rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2015-69-77rsp-2041Research ArticleПРОГРАММА НЕПРЕРЫВНОГО ПОСЛЕДИПЛОМНОГО ОБРАЗОВАНИЯ ВРАЧЕЙPOSTGRADUATE PROGRAM OF CONTINUING MEDICAL EDUCATIONЛегочная артериальная гипертензия при системных заболеваниях соединительной тканиPULMONARY ARTERIAL HYPERTENSION IN CONNECTIVE TISSUE DISEASESВолковА. В.VolkovA. V.

заведующий лабораторией инструментальной диагностики ФГБНУ НИИР им. В.А. Насоновой, канд. мед. наук 

sandyvlk@yahoo.comФГБНУ Научно- исследовательский институт ревматологии им. В.А. Насоновой, Москва, Россия 115522 Москва, Каширское шоссе, 34АРоссияV.A. Nasonova Research Institute of Rheumatology, Moscow, Russia 34A, Kashirskoe Shosse, Moscow 115522Russian Federation2015120320155316977Copyright © Волков А.В., 20152015Волков А.В.Volkov A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/2041

В лекции рассматривается проблема одного из редких проявлений системных заболеваний – легочной артериальной гипертензии. Указывается необходимость ранней диагностики, тщательной дифференциальной диагностики, верификации диагноза с применением инвазивных способов оценки центральной гемодинамики. Представлена модель скрининга больных с системной склеродермией, упрощающая определение показаний для назначения методов, позволяющих верифицировать диагноз. Описаны современные подходы к лекарственной терапии, обсуждаются вопросы улучшения выживаемости пациентов с этой прогностически неблагоприятной патологией.

The lecture considers the problem of one of the rare manifestations of systemic diseases (pulmonary arterial hypertension) and shows the need for early diagnosis, careful differential diagnosis, and verification of diagnosis, by applying invasive procedures to evaluate central hemodynamics. It gives a model for screening patients with systemic sclerosis, which simplifies the determination of indications for the use of diagnostic verification methods. Current approaches to drug therapy are described and the issues of better survival of patients with poor prognosis of this disorder are discussed. 

легочная артериальная гипертензиясистемные заболевания соединительной тканисис- темная склеродермияpulmonary arterial hypertensionconnective tissue diseasessystemic sclerosisReferencesChung L, Liu J, Parsons L, et al. Characterization of connective tissue disease-associated pulmonary arterial hypertension from REVEAL: identifying systemic sclerosis as a unique phenotype. Chest. 2010;138(6):1383–94. DOI: 10.1378/chest.10-0260Chung L, Liu J, Parsons L, et al. Characterization of connective tissue disease-associated pulmonary arterial hypertension from REVEAL: identifying systemic sclerosis as a unique phenotype. Chest. 2010;138(6):1383–94. DOI: 10.1378/chest.10-0260Badesch DB, Raskob GE, Elliott CG, et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest. 2010;137(2):376–87. DOI: 10.1378/chest.09-1140Badesch DB, Raskob GE, Elliott CG, et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest. 2010;137(2):376–87. DOI: 10.1378/chest.09-1140Yang X, Mardekian K, Sanders KN, et al. Prevalence of pulmonary arterial hypertension in patients with connective tissue diseases: a systematic review of the literature. Clin Rheumatol. 2013;32(10):1519–31. DOI: 10.1007/s10067-013-2307-2Yang X, Mardekian K, Sanders KN, et al. Prevalence of pulmonary arterial hypertension in patients with connective tissue diseases: a systematic review of the literature. Clin Rheumatol. 