Risk factors for severity and manifestations in systemic sclerosis and prediction of disease course

Expert Review of Clinical Immunology

Volumn 12, Issue 2, 2016, Pages 115-135

  Becker, Mike O ^a   Riemekasten, Gabriela ^b  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^b UNIVERSITY HOSPITAL SCHLESWIG HOLSTEIN   (Germany)

Author keywords

Fibrosis; Mortality; Organ involvement; Predictive factors; Pulmonary hypertension; Scleroderma; Skin thickening; Systemic sclerosis

Indexed keywords

ABDOMINAL PAIN; BLOATING; CARDIOPULMONARY EXERCISE TEST; CLINICAL FEATURE; COLITIS; DISEASE ACTIVITY; DISEASE ASSOCIATION; DISEASE COURSE; DISEASE SEVERITY; ECHOCARDIOGRAPHY; FECES INCONTINENCE; GASTROINTESTINAL REFLUX; HUMAN; HYPERALIMENTATION; INTERSTITIAL LUNG DISEASE; INTESTINE PSEUDOOBSTRUCTION; LUNG ARTERY PRESSURE; MALABSORPTION; MALNUTRITION; MORTALITY; NAUSEA; PROGNOSIS; PULMONARY HYPERTENSION; RECTUM PROLAPSE; REVIEW; RISK FACTOR; SKIN FIBROSIS; SKINFOLD; SYSTEMIC SCLEROSIS; TELANGIECTASIA; AUTOIMMUNITY; FIBROSIS; IMMUNOLOGY; METABOLISM; PATHOLOGY; SEVERITY OF ILLNESS INDEX; VASCULAR DISEASE;

BIOLOGICAL MARKER;

AUTOIMMUNITY; BIOMARKERS; DISEASE PROGRESSION; FIBROSIS; HUMANS; PROGNOSIS; RISK FACTORS; SCLERODERMA, SYSTEMIC; SEVERITY OF ILLNESS INDEX; VASCULAR DISEASES;

EID: 84957440121     PISSN: 1744666X     EISSN: 17448409     Source Type: Journal    
DOI: 10.1586/1744666X.2016.1115717     Document Type: Review

References (253)

1. Koenig M, Joyal F, Fritzler MJ, et al. Autoantibodies and microvascular damage are independent predictive factors for the progression of Raynaud's phenomenon to systemic sclerosis: a twenty-year prospective study of 586 patients, with validation of proposed criteria for early systemic sclerosis. Arthritis Rheum. 2008;58 (12):3902-3912.
2. Ingegnoli F, Boracchi P, Gualtierotti R, et al. Improving outcome prediction of systemic sclerosis from isolated Raynaud's phenomenon: role of autoantibodies and nailfold capillaroscopy. Rheumatology (Oxford). 2010;49 (4):797-805.
3. Avouac J, Fransen J, Walker UA, et al. Preliminary criteria for the very early Diagnosis of systemic sclerosis: results of a Delphi Consensus Study from EULAR Scleroderma Trials and Research Group. Ann Rheum Dis. 2011;70 (3):476-481.
4. van 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. Arthritis Rheum. 2013;65(11):2737-2747.
5. Minier T, Guiducci S, Bellando-Randone S, et al. Preliminary analysis of the very early Diagnosis of systemic sclerosis (VEDOSS) EUSTAR multicentre study: evidence for puffy fingers as a pivotal sign for suspicion of systemic sclerosis. Ann Rheum Dis. 2014;73(12):2087-2093.
6. Bruni C, Guiducci S, Bellando-Randone S, et al. Digital ulcers as a sentinel sign for early internal organ involvement in very early systemic sclerosis. Rheumatology (Oxford). 2015;54(1):72-76.
7. Lepri G, Guiducci S, Bellando-Randone S, et al. Evidence for oesophageal and anorectal involvement in very early systemic sclerosis (VEDOSS): report from a single VEDOSS/EUSTAR centre. Ann Rheum Dis. 2015;74 (1):124-128.
8. Elhai M, Meune C, Avouac J, et al. Trends in mortality in patients with systemic sclerosis over 40 years: a systematic review and meta-analysis of cohort studies. Rheumatology (Oxford). 2012;51(6):1017-1026.
9. 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 (2):139-153.
10. Steen VD, Medsger TA. Changes in causes of death in systemic sclerosis, 1972-2002. Ann Rheum Dis. 2007;66 (7):940-944.
11. Komocsi A, Vorobcsuk A, Faludi R, et al. The impact of cardiopulmonary manifestations on the mortality of SSc: a systematic review and meta-analysis of observational studies. Rheumatology (Oxford). 2012;51(6):1027-1036.
12. Avouac J, Walker UA, Hachulla E, et al. Joint and tendon involvement predict disease progression in systemic sclerosis: a EUSTAR prospective study. Ann Rheum Dis. 2014 Aug 27 pii: annrheumdis-2014-205295. doi:10. 1136/ annrheumdis-2014-205295 [Epub ahead of print].
13. Dore A, Lucas M, Ivanco D, et al. Significance of palpable tendon friction rubs in early diffuse cutaneous systemic sclerosis. Arthritis Care Res (Hoboken). 2013;65(8):1385-1389.
14. Mihai C, Landewe R, van der Heijde D, et al. Digital ulcers predict a worse disease course in patients with systemic sclerosis. Ann Rheum Dis. 2015 Feb 16
15. Hussein H, Lee P, Chau C, et al. The effect of male sex on survival in systemic sclerosis. J Rheumatol. 2014;41 (11):2193-2200.
16. Alba MA, Velasco C, Simeon CP, et al. Early-versus lateonset systemic sclerosis: differences in clinical presentation and outcome in 1037 patients. Medicine (Baltimore). 2014;93(2):73-81.
17. Tyndall AJ, Bannert B, Vonk M, et al. Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis. 2010;69(10):1809-1815.
18. Onishi A, Sugiyama D, Kumagai S, et al. Cancer incidence in systemic sclerosis: meta-analysis of population-based cohort studies. Arthritis Rheum. 2013;65(7):1913-1921.
19. Colaci M, Giuggioli D, Sebastiani M, et al. Lung cancer in scleroderma: results from an Italian rheumatologic center and review of the literature. Autoimmun Rev. 2013;12 (3):374-379.
20. Hesselstrand R, Scheja A, Akesson A. Mortality and causes of death in a Swedish series of systemic sclerosis patients. Ann Rheum Dis. 1998;57(11):682-686.
21. Moinzadeh P, Aberer E, Ahmadi-Simab K, et al. Disease progression in systemic sclerosis-overlap syndrome is significantly different from limited and diffuse cutaneous systemic sclerosis. Ann Rheum Dis. 2015;74(4):730-737.
22. Moinzadeh P, Fonseca C, Hellmich M, et al. Association of anti-RNA polymerase III autoantibodies and cancer in scleroderma. Arthritis Res Ther. 2014;16(1):R53.
23. Joseph CG, Darrah E, Shah AA, et al. Association of the autoimmune disease scleroderma with an immunologic response to cancer. Science. 2014;343(6167):152-157.
