One year in review 2017: Systemic sclerosis

Clinical and Experimental Rheumatology

Volumn 35, Issue , 2017, Pages S3-S20

  Barsotti, Simone ^a,b   Bruni, Cosimo ^c   Orlandi, Martina ^c   Della Rossa, Alessandra ^a   Marasco, Emiliano ^d   Codullo, Veronica ^d   Guiducci, Serena ^c  

^a UNIVERSITY OF PISA   (Italy)

^b UNIVERSITY OF SIENA   (Italy)

^c UNIVERSITY OF FLORENCE   (Italy)

^d FONDAZIONE IRCCS POLICLINICO SAN MATTEO   (Italy)

Author keywords

Diagnosis; Pathogenesis; Systemic sclerosis; Treatment

Indexed keywords

AMBRISENTAN; AZATHIOPRINE; BIOLOGICAL MARKER; CD2 ANTIGEN; CHEMOKINE; CXCL4 CHEMOKINE; CYCLOPHOSPHAMIDE; ENDOTHELIN RECEPTOR ANTAGONIST; HLA ANTIGEN; HLA DQA1 ANTIGEN; HLA DRB1 ANTIGEN; INTERLEUKIN 10; MYCOPHENOLATE MOFETIL; PHOSPHODIESTERASE V INHIBITOR; PIRFENIDONE; PLACEBO; PROGRAMMED DEATH 1 LIGAND 1; PROGRAMMED DEATH 1 LIGAND 2; PROGRAMMED DEATH 1 RECEPTOR; PROTEIN KL 6; RIOCIGUAT; RITUXIMAB; SELEXIPAG; SURFACTANT PROTEIN D; TADALAFIL; TRANSFORMING GROWTH FACTOR BETA1; TREPROSTINIL; UNCLASSIFIED DRUG;

AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION; CD8+ T LYMPHOCYTE; CELLULAR IMMUNITY; CHROMOSOME INACTIVATION; EXTRACORPOREAL SHOCK WAVE THERAPY; GENE; GENE FREQUENCY; GENE LOCUS; GENETIC PREDISPOSITION; GENETIC RISK; GENETIC SUSCEPTIBILITY; GENETIC VARIATION; GENOTYPE; HUMAN; INFLAMMATION; KIR2DL2 GENE; KIR2DS2 GENE; KIR2DS3 GENE; KIR3DL1 GENE; LUNG FIBROSIS; MEMORY CELL; NONHUMAN; PATHOGENESIS; PHYSICAL MEDICINE; PRIORITY JOURNAL; PULMONARY HYPERTENSION; REVIEW; RISK ASSESSMENT; RISK FACTOR; SINGLE NUCLEOTIDE POLYMORPHISM; SKIN FIBROSIS; SYSTEMIC SCLEROSIS; VASCULAR DISEASE; ANIMAL; COMBINATION DRUG THERAPY; HEMATOPOIETIC STEM CELL TRANSPLANTATION;

ANIMALS; BIOMARKERS; DRUG THERAPY, COMBINATION; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; SCLERODERMA, SYSTEMIC;

EID: 85031672564     PISSN: 0392856X     EISSN: 1593098X     Source Type: Journal    
DOI: None     Document Type: Review

References (169)

