Pulmonary vascular disease in systemic sclerosis (scleroderma): Treatment
- John Varga, MD
John Varga, MD
- John and Nancy Hughes Professor of Medicine
- Northwestern University Feinberg School of Medicine
- Virginia Steen, MD
Virginia Steen, MD
- Professor of Medicine
- Georgetown University Medical Center
- Paul Hassoun, MD
Paul Hassoun, MD
- Professor of Medicine
- Department of Medicine, Johns Hopkins University
- Section Editors
- Talmadge E King, Jr, MD
Talmadge E King, Jr, MD
- Editor-in-Chief — Pulmonary and Critical Care Medicine
- Section Editor — Interstitial Lung Disease
- Dean, School of Medicine
- Vice Chancellor, Medical Affairs
- University of California San Francisco
- John S Axford, DSc, MD, FRCP, FRCPCH
John S Axford, DSc, MD, FRCP, FRCPCH
- Section Editor — Scleroderma
- Emeritus Professor of Rheumatology
- St George's University of London
Pulmonary complications of systemic sclerosis (SSc) are both frequent and the leading cause of SSc-related death [1,2]. The most common pulmonary manifestations of SSc are the following:
●Pulmonary arterial hypertension (PAH)
●Interstitial lung disease (ILD)
●Pulmonary hypertension (PH) due to ILD
●A combination of ILD and PAHTo continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Steen VD, Medsger TA. Changes in causes of death in systemic sclerosis, 1972-2002. Ann Rheum Dis 2007; 66:940.
- Ferri C, Valentini G, Cozzi F, et al. Systemic sclerosis: demographic, clinical, and serologic features and survival in 1,012 Italian patients. Medicine (Baltimore) 2002; 81:139.
- Sanchez O, Sitbon O, Jaïs X, et al. Immunosuppressive therapy in connective tissue diseases-associated pulmonary arterial hypertension. Chest 2006; 130:182.
- Ngian GS, Stevens W, Prior D, et al. Predictors of mortality in connective tissue disease-associated pulmonary arterial hypertension: a cohort study. Arthritis Res Ther 2012; 14:R213.
- Johnson SR, Granton JT, Tomlinson GA, et al. Warfarin in systemic sclerosis-associated and idiopathic pulmonary arterial hypertension. A Bayesian approach to evaluating treatment for uncommon disease. J Rheumatol 2012; 39:276.
- Hassoun PM. Therapies for scleroderma-related pulmonary arterial hypertension. Expert Rev Respir Med 2009; 3:187.
- Impens AJ, Wangkaew S, Seibold JR. The 6-minute walk test in scleroderma--how measuring everything measures nothing. Rheumatology (Oxford) 2008; 47 Suppl 5:v68.
- Kowal-Bielecka O, Avouac J, Pittrow D, et al. Echocardiography as an outcome measure in scleroderma-related pulmonary arterial hypertension: a systematic literature analysis by the EPOSS group. J Rheumatol 2010; 37:105.
- Rubin LJ, Badesch DB, Barst RJ, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 2002; 346:896.
- Denton CP, Pope JE, Peter HH, et al. Long-term effects of bosentan on quality of life, survival, safety and tolerability in pulmonary arterial hypertension related to connective tissue diseases. Ann Rheum Dis 2008; 67:1222.
- Koh ET, Lee P, Gladman DD, Abu-Shakra M. Pulmonary hypertension in systemic sclerosis: an analysis of 17 patients. Br J Rheumatol 1996; 35:989.
- Kawut SM, Taichman DB, Archer-Chicko CL, et al. Hemodynamics and survival in patients with pulmonary arterial hypertension related to systemic sclerosis. Chest 2003; 123:344.
- Pulido T, Adzerikho I, Channick RN, et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med 2013; 369:809.
- Galiè N, Olschewski H, Oudiz RJ, et al. Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2. Circulation 2008; 117:3010.
- Günther S, Jaïs X, Maitre S, et al. Computed tomography findings of pulmonary venoocclusive disease in scleroderma patients presenting with precapillary pulmonary hypertension. Arthritis Rheum 2012; 64:2995.