24. Shah AA, Rosen A, Hummers L, et al. Close temporal relationship between onset of cancer and scleroderma in patients with RNA polymerase I/III antibodies. Arthritis Rheum. 2010;62(9):2787-2795.
25. Walker UA, Tyndall A, Czirjak L, et al. Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials And Research group database. Ann Rheum Dis. 2007;66(6):754-763.
26. Meier FM, Frommer KW, Dinser R, et al. Update on the profile of the EUSTAR cohort: an analysis of the EULAR Scleroderma Trials and Research group database. Ann Rheum Dis. 2012;71(8):1355-1360.
27. Nihtyanova SI, Denton CP. Autoantibodies as predictive tools in systemic sclerosis. Nat Rev Rheumatol. 2010;6 (2):112-116.
28. Farina G, Lafyatis D, Lemaire R, et al. A four-gene biomarker predicts skin disease in patients with diffuse cutaneous systemic sclerosis. Arthritis Rheum. 2010;62 (2):580-588.
29. Hesselstrand R, Kassner A, Heinegard D, et al. COMP: a candidate molecule in the pathogenesis of systemic sclerosis with a potential as a disease marker. Ann Rheum Dis. 2008;67(9):1242-1248.
30. Assassi S, Wu M, Tan FK, et al. Skin gene expression correlates of severity of interstitial lung disease in systemic sclerosis. Arthritis Rheum. 2013;65(11):2917-2927.
31. Guiducci S, Distler JH, Jungel A, et al. The relationship between plasma microparticles and disease manifestations in patients with systemic sclerosis. Arthritis Rheum. 2008;58(9):2845-2853.
32. Distler JH, Pisetsky DS, Huber LC, et al. Microparticles as regulators of inflammation: novel players of cellular crosstalk in the rheumatic diseases. Arthritis Rheum. 2005;52(11):3337-3348.
33. Pisetsky DS, Ullal AJ, Gauley J, et al. Microparticles as meDiators and biomarkers of rheumatic disease. Rheumatology (Oxford). 2012;51(10):1737-1746.
34. Distler JH, Akhmetshina A, Dees C, et al. Induction of apoptosis in circulating angiogenic cells by microparticles. Arthritis Rheum. 2011;63(7):2067-2077.
35. Maugeri N, Franchini S, Campana L, et al. Circulating platelets as a source of the damage-associated molecular pattern HMGB1 in patients with systemic sclerosis. Autoimmunity. 2012;45(8):584-587.
36. Kavian N, Marut W, Servettaz A, et al. Pantethine prevents murine systemic sclerosis through the inhibition of microparticle shedDing. Arthritis Rheumatol. 2015;67 (7):1881-1890.
37. Maurer B, Graf N, Michel BA, et al. Prediction of worsening of skin fibrosis in patients with diffuse cutaneous systemic sclerosis using the EUSTAR database. Ann Rheum Dis. 2015;74(6):1124-1131.
38. Amjadi S, Maranian P, Furst DE, et al. Course of the modified Rodnan skin thickness score in systemic sclerosis clinical trials: analysis of three large multicenter, double-blind, randomized controlled trials. Arthritis Rheum. 2009;60(8):2490-2498.
39. Whitfield ML, Finlay DR, Murray JI, et al. Systemic and cell type-specific gene expression patterns in scleroderma skin. Proc Natl Acad Sci U S A. 2003;100 (21):12319-12324.
40. Barnett AJ, Miller MH, Littlejohn GO. A survival study of patients with scleroderma Diagnosed over 30 years (1953-1983): the value of a simple cutaneous classification in the early stages of the disease. J Rheumatol. 1988;15(2):276-283.
41. Scussel-Lonzetti L, Joyal F, Raynauld JP, et al. Predicting mortality in systemic sclerosis: analysis of a cohort of 309 French CanaDian patients with emphasis on features at Diagnosis as predictive factors for survival. Medicine (Baltimore). 2002;81(2):154-167.
42. Al-Dhaher FF, Pope JE, Ouimet JM. Determinants of morbidity and mortality of systemic sclerosis in Canada. Semin Arthritis Rheum. 2010;39(4):269-277.
43. Hachulla E, Carpentier P, Gressin V, et al. Risk factors for death and the 3-year survival of patients with systemic sclerosis: the French ItinerAIR-Sclerodermie study. Rheumatology (Oxford). 2009;48(3):304-308.
44. Domsic RT, Rodriguez-Reyna T, Lucas M, et al. Skin thickness progression rate: a predictor of mortality and early internal organ involvement in diffuse scleroderma. Ann Rheum Dis. 2011;70(1):104-109.
45. Domsic RT, Nihtyanova SI, Wisniewski SR, et al. Derivation and validation of a prediction rule for two-year mortality in early diffuse cutaneous systemic sclerosis. Arthritis Rheumatol. 2014;66(6):1616-1624.
46. Shand L, Lunt M, Nihtyanova S, et al. Relationship between change in skin score and disease outcome in diffuse cutaneous systemic sclerosis: application of a latent linear trajectory model. Arthritis Rheum. 2007;56(7):2422-2431.
47. Okano Y, Steen VD, Medsger TA Jr. Autoantibody reactive with RNA polymerase III in systemic sclerosis. Ann Intern Med. 1993;119(10):1005-1013.
48. Nihtyanova SI, Schreiber BE, Ong VH, et al. Prediction of pulmonary complications and long-term survival in systemic sclerosis. Arthritis Rheumatol. 2014;66 (6):1625-1635.
49. Behr J, Vogelmeier C, Beinert T, et al. Bronchoalveolar lavage for evaluation and management of scleroderma disease of the lung. Am J Respir Crit Care Med. 1996;154 (2 Pt 1):400-406.
50. Wells AU, Hansell DM, Rubens MB, et al. Fibrosing alveolitis in systemic sclerosis. Bronchoalveolar lavage finDings in relation to computed tomographic appearance. Am J Respir Crit Care Med. 1994;150(2):462-468.
51. Goh NS, Veeraraghavan S, Desai SR, et al. Bronchoalveolar lavage cellular profiles in patients with systemic sclerosisassociated interstitial lung disease are not predictive of disease progression. Arthritis Rheum. 2007;56 (6):2005-2012.
52. Strange C, Bolster MB, Roth MD, et al. Bronchoalveolar lavage and response to cyclophosphamide in scleroderma interstitial lung disease. Am J Respir Crit Care Med. 2008;177(1):91-98.
53. Hant FN, Ludwicka-Bradley A, Wang HJ, et al. Surfactant protein D and KL-6 as serum biomarkers of interstitial lung disease in patients with scleroderma. J Rheumatol. 2009;36(4):773-780.
54. Hasegawa M, Fujimoto M, Hamaguchi Y, et al. Use of serum clara cell 16-kDa (CC16) levels as a potential indicator of active pulmonary fibrosis in systemic sclerosis. J Rheumatol. 2011;38(5):877-884.
55. Yanaba K, Hasegawa M, Hamaguchi Y, et al. Longitudinal analysis of serum KL-6 levels in patients with systemic sclerosis: association with the activity of pulmonary fibrosis. Clin Exp Rheumatol. 2003;21(4):429-436.
56. Yamane K, Ihn H, Kubo M, et al. Serum levels of KL-6 as a useful marker for evaluating pulmonary fibrosis in patients with systemic sclerosis. J Rheumatol. 2000;27 (4):930-934.