2013;32(10):1519–31. DOI: 10.1007/s10067-013-2307-2Van den Hoogen F, Khanna D, Fransen J, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League Against Rheumatism Collaborative Initiative. Ann Rheum Dis. 2013;72(11):1747–55. DOI: 10.1136/annrheumdis-2013-204424Van den Hoogen F, Khanna D, Fransen J, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League Against Rheumatism Collaborative Initiative. Ann Rheum Dis. 2013;72(11):1747–55. DOI: 10.1136/annrheumdis-2013-204424Amigues JM, Cantagrel A, Abbal M, Mazieres B. Comparative study of 4 diagnosis criteria sets for mixed connective tissue disease in patients with anti-RNP antibodies. Autoimmunity Group of the Hospitals of Toulouse. J Rheumatol. 1996; 23(12):2055–62.Amigues JM, Cantagrel A, Abbal M, Mazieres B. Comparative study of 4 diagnosis criteria sets for mixed connective tissue disease in patients with anti-RNP antibodies. Autoimmunity Group of the Hospitals of Toulouse. J Rheumatol. 1996; 23(12):2055–62.Launay D, Sitbon O, Hachulla E, et al. Survival in systemic sclerosis-associated pulmonary arterial hypertension in the modern management era. Ann Rheum Dis. 2013;72(12):1940–6. DOI: 10.1136/annrheumdis-2012-202489Launay D, Sitbon O, Hachulla E, et al. Survival in systemic sclerosis-associated pulmonary arterial hypertension in the modern management era. Ann Rheum Dis. 2013;72(12):1940–6. DOI: 10.1136/annrheumdis-2012-202489Avouac J, Airo P, Meune C, et al. Prevalence of pulmonary hypertension in systemic sclerosis in European Caucasians and metaanalysis of 5 studies. J Rheumatol. 2010;37(11):2290–8. DOI: 10.3899/jrheum.100245Avouac J, Airo P, Meune C, et al. Prevalence of pulmonary hypertension in systemic sclerosis in European Caucasians and metaanalysis of 5 studies. J Rheumatol. 2010;37(11):2290–8. DOI: 10.3899/jrheum.100245Iudici M, Codullo V, Giuggioli D, et al. Pulmonary hypertension in systemic sclerosis: prevalence, incidence and predictive factors in a large multicentric Italian cohort. Clin Exp Rheumatol. 2013;31(2 Suppl 76):31–6.Iudici M, Codullo V, Giuggioli D, et al. Pulmonary hypertension in systemic sclerosis: prevalence, incidence and predictive factors in a large multicentric Italian cohort. Clin Exp Rheumatol. 2013;31(2 Suppl 76):31–6.Mathai SP, Hassoun PM. Pulmonary arterial hypertension in connective tissue diseases. Heart Fail Clin. 2012;8(3):413–25. DOI: 10.1016/j.hfc.2012.04.001Mathai SP, Hassoun PM. Pulmonary arterial hypertension in connective tissue diseases. Heart Fail Clin. 2012;8(3):413–25. DOI: 10.1016/j.hfc.2012.04.001Gü ndü z OH, Fertig N, Lucas M, Medsger TA Jr. Systemic sclerosis with renal crisis and pulmonary hypertension: a report of eleven cases. Arthritis Rheum. 2001;44(7):1663–6. DOI: 10.1002/1529-0131(200107)44:7<1663::AID-ART290>3.0.CO;2CGü ndü z OH, Fertig N, Lucas M, Medsger TA Jr. Systemic sclerosis with renal crisis and pulmonary hypertension: a report of eleven cases. Arthritis Rheum. 2001;44(7):1663–6. DOI: 10.1002/1529-0131(200107)44:7<1663::AID-ART290>3.0.CO;2CLaunay D, Mouthon L, Hachulla E, et al. Prevalence and characteristics of moderate to severe pulmonary hypertension in systemic sclerosis with and without interstitial lung disease. J Rheumatol. 2007;34(5):1005–11.Launay D, Mouthon L, Hachulla E, et al. Prevalence and characteristics of moderate to severe pulmonary hypertension in systemic sclerosis with and without interstitial lung disease. J Rheumatol. 2007;34(5):1005–11.Чазова ИЕ, Авдеев СН, Царева НА и др. Клинические рекомендации по диагностике и лечению легочной гипертонии. Терапевтический архив. 2014;86(9):4–23 [Chazova IE, Avdeev SN, Tsareva NA, et al. Clinical guidelines for the diagnosis and treatment of pulmonary hypertension. Terapevticheskii arkhiv = Therapeutic Archive. 