-192. Arthritis Rheum 56:323–333CrossRefPubMed

84.

Rice LM, Padilla CM, McLaughlin SR et al (2015) Fresolimumab treatment decreases biomarkers and improves clinical symptoms in systemic sclerosis patients. J Clin Invest 125:2795–2807CrossRefPubMedPubMedCentral

85.

Yoo WH (2012) Successful treatment of steroid and cyclophosphamide-resistant diffuse scleroderma-associated interstitial lung disease with rituximab. Rheumatol Int 32:795–798CrossRefPubMed

86.

Bosello S, De Santis M, Lama G et al (2010) B cell depletion in diffuse progressive systemic sclerosis: safety, skin score modification and IL-6 modulation in an up to thirty-six months follow-up open-label trial. Arthritis Res Ther 12:R54CrossRefPubMedPubMedCentral

87.

Jordan S, Distler JH, Maurer B et al (2015) Effects and safety of rituximab in systemic sclerosis: an analysis from the European Scleroderma Trial and Research (EUSTAR) group. Ann Rheum Dis 74:1188–1194CrossRefPubMed

88.

Shima Y, Kuwahara Y, Murota H et al (2010) The skin of patients with systemic sclerosis softened during the treatment with anti-IL-6 receptor antibody tocilizumab. Rheumatology (Oxford) 49:2408–2412CrossRef

89.

Fernandes das Neves M, Oliveira S, Amaral MC et al (2015) Treatment of systemic sclerosis with tocilizumab. Rheumatology (Oxford) 54:371–372CrossRef

90.

Khanna D, Denton CP, Jahreis A et al (2016) Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis (faSScinate): a phase 2, randomised, controlled trial. Lancet 25(387):2630–2640CrossRef

91.

Distler JH, Jordan S, Airo P et al (2011) Is there a role for TNFα antagonists in the treatment of SSc? EUSTAR expert consensus development using the Delphi technique. Clin Exp Rheumatol 29:S40–S45PubMed

92.

Elhai M, Meunier M, Matucci-Cerinic M et al (2013) EUSTAR (EULAR Scleroderma Trials and Research group). Outcomes of patients with systemic sclerosis-associated polyarthritis and myopathy treated with tocilizumab or abatacept: a EUSTAR observational study. Ann Rheum Dis 72:1217–1220CrossRefPubMed

93.

Van Laar JM, Farge D, Sont JK et al (2014) EBMT/EULAR Scleroderma Study Group. JAMA 311:2490–2498CrossRefPubMed

94.

Burt RK, Shah SJ, Dill K, Grant T, Gheorghiade M, Schroeder J, Craig R, Hirano I, Marshall K, Ruderman E, Jovanovic B, Milanetti F, Jain S, Boyce K, Morgan A, Carr J, Barr W (2011) 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. Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial. Lancet 378:498–506CrossRefPubMed

95.

Van Laar JM, Nihtyanova SI, Naraghi K, Denton CP, Tyndall A (2013) Autologous HSCT for systemic sclerosis. Lancet 381:2079–2080CrossRefPubMed

96.

Khan IY, Singer LG, de Perrot M et al (2013) Survival after lung transplantation in systemic sclerosis. A systematic review. Respir Med 107:2081–2087CrossRefPubMed

Titel: Interstitial lung disease in systemic sclerosis: current and future treatment
verfasst von: Roberto Giacomelli
Vasiliki Liakouli
Onorina Berardicurti
Piero Ruscitti
Paola Di Benedetto
Francesco Carubbi
Giuliana Guggino
Salvatore Di Bartolomeo
Francesco Ciccia
Giovanni Triolo
Paola Cipriani
Publikationsdatum: 06.01.2017
Verlag: Springer Berlin Heidelberg
Erschienen in: Rheumatology International / Ausgabe 6/2017
Print ISSN: 0172-8172
Elektronische ISSN: 1437-160X
DOI: https://doi.org/10.1007/s00296-016-3636-7

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Interstitial lung disease in systemic sclerosis: current and future treatment

Abstract

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

15% bedauern gewählte Blasenkrebs-Therapie

Costims – das nächste heiße Ding in der Krebstherapie?

Update Innere Medizin

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 6/2017

Pain, social support and depressive symptoms in patients with rheumatoid arthritis: testing the stress-buffering hypothesis

Sarcopenia in rheumatoid arthritis: prevalence, influence of disease activity and associated factors

Pain rather than self-reported sedentary time explains variation in perceived health and activity limitation in persons with rheumatoid arthritis: a cross sectional study in Sweden

Inflammatory status and uricaemia determine HDL-cholesterol levels in hypertensive adults over 65: an analysis of the FAPRES register

Renal vasculitis presenting with acute kidney injury

Belimumab use, clinical outcomes and glucocorticoid reduction in patients with systemic lupus erythematosus receiving belimumab in clinical practice settings: results from the OBSErve Canada Study

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

15% bedauern gewählte Blasenkrebs-Therapie

Costims – das nächste heiße Ding in der Krebstherapie?

Update Innere Medizin