57. Hesselstrand R, Wildt M, Bozovic G, et al. Biomarkers from bronchoalveolar lavage fluid in systemic sclerosis patients with interstitial lung disease relate to severity of lung fibrosis. Respir Med. 2013;107(7):1079-1086.
58. Asano Y, Ihn H, Yamane K, et al. Clinical significance of surfactant protein D as a serum marker for evaluating pulmonary fibrosis in patients with systemic sclerosis. Arthritis Rheum. 2001;44(6):1363-1369.
59. Yanaba K, Hasegawa M, Takehara K, et al. Comparative study of serum surfactant protein-D and KL-6 concentrations in patients with systemic sclerosis as markers for monitoring the activity of pulmonary fibrosis. J Rheumatol. 2004;31(6):1112-1120.
60. Bonella F, Volpe A, Caramaschi P, et al. Surfactant protein D and KL-6 serum levels in systemic sclerosis: correlation with lung and systemic involvement. Sarcoidosis Vasc Diffuse Lung Dis. 2011;28(1):27-33.
61. Takahashi H, Kuroki Y, Tanaka H, et al. Serum levels of surfactant proteins A and D are useful biomarkers for interstitial lung disease in patients with progressive systemic sclerosis. Am J Respir Crit Care Med. 2000;162 (1):258-263.
62. Hesselstrand R, Andreasson K, Wuttge DM, et al. Increased serum COMP predicts mortality in SSc: results from a longitudinal study of interstitial lung disease. Rheumatology (Oxford). 2012;51(5):915-920.
63. Nordenbaek C, Johansen JS, Halberg P, et al. High serum levels of YKL-40 in patients with systemic sclerosis are associated with pulmonary involvement. Scand J Rheumatol. 2005;34(4):293-297.
64. Ohnishi H, Yokoyama A, Kondo K, et al. Comparative study of KL-6, surfactant protein-A, surfactant protein-D, and monocyte chemoattractant protein-1 as serum markers for interstitial lung diseases. Am J Respir Crit Care Med. 2002;165(3):378-381.
65. Prasse A, Pechkovsky DV, Toews GB, et al. CCL18 as an indicator of pulmonary fibrotic activity in idiopathic interstitial pneumonias and systemic sclerosis. Arthritis Rheum. 2007;56(5):1685-1693.
66. Manetti M, Guiducci S, Romano E, et al. Increased serum levels and tissue expression of matrix metalloproteinase-12 in patients with systemic sclerosis: correlation with severity of skin and pulmonary fibrosis and vascular damage. Ann Rheum Dis. 2012;71(6):1064-1072.
67. Andersen GN, Nilsson K, Pourazar J, et al. Bronchoalveolar matrix metalloproteinase 9 relates to restrictive lung function impairment in systemic sclerosis. Respir Med. 2007;101(10):2199-2206.
68. Antonelli A, Ferri C, Fallahi P, et al. CXCL10 (alpha) and CCL2 (beta) chemokines in systemic sclerosis-a longitudinal study. Rheumatology (Oxford). 2008;47(1):45-49.
69. Wuttge DM, Wildt M, Geborek P, et al. Serum IL-15 in patients with early systemic sclerosis: a potential novel marker of lung disease. Arthritis Res Ther. 2007;9(5):R85.
70. Azab NA, Rady HM, Marzouk SA. Elevated serum TRAIL levels in scleroderma patients and its possible association with pulmonary involvement. Clin Rheumatol. 2012;31 (9):1359-1364.
71. Xu X, Wu WY, Tu WZ, et al. Increased expression of S100A8 and S100A9 in patients with diffuse cutaneous systemic sclerosis. A correlation with organ involvement and immunological abnormalities. Clin Rheumatol. 2013;32(10):1501-1510.
72. Nikitorowicz-Buniak J, Shiwen X, Denton CP, et al. Abnormally differentiating keratinocytes in the epidermis of systemic sclerosis patients show enhanced secretion of CCN2 and S100A9. J Invest Dermatol. 2014;134(11):2693-2702.
73. Bhattacharyya S, Kelley K, Melichian DS, et al. Toll-like receptor 4 signaling augments transforming growth factor-beta responses: a novel mechanism for maintaining and amplifying fibrosis in scleroderma. Am J Pathol. 2013;182(1):192-205.
74. van Bon L, Cossu M, Loof A, et al. Proteomic analysis of plasma identifies the Toll-like receptor agonists S100A8/A9 as a novel possible marker for systemic sclerosis phenotype. Ann Rheum Dis. 2014;73(8):1585-1589.
75. Servettaz A, Tamby MC, Guilpain P, et al. Anti-endothelial cell antibodies from patients with limited cutaneous systemic sclerosis bind to centromeric protein B (CENP-B). Clin Immunol. 2006;120(2):212-219.
76. Riemekasten G, Philippe A, Nather M, et al. Involvement of functional autoantibodies against vascular receptors in systemic sclerosis. Ann Rheum Dis. 2011;70(3):530-536.
77. Magro CM, Ross P, Marsh CB, et al. The role of antiendothelial cell antibody-meDiated microvascular injury in the evolution of pulmonary fibrosis in the setting of collagen vascular disease. Am J Clin Pathol. 2007;127 (2):237-247.
78. Magro CM, Waldman WJ, Knight DA, et al. Idiopathic pulmonary fibrosis related to endothelial injury and antiendothelial cell antibodies. Hum Immunol. 2006;67(4-5):284-297.
79. Bogatkevich GS, Ludwicka-Bradley A, Nietert PJ, et al. Antiinflammatory and antifibrotic effects of the oral direct thrombin inhibitor dabigatran etexilate in a murine model of interstitial lung disease. Arthritis Rheum. 2011;63(5):1416-1425.
80. Sato S, Hayakawa I, Hasegawa M, et al. Function blocking autoantibodies against matrix metalloproteinase-1 in patients with systemic sclerosis. J Invest Dermatol. 2003;120(4):542-547.
81. 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):1005-1011.
82. Mathai SC, Hummers LK, Champion HC, et al. Survival in pulmonary hypertension associated with the scleroderma spectrum of diseases: impact of interstitial lung disease. Arthritis Rheum. 2009;60(2):569-577.
83. Chang B, Wigley FM, White B, et al. Scleroderma patients with combined pulmonary hypertension and interstitial lung disease. J Rheumatol. 2003;30(11):2398-2405.
84. Nihtyanova SI, Tang EC, Coghlan JG, et al. Improved survival in systemic sclerosis is associated with better ascertainment of internal organ disease: a retrospective cohort study. QJM. 2010;103(2):109-115.
85. Schmidt K, Martinez-Gamboa L, Meier S, et al. Bronchoalveoloar lavage fluid cytokines and chemokines as markers and predictors for the outcome of interstitial lung disease in systemic sclerosis patients. Arthritis Res Ther. 2009;11(4):R111.
86. Sfriso P, Cozzi F, Oliviero F, et al. CXCL11 in bronchoalveolar lavage fluid and pulmonary function decline in systemic sclerosis. Clin Exp Rheumatol. 2012;30(2 Suppl 71):S71-S75.