1. BARSOTTI S, STAGNARO C, DELLA ROSSA A: Systemic sclerosis: a critical digest of the recent literature. Clin Exp Rheumatol 2015; 33 (Suppl. 91): S3-14
2. GUO S, LI Y, WANG Y et al.: Copy number variation of HLA-DQA1 and APOBEC3A/3B contribute to the susceptibility of systemic sclerosis in the Chinese Han population. J Rheumatol 2016; 43: 880-6
3. KANAAN SB, ONAT OE, BALANDRAUD N et al.: Evaluation of X chromosome inactivation with respect to HLA genetic susceptibility in rheumatoid arthritis and systemic Sclerosis. PLoS One 2016; 11: e0158550
4. LEE JS, PARK JK, KIM HJ, LEE HK, SONG YW, LEE EB: Negatively-charged amino acids at the peptide-binding pocket of HLA-DPB1 alleles are associated with susceptibility to anti-topoisomerase I-positive systemic sclerosis. Hum Immunol 2016; 77: 550-4
5. STEVENS AM, KANAAN SB, TOROK KS et al.: Brief report: HLA-DRB1, DQA1, and DQB1 in juvenile-onset systemic sclerosis. Arthritis Rheumatol 2016; 68: 2772-7
6. TOZKIR JD, TOZKIR H, GüRKAN H et al.: The investigation of killer cell immunoglobulin-like receptor genotyping in patients with systemic lupus erytematosus and sys temic sclerosis. Clin Rheumatol 2016; 35: 919-25
7. PEHLIVAN Y, YOLBAS S, CETIN GY et al.: Investigation of the association between Rho/ Rho-kinase gene polymorphisms and systemic sclerosis. Rheumatol Int 2016; 36: 421-7
8. HUANG X-L, WU G-C, WANG Y-J et al.: Association of interleukin-1 family cytokines single nucleotide polymorphisms with susceptibility to systemic sclerosis: an independent case-control study and a metaanalysis. Immunol Res 2016; 64: 1041-52
9. MAK ACY, TANG PLF, CLEVELAND C et al.: Brief Report: Whole-Exome Sequencing for Identification of Potential Causal Variants for Diffuse Cutaneous Systemic Sclerosis. Arthritis Rheumatol 2016; 68: 2257-62
10. GAO L, EMOND MJ, LOUIE T et al.: Identification of rare variants in ATP8B4 as a risk factor for systemic sclerosis by whole-exome sequencing. Arthritis Rheumatol 2016; 68: 191-200
11. LOFGREN S, HINCHCLIFF M, CARNS M et al.: Integrated, multicohort analysis of systemic sclerosis identifies robust transcriptional signature of disease severity. JCI Insight 2016; 1: e89073
12. RECH TF, MORAES SBC, BREDEMEIER M et al.: Matrix metalloproteinase gene polymorphisms and susceptibility to systemic sclerosis. Genet Mol Res 2016; 15
13. KOUMAKIS E, BOUAZIZ M, DIEUDé P et al.: A candidate gene study identifies a haplotype of CD2 as novel susceptibility factor for systemic sclerosis. Clin Exp Rheumatol 2016; 34 (Suppl. 100): S43-8
14. KAMAL A, GAMAL SM, ELGENGEHY FT, ALKEMARY AK, SIAM I: Association of VDR ApaI and TaqI gene polymorphisms with the risk of scleroderma and Behçet's disease. Immunol Invest 2016; 45: 531-42
15. XU Y, WANG W, TIAN Y, LIU J, YANG R: Polymorphisms in STAT4 and IRF5 increase the risk of systemic sclerosis: a meta-analysis. Int J Dermatol 2016; 55: 408-16
16. LóPEZ-ISAC E, CAMPILLO-DAVO D, BOSSINI-CASTILLO L et al.: Influence of TYK2 in systemic sclerosis susceptibility: a new locus in the IL-12 pathway. Ann Rheum Dis 2016; 75: 1521-6
17. KOCA SS, PEHLIVAN Y, KARA M et al.: The IL-33 gene is related to increased susceptibility to systemic sclerosis. Rheumatol Int 2016; 36: 579-84
18. BARANSKA M, RYCHLIK-SYCH M, KASZUBA A, DZIANKOWSKA-BARTKOWIAK B, SKRETKOWICZ J, WASZCZYKOWSKA E: Genetic polymorphism of CYP2D6 in patients with systemic lupus erythematosus and systemic sclerosis. Autoimmunity 2016: 1-6. [Epub ahead of print]
19. ZHAO J-H, DUAN Y, WANG Y-J, HUANG X-L, YANG G-J, WANG J: The influence of different solvents on systemic sclerosis. J Clin Rheumatol 2016; 22: 253-9
20. WEI P, YANG Y, GUO X et al.: Identification of an association of TNFAIP3 polymorphisms with matrix metalloproteinase expression in fibroblasts in an integrative study of systemic sclerosis-associated genetic and environmental factors. Arthritis Rheumatol 2016; 68: 749-60
21. COSSU M, van BON L, NIERKENS S et al.: The magnitude of cytokine production by stimulated CD56(+) cells is associated with early stages of systemic sclerosis. Clin Immunol 2016; 173: 76-80
22. OKRóJ M, JOHANSSON M, SAXNE T, BLOM AM, HESSELSTRAND R: Analysis of complement biomarkers in systemic sclerosis indicates a distinct pattern in scleroderma renal crisis. Arthritis Res Ther 2016; 18: 267
23. YOSHIZAKI A, TANIGUCHI T, SAIGUSA R et al.: Nucleosome in patients with systemic sclerosis: possible association with immunological abnormalities via abnormal activation of T and B cells. Ann Rheum Dis 2016; 75: 1858-65
24. SIMON D, BALOGH P, BOGNáR A et al.: Reduced non-switched memory B cell subsets cause imbalance in B cell repertoire in systemic sclerosis. Clin Exp Rheumatol 2016; 34 (Suppl. 100): S30-36