2014;86(9):4–23 (In Russ.)].Чазова ИЕ, Авдеев СН, Царева НА и др. Клинические рекомендации по диагностике и лечению легочной гипертонии. Терапевтический архив. 2014;86(9):4–23 [Chazova IE, Avdeev SN, Tsareva NA, et al. Clinical guidelines for the diagnosis and treatment of pulmonary hypertension. Terapevticheskii arkhiv = Therapeutic Archive. 2014;86(9):4–23 (In Russ.)].Schwaiger JP, Khanna D, Gerry Coghlan J. Screening patients with scleroderma for pulmonary arterial hypertension and implications for other at-risk populations. Eur Respir Rev. 2013;22(130):515–25. DOI: 10.1183/09059180.00006013Schwaiger JP, Khanna D, Gerry Coghlan J. Screening patients with scleroderma for pulmonary arterial hypertension and implications for other at-risk populations. Eur Respir Rev. 2013;22(130):515–25. DOI: 10.1183/09059180.00006013Steen V, Medsger TA Jr. Predictors of isolated pulmonary hypertension in patients with systemic sclerosis and limited cutaneous involvement. Arthritis Rheum. 2003;48(2):516–22. DOI: 10.1002/art.10775Steen V, Medsger TA Jr. Predictors of isolated pulmonary hypertension in patients with systemic sclerosis and limited cutaneous involvement. Arthritis Rheum. 2003;48(2):516–22. DOI: 10.1002/art.10775Mukerjee D, St George D, Knight C, et al. Echocardiography and pulmonary function as screening tests for pulmonary arterial hypertension in systemic sclerosis. Rheumatology (Oxford). 2004;43(4):461–6. DOI: 10.1093/rheumatology/keh067Mukerjee D, St George D, Knight C, et al. Echocardiography and pulmonary function as screening tests for pulmonary arterial hypertension in systemic sclerosis. Rheumatology (Oxford). 2004;43(4):461–6. DOI: 10.1093/rheumatology/keh067Hachulla E, Gressin V, Guillevin L, et al. Early detection of pulmonary arterial hypertension in systemic sclerosis: a French nationwide prospective multicenter study. Arthritis Rheum. 2005;52(12):3792–800. DOI: 10.1002/art.21433Hachulla E, Gressin V, Guillevin L, et al. Early detection of pulmonary arterial hypertension in systemic sclerosis: a French nationwide prospective multicenter study. Arthritis Rheum. 2005;52(12):3792–800. DOI: 10.1002/art.21433Hurdman J, Condliffe R, Elliot CA, et al. ASPIRE registry: Assessing the Spectrum of Pulmonary hypertension Identified at a REferral Centre. Eur Respir J. 2012;39(4):945–55. DOI: 10.1183/09031936.00078411Hurdman J, Condliffe R, Elliot CA, et al. ASPIRE registry: Assessing the Spectrum of Pulmonary hypertension Identified at a REferral Centre. Eur Respir J. 2012;39(4):945–55. DOI: 10.1183/09031936.00078411Gü nther S, Jais X, Maitre S, et al. Computed tomography findings of pulmonary venoocclusive disease in scleroderma patients presenting with precapillary pulmonary hypertension. Arthritis Rheum. 2012;64(9):2995–3005. DOI: 10.1002/art.34501Gü nther S, Jais X, Maitre S, et al. Computed tomography findings of pulmonary venoocclusive disease in scleroderma patients presenting with precapillary pulmonary hypertension. Arthritis Rheum. 2012;64(9):2995–3005. DOI: 10.1002/art.34501Dorfmuller P, Humbert M, Perros F, et al. Fibrous remodeling of the pulmonary venous system in pulmonary arterial hypertension associated with connective tissue diseases. Hum Pathol. 2007;38(6):893–902. DOI: 10.1016/j.humpath.2006.11.022Dorfmuller P, Humbert M, Perros F, et al. Fibrous remodeling of the pulmonary venous system in pulmonary arterial hypertension associated with connective tissue diseases. Hum Pathol. 