87. Sato S, Nagaoka T, Hasegawa M, et al. Elevated serum KL-6 levels in patients with systemic sclerosis: association with the severity of pulmonary fibrosis. Dermatology. 2000;200(3):196-201.
88. Yanaba K, Asano Y, Tada Y, et al. Clinical significance of serum growth differentiation factor-15 levels in systemic sclerosis: association with disease severity. Mod Rheumatol. 2012;22(5):668-675.
89. Lambrecht S, Smith V, De Wilde K, et al. Growth differentiation factor 15, a marker of lung involvement in systemic sclerosis, is involved in fibrosis development but is not indispensable for fibrosis development. Arthritis Rheumatol. 2014;66(2):418-427.
90. De Lauretis A, Sestini P, Pantelidis P, et al. Serum interleukin 6 is predictive of early functional decline and mortality in interstitial lung disease associated with systemic sclerosis. J Rheumatol. 2013;40(4):435-446.
91. Liu X, Mayes MD, Pedroza C, et al. Does C-reactive protein predict the long-term progression of interstitial lung disease and survival in patients with early systemic sclerosis? Arthritis Care Res (Hoboken). 2013;65(8):1375-1380.
92. Tiev KP, Hua-Huy T, Kettaneh A, et al. Serum CC chemokine ligand-18 predicts lung disease worsening in systemic sclerosis. Eur Respir J. 2011;38(6):1355-1360.
93. Schupp J, Becker M, Gunther J, et al. Serum CCL18 is predictive for lung disease progression and mortality in systemic sclerosis. Eur Respir J. 2014;43(5):1530-1532.
94. Elhaj M, Charles J, Pedroza C, et al. Can serum surfactant protein D or CC-chemokine ligand 18 predict outcome of interstitial lung disease in patients with early systemic sclerosis? J Rheumatol. 2013;40(7):1114-1120.
95. Tashkin DP, Elashoff R, Clements PJ, et al. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med. 2006;354(25):2655-2666.
96. Becker MO, Schohe A, Weinert K, et al. Responders to cyclophosphamide: results of a single-centre analysis among systemic sclerosis patients. Ann Rheum Dis. 2012;71(12):2061-2062.
97. Goh NS, Desai SR, Veeraraghavan S, et al. Interstitial lung disease in systemic sclerosis: a simple staging system. Am J Respir Crit Care Med. 2008;177(11):1248-1254.
98. Moore OA, Goh N, Corte T, et al. 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). 2013;52 (1):155-160.
99. Swigris JJ, Zhou X, Wamboldt FS, et al. Exercise peripheral oxygen saturation (SpO2) accurately reflects arterial oxygen saturation (SaO2) and predicts mortality in systemic sclerosis. Thorax. 2009;64(7):626-630.
100. Bouros D, Wells AU, Nicholson AG, et al. Histopathologic subsets of fibrosing alveolitis in patients with systemic sclerosis and their relationship to outcome. Am J Respir Crit Care Med. 2002;165(12):1581-1586.
101. van Bon L, Affandi AJ, Broen J, et al. Proteome-wide analysis and CXCL4 as a biomarker in systemic sclerosis. N Engl J Med. 2014;370(5):433-443.
102. Yaqub A, Chung L. Epidemiology and risk factors for pulmonary hypertension in systemic sclerosis. Curr Rheumatol Rep. 2013;15(1):302.
103. Hoeper MM, Bogaard HJ, Condliffe R, et al. Definitions and Diagnosis of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D42-D50.
104. Hunzelmann N, Genth E, Krieg T, et al. The registry of the German Network for Systemic Scleroderma: frequency of disease subsets and patterns of organ involvement. Rheumatology (Oxford). 2008;47(8):1185-1192.
105. Chang B, Schachna L, White B, et al. Natural history of mild-moderate pulmonary hypertension and the risk factors for severe pulmonary hypertension in scleroderma. J Rheumatol. 2006;33(2):269-274.
106. Cox SR, Walker JG, Coleman M, et al. Isolated pulmonary hypertension in scleroderma. Intern Med J. 2005;35 (1):28-33.
107. Hinchcliff M, Fischer A, Schiopu E, et al. Pulmonary hypertension assessment and recognition of outcomes in scleroderma (PHAROS): baseline characteristics and description of study population. J Rheumatol. 2011;38 (10):2172-2179.
108. Arends SJ, Damoiseaux JG, Duijvestijn AM, et al. Functional implications of IgG anti-endothelial cell antibodies in pulmonary arterial hypertension. Autoimmunity. 2013;46(7):463-470.
109. Becker MO, Kill A, Kutsche M, et al. Vascular receptor autoantibodies in pulmonary arterial hypertension associated with systemic sclerosis. Am J Respir Crit Care Med. 2014;190(7):808-817.
110. Pendergrass SA, Hayes E, Farina G, et al. Limited systemic sclerosis patients with pulmonary arterial hypertension show biomarkers of inflammation and vascular injury. PLoS One. 2010;5(8):e12106.
111. Jurisic Z, Martinovic-Kaliterna D, Marasovic-Krstulovic D, et al. Relationship between interleukin-6 and carDiac involvement in systemic sclerosis. Rheumatology (Oxford). 2013;52(7):1298-1302.
112. George PM, Oliver E, Dorfmuller P, et al. Evidence for the involvement of type I interferon in pulmonary arterial hypertension. Circ Res. 2014;114(4):677-688.
113. Risbano MG, Meadows CA, Coldren CD, et al. Altered immune phenotype in peripheral blood cells of patients with scleroderma-associated pulmonary hypertension. Clin Transl Sci. 2010;3(5):210-218.
114. Humbert M, Yaici A, de Groote P, et al. Screening for pulmonary arterial hypertension in patients with systemic sclerosis: clinical characteristics at Diagnosis and longterm survival. Arthritis Rheum. 2011;63(11):3522-3530.
115. Bae S, Saggar R, Bolster MB, et al. Baseline characteristics and follow-up in patients with normal haemodynamics versus borderline mean pulmonary arterial pressure in systemic sclerosis: results from the PHAROS registry. Ann Rheum Dis. 2012;71(8):1335-1342.
116. Mininni S, Diricatti G, Vono MC, et al. Noninvasive evaluation of right ventricle systolic pressure during dynamic exercise by saline-enhanced Doppler echocardiography in progressive systemic sclerosis. Angiology. 1996;47 (5):467-474.
117. Alkotob ML, Soltani P, Sheatt MA, et al. Reduced exercise capacity and stress-induced pulmonary hypertension in patients with scleroderma. Chest. 2006;130(1):176-181.
118. Kovacs 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):881-886.
119. Kovacs 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):1257-1262.
120. Valerio CJ, Schreiber BE, Handler CE, et al. Borderline mean pulmonary artery pressure in patients with systemic sclerosis: transpulmonary gradient predicts risk of developing pulmonary hypertension. Arthritis Rheum. 2013;65(4):1074-1084.
121. Mukerjee D, St George D, Coleiro B, et al. Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension: application of a registry approach. Ann Rheum Dis. 2003;62(11):1088-1093.