25. MAVROPOULOS A, SIMOPOULOU T, VARNA A et al.: Breg cells are numerically decreased and functionally impaired in patients with systemic sclerosis. Arthritis Rheumatol 2016; 68: 494-504
26. KLEIN M, SCHMALZING M, ALMANZAR G et al.: Contribution of CD8+ T cells to inflammatory cytokine production in systemic sclerosis (SSc). Autoimmunity 2016; 49: 532-46
27. LEI L, ZHAO C, QIN F, HE Z-Y, WANG X, ZHONG X-N: Th17 cells and IL-17 promote the skin and lung inflammation and fibrosis process in a bleomycin-induced murine model of systemic sclerosis. Clin Exp Rheumatol 2016; 34 (Suppl. 100): S14-22
28. ALMANZAR G, KLEIN M, SCHMALZING M et al.: Disease manifestation and inflammatory activity as modulators of th17/treg balance and RORC/FoxP3 methylation in systemic sclerosis. Int Arch Allergy Immunol 2016; 171: 141-54
29. ROAN F, STOKLASEK TA, WHALEN E et al.: CD4+ Group 1 innate lymphoid cells (ilc) form a functionally distinct ILC subset that is increased in systemic sclerosis. J Immunol 2016; 196: 2051-62
30. WOHLFAHRT T, USHERENKO S, ENGLBRECHT M et al.: Type 2 innate lymphoid cell counts are increased in patients with systemic sclerosis and correlate with the extent of fibrosis. Ann Rheum Dis 2016; 75: 623-26
31. HENRIQUES A, SILVA C, SANTIAGO M et al.: Subset-specific alterations in frequencies and functional signatures of δ T cells in systemic sclerosis patients. Inflamm Res 2016; 65: 985-94
32. LI G, LARREGINA AT, DOMSIC RT et al.: Skin-resident effector memory CD8+ CD28-T Cells exhibit a profibrotic phenotype in patients with systemic sclerosis. J Invest Dermatol 2017; 137: 1042-50
33. ELHAI M, AVOUAC J, HOFFMANN-VOLD AM et al.: OX40L blockade protects against inflammation-driven fibrosis. Proc Natl Acad Sci 2016; 113: E3901-E3910
34. BRKIC Z, van BON L, COSSU M et al.: The interferon type I signature is present in systemic sclerosis before overt fibrosis and might contribute to its pathogenesis through high BAFF gene expression and high collagen synthesis. Ann Rheum Dis 2016; 75: 1567-73
35. TSOU P-S, RABQUER BJ, OHARA RA et al.: Scleroderma dermal microvascular endothelial cells exhibit defective response to proangiogenic chemokines. Rheumatology (Oxford) 2016; 55: 745-54
36. TSOU P-S, WREN JD, AMIN MA et al.: Histone deacetylase 5 is overexpressed in scleroderma endothelial cells and impairs angiogenesis via repression of proangiogenic factors. Arthritis Rheumatol 2016; 68: 2975-85
37. McMAHAN ZH, COTTRELL TR, WIGLEY FM et al.: Enrichment of scleroderma vascular disease-associated autoantigens in endothelial lineage cells. Arthritis Rheumatol 2016; 68: 2540-9
38. PATSCHAN S, TAMPE D, MüLLER C et al.: Early endothelial progenitor cells (eEPCs) in systemic sclerosis (SSc)-dynamics of cellular regeneration and mesenchymal transdifferentiation. BMC Musculoskelet Disord 2016; 17: 339
39. MENDOZA FA, PIERA-VELAZQUEZ S, FARBER JL, FEGHALI-BOSTWICK C, JIMéNEZ SA: Endothelial cells expressing endothelial and mesenchymal cell gene products in lung tissue from patients with systemic sclerosisassociated interstitial lung disease. Arthritis Rheumatol 2016; 68: 210-7
40. ROMANO E, CHORA I, MANETTI M et al.: Decreased expression of neuropilin-1 as a novel key factor contributing to peripheral microvasculopathy and defective angiogenesis in systemic sclerosis. Ann Rheum Dis 2016; 75: 1541-9
41. JAFARINEJAD-FARSANGI S, FARAZMAND A, GHARIBDOOST F et al.: Inhibition of microRNA-21 induces apoptosis in dermal fibroblasts of patients with systemic sclerosis. Int J Dermatol 2016; 55: 1259-67
42. WANG Z, JINNIN M, NAKAMURA K et al.: Long non-coding RNA TSIX is upregulated in scleroderma dermal fibroblasts and controls collagen mRNA stabilization. Exp Dermatol 2016; 25: 131-6
43. AKASHI K, SAEGUSA J, SENDO S et al.: Knockout of endothelin type B receptor signaling attenuates bleomycin-induced skin sclerosis in mice. Arthritis Res Ther 2016; 18: 113
44. CORALLO C, SANTUCCI A, BERNARDINI G et al.: Proteomic investigation of dermal fibroblasts isolated from affected and unaffected skin samples from patients with limited cutaneous systemic sclerosis: 2 Distinct Entities? J Rheumatol 2017; 44: 40-48
45. WANG Z, NAKAMURA K, JINNIN M et al.: Establishment and gene expression analysis of disease-derived induced pluripotent stem cells of scleroderma. J Dermatol Sci 2016; 84: 186-96
46. TRUCHETET M-E, DEMOURES B, EDUARDO GUIMARAES J et al.: Platelets induce thymic stromal lymphopoietin production by endothelial cells: contribution to fibrosis in human systemic sclerosis. Arthritis Rheumatol 2016; 68: 2784-94
47. PALUMBO-ZERR K, SOARE A, ZERR P et al.: Composition of TWIST1 dimers regulates fibroblast activation and tissue fibrosis. Ann Rheum Dis 2017; 76: 244-51
48. WEI J, ZHU H, LORD G et al.: Nrf2 exerts cell-autonomous antifibrotic effects: compromised function in systemic sclerosis and therapeutic rescue with a novel heterocyclic chalcone derivative. Transl Res 2017; 183: 71-86.e1