2007;38(6):893–902. DOI: 10.1016/j.humpath.2006.11.022Badesch 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(10):2244–9. DOI: 10.3899/jrheum.081277Badesch 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(10):2244–9. DOI: 10.3899/jrheum.081277Badesch 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(6):425–34. DOI: 10.7326/0003-4819-1326-200003210-00002Badesch 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(6):425–34. DOI: 10.7326/0003-4819-1326-200003210-00002Pulido T, Adzerikho I, Channick RN, et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013;369(9):809–18. DOI: 10.1056/NEJMoa1213917Pulido T, Adzerikho I, Channick RN, et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013;369(9):809–18. DOI: 10.1056/NEJMoa1213917Coghlan JC, Denton CP, Grü nig E, et al. Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study. Ann Rheum Dis. 2014;73(7):1340–9. DOI: 10.1136/annrheumdis-2013-203301Coghlan JC, Denton CP, Grü nig E, et al. Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study. Ann Rheum Dis. 2014;73(7):1340–9. DOI: 10.1136/annrheumdis-2013-203301Kovacs G, Maier R, Aberer E, et al. Borderline pulmonary arterial pressure is associated with decreased exercise capacity in scleroderma. Am J Respir Crit Care Med. 2009;180(9):881–6. DOI: 10.1164/rccm.200904-0563OCKovacs G, Maier R, Aberer E, et al. Borderline pulmonary arterial pressure is associated with decreased exercise capacity in scleroderma. Am J Respir Crit Care Med. 2009;180(9):881–6. DOI: 10.1164/rccm.200904-0563OCBadesch DB, Champion HC, Sanchez MA, et al. Diagnosis and assessment of pulmonary arterial hypertension. J Am Coll Cardiol. 2009;54(1 Suppl):S55–66. DOI: 10.1016/j.jacc.2009.04.011Badesch DB, Champion HC, Sanchez MA, et al. Diagnosis and assessment of pulmonary arterial hypertension. J Am Coll Cardiol. 2009;54(1 Suppl):S55–66. DOI: 10.1016/j.jacc.2009.04.011Saggar R, Khanna D, Shapiro S, et al. Brief report: effect of ambrisentan treatment on exercise-induced pulmonary hypertension in systemic sclerosis: a prospective single-center, open-label pilot study. Arthritis Rheum. 2012;64(12):4072–7. DOI: 10.1002/art.34614Saggar R, Khanna D, Shapiro S, et al. Brief report: effect of ambrisentan treatment on exercise-induced pulmonary hypertension in systemic sclerosis: a prospective single-center, open-label pilot study. Arthritis Rheum. 2012;64(12):4072–7. DOI: 10.1002/art.34614Hoeper M, Bogaard HJ, Condliffe R, et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D42–50. DOI: 10.1016/j.jacc.2013.10.032Hoeper M, Bogaard HJ, Condliffe R, et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D42–50. DOI: 10.1016/j.jacc.2013.10.032Saggar R, Khanna D, Furst DE, et al. Exercise-induced pulmonary hypertension associated with systemic sclerosis. Arthritis Rheum. 2010;62:3741–50. DOI: 10.1002/art.27695Saggar R, Khanna D, Furst DE, et al. Exercise-induced pulmonary hypertension associated with systemic sclerosis. Arthritis Rheum. 2010;62:3741–50. DOI: 10.1002/art.27695Kovacs G, Maier R, Aberer E, et al. Pulmonary arterial hypertension therapy may be safe and effective in patients with systemic sclerosis and borderline pulmonary artery pressure. Arthritis Rheum. 2012;64(4):1257–62. DOI: 10.1002/art.33460Kovacs G, Maier R, Aberer E, et al. Pulmonary arterial hypertension therapy may be safe and effective in patients with systemic sclerosis and borderline pulmonary artery pressure. Arthritis Rheum. 