122. Hachulla 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):3792-3800.
123. Hachulla E, de Groote P, Gressin V, et al. The three-year incidence of pulmonary arterial hypertension associated with systemic sclerosis in a multicenter nationwide longitudinal study in France. Arthritis Rheum. 2009;60 (6):1831-1839.
124. Avouac 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):2290-2298.
125. Hachulla E, Clerson P, Airo P, et al. Value of systolic pulmonary arterial pressure as a prognostic factor of death in the systemic sclerosis EUSTAR population. Rheumatology (Oxford). 2015;54(7):1262-1269.
126. Steen V, Medsger TA Jr. Predictors of isolated pulmonary hypertension in patients with systemic sclerosis and limited cutaneous involvement. Arthritis Rheum. 2003;48 (2):516-522.
127. Allanore Y, Borderie D, Avouac J, et al. High N-terminal pro-brain natriuretic peptide levels and low diffusing capacity for carbon monoxide as independent predictors of the occurrence of precapillary pulmonary arterial hypertension in patients with systemic sclerosis. Arthritis Rheum. 2008;58(1):284-291.
128. Gladue H, Steen V, Allanore Y, et al. Combination of echocardiographic and pulmonary function test measures improves sensitivity for Diagnosis of systemic sclerosisassociated pulmonary arterial hypertension: analysis of 2 cohorts. J Rheumatol. 2013;40(10):1706-1711.
129. Dumitrescu D, Oudiz RJ, Karpouzas G, et al. Developing pulmonary vasculopathy in systemic sclerosis, detected with non-invasive cardiopulmonary exercise testing. PLoS One. 2010;5(12):e14293.
130. Ninaber MK, Hamersma WB, Schuerwegh AJ, et al. Increased respiratory drive relates to severity of dyspnea in systemic sclerosis. BMC Pulm Med. 2014;14:57.
131. Burt RK, Oliveira MC, Shah SJ, et al. CarDiac involvement and treatment-related mortality after non-myeloablative haemopoietic stem-cell transplantation with unselected autologous peripheral blood for patients with systemic sclerosis: a retrospective analysis. Lancet. 2013;381 (9872):1116-1124.
132. Williams MH, Handler CE, Akram R, et al. Role of N-terminal brain natriuretic peptide (N-TproBNP) in scleroderma-associated pulmonary arterial hypertension. Eur Heart J. 2006;27(12):1485-1494.
133. Cavagna L, Caporali R, Klersy C, et al. Comparison of brain natriuretic peptide (BNP) and NT-proBNP in screening for pulmonary arterial hypertension in patients with systemic sclerosis. J Rheumatol. 2010;37(10):2064-2070.
134. Thakkar V, Stevens WM, Prior D, et al. N-terminal probrain natriuretic peptide in a novel screening algorithm for pulmonary arterial hypertension in systemic sclerosis: a case-control study. Arthritis Res Ther. 2012;14(3):R143.
135. Avouac J, Meune C, Chenevier-Gobeaux C, et al. CarDiac biomarkers in systemic sclerosis: contribution of highsensitivity carDiac troponin in addition to N-terminal pro-brain natriuretic peptide. Arthritis Care Res (Hoboken). 2015;67(7):1022-1030.
136. Miller L, Chartrand S, Koenig M, et al. Left heart disease: a frequent cause of early pulmonary hypertension in systemic sclerosis, unrelated to elevated NT-proBNP levels or overt carDiac fibrosis but associated with increased levels of MR-proANP and MR-proADM: retrospective analysis of a French CanaDian cohort. Scand J Rheumatol. 2014;43 (4):314-323.
137. Schreiber BE, Valerio CJ, Keir GJ, et al. Improving the detection of pulmonary hypertension in systemic sclerosis using pulmonary function tests. Arthritis Rheum. 2011;63 (11):3531-3539.
138. Meune C, Avouac J, Airo P, et al. Prediction of pulmonary hypertension related to systemic sclerosis by an index based on simple clinical observations. Arthritis Rheum. 2011;63(9):2790-2796.
139. Coghlan JG, Denton CP, Grunig E, et al. Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study. Ann Rheum Dis. 2014;73 (7):1340-1349.
140. Hao Y, Thakkar V, Stevens W, et al. A comparison of the predictive accuracy of three screening models for pulmonary arterial hypertension in systemic sclerosis. Arthritis Res Ther. 2015;17(1):7.
141. Riccieri V, Vasile M, Iannace N, et al. Systemic sclerosis patients with and without pulmonary arterial hypertension: a nailfold capillaroscopy study. Rheumatology (Oxford). 2013;52(8):1525-1528.
142. Sebastiani M, Manfredi A, Colaci M, et al. Capillaroscopic skin ulcer risk index: a new prognostic tool for digital skin ulcer development in systemic sclerosis patients. Arthritis Rheum. 2009;61(5):688-694.
143. Sebastiani M, Manfredi A, Vukatana G, et al. Predictive role of capillaroscopic skin ulcer risk index in systemic sclerosis: a multicentre validation study. Ann Rheum Dis. 2012;71(1):67-70.
144. Castellvi I, Simeon-Aznar CP, Sarmiento M, et al. Association between nailfold capillaroscopy finDings and pulmonary function tests in patients with systemic sclerosis. J Rheumatol. 2015;42(2):222-227.
145. Zompatori M, Leone MB, Giannotta M, et al. Pulmonary hypertension and systemic sclerosis: the role of high-resolution computed tomography. Radiol Med. 2013;118 (8):1360-1372.
146. McCall RK, Ravenel JG, Nietert PJ, et al. Relationship of main pulmonary artery Diameter to pulmonary arterial pressure in scleroderma patients with and without interstitial fibrosis. J Comput Assist Tomogr. 2014;38 (2):163-168.
147. Rodriguez-Reyna TS, Morelos-Guzman M, Hernandez-Reyes P, et al. Assessment of myocarDial fibrosis and microvascular damage in systemic sclerosis by magnetic resonance imaging and coronary angiotomography. Rheumatology (Oxford). 2015;54(4):647-654.
148. Hachulla AL, Launay D, Gaxotte V, et al. CarDiac magnetic resonance imaging in systemic sclerosis: a cross-sectional observational study of 52 patients. Ann Rheum Dis. 2009;68(12):1878-1884.
149. Di Cesare E, Battisti S, Di Sibio A, et al. Early assessment of sub-clinical carDiac involvement in systemic sclerosis (SSc) using delayed enhancement carDiac magnetic resonance (CE-MRI). Eur J Radiol. 2013;82(6):e268-e273.
150. Hesselstrand R, Scheja A, Wuttge DM, et al. Enlarged right-sided dimensions and fibrosis of the right ventricular insertion point on cardiovascular magnetic resonance imaging is seen early in patients with pulmonary arterial hypertension associated with connective tissue disease. Scand J Rheumatol. 2011;40(2):133-138.
151. Dimitroulas T, Mavrogeni S, Kitas GD. Imaging modalities for the Diagnosis of pulmonary hypertension in systemic sclerosis. Nat Rev Rheumatol. 2012;8(4):203-213.
152. Gopal DM, Doldt B, Finch K, et al. Relation of novel echocardiographic measures to invasive hemodynamic assessment in scleroderma-associated pulmonary arterial hypertension. Arthritis Care Res (Hoboken). 2014;66 (9):1386-1394.