49. KANNO Y, SHU E, KANOH H, SEISHIMA M: The Antifibrotic Effect of a2AP neutralization in systemic sclerosis dermal fibroblasts and mouse models of systemic sclerosis. J Invest Dermatol 2016; 136: 762-9
50. BHATTACHARYYA S, WANG W, MORALESNEBREDA L et al.: Tenascin-C drives persistence of organ fibrosis. Nat Commun 2016; 7: 11703
51. FANG F, MARANGONI RG, ZHOU X et al.: Toll-like receptor 9 signaling is augmented in systemic sclerosis and elicits transforming growth factor β-dependent fibroblast activation. Arthritis Rheumatol 2016; 68: 1989-2002
52. CIECHOMSKA M, O'REILLY S, PRZYBORSKI S, OAKLEY F, BOGUNIA-KUBIK K, van LAAR JM: Histone demethylation and toll-like receptor 8-dependent cross-talk in monocytes promotes transdifferentiation of fibroblasts in systemic sclerosis Via Fra-2. Arthritis Rheumatol 2016; 68: 1493-504
53. UEHARA A, MOTEGI S-I, YAMADA K et al.: Mechanistic insight into the norepinephrineinduced fibrosis in systemic sclerosis. Sci Rep 2016; 6: 34012
54. AKAMATA K, WEI J, BHATTACHARYYA M et al.: SIRT3 is attenuated in systemic sclerosis skin and lungs, and its pharmacologic activation mitigates organ fibrosis. Oncotarget 2016; 7: 69321-36
55. NAKAYAMA W, JINNIN M, TOMIZAWA Y et al.: Dysregulated interleukin-23 signalling contributes to the increased collagen production in scleroderma fibroblasts via balancing microRNA expression. Rheumatology (Oxford) 2017; 56: 145-55
56. LU X, TANG Q, LINDH M et al.: The host defense peptide LL-37 a possible inducer of the type I interferon system in patients with polymyositis and dermatomyositis. J Autoimmun 2017; 78: 46-56
57. TAKAHASHI T, ASANO Y, NAKAMURA K et al.: A potential contribution of antimicrobial peptide LL-37 to tissue fibrosis and vasculopathy in systemic sclerosis. Br J Dermatol 2016; 175: 1195-203
58. O'REILLY S, CIECHOMSKA M, FULLARD N, PRZYBORSKI S, van LAAR JM: IL-13 mediates collagen deposition via STAT6 and microRNA-135b: a role for epigenetics. Sci Rep 2016; 6: 25066
59. CASTELINO FV., BAIN G, PACE VA et al.: An autotaxin/lysophosphatidic acid/interleukin-6 amplification loop drives scleroderma fibrosis. Arthritis Rheumatol 2016; 68: 2964-74
60. GOSWAMI R, COHEN J, SHARMA S et al.: TRPV4 ION channel is associated with scleroderma. J Invest Dermatol 2017; 137: 962-5
61. MANETTI M, ROSA I, FAZI M et al.: Systemic sclerosis-like histopathological features in the myocardium of uPAR-deficient mice. Ann Rheum Dis 2016; 75: 474-8
62. CIPRIANI P, BENEDETTO P DI, DIETRICH H et al.: Searching for a good model for systemic sclerosis: the molecular profile and vascular changes occurring in UCD-200 chickens strongly resemble the early phase of human systemic sclerosis. Arch Med Sci 2016; 4: 828-43
63. TSUJINO K, REED NI, ATAKILIT A, REN X, SHEPPARD D: Transforming growth factor-β plays divergent roles in modulating vascular remodeling, inflammation, and pulmonary fibrosis in a murine model of scleroderma. Am J Physiol Lung Cell Mol Physiol 2017; 312: L22-L31
64. KAVIAN N, MEHLAL S, MARUT W et al.: Imbalance of the vanin-1 pathway in systemic sclerosis. J Immunol 2016; 197: 3326-35
65. van BON L, COSSU M, SCHARSTUHL A et al.: Low heme oxygenase-1 levels in patients with systemic sclerosis are associated with an altered Toll-like receptor response: another role for CXCL4? Rheumatology (Oxford) 2016; 55: 2066-73
66. OGAWA Y, MORIKAWA S, OKANO H et al.: MHC-compatible bone marrow stromal/ stem cells trigger fibrosis by activating host T cells in a scleroderma mouse model. Elife 2016; 5: e09394
67. LUO J, LIU X, LIU J, JIANG M, LUO M, ZHAO J: Activation of TGF-β1 by AQP3-mediated h2o2 transport into fibroblasts of a bleomycin-induced mouse model of scleroderma. J Invest Dermatol 2016; 136: 2372-9
68. DANTAS AT, GONçALVES SMC, de ALMEIDA AR et al.: Reassessing the role of the active TGF-β1 as a biomarker in systemic sclerosis: association of serum levels with clinical manifestations. Dis Markers 2016; 2016: 6064830
69. ABDEL-MAGIED RA, KAMEL SR, SAID AF, ALI HM, ABDEL GAWAD EA, MOUSSA MM: Serum interleukin-6 in systemic sclerosis and its correlation with disease parameters and cardiopulmonary involvement. Sarcoidosis Vasc Diffus lung Dis 2016; 33: 321-30
70. FUKASAWA T, YOSHIZAKI A, EBATA S et al.: Contribution of soluble forms of programmed death 1 and programmed death ligand 2 to disease severity and progression in systemic sclerosis. Arthritis Rheumatol 2017; 69: 1879-90
71. 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: 433-43
72. VALENTINI G, RICCARDI A, VETTORI S et al.: CXCL4 in undifferentiated connective tissue disease at risk for systemic sclerosis (SSc) (previously referred to as very early SSc). Clin Exp Med 2017; 17: 411-4