2012;64(4):1257–62. DOI: 10.1002/art.33460Galie N, Manes A, Negro L, et al. A meta-analysis of randomized controlled trials in pulmonary arterial hypertension. Eur Heart J. 2009;30(4):394–403. DOI: 10.1093/eurheartj/ehp022Galie N, Manes A, Negro L, et al. A meta-analysis of randomized controlled trials in pulmonary arterial hypertension. Eur Heart J. 2009;30(4):394–403. DOI: 10.1093/eurheartj/ehp022Miyamichi-Yamamoto S, Fukumoto Y, Sugimura K, et al. Intensive immunosuppressive therapy improves pulmonary hemodynamics and long-term prognosis in patients with pulmonary arterial hypertension associated with connective tissue disease. Circ J. 2011;75(11):2668–74. DOI: 10.1253/circj.CJ-11-0473Miyamichi-Yamamoto S, Fukumoto Y, Sugimura K, et al. Intensive immunosuppressive therapy improves pulmonary hemodynamics and long-term prognosis in patients with pulmonary arterial hypertension associated with connective tissue disease. Circ J. 2011;75(11):2668–74. DOI: 10.1253/circj.CJ-11-0473Mathai S, Hassoun P. Therapy for pulmonary arterial hypertension associated with systemic sclerosis. Curr Opin Rheum. 2009;21(6):642–8. DOI: 10.1097/BOR.0b013e3283307dc8Mathai S, Hassoun P. Therapy for pulmonary arterial hypertension associated with systemic sclerosis. Curr Opin Rheum. 2009;21(6):642–8. DOI: 10.1097/BOR.0b013e3283307dc8Channick RN, Simonneau G, Sitbon O, et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet. 2001;358(9288):1119–23. DOI: 10.1016/S01406736(01)06250-XChannick RN, Simonneau G, Sitbon O, et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet. 2001;358(9288):1119–23. DOI: 10.1016/S01406736(01)06250-XRubin LJ, Badesch DB, Barst RJ, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med. 2002;346(12):896–903. DOI: 10.1056/NEJMoa012212Rubin LJ, Badesch DB, Barst RJ, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med. 2002;346(12):896–903. DOI: 10.1056/NEJMoa012212Galie N, Ghofrani HA, Torbicki A, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med. 2005;353(20):2148–57. DOI: 10.1056/NEJMoa050010Galie N, Ghofrani HA, Torbicki A, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med. 2005;353(20):2148–57. DOI: 10.1056/NEJMoa050010Galie 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(23):3010–9. DOI: 10.1161/CIRCULATIONAHA.107.742510Galie 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(23):3010–9. DOI: 10.1161/CIRCULATIONAHA.107.742510Launay D, Sitbon O, Le Pavec J, et al. Long-term outcome of systemic sclerosis-associated pulmonary arterial hypertension treated with bosentan as first-line monotherapy followed or not by the addition of prostanoid or sildenafil. Rheumatology. 2010:49(3):490–500. DOI: 10.1093/rheumatology/kep398Launay D, Sitbon O, Le Pavec J, et al. Long-term outcome of systemic sclerosis-associated pulmonary arterial hypertension treated with bosentan as first-line monotherapy followed or not by the addition of prostanoid or sildenafil. Rheumatology. 2010:49(3):490–500. DOI: 10.1093/rheumatology/kep398Sitbon O, McLaughlin VV, Badesch DB, et al. Survival in patients with class III idiopathic pulmonary arterial hypertension treated with first line oral bosentan compared with an historical cohort of patients started on intravenous epoprostenol. Thorax. 2005;60(2):1025–30.DOI: 10.1136/thx.2005.040618Sitbon O, McLaughlin VV, Badesch DB, et al. Survival in patients with class III idiopathic pulmonary arterial hypertension treated with first line oral bosentan compared with an historical cohort of patients started on intravenous epoprostenol. Thorax. 2005;60(2):1025–30.DOI: 10.1136/thx.2005.040618Мартынюк ТВ, Зыков КА, Антонова ОЮ и др.Влияние бозентана на клинический статус и клеточное звено иммунитета у больных с идиопатической легочной гипертензией. Терапевтический архив. 2013;85(1):25–31 [Martyniuk TV, Zykov KA, Antonova OYu, et al. Effect of bosentan on the clinical status and cellular immunity of patients with idiopathic pulmonary hypertension. Terapevticheskii arkhiv = Therapeutic Archive. 