153. Yang T, Liang Y, Zhang Y, et al. Echocardiographic parameters in patients with pulmonary arterial hypertension: correlations with right ventricular ejection fraction derived from carDiac magnetic resonance and hemodynamics. PLoS One. 2013;8(8):e71276.
154. Koh ET, Lee P, Gladman DD, et al. Pulmonary hypertension in systemic sclerosis: an analysis of 17 patients. Br J Rheumatol. 1996;35(10):989-993.
155. 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):1940-1946.
156. Lefevre G, Dauchet L, Hachulla E, et al. Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension: a systematic review and meta-analysis. Arthritis Rheum. 2013;65(9):2412-2423.
157. Launay D, Humbert M, Berezne A, et al. Clinical characteristics and survival in systemic sclerosis-related pulmonary hypertension associated with interstitial lung disease. Chest. 2011;140(4):1016-1024.
158. Chung L, Farber HW, Benza R, et al. Unique predictors of mortality in patients with pulmonary arterial hypertension associated with systemic sclerosis in the REVEAL registry. Chest. 2014;146(6):1494-1504.
159. Kill A, Tabeling C, Undeutsch R, et al. Autoantibodies to angiotensin and endothelin receptors in systemic sclerosis induce cellular and systemic events associated with disease pathogenesis. Arthritis Res Ther. 2014;16(1):R29.
160. Gunther J, Rademacher J, van Laar JM, et al. Functional autoantibodies in systemic sclerosis. Semin Immunopathol. 2015;37(5):529-542.
161. Desai CS, Lee DC, Shah SJ. Systemic sclerosis and the heart: current Diagnosis and management. Curr Opin Rheumatol. 2011;23(6):545-554.
162. McWhorter JE, LeRoy EC. PericarDial disease in scleroderma (systemic sclerosis). Am J Med. 1974;57 (4):566-575.
163. D'Angelo WA, Fries JF, Masi AT, et al. Pathologic observations in systemic sclerosis (scleroderma). A study of fiftyeight autopsy cases and fifty-eight matched controls. Am J Med. 1969;46(3):428-440.
164. Bulkley BH, Ridolfi RL, Salyer WR, et al. MyocarDial lesions of progressive systemic sclerosis. A cause of carDiac dysfunction. Circulation. 1976;53(3):483-490.
165. Mueller KA, Mueller II, Eppler D, et al. Clinical and histopathological features of patients with systemic sclerosis undergoing endomyocarDial biopsy. PLoS One. 2015;10 (5):e0126707.
166. Mahoney WM Jr., Fleming JN, Schwartz SM. A unifying hypothesis for scleroderma: identifying a target cell for scleroderma. Curr Rheumatol Rep. 2011;13(1):28-36.
167. Katsumoto TR, Whitfield ML, Connolly MK. The pathogenesis of systemic sclerosis. Annu Rev Pathol. 2011;6:509-537.
168. Kahan A, Allanore Y. Primary myocarDial involvement in systemic sclerosis. Rheumatology (Oxford). 2006;45(Suppl 4):iv14-17.
169. Allanore Y, Meune C. Primary myocarDial involvement in systemic sclerosis: evidence for a microvascular origin. Clin Exp Rheumatol. 2010;28(5 Suppl 62):S48-S53.
170. Gustafsson R, Mannting F, Kazzam E, et al. Cold-induced reversible myocarDial ischaemia in systemic sclerosis. Lancet. 1989;2(8661):475-479.
171. Morelli S, Sgreccia A, Ferrante L, et al. Relationships between electrocardiographic and echocardiographic finDings in systemic sclerosis (scleroderma). Int J Cardiol. 1996;57(2):151-160.
172. Follansbee WP, Curtiss EI, Rahko PS, et al. The electrocardiogram in systemic sclerosis (scleroderma). Study of 102 consecutive cases with functional correlations and review of the literature. Am J Med. 1985;79(2):183-192.
173. Follansbee WP, Zerbe TR, Medsger TA Jr. CarDiac and skeletal muscle disease in systemic sclerosis (scleroderma): a high risk association. Am Heart J. 1993;125 (1):194-203.
174. Perera A, Fertig N, Lucas M, et al. Clinical subsets, skin thickness progression rate, and serum antibody levels in systemic sclerosis patients with anti-topoisomerase I antibody. Arthritis Rheum. 2007;56 (8):2740-2746.
175. Elhai M, Avouac J, Walker UA, et al. A gender gap in primary and secondary heart dysfunctions in systemic sclerosis: a EUSTAR prospective study. Ann RheumDis. 2014 Oct 23
176. Follansbee WP, Curtiss EI, Medsger TA Jr., et al. MyocarDial function and perfusion in the CREST syndrome variant of progressive systemic sclerosis. Exercise radionuclide evaluation and comparison with diffuse scleroderma. Am J Med. 1984;77(3):489-496.
177. Follansbee WP, Curtiss EI, Medsger TA Jr., et al. Physiologic abnormalities of carDiac function in progressive systemic sclerosis with diffuse scleroderma. N Engl J Med. 1984;310(3):142-148.
178. Kerr LD, Spiera H. Myocarditis as a complication in scleroderma patients with myositis. Clin Cardiol. 1993;16 (12):895-899.
179. Hughes M, Lilleker JB, Herrick AL, et al. CarDiac troponin testing in idiopathic inflammatory myopathies and systemic sclerosis-spectrum disorders: biomarkers to distinguish between primary carDiac involvement and lowgrade skeletal muscle disease activity. Ann Rheum Dis. 2015;74(5):795-798.
180. Burt RK, Shah SJ, Dill K, et al. 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. Lancet. 2011;378(9790):498-506.
181. Allanore Y, Meune C, Vonk MC, et al. Prevalence and factors associated with left ventricular dysfunction in the EULAR Scleroderma Trial and Research group (EUSTAR) database of patients with systemic sclerosis. Ann Rheum Dis. 2010;69(1):218-221.
182. Matias C, Isla LP, Vasconcelos M, et al. Speckle-trackingderived strain and strain-rate analysis: a technique for the evaluation of early alterations in right ventricle systolic function in patients with systemic sclerosis and normal pulmonary artery pressure. J Cardiovasc Med. 2009;10 (2):129-134.
183. Schattke S, Knebel F, Grohmann A, et al. Early right ventricular systolic dysfunction in patients with systemic sclerosis without pulmonary hypertension: a Doppler Tissue and Speckle Tracking echocardiography study. Cardiovasc Ultrasound. 2010;8:3.
184. Spethmann S, Dreger H, Schattke S, et al. Two-dimensional speckle tracking of the left ventricle in patients with systemic sclerosis for an early detection of myocarDial involvement. Eur Heart J Cardiovasc Imaging. 2012;13(10):863-870.
185. Spethmann S, Rieper K, Riemekasten G, et al. Echocardiographic follow-up of patients with systemic sclerosis by 2D speckle tracking echocardiography of the left ventricle. Cardiovasc Ultrasound. 2014;12:13.
186. Meune C, Avouac J, Wahbi K, et al. CarDiac involvement in systemic sclerosis assessed by tissue-doppler echocardiography during routine care: a controlled study of 100 consecutive patients. Arthritis Rheum. 2008;58(6):1803-1809.
187. Yiu KH, Schouffoer AA, Marsan NA, et al. Left ventricular dysfunction assessed by speckle-tracking strain analysis in patients with systemic sclerosis: relationship to functional capacity and ventricular arrhythmias. Arthritis Rheum. 2011;63(12):3969-3978.
188. Mavrogeni S, Sfikakis PP, Gialafos E, et al. CarDiac tissue characterization and the Diagnostic value of cardiovascular magnetic resonance in systemic connective tissue diseases. Arthritis Care Res (Hoboken). 2014;66(1):104-112.
189. Tzelepis GE, Kelekis NL, Plastiras SC, et al. Pattern and distribution of myocarDial fibrosis in systemic sclerosis: a delayed enhanced magnetic resonance imaging study. Arthritis Rheum. 2007;56(11):3827-3836.
190. Ntusi NA, Piechnik SK, Francis JM, et al. Subclinical myocarDial inflammation and diffuse fibrosis are common in systemic sclerosis-a clinical study using myocarDial T1-mapping and extracellular volume quantification. J Cardiovasc Magn Reson. 2014;16:21.
191. Mavrogeni S, Bratis K, Karabela G, et al. Cardiovascular Magnetic Resonance Imaging clarifies carDiac pathophysiology in early, asymptomatic diffuse systemic sclerosis. Inflamm Allergy Drug Targets. 2015 Sep 16 [Epub ahead of print].
192. Thuny F, Lovric D, Schnell F, et al. Quantification of myocarDial extracellular volume fraction with carDiac MR imaging for early detection of left ventricle involvement in systemic sclerosis. Radiology. 2014;271(2):373-380.
193. Pieroni M, De Santis M, Zizzo G, et al. Recognizing and treating myocarditis in recent-onset systemic sclerosis heart disease: potential utility of immunosuppressive therapy in carDiac damage progression. Semin Arthritis Rheum. 2014;43(4):526-535.
194. Vignaux O, Allanore Y, Meune C, et al. Evaluation of the effect of nifedipine upon myocarDial perfusion and contractility using carDiac magnetic resonance imaging and tissue Doppler echocardiography in systemic sclerosis. Ann Rheum Dis. 2005;64(9):1268-1273.
195. Pingitore A, Guiducci S, Conforti ML, et al. Early detection of myocarDial and pulmonary oedema with MRI in an asymptomatic systemic sclerosis patient: successful recovery with pulse steroid. Rheumatology (Oxford). 2013;52(10):1920-1921.
196. Assassi S, Del Junco D, Sutter K, et al. Clinical and genetic factors predictive of mortality in early systemic sclerosis. Arthritis Rheum. 2009;61(10):1403-1411.
197. Draeger HT, Assassi S, Sharif R, et al. Right bundle branch block: a predictor of mortality in early systemic sclerosis. PLoS One. 2013;8(10):e78808.
198. Kirby DF, Chatterjee S. Evaluation and management of gastrointestinal manifestations in scleroderma. Curr Opin Rheumatol. 2014;26(6):621-629.
199. Abignano G, Scott N, Wollheim FA, et al. Collagenous colitis in systemic sclerosis: an overlooked and treatable complication. J Clin Rheumatol. 2014;20(5):278-282.
200. Verne GN, Eaker EY, Hardy E, et al. Effect of octreotide and erythromycin on idiopathic and scleroderma-associated intestinal pseudoobstruction. Dig Dis Sci. 1995;40 (9):1892-1901.
201. Perlemuter G, Cacoub P, Chaussade S, et al. Octreotide treatment of chronic intestinal pseudoobstruction secondary to connective tissue diseases. Arthritis Rheum. 1999;42(7):1545-1549.
202. Thoua NM, Bunce C, Brough G, et al. Assessment of gastrointestinal symptoms in patients with systemic sclerosis in a UK tertiary referral centre. Rheumatology (Oxford). 2010;49(9):1770-1775.
203. Omair MA, Lee P. Effect of gastrointestinal manifestations on quality of life in 87 consecutive patients with systemic sclerosis. J Rheumatol. 2012;39(5):992-996.
204. Bodukam V, Hays RD, Maranian P, et al. Association of gastrointestinal involvement and depressive symptoms in patients with systemic sclerosis. Rheumatology (Oxford). 2011;50(2):330-334.
205. Thonhofer R, Siegel C, Trummer M, et al. Early endoscopy in systemic sclerosis without gastrointestinal symptoms. Rheumatol Int. 2012;32(1):165-168.
206. Bae S, Allanore Y, Coustet B, et al. Development and validation of French version of the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument. Clin Exp Rheumatol. 2011;29(2 Suppl 65): S15-S21.
207. Nagaraja V, Hays RD, Khanna PP, et al. Construct validity of the Patient-Reported Outcomes Measurement Information System gastrointestinal symptom scales in systemic sclerosis. Arthritis Care Res (Hoboken). 2014;66 (11):1725-1730.
208. Hung EW, Mayes MD, Sharif R, et al. Gastric antral vascular ectasia and its clinical correlates in patients with early diffuse systemic sclerosis in the SCOT trial. J Rheumatol. 2013;40(4):455-460.
209. Ghrenassia E, Avouac J, Khanna D, et al. Prevalence, correlates and outcomes of gastric antral vascular ectasia in systemic sclerosis: a EUSTAR case-control study. J Rheumatol. 2014;41(1):99-105.
210. Ingraham KM, O'Brien MS, Shenin M, et al. Gastric antral vascular ectasia in systemic sclerosis: demographics and disease predictors. J Rheumatol. 2010;37(3):603-607.
211. Marie I, Levesque H, Ducrotte P, et al. Manometry of the upper intestinal tract in patients with systemic sclerosis: a prospective study. Arthritis Rheum. 1998;41(10):1874-1883.
212. Tutuian R, Castell DO. Combined multichannel intraluminal impedance and manometry clarifies esophageal function abnormalities: study in 350 patients. Am J Gastroenterol. 2004;99(6):1011-1019.
213. Leighton JA, Valdovinos MA, Pemberton JH, et al. Anorectal dysfunction and rectal prolapse in progressive systemic sclerosis. Dis Colon Rectum. 1993;36(2):182-185.
214. Franck-Larsson K, Graf W, Eeg-Olofsson KE, et al. Physiological and structural anorectal abnormalities in patients with systemic sclerosis and fecal incontinence. Scand J Gastroenterol. 2014;49(9):1076-1083.
215. Jaffin BW, Chang P, Spiera H. Fecal incontinence in scleroderma. Clinical features, anorectal manometric finDings, and their therapeutic implications. J Clin Gastroenterol. 1997;25(3):513-517.
216. Bartosik I, Andreasson K, Starck M, et al. Vascular events are risk factors for anal incontinence in systemic sclerosis: a study of morphology and functional properties measured by anal endosonography and manometry. Scand J Rheumatol. 2014;43(5):391-397.
217. Savarino E, Carbone R, Marabotto E, et al. Gastro-oesophageal reflux and gastric aspiration in idiopathic pulmonary fibrosis patients. Eur Respir J. 2013;42(5):1322-1331.
218. Savarino E, Bazzica M, Zentilin P, et al. Gastroesophageal reflux and pulmonary fibrosis in scleroderma: a study using pH-impedance monitoring. Am J Respir Crit Care Med. 2009;179(5):408-413.
219. Marie I, Dominique S, Levesque H, et al. Esophageal involvement and pulmonary manifestations in systemic sclerosis. Arthritis Rheum. 2001;45(4):346-354.
220. Marie I, Ducrotte P, Denis P, et al. Oesophageal mucosal involvement in patients with systemic sclerosis receiving proton pump inhibitor therapy. Aliment Pharmacol Ther. 2006;24(11-12):1593-1601.
221. Raghu G, Freudenberger TD, Yang S, et al. High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis. Eur Respir J. 2006;27(1):136-142.
222. Hershcovici T, Jha LK, Johnson T, et al. Systematic review: the relationship between interstitial lung diseases and gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2011;34(11-12):1295-1305.
223. Christmann RB, Wells AU, Capelozzi VL, et al. Gastroesophageal reflux incites interstitial lung disease in systemic sclerosis: clinical, radiologic, histopathologic, and treatment evidence. Semin Arthritis Rheum. 2010;40 (3):241-249.
224. Lee JS, Collard HR, Anstrom KJ, et al. Anti-acid treatment and disease progression in idiopathic pulmonary fibrosis: an analysis of data from three randomised controlled trials. Lancet Respir Med. 2013;1(5):369-376.
225. Lee JS, Ryu JH, Elicker BM, et al. Gastroesophageal reflux therapy is associated with longer survival in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011;184(12):1390-1394.
226. Kawaguchi Y, Nakamura Y, Matsumoto I, et al. Muscarinic-3 acetylcholine receptor autoantibody in patients with systemic sclerosis: contribution to severe gastrointestinal tract dysmotility. Ann Rheum Dis. 2009;68(5):710-714.
227. Andreasson K, Scheja A, Saxne T, et al. Faecal calprotectin: a biomarker of gastrointestinal disease in systemic sclerosis. J Intern Med. 2011;270(1):50-57.
228. Marie I, Leroi AM, Menard JF, et al. Fecal calprotectin in systemic sclerosis and review of the literature. Autoimmun Rev. 2015;14(6):547-554.
229. Caporali R, Caccialanza R, Bonino C, et al. Disease-related malnutrition in outpatients with systemic sclerosis. Clinical Nutrition. 2012;31(5):666-671.
230. Baron M, Hudson M, Steele R, CanaDian Scleroderma Research G. Malnutrition is common in systemic sclerosis: results from the CanaDian scleroderma research group database. J Rheumatol. 2009;36(12):2737-2743.
231. Mecoli C, Purohit S, Sandorfi N, et al. Mortality, recurrence, and hospital course of patients with systemic sclerosis-related acute intestinal pseudo-obstruction. J Rheumatol. 2014;41(10):2049-2054.
232. Krause L, Becker MO, Brueckner CS, et al. Nutritional status as marker for disease activity and severity predicting mortality in patients with systemic sclerosis. Ann Rheum Dis. 2010;69(11):1951-1957.
233. Steen VD. Scleroderma renal crisis. Rheum Dis Clin North Am. 2003;29(2):315-333.
234. Guillevin L, Berezne A, Seror R, et al. Scleroderma renal crisis: a retrospective multicentre study on 91 patients and 427 controls. Rheumatology (Oxford). 2012;51 (3):460-467.
235. Teixeira L, Mouthon L, Mahr A, et al. Mortality and risk factors of scleroderma renal crisis: a French retrospective study of 50 patients. Ann Rheum Dis. 2008;67(1):110-116.
236. Seiberlich B, Hunzelmann N, Krieg T, et al. IntermeDiate molecular weight proteinuria and albuminuria identify scleroderma patients with increased morbidity. Clin Nephrol. 2008;70(2):110-117.
237. Steen VD, Costantino JP, Shapiro AP, et al. Outcome of renal crisis in systemic sclerosis: relation to availability of angiotensin converting enzyme (ACE) inhibitors. Ann Intern Med. 1990;113(5):352-357.
238. Walker JG, Ahern MJ, Smith MD, et al. Scleroderma renal crisis: poor outcome despite aggressive antihypertensive treatment. Intern Med J. 2003;33(5-6):216-220.
239. Penn H, Howie AJ, Kingdon EJ, et al. Scleroderma renal crisis: patient characteristics and long-term outcomes. QJM. 2007;100(8):485-494.
240. Steen VD, Medsger TA Jr., Osial TA Jr., et al. Factors predicting development of renal involvement in progressive systemic sclerosis. Am J Med. 1984;76(5):779-786.
241. DeMarco PJ, Weisman MH, Seibold JR, et al. Predictors and outcomes of scleroderma renal crisis: the high-dose versus low-dose D-penicillamine in early diffuse systemic sclerosis trial. Arthritis Rheum. 2002;46(11):2983-2989.
242. Steen VD, Medsger TA Jr. Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis. Arthritis Rheum. 1998;41(9):1613-1619.
243. Muangchan C, HarDing S, Khimdas S, et al. Association of C-reactive protein with high disease activity in systemic sclerosis: results from the CanaDian Scleroderma Research Group. Arthritis Care Res (Hoboken). 2012;64 (9):1405-1414.
244. Medsger TA Jr., Silman AJ, Steen VD, et al. A disease severity scale for systemic sclerosis: development and testing. J Rheumatol. 1999;26(10):2159-2167.
245. Valentini G, Della Rossa A, Bombardieri S, et al. European multicentre study to define disease activity criteria for systemic sclerosis. II. Identification of disease activity variables and development of preliminary activity indexes. Ann Rheum Dis. 2001;60(6):592-598.
246. Valentini G, D'Angelo S, Della Rossa A, et al. European Scleroderma Study Group to define disease activity criteria for systemic sclerosis. IV. Assessment of skin thickening by modified Rodnan skin score. Ann Rheum Dis. 2003;62(9):904-905.
247. Fransen J, Popa-Diaconu D, Hesselstrand R, et al. Clinical prediction of 5-year survival in systemic sclerosis: validation of a simple prognostic model in EUSTAR centres. Ann Rheum Dis. 2011;70(10):1788-1792.
248. Jablonska J. Interspecific relations in some mites of the superfamily Analgesoidea. Wiad Parazytol. 1974;20 (5):759-762.
249. Huncke BH, Jabaay GA, Sullivan R. Chemonucleolysis. A preliminary report. Med Trial Tech Q. 1974;Annual:80-88.
250. Milano A, Pendergrass SA, Sargent JL, et al. Molecular subsets in the gene expression signatures of scleroderma skin. PLoS One. 2008;3(7):e2696.
251. Sargent JL, Milano A, Connolly MK, et al. Scleroderma gene expression and pathway signatures. Curr Rheumatol Rep. 2008;10(3):205-211.
252. Lahdensuu M, Rokkanen P, Jaattela A, et al. Biochemical monitoring of multiple injury patients. Resuscitation. 1974;3(4):273-279.
253. Ward PA, Jabaley ME. Muscle survival following free muscle transfer with microvascular anastomosis. Surg Forum. 1974;25:511-512.