73. VOLKMANN ER, TASHKIN DP, ROTH MD et al.: Changes in plasma CXCL4 levels are associated with improvements in lung function in patients receiving immunosuppressive therapy for systemic sclerosis-related interstitial lung disease. Arthritis Res Ther 2016; 18: 305
74. WU M, BARON M, PEDROZA C et al.: CCL2 in the circulation predicts long-term progression of interstitial lung disease in patients with early systemic sclerosis: data from two independent cohorts. Arthritis Rheumatol 2017; 69: 1871-8
75. ROLLA G, FUSARO E, NICOLA S et al.: Th-17 cytokines and interstitial lung involvement in systemic sclerosis. J Breath Res 2016; 10: 46013
76. MIYAGAWA T, ASANO Y, de MESTIER Y et al.: Serum H-ficolin levels: clinical association with interstitial lung disease in patients with systemic sclerosis. J Dermatol 2017. [Epub ahead of print]
77. YAMAKAWA H, HAGIWARA E, KITAMURA H et al.: Serum KL-6 and surfactant protein-D as monitoring and predictive markers of interstitial lung disease in patients with systemic sclerosis and mixed connective tissue disease. J Thorac Dis 2017; 9: 362-71
78. HAO Y, HUDSON M, BARON M et al.: Early mortality in a multinational systemic sclerosis inception cohort. Arthritis Rheumatol 2017; 69: 1067-77
79. SHAH AA, ROSEN A, HUMMERS L, WIGLEY F, CASCIOLA-ROSEN L: Close temporal relationship between onset of cancer and scleroderma in patients with RNA polymerase I/III antibodies. Arthritis Rheum 2010; 62: 2787-95
80. KUWANA M: A to-do list at diagnosis of systemic sclerosis with positive anti-rna polymerase III antibodies. J Rheumatol 2017; 44: 550-2
81. LAZZARONI M-G, CAVAZZANA I, COLOMBO E et al.: Malignancies in patients with anti-RNA polymerase III antibodies and systemic sclerosis: analysis of the EULAR scleroderma trials and research cohort and possible recommendations for screening. J Rheumatol 2017; 44: 639-47
82. MORRISROE K, STEVENS W, HUQ M et al.: Survival and quality of life in incident systemic sclerosis-related pulmonary arterial hypertension. Arthritis Res Ther 2017; 19: 122
83. GALIE N, HUMBERT M, VACHIERY J-L et al.: 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endor. Eur Respir J 2015; 46: 903-75
84. MORRISROE K, STEVENS W, SAHHAR J, RABUSA C, NIKPOUR M, PROUDMAN S: Epidemiology and disease characteristics of systemic sclerosis-related pulmonary arterial hypertension: results from a real-life screening programme. Arthritis Res Ther 2017; 19: 42
85. COGHLAN JG, DENTON CP, GRüNIG E et al.: Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study. Ann Rheum Dis 2014; 73: 1340-9
86. GALIE N, HOEPER MM, HUMBERT M et al.: Guidelines for the diagnosis and treatment of pulmonary hypertension: the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the Internat. Eur Heart J 2009; 30: 2493-537
87. GUILLéN-DEL CASTILLO A, CALLEJAS MORAGA EL, GARCíA G et al.: High sensitivity and negative predictive value of the DETECT algorithm for an early diagnosis of pulmonary arterial hypertension in systemic sclerosis: application in a single center. Arthritis Res Ther 2017; 19
88. MARON BA, HESS E, MADDOX TM et al.: Association of borderline pulmonary hypertension with mortality and hospitalization in a large patient cohort: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program. Circulation 2016; 133: 1240-8
89. VANDECASTEELE E, DRIEGHE B, MELSENS K et al.: Screening for pulmonary arterial hypertension in an unselected prospective systemic sclerosis cohort. Eur Respir J 2017; 49: 1602275
90. DIAB N, HASSOUN PM: Pulmonary arterial hypertension: screening challenges in systemic sclerosis and future directions. Eur Respir J 2017; 49
91. D'ANDREA A, D'ALTO M, DI MAIO M et al.: Right atrial morphology and function in patients with systemic sclerosis compared to healthy controls: a two-dimensional strain study. Clin Rheumatol 2016; 35: 1733-42
92. CARREIRA PE, CARMONA L, JOVEN BE et al.: Clinical determinants of elevated systolic pulmonary artery pressure measured by transthoracic Doppler echocardiography in early systemic sclerosis. Clin Exp Rheumatol 2017; 35 (Suppl. 106): S114-121
93. CHUNG L, FAIRCHILD RM, FURST DE et al.: Utility of B-type natriuretic peptides in the assessment of patients with systemic sclerosis-associated pulmonary hypertension in the PHAROS registry. Clin Exp Rheumatol 2017; 35 (Suppl. 106): S106-113
94. DUMITRESCU D, NAGEL C, KOVACS G et al.: Cardiopulmonary exercise testing for detecting pulmonary arterial hypertension in systemic sclerosis. Heart 2017; 103: 774-82
95. LAU EMT, THAKKAR V, HUMBERT M, HERVE P: To stress or not to stress? Exercise pulmonary haemodynamic testing in systemic sclerosis. Eur Respir J 2016; 48: 1549-52
96. STAMM A, SAXER S, LICHTBLAU M et al.: Exercise pulmonary haemodynamics predict outcome in patients with systemic sclerosis. Eur Respir J 2016; 48: 1658-67