2013;85(1):25–31 (In Russ.)].Мартынюк ТВ, Зыков КА, Антонова ОЮ и др.Влияние бозентана на клинический статус и клеточное звено иммунитета у больных с идиопатической легочной гипертензией. Терапевтический архив. 2013;85(1):25–31 [Martyniuk TV, Zykov KA, Antonova OYu, et al. Effect of bosentan on the clinical status and cellular immunity of patients with idiopathic pulmonary hypertension. Terapevticheskii arkhiv = Therapeutic Archive. 2013;85(1):25–31 (In Russ.)].Badesch DB, Hill NS, Burgess G, et al. Sildenafil for pulmonary arterial hypertension associated with connective tissue disease. J Rheumatol. 2007;34(12):2417–22.Badesch DB, Hill NS, Burgess G, et al. Sildenafil for pulmonary arterial hypertension associated with connective tissue disease. J Rheumatol. 2007;34(12):2417–22.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(6):425–34. DOI: 10.7326/0003-4819-1326-200003210-00002Badesch 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(6):425–34. DOI: 10.7326/0003-4819-1326-200003210-00002Matucci-Cerinic M, Denton CP, Furst DE, et al. Bosentan treatment of digital ulcers related to systemic sclerosis: results from the RAPIDS-2 randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2011;70(1):32–8. DOI: 10.1136/ard.2010.130658Matucci-Cerinic M, Denton CP, Furst DE, et al. Bosentan treatment of digital ulcers related to systemic sclerosis: results from the RAPIDS-2 randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2011;70(1):32–8. DOI: 10.1136/ard.2010.130658Nguyen VA, Eisendle K, Gruber I, et al. Effect of the dual endothelin receptor antagonist bosentan on Raynaud's phenomenon secondary to systemic sclerosis: a double-blind prospective, randomized, placebo-controlled pilot study. Rheumatology (Oxford). 2010;49(3):583–7. DOI: 10.1093/rheumatology/kep413Nguyen VA, Eisendle K, Gruber I, et al. Effect of the dual endothelin receptor antagonist bosentan on Raynaud's phenomenon secondary to systemic sclerosis: a double-blind prospective, randomized, placebo-controlled pilot study. Rheumatology (Oxford). 2010;49(3):583–7. DOI: 10.1093/rheumatology/kep413Wigley FM, Wise RA, Seibold JR, et al. Intravenous iloprost infusion in patients with Raynaud's phenomenon secondary to systemic sclerosis. A multicenter, placebo-controlled, double-blind study. Ann Int Med. 1994;120(3):199–206. DOI: 10.7326/00034819-120-3-199402010-00004Wigley FM, Wise RA, Seibold JR, et al. Intravenous iloprost infusion in patients with Raynaud's phenomenon secondary to systemic sclerosis. A multicenter, placebo-controlled, double-blind study. Ann Int Med. 1994;120(3):199–206. DOI: 10.7326/00034819-120-3-199402010-00004Scorza R, Caronni M, Mascagni B, et al. Effect of long-term cyclic iloprost therapy in systemic sclerosis with Raynaud's phenomenon. A randomized controlled study. Clin Exp Rheum. 2001;19(5):503–8.Scorza R, Caronni M, Mascagni B, et al. Effect of long-term cyclic iloprost therapy in systemic sclerosis with Raynaud's phenomenon. A randomized controlled study. Clin Exp Rheum. 2001;19(5):503–8.Airo P, Rossi M, Scarsi M, et al. Disease-modifying effects of long-term cyclic iloprost therapy in systemic sclerosis. A retrospective analysis and comparison with a control group. Clin Exp Rheumatol. 2007; 25(5):722–36.Airo P, Rossi M, Scarsi M, et al. Disease-modifying effects of long-term cyclic iloprost therapy in systemic sclerosis. A retrospective analysis and comparison with a control group. Clin Exp Rheumatol. 2007; 25(5):722–36.

The authors declare that there are no conflicts of interest present.