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 PAH
- 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
- SUMMARY AND RECOMMENDATIONS