97. RAMJUG S, HUSSAIN N, HURDMAN J et al.: Idiopathic and systemic sclerosis-associated pulmonary arterial hypertension: a comparison of demographic, hemodynamic, and mri characteristics and outcomes. Chest 2017; 152: 92-102
98. MAVROGENI SI, SCHWITTER J, GARGANI L et al.: Cardiovascular magnetic resonance in systemic sclerosis: 'Pearls and pitfalls.' Semin Arthritis Rheum 2017; 47: 79-85
99. BOURJI KI, KELEMEN BW, MATHAI SC et al.: Poor survival in patients with scleroderma and pulmonary hypertension due to heart failure with preserved ejection fraction. Pulm Circ 2017; 7: 409-20
100. GOH NSL, DESAI SR, VEERARAGHAVAN S et al.: Interstitial lung disease in systemic sclerosis: a simple staging system. Am J Respir Crit Care Med 2008; 177: 1248-54
101. GOH NS, HOYLES RK, DENTON CP et al.: Short-term pulmonary function trends are predictive of mortality in interstitial lung disease associated with systemic sclerosis. Arthritis Rheumatol 2017; 69: 1670-8
102. ARIANI A, SILVA M, SELETTI V et al.: Quantitative chest computed tomography is associated with two prediction models of mortality in interstitial lung disease related to systemic sclerosis. Rheumatology 2017; 56: 922-7
103. HOA S, STERN EP, DENTON CP, HUDSON M: Towards developing criteria for scleroderma renal crisis: A scoping review. Autoimmun Rev 2017; 16: 407-15
104. MELSENS K, DE KEYSER F, DECUMAN S, PIETTE Y, VANDECASTEELE E, SMITH V: Disease activity indices in systemic sclerosis: a systematic literature review. Clin Exp Rheumatol 2016; 34 (Suppl. 100): S186-92
105. 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: 592-8
106. NEVSKAYA T, BARON M, POPE JE: Predictive value of European Scleroderma Group Activity Index in an early scleroderma cohort. Rheumatology 2017; 56: 1111-22
107. VALENTINI G, IUDICI M, WALKER UA et al.: The European Scleroderma Trials and Research group (EUSTAR) task force for the development of revised activity criteria for systemic sclerosis: derivation and validation of a preliminarily revised EUSTAR activity index. Ann Rheum Dis 2017; 76: 270-6
108. MEDSGER TA, BOMBARDIERI S, CZIRJAK L, SCORZA R, DELLA ROSSA A, BENCIVELLI W: Assessment of disease severity and prognosis. Clin Exp Rheumatol 2003; 21 (Suppl. 29): S42-46
109. CLEMENTS PJ, LACHENBRUCH PA, SEIBOLD JR et al.: Skin thickness score in systemic sclerosis: an assessment of interobserver variability in 3 independent studies. J Rheumatol 1993; 20: 1892-6
110. 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: 1124-31
111. DOBROTA R, MAURER B, GRAF N et al.: Prediction of improvement in skin fibrosis in diffuse cutaneous systemic sclerosis: a EUSTAR analysis. Ann Rheum Dis 2016; 75: 1743-8
112. MAN A, CORREA JK, ZIEMEK J, SIMMS RW, FELSON DT, LAFYATIS R: Development and validation of a patient-reported outcome instrument for skin involvement in patients with systemic sclerosis. Ann Rheum Dis 2017; 76: 1374-80
113. STEEN VD, MEDSGER TA: The value of the Health Assessment Questionnaire and special patient-generated scales to demonstrate change in systemic sclerosis patients over time. Arthritis Rheum 1997; 40: 1984-91
114. POPE J: Measures of systemic sclerosis (scleroderma): Health Assessment Questionnaire (HAQ) and Scleroderma HAQ (SHAQ), physician-and patient-rated global assessments, Symptom Burden Index (SBI), University of California, Los Angeles, Scleroderma Clinical Trials. Arthritis Care Res 2011; 63 (Suppl. 1): S98-111
115. JAEGER VK, DISTLER O, MAURER B et al.: Functional disability and its predictors in systemic sclerosis: a study from the DeSScipher project within the EUSTAR group. Rheumatology 2017. [Epub ahead of print]
116. AVOUAC J, ALLANORE Y: Targeted immunotherapies in systemic sclerosis. Clin Exp Rheumatol 2014; 3 (Suppl. 81): 165-72
117. SCHUPP JC, KOHLER T, MULLER-QUERNHEIM J: Usefulness of cyclophosphamide pulse therapy in interstitial lung diseases. Respiration 2016; 91: 296-301
118. WOYTALA PJ, MORGIEL E, LUCZAK A, CZESAK-WOYTALA K, WILAND P: The safety of intravenous cyclophosphamide in the treatment of rheumatic diseases. Adv Clin Exp Med 2016; 25: 479-84
119. ABIGNANO G, BISSELL L-A, EMERY P, DEL GALDO F, BUCH MH: Does high-dose extended course cyclophosphamide and methylprednisolone pulse therapy have a role in the management of systemic sclerosis-related interstitial lung disease? Rheumatology 2016; 55: 2273-5
120. KUNDU S, PAUL S, HARIPRASATH K, AGARWAL R, GHOSH S, BISWAS D: Effect of Sequential intravenous pulse cyclophosphamide-azathioprine in systemic sclerosisinterstitial lung disease: an open-label study. Indian J Chest Dis Allied Sci 2016; 58: 7-10
121. VOLKMANN ER, TASHKIN DP, LI N et al.: Mycophenolate mofetil versus placebo for systemic sclerosis-related interstitial lung disease: an analysis of scleroderma lung studies I and II. Arthritis Rheumatol 2017; 69: 1451-60
122. SHENOY PD, BAVALIYA M, SASHIDHARAN S, NALIANDA K, SREENATH S: Cyclophosphamide versus mycophenolate mofetil in scleroderma interstitial lung disease (SSc-ILD) as induction therapy: a single-centre, retrospective analysis. Arthritis Res Ther 2016; 18: 123
123. TASHKIN DP, ROTH MD, CLEMENTS PJ et al.: Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial. Lancet Respir Med 2016; 4: 708-19
124. OWEN C, NGIAN G-S, ELFORD K et al.: Mycophenolate mofetil is an effective and safe option for the management of systemic sclerosis-associated interstitial lung disease: results from the Australian Scleroderma Cohort Study. Clin Exp Rheumatol 2016; 34 (Suppl. 100): S170-6
125. NAMAS R, TASHKIN DP, FURST DE et al.: Efficacy of mycophenolate mofetil and oral cyclophosphamide on skin thickness: Posthoc analyses from the Scleroderma Lung Study I and II. Arthritis Care Res May 2017
126. YOSHIZAKI A: B cell abnormalities and therapeutic strategies in systemic sclerosis. Nihon Rinsho Meneki Gakkai Kaishi 2016; 39: 197-206
127. DAOUSSIS D, TSAMANDAS A, ANTONOPOULOS I et al.: B cell depletion therapy upregulates Dkk-1 skin expression in patients with systemic sclerosis: association with en hanced resolution of skin fibrosis. Arthritis Res Ther 2016; 18: 118
128. DAOUSSIS D, MELISSAROPOULOS K, SAKELLAROPOULOS G et al.: A multicenter, open-label, comparative study of B-cell depletion therapy with Rituximab for systemic sclerosis-associated interstitial lung disease. Semin Arthritis Rheum 2017; 46: 625-31
129. LEPRI G, AVOUAC J, AIRO P et al.: Effects of rituximab in connective tissue disorders related interstitial lung disease. Clin Exp Rheumatol 2016; 34 (Suppl. 100): S181-5
130. VILELA VS, MARETTI GB, GAMA LM da S et al.: Rituximab for the therapy of systemic sclerosis: a series of 10 cases in a single center. Rev Bras Reumatol 2016; 56: 458-63
131. POORMOGHIM H, ANDALIB E, ALMASI AR, HADIBIGI E: Systemic sclerosis and calcinosis cutis: response to rituximab. J Clin Pharm Ther 2016; 41: 94-6
132. DUBOS M, LY K, MARTEL C, FAUCHAIS AL: Is rituximab an effective treatment of refractory calcinosis? BMJ Case Rep 2016; 2016
133. HUMBERT M, COGHLAN JG, GHOFRANI H-A et al.: Riociguat for the treatment of pulmonary arterial hypertension associated with connective tissue disease: results from PATENT-1 and PATENT-2. Ann Rheum Dis 2017; 76: 422-6
134. DISTLER O, POPE J, DENTON C et al.: RISESSc: Riociguat in diffuse cutaneous systemic sclerosis. Respir Med 2017; 122 (Suppl): S14-7
135. VOLKMANN ER, TASHKIN DP: Treatment of systemic sclerosis-related interstitial lung disease: a review of existing and emerging therapies. Ann Am Thorac Soc 2016; 13: 2045-56
136. KHANNA D, ALBERA C, FISCHER A et al.: An Open-label, Phase II Study of the Safety and Tolerability of Pirfenidone in Patients with Scleroderma-associated Interstitial Lung Disease: the LOTUSS Trial. J Rheumatol 2016; 43: 1672-9
137. MOINZADEH P, RIEMEKASTEN G, SIEGERT E et al.: Vasoactive therapy in systemic sclerosis: real-life therapeutic practice in more than 3000 patients. J Rheumatol 2016; 43: 66-74
138. SUMIDA H, ASANO Y, HATANO M et al.: Effect of ambrisentan on peripheral circulation in patients with systemic sclerosis. Mod Rheumatol 2016; 26: 454-7
139. MATUCCI-CERINIC M, DENTON CP, FURST DE et al.: Bosentan treatment of digital ulcers related to systemic sclerosis: results from the RAPIDS-2 randomised, doubleblind, placebo-controlled trial. Ann Rheum Dis 2011; 70: 32-8
140. KHANNA D, DENTON CP, MERKEL PA et al.: Effect of Macitentan on the Development of New Ischemic Digital Ulcers in Patients With Systemic Sclerosis: DUAL-1 and DUAL-2 Randomized Clinical Trials. JAMA 2016; 315: 1975-88
141. PAN Y, HU C, CHEN PH et al.: Association of oral endothelin receptor antagonists with risks of cardiovascular events and mortality: meta-analysis of randomized controlled trials. Eur J Clin Pharmacol 2017; 73: 267-78
142. DELLA ROSSA A, DOVERI M, D'ASCANIO A et al.: Oral sildenafil in skin ulcers secondary to systemic sclerosis. Scand J Rheumatol 2011; 40: 323-5
143. HACHULLA E, HATRON P-Y, CARPENTIER P et al.: Efficacy of sildenafil on ischaemic digital ulcer healing in systemic sclerosis: the placebo-controlled SEDUCE study. Ann Rheum Dis 2016; 75: 1009-15
144. SHAH AA, SCHIOPU E, CHATTERJEE S et al.: The recurrence of digital ulcers in patients with systemic sclerosis after discontinuation of oral treprostinil. J Rheumatol 2016; 43: 1665-71
145. GAILLARD-BIGOT F, ROUSTIT M, BLAISE S et al.: Treprostinil iontophoresis improves digital blood flow during local cooling in systemic sclerosis. Microcirculation 2016; 23: 266-70
146. GAINE S, CHIN K, COGHLAN G et al.: Selexipag for the treatment of connective tissue disease-associated pulmonary arterial hypertension. Eur Respir J 2017; 50
147. COGHLAN JG, GALIE N, BARBERà JA et al.: Initial combination therapy with ambrisentan and tadalafil in connective tissue diseaseassociated pulmonary arterial hypertension (CTD-PAH): subgroup analysis from the AMBITION trial. Ann Rheum Dis 2017; 76: 1219-27
148. LAMMI MR, MATHAI SC, SAKETKOO LA et al.: Association between initial oral therapy and outcomes in systemic sclerosis-related pulmonary arterial hypertension. Arthritis Rheumatol 2016; 68: 740-8
149. BELLANDO-RANDONE S, LEPRI G, BRUNI C et al.: Combination therapy with Bosentan and Sildenafil improves Raynaud's phenomenon and fosters the recovery of microvascular involvement in systemic sclerosis. Clin Rheumatol 2016; 35: 127-32
150. CESTELLI V, MANFREDI A, SEBASTIANI M et al.: Effect of treatment with iloprost with or without bosentan on nailfold videocapillaroscopic alterations in patients with systemic sclerosis. Mod Rheumatol 2017; 27: 110-4
151. DEL PAPA N, ONIDA F, ZACCARA E et al.: Autologous hematopoietic stem cell transplantation has better outcomes than conventional therapies in patients with rapidly progressive systemic sclerosis. Bone Marrow Transplant 2017; 52: 53-8
152. HOU Y, LI H-J, LI M-T, XU D, ZHOU D-B, ZENG X-F: A successful case of second autologous haematopoietic stem cell transplantation for post-transplant systemic sclerosis relapse. Clin Exp Rheumatol 2016; 34 (Suppl. 100): S207
153. BLANK N, LISENKO K, PAVEL P, BRUCKNER T, HO AD, WUCHTER P: Low-dose cyclophosphamide effectively mobilizes peripheral blood stem cells in patients with autoimmune disease. Eur J Haematol 2016; 97: 78-82
154. SAUTEREAU N, DAUMAS A, TRUILLET R et al.: Efficacy of Autologous Microfat Graft on Facial Handicap in Systemic Sclerosis Patients. Plast Reconstr Surg Glob Open 2016; 4: e660
155. GUILLAUME-JUGNOT P, DAUMAS A, MAGALON J et al.: Autologous adiposederived stromal vascular fraction in patients with systemic sclerosis: 12-month followup. Rheumatology (Oxford) 2016; 55: 301-6
156. DAUMAS A, MAGALON J, JOUVE E et al.: Long-term follow-up after autologous adipose-derived stromal vascular fraction injection into fingers in systemic sclerosis patients. Curr Res Transl Med 2017; 65: 40-3
157. BRASCHI F, BARTOLI F, BRUNI C et al.: Lidocaine controls pain and allows safe wound bed preparation and debridement of digital ulcers in systemic sclerosis: a retrospective study. Clin Rheumatol 2017; 36: 209-12
158. UGHI N, CROTTI C, INGEGNOLI F: Effectiveness and safety of oxycodone/naloxone in the management of chronic pain in patients with systemic sclerosis with recurrent digital ulcers: two case reports. Clin Interv Aging 2016; 11: 307-11
159. SAITO S, ISHII T, KAMOGAWA Y et al.: Extracorporeal shock wave therapy for digital ulcers of systemic sclerosis: a phase 2 pilot study. Tohoku J Exp Med 2016; 238: 39-47
160. MAHMOOD M, WILKINSON J, MANNING J, HERRICK AL: History of surgical debridement, anticentromere antibody, and disease duration are associated with calcinosis in patients with systemic sclerosis. Scand J Rheumatol 2016; 45: 114-7
161. BLUMHARDT S, FREY DP, TONIOLO M, ALKADHI H, HELD U, DISTLER O: Safety and efficacy of extracorporeal shock wave therapy (ESWT) in calcinosis cutis associated with systemic sclerosis. Clin Exp Rheumatol 2016; 34 (Suppl. 100): S177-80
162. Del BARRIO-DIAZ P, MOLL-MANZUR C, ALVAREZ-VELIZ S, VERA-KELLET C: Topical sodium metabisulfite for the treatment of calcinosis cutis: a promising new therapy. Br J Dermatol 2016; 175: 608-11
163. YOUNG A, NAMAS R, DODGE C, KHANNA D: Hand impairment in systemic sclerosis: various manifestations and currently available treatment. Curr Treatm Opt Rheumatol 2016; 2: 252-69
164. STEFANANTONI K, SCIARRA I, IANNACE N et al.: Occupational therapy integrated with a self-administered stretching program on systemic sclerosis patients with hand involvement. Clin Exp Rheumatol 2016; 34 (Suppl. 100): S157-61
165. SAKKAS LI: Spotlight on tocilizumab and its potential in the treatment of systemic sclerosis. Drug Des Devel Ther 2016; 10: 2723-8
166. DISTLER O, DISTLER JHW: Tocilizumab for systemic sclerosis: implications for future trials. Lancet 2016; 387: 2580-1
167. KHANNA D, DENTON CP, JAHREIS A et al.: Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis (faSScinate): a phase 2, randomised, controlled trial. Lancet 2016; 387: 2630-40
168. Effects of selexipag in adults with raynaud's phenomenon secondary to systemic sclerosis. 2014. Retrieved from http:// clinicaltrials.gov/ct2 (Identification No. NCT02260557)
169. Abituzumab in SSc-ILD. 2016. Retrieved from http://clinicaltrials.gov/ct2 (Identification No. NCT02745145)