- Raghu G, Behr J, Brown KK, et al. Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial. Ann Intern Med 2013; 158:641.
- Galiè N, Ghofrani HA, Torbicki A, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 2005; 353:2148.
- Badesch DB, Hill NS, Burgess G, et al. Sildenafil for pulmonary arterial hypertension associated with connective tissue disease. J Rheumatol 2007; 34:2417.
- Ghofrani HA, Galiè N, Grimminger F, et al. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med 2013; 369:330.
- Ghofrani HA, Grimminger F, Grünig E, et al. Predictors of long-term outcomes in patients treated with riociguat for pulmonary arterial hypertension: data from the PATENT-2 open-label, randomised, long-term extension trial. Lancet Respir Med 2016; 4:361.
- Humbert M, Coghlan JG, Ghofrani HA, et al. Riociguat for the treatment of pulmonary arterial hypertension associated with connective tissue disease: results from PATENT-1 and PATENT-2. Ann Rheum Dis 2017; 76:422.
- Badesch DB, Tapson VF, McGoon MD, et al. Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial. Ann Intern Med 2000; 132:425.
- Badesch DB, McGoon MD, Barst RJ, et al. Longterm survival among patients with scleroderma-associated pulmonary arterial hypertension treated with intravenous epoprostenol. J Rheumatol 2009; 36:2244.
- Voswinckel R, Reichenberger F, Gall H, et al. Metered dose inhaler delivery of treprostinil for the treatment of pulmonary hypertension. Pulm Pharmacol Ther 2009; 22:50.
- Oudiz RJ, Schilz RJ, Barst RJ, et al. Treprostinil, a prostacyclin analogue, in pulmonary arterial hypertension associated with connective tissue disease. Chest 2004; 126:420.
- Launay D, Hachulla E, Hatron PY, et al. Aerosolized iloprost in CREST syndrome related pulmonary hypertension. J Rheumatol 2001; 28:2252.
- Johnson SR, Brode SK, Mielniczuk LM, Granton JT. Dual therapy in IPAH and SSc-PAH. A qualitative systematic review. Respir Med 2012; 106:730.
- Gaine S, Chin K, Coghlan G, et al. Selexipag for the treatment of connective tissue disease-associated pulmonary arterial hypertension. Eur Respir J 2017; 50.
- Galiè N, Barberà JA, Frost AE, et al. Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension. N Engl J Med 2015; 373:834.
- Coghlan JG, Galiè N, Barberà JA, et al. Initial combination therapy with ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH): subgroup analysis from the AMBITION trial. Ann Rheum Dis 2017; 76:1219.
- Hassoun PM, Zamanian RT, Damico R, et al. Ambrisentan and Tadalafil Up-front Combination Therapy in Scleroderma-associated Pulmonary Arterial Hypertension. Am J Respir Crit Care Med 2015; 192:1102.
- Lammi MR, Mathai SC, Saketkoo LA, et al. Association Between Initial Oral Therapy and Outcomes in Systemic Sclerosis-Related Pulmonary Arterial Hypertension. Arthritis Rheumatol 2016; 68:740.
- Schachna L, Medsger TA Jr, Dauber JH, et al. Lung transplantation in scleroderma compared with idiopathic pulmonary fibrosis and idiopathic pulmonary arterial hypertension. Arthritis Rheum 2006; 54:3954.
- Saggar R, Khanna D, Furst DE, et al. Systemic sclerosis and bilateral lung transplantation: a single centre experience. Eur Respir J 2010; 36:893.
- GENERAL MEASURES
- Supportive therapies
- PULMONARY ARTERIAL HYPERTENSION-DIRECTED THERAPY
- Calcium channel blockers
- Endothelin-1 receptor antagonists
- - Nonselective
- - Selective
- Nitric oxide-cyclic guanosine monophosphate enhancers
- - Phosphodiesterase type 5 inhibitors
- - Guanylate cyclase stimulant
- Prostacyclin pathway agonists
- - Epoprostenol
- - Treprostinil
- - Iloprost
- - Selexipag
- Combination therapy
- LUNG TRANSPLANTATION
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS