Abstract
The focus of this review is to increase awareness of pulmonary arterial hypertension (PAH) in patients with rheumatic diseases. Epidemiology and pathogenesis of PAH in rheumatic diseases is reviewed, with recommendations for early screening and diagnosis and suggestion of possible role of immunosuppressive therapy in treatment for PAH in rheumatic diseases. A MEDLINE search for articles published between January 1970 and June 2012 was conducted using the following keywords: pulmonary hypertension, scleroderma, systemic sclerosis, pulmonary arterial hypertension, connective tissues disease, systemic lupus erythematosus, mixed connective tissue disease, rheumatoid arthritis, Sjogren’s syndrome, vasculitis, sarcoidosis, inflammatory myopathies, dermatomyositis, ankylosing spondylitis, spondyloarthropathies, diagnosis and treatment. Pathogenesis and disease burden of PAH in rheumatic diseases was highlighted, with emphasis on early consideration and workup of PAH. Screening recommendations and treatment were touched upon. PAH is most commonly seen in systemic sclerosis and may be seen in isolation or in association with interstitial lung disease. Several pathophysiologic processes have been identified including an obliterative vasculopathy, veno-occlusive disease, formation of microthrombi and pulmonary fibrosis. PAH in systemic lupus erythematosus is associated with higher prevalence of antiphospholipid and anticardiolipin antibodies and the presence of Raynaud’s phenomenon. Endothelial proliferation with vascular remodeling, abnormal coagulation with thrombus formation and immune-mediated vasculopathy are the postulated mechanisms. Improvement with immunosuppressive medications has been reported. Pulmonary fibrosis, extrinsic compression of pulmonary arteries and granulomatous vasculitis have been reported in patients with sarcoidosis. Intimal and medial hyperplasia with luminal narrowing has been observed in Sjogren’s syndrome, mixed connective tissue disease and inflammatory myopathies. Pulmonary arterial hypertension (PAH) associated with rheumatic diseases carries a particularly grim prognosis with faster progression of disease and poor response to therapy. Though largely associated with systemic sclerosis, it is being increasingly recognized in other rheumatic diseases. An underlying inflammatory component may explain the poor response to therapy in patients with rheumatic diseases and is a rationale for consideration of immunosuppressive therapy in conjunction with vasodilator therapy in treatment for PAH. Further studies identifying pathogenetic pathways and possible targets of therapy, especially the role of immunomodulatory medications, are warranted.
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References
Chatterjee S (2011) Pulmonary hypertension in systemic sclerosis. Semin Arthritis Rheum 41(1):19–37
Agarwal R, Gomberg-Maitland M (2011) Current therapeutics and practical management strategies for pulmonary arterial hypertension. Am Heart J 162(2):201–213
Distler O, Pignone A (2006) Pulmonary arterial hypertension and rheumatic diseases–from diagnosis to treatment. Rheumatology (Oxford) 45(Suppl 4):iv22–iv25
Fisher MR, Mathai SC, Champion HC, Girgis RE, Housten-Harris T, Hummers L et al (2006) Clinical differences between idiopathic and scleroderma-related pulmonary hypertension. Arthritis Rheum 54(9):3043–3050
Task Force for Diagnosis and Treatment of Pulmonary Hypertension of European Society of Cardiology (ESC), European Respiratory Society (ERS), International Society of Heart and Lung Transplantation (ISHLT), Galie N, Hoeper MM, Humbert M et al (2009) Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J 34(6):1219–1263
McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR et al (2009) ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol 53(17):1573–1619
Steen VD, Medsger TA (2007) Changes in causes of death in systemic sclerosis, 1972–2002. Ann Rheum Dis 66(7):940–944
Condliffe R, Kiely DG, Peacock AJ, Corris PA, Gibbs JS, Vrapi F et al (2009) Connective tissue disease-associated pulmonary arterial hypertension in the modern treatment era. Am J Respir Crit Care Med 179(2):151–157
Lambova S, Muller-Ladner U (2010) Pulmonary arterial hypertension in systemic sclerosis. Autoimmun Rev 9(11):761–770
Pope JE, Lee P, Baron M, Dunne J, Smith D, Docherty PS et al (2005) Prevalence of elevated pulmonary arterial pressures measured by echocardiography in a multicenter study of patients with systemic sclerosis. J Rheumatol 32(7):1273–1278
Wigley FM, Lima JA, Mayes M, McLain D, Chapin JL, Ward-Able C (2005) The prevalence of undiagnosed pulmonary arterial hypertension in subjects with connective tissue disease at the secondary health care level of community-based rheumatologists (the UNCOVER study). Arthritis Rheum 52(7):2125–2132
Johnson SR, Granton JT (2011) Pulmonary hypertension in systemic sclerosis and systemic lupus erythematosus. Eur Respir Rev 20(122):277–286
Hachulla E, Gressin V, Guillevin L, Carpentier P, Diot E, Sibilia J et al (2005) Early detection of pulmonary arterial hypertension in systemic sclerosis: a French nationwide prospective multicenter study. Arthritis Rheum 52(12):3792–3800
Walker UA, Tyndall A, Czirjak L, Denton C, Farge-Bancel D, Kowal-Bielecka O 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(6):754–763
Jeffery TK, Morrell NW (2002) Molecular and cellular basis of pulmonary vascular remodeling in pulmonary hypertension. Prog Cardiovasc Dis 45(3):173–202
Okano Y, Steen VD, Medsger TA Jr (1992) Autoantibody to U3 nucleolar ribonucleoprotein (fibrillarin) in patients with systemic sclerosis. Arthritis Rheum 35(1):95–100
Okawa-Takatsuji M, Aotsuka S, Fujinami M, Uwatoko S, Kinoshita M, Sumiya M (1999) Up-regulation of intercellular adhesion molecule-1 (ICAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1) and class II MHC molecules on pulmonary artery endothelial cells by antibodies against U1-ribonucleoprotein. Clin Exp Immunol 116(1):174–180
Steen V, Medsger TA Jr (2003) Predictors of isolated pulmonary hypertension in patients with systemic sclerosis and limited cutaneous involvement. Arthritis Rheum 48(2):516–522
Denton CP, Cailes JB, Phillips GD, Wells AU, Black CM, Bois RM (1997) Comparison of Doppler echocardiography and right heart catheterization to assess pulmonary hypertension in systemic sclerosis. Br J Rheumatol 36(2):239–243
Fischer A, Swigris JJ, Groshong SD, Cool CD, Sahin H, Lynch DA et al (2008) Clinically significant interstitial lung disease in limited scleroderma: histopathology, clinical features, and survival. Chest 134(3):601–605
Schachna L, Wigley FM, Chang B, White B, Wise RA, Gelber AC (2003) Age and risk of pulmonary arterial hypertension in scleroderma. Chest 124(6):2098–2104
Hachulla E, Launay D, Mouthon L, Sitbon O, Berezne A, Guillevin L et al (2009) Is pulmonary arterial hypertension really a late complication of systemic sclerosis? Chest 136(5):1211–1219
Kawut SM, Taichman DB, Archer-Chicko CL, Palevsky HI, Kimmel SE (2003) Hemodynamics and survival in patients with pulmonary arterial hypertension related to systemic sclerosis. Chest 123(2):344–350
Koh ET, Lee P, Gladman DD, Abu-Shakra M (1996) Pulmonary hypertension in systemic sclerosis: an analysis of 17 patients. Br J Rheumatol 35(10):989–993
Hassoun PM (2009) Pulmonary arterial hypertension complicating connective tissue diseases. Semin Respir Crit Care Med 30(4):429–439
Williams MH, Handler CE, Akram R, Smith CJ, Das C, Smee J et al (2006) Role of N-terminal brain natriuretic peptide (N-TproBNP) in scleroderma-associated pulmonary arterial hypertension. Eur Heart J 27(12):1485–1494
Forfia PR, Mathai SC, Fisher MR, Housten-Harris T, Hemnes AR, Champion HC et al (2008) Hyponatremia predicts right heart failure and poor survival in pulmonary arterial hypertension. Am J Respir Crit Care Med 177(12):1364–1369
Yousem SA (1990) The pulmonary pathologic manifestations of the CREST syndrome. Hum Pathol 21(5):467–474
Al-Sabbagh MR, Steen VD, Zee BC, Nalesnik M, Trostle DC, Bedetti CD et al (1989) Pulmonary arterial histology and morphometry in systemic sclerosis: a case-control autopsy study. J Rheumatol 16(8):1038–1042
Tuder RM, Cool CD, Geraci MW, Wang J, Abman SH, Wright L et al (1999) Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am J Respir Crit Care Med 159(6):1925–1932
Morelli S, Ferri C, Di Francesco L, Baldoncini R, Carlesimo M, Bottoni U et al (1995) Plasma endothelin-1 levels in patients with systemic sclerosis: influence of pulmonary or systemic arterial hypertension. Ann Rheum Dis 54(9):730–734
Overbeek MJ, Vonk MC, Boonstra A, Voskuyl AE, Vonk-Noordegraaf A, Smit EF et al (2009) Pulmonary arterial hypertension in limited cutaneous systemic sclerosis: a distinctive vasculopathy. Eur Respir J 34(2):371–379
Morassut PA, Walley VM, Smith CD (1992) Pulmonary veno-occlusive disease and the CREST variant of scleroderma. Can J Cardiol 8(10):1055–1058
Saito A, Takizawa H, Ito K, Yamamoto K, Oka T (2003) A case of pulmonary veno-occlusive disease associated with systemic sclerosis. Respirology 8(3):383–385
Dorfmuller P, Humbert M, Perros F, Sanchez O, Simonneau G, Muller KM et al (2007) Fibrous remodeling of the pulmonary venous system in pulmonary arterial hypertension associated with connective tissue diseases. Hum Pathol 38(6):893–902
Cool CD, Kennedy D, Voelkel NF, Tuder RM (1997) Pathogenesis and evolution of plexiform lesions in pulmonary hypertension associated with scleroderma and human immunodeficiency virus infection. Hum Pathol 28(4):434–442
Mathai SC, Hummers LK, Champion HC, Wigley FM, Zaiman A, Hassoun PM et al (2009) Survival in pulmonary hypertension associated with the scleroderma spectrum of diseases: impact of interstitial lung disease. Arthritis Rheum 60(2):569–577
Sanchez O, Sitbon O, Jais X, Simonneau G, Humbert M (2006) Immunosuppressive therapy in connective tissue diseases-associated pulmonary arterial hypertension. Chest 130(1):182–189
Charoenpan P, Sukumalchantra Y, Ayuthya WI (1977) Pulmonary hypertension in systemic lupus erythematosus: a case report. J Med Assoc Thai 60(12):670–675
Quismorio FP Jr, Sharma O, Koss M, Boylen T, Edmiston AW, Thornton PJ et al (1984) Immunopathologic and clinical studies in pulmonary hypertension associated with systemic lupus erythematosus. Semin Arthritis Rheum 13(4):349–359
Sanchez O, Humbert M, Sitbon O, Simonneau G (1999) Treatment of pulmonary hypertension secondary to connective tissue diseases. Thorax 54(3):273–277
Haas C (2004) Pulmonary hypertension associated with systemic lupus erythematosus. Bull Acad Natl Med 188(6):985–997 (discussion 997)
Winslow TM, Ossipov MA, Fazio GP, Simonson JS, Redberg RF, Schiller NB (1995) Five-year follow-up study of the prevalence and progression of pulmonary hypertension in systemic lupus erythematosus. Am Heart J 129(3):510–515
Kamel SR, Omar GM, Darwish AF, Asklany HT, Ellabban AS (2011) Asymptomatic pulmonary hypertension in systemic lupus erythematosus. Clin Med Insights Arthritis Musculoskelet Disord 4:77–86
Goupille P, Fauchier L, Babuty D, Fauchier JP, Valat JP (1994) Precapillary pulmonary hypertension dramatically improved with high doses of corticosteroids during systemic lupus erythematosus. J Rheumatol 21(10):1976–1977
Asherson RA, Higenbottam TW, Dinh Xuan AT, Khamashta MA, Hughes GR (1990) Pulmonary hypertension in a lupus clinic: experience with twenty-four patients. J Rheumatol 17(10):1292–1298
Magliano M, Isenberg DA, Hillson J (2002) Pulmonary hypertension in autoimmune rheumatic diseases: where are we now? Arthritis Rheum 46(8):1997–2009
Farber HW, Loscalzo J (2004) Pulmonary arterial hypertension. N Engl J Med 351(16):1655–1665
Cefle A, Inanc M, Sayarlioglu M, Kamali S, Gul A, Ocal L et al (2011) Pulmonary hypertension in systemic lupus erythematosus: relationship with antiphospholipid antibodies and severe disease outcome. Rheumatol Int 31(2):183–189
Atsumi T, Khamashta MA, Haworth RS, Brooks G, Amengual O, Ichikawa K et al (1998) Arterial disease and thrombosis in the antiphospholipid syndrome: a pathogenic role for endothelin 1. Arthritis Rheum 41(5):800–807
Shen JY, Chen SL, Wu YX, Tao RQ, Gu YY, Bao CD et al (1999) Pulmonary hypertension in systemic lupus erythematosus. Rheumatol Int 18(4):147–151
Petri M, Rheinschmidt M, Whiting-O’Keefe Q, Hellmann D, Corash L (1987) The frequency of lupus anticoagulant in systemic lupus erythematosus. A study of sixty consecutive patients by activated partial thromboplastin time, Russell viper venom time, and anticardiolipin antibody level. Ann Intern Med 106(4):524–531
Anderson NE, Ali MR (1984) The lupus anticoagulant, pulmonary thromboembolism, and fatal pulmonary hypertension. Ann Rheum Dis 43(5):760–763
Asherson RA, Harris EN, Bernstein RM, Mackworth-Young CG, Hughes GR (1984) Immunological studies in ‘primary’ idiopathic pulmonary hypertension. Eur J Rheumatol Inflamm 7(3):75–79
Kasparian A, Floros A, Gialafos E, Kanakis M, Tassiopoulos S, Kafasi N et al (2007) Raynaud’s phenomenon is correlated with elevated systolic pulmonary arterial pressure in patients with systemic lupus erythematosus. Lupus 16(7):505–508
Alarcon-Segovia D, Deleze M, Oria CV, Sanchez-Guerrero J, Gomez-Pacheco L, Cabiedes J et al (1989) Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lupus erythematosus. A prospective analysis of 500 consecutive patients. Medicine (Baltimore) 68(6):353–365
Fois E, Le Guern V, Dupuy A, Humbert M, Mouthon L, Guillevin L (2010) Noninvasive assessment of systolic pulmonary artery pressure in systemic lupus erythematosus: retrospective analysis of 93 patients. Clin Exp Rheumatol 28(6):836–841
Asherson RA, Oakley CM (1986) Pulmonary hypertension and systemic lupus erythematosus. J Rheumatol 13(1):1–5
Yoshio T, Masuyama J, Mimori A, Takeda A, Minota S, Kano S (1995) Endothelin-1 release from cultured endothelial cells induced by sera from patients with systemic lupus erythematosus. Ann Rheum Dis 54(5):361–365
Sharp GC, Irvin WS, Tan EM, Gould RG, Holman HR (1972) Mixed connective tissue disease–an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA). Am J Med 52(2):148–159
Sullivan WD, Hurst DJ, Harmon CE, Esther JH, Agia GA, Maltby JD et al (1984) A prospective evaluation emphasizing pulmonary involvement in patients with mixed connective tissue disease. Medicine (Baltimore) 63(2):92–107
Burdt MA, Hoffman RW, Deutscher SL, Wang GS, Johnson JC, Sharp GC (1999) Long-term outcome in mixed connective tissue disease: longitudinal clinical and serologic findings. Arthritis Rheum 42(5):899–909
Bull TM, Fagan KA, Badesch DB (2005) Pulmonary vascular manifestations of mixed connective tissue disease. Rheum Dis Clin North Am 31(3):451–64, vi
Lundberg IE (2005) The prognosis of mixed connective tissue disease. Rheum Dis Clin North Am 31(3):535–547 (vii–viii)
Alpert MA, Goldberg SH, Singsen BH, Durham JB, Sharp GC, Ahmad M et al (1983) Cardiovascular manifestations of mixed connective tissue disease in adults. Circulation 68(6):1182–1193
Kasukawa R, Nishimaki T, Takagi T, Miyawaki S, Yokohari R, Tsunematsu T (1990) Pulmonary hypertension in connective tissue disease. Clinical analysis of sixty patients in multi-institutional study. Clin Rheumatol 9(1):56–62
Gondran G, Fauchais A, Lambert M, Ly K, Launay D, Queyrel V et al (2008) Primary Sjogren’s syndrome in men. Scand J Rheumatol 37(4):300–305
Garcia-Carrasco M, Ramos-Casals M, Rosas J, Pallares L, Calvo-Alen J, Cervera R et al (2002) Primary Sjogren syndrome: clinical and immunologic disease patterns in a cohort of 400 patients. Medicine (Baltimore) 81(4):270–280
Kelly C, Gardiner P, Pal B, Griffiths I (1991) Lung function in primary Sjogren’s syndrome: a cross sectional and longitudinal study. Thorax 46(3):180–183
Constantopoulos SH, Papadimitriou CS, Moutsopoulos HM (1985) Respiratory manifestations in primary Sjogren’s syndrome. A clinical, functional, and histologic study. Chest 88(2):226–229
Hatron PY, Tillie-Leblond I, Launay D, Hachulla E, Fauchais AL, Wallaert B (2011) Pulmonary manifestations of Sjogren’s syndrome. Presse Med 40(1 Pt 2):e49–e64
Launay D, Hachulla E, Hatron PY, Jais X, Simonneau G, Humbert M (2007) Pulmonary arterial hypertension: a rare complication of primary Sjogren syndrome: report of 9 new cases and review of the literature. Medicine (Baltimore) 86(5):299–315
Keith MP, Moratz C, Tsokos GC (2007) Anti-RNP immunity: implications for tissue injury and the pathogenesis of connective tissue disease. Autoimmun Rev 6(4):232–236
Nunes H, Humbert M, Capron F, Brauner M, Sitbon O, Battesti JP et al (2006) Pulmonary hypertension associated with sarcoidosis: mechanisms, haemodynamics and prognosis. Thorax 61(1):68–74
Shigemitsu H, Nagai S, Sharma OP (2007) Pulmonary hypertension and granulomatous vasculitis in sarcoidosis. Curr Opin Pulm Med 13(5):434–438
Shorr AF, Helman DL, Davies DB, Nathan SD (2005) Pulmonary hypertension in advanced sarcoidosis: epidemiology and clinical characteristics. Eur Respir J 25(5):783–788
Sulica R, Teirstein AS, Kakarla S, Nemani N, Behnegar A, Padilla ML (2005) Distinctive clinical, radiographic, and functional characteristics of patients with sarcoidosis-related pulmonary hypertension. Chest 128(3):1483–1489
Handa T, Nagai S, Miki S, Fushimi Y, Ohta K, Mishima M et al (2006) Incidence of pulmonary hypertension and its clinical relevance in patients with sarcoidosis. Chest 129(5):1246–1252
Fisher KA, Serlin DM, Wilson KC, Walter RE, Berman JS, Farber HW (2006) Sarcoidosis-associated pulmonary hypertension: outcome with long-term epoprostenol treatment. Chest 130(5):1481–1488
Schwarz MI (1992) Pulmonary and cardiac manifestations of polymyositis-dermatomyositis. J Thorac Imaging 7(2):46–54
Caldwell IW, Aitchison JD (1956) Pulmonary hypertension in dermatomyositis. Br Heart J 18(2):273–276
Bunch TW, Tancredi RG, Lie JT (1981) Pulmonary hypertension in polymyositis. Chest 79(1):105–107
Grateau G, Roux ME, Franck N, Bachmeyer C, Taulera O, Forest M et al (1993) Pulmonary hypertension in a case of dermatomyositis. J Rheumatol 20(8):1452–1453
Yaqub S, Moder KG, Lacy MQ (2004) Severe, reversible pulmonary hypertension in a patient with monoclonal gammopathy and features of dermatomyositis. Mayo Clin Proc 79(5):687–689
Minai OA (2009) Pulmonary hypertension in polymyositis-dermatomyositis: clinical and hemodynamic characteristics and response to vasoactive therapy. Lupus 18(11):1006–1010
Denbow CE, Lie JT, Tancredi RG, Bunch TW (1979) Cardiac involvement in polymyositis: a clinicopathologic study of 20 autopsied patients. Arthritis Rheum 22(10):1088–1092
Hebert CA, Byrnes TJ, Baethge BA, Wolf RE, Kinasewitz GT (1990) Exercise limitation in patients with polymyositis. Chest 98(2):352–357
Castro GW, Appenzeller S, Bertolo MB, Costallat LT (2006) Isolated pulmonary hypertension secondary to rheumatoid arthritis. Clin Rheumatol 25(6):901–903
Gonzalez-Juanatey C, Testa A, Garcia-Castelo A, Garcia-Porrua C, Llorca J, Ollier WE et al (2004) Echocardiographic and Doppler findings in long-term treated rheumatoid arthritis patients without clinically evident cardiovascular disease. Semin Arthritis Rheum 33(4):231–238
Udayakumar N, Venkatesan S, Rajendiran C (2008) Pulmonary hypertension in rheumatoid arthritis–relation with the duration of the disease. Int J Cardiol 127(3):410–412
Handa T, Nagai S, Kawabata D, Nagao T, Takemura M, Kitaichi M et al (2005) Long-term clinical course of a patient with anti PL-12 antibody accompanied by interstitial pneumonia and severe pulmonary hypertension. Intern Med 44(4):319–325
Taniguchi Y, Horino T, Kato T, Terada Y (2010) Acute pulmonary arterial hypertension associated with anti-synthetase syndrome. Scand J Rheumatol 39(2):179–180
Chatterjee S, Farver C (2010) Severe pulmonary hypertension in Anti-Jo-1 syndrome. Arthritis Care Res (Hoboken) 62(3):425–429
Launay D, Souza R, Guillevin L, Hachulla E, Pouchot J, Simonneau G et al (2006) Pulmonary arterial hypertension in ANCA-associated vasculitis. Sarcoidosis Vasc Diffuse Lung Dis 23(3):223–228
Coghlan JG, Handler C (2006) Connective tissue associated pulmonary arterial hypertension. Lupus 15(3):138–142
Minai OA, Budev MM (2007) Treating pulmonary arterial hypertension: cautious hope in a deadly disease. Cleve Clin J Med 74(11):789–793 (797–800, 802 passim)
Fagan KA, Badesch DB (2002) Pulmonary hypertension associated with connective tissue disease. Prog Cardiovasc Dis 45(3):225–234
Shitrit D, Amital A, Peled N, Raviv Y, Medalion B, Saute M et al (2009) Lung transplantation in patients with scleroderma: case series, review of the literature, and criteria for transplantation. Clin Transplant 23(2):178–183
Massad MG, Powell CR, Kpodonu J, Tshibaka C, Hanhan Z, Snow NJ et al (2005) Outcomes of lung transplantation in patients with scleroderma. World J Surg 29(11):1510–1515
Schachna L, Medsger TA Jr, Dauber JH, Wigley FM, Braunstein NA, White B et al (2006) Lung transplantation in scleroderma compared with idiopathic pulmonary fibrosis and idiopathic pulmonary arterial hypertension. Arthritis Rheum 54(12):3954–3961
Launay D, Mouthon L, Hachulla E, Pagnoux C, de Groote P, Remy-Jardin M et al (2007) Prevalence and characteristics of moderate to severe pulmonary hypertension in systemic sclerosis with and without interstitial lung disease. J Rheumatol 34(5):1005–1011
ten Freyhaus H, Dumitrescu D, Berghausen E, Vantler M, Caglayan E, Rosenkranz S (2012) Imatinib mesylate for the treatment of pulmonary arterial hypertension. Expert Opin Investig Drugs 21(1):119–134
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Shahane, A. Pulmonary hypertension in rheumatic diseases: epidemiology and pathogenesis. Rheumatol Int 33, 1655–1667 (2013). https://doi.org/10.1007/s00296-012-2659-y
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DOI: https://doi.org/10.1007/s00296